tag:blogger.com,1999:blog-14814401588405494552023-11-15T06:27:23.869-08:00Warburg's Lens: A Mathematical oncology pre-print discussion forumAn open forum to aggregate open access pre-prints related to mathematical oncology for discussion.Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.comBlogger151125tag:blogger.com,1999:blog-1481440158840549455.post-47390932746372462242017-10-16T11:31:00.002-07:002017-10-16T11:31:28.009-07:00sigQC: A procedural approach for standardising the evaluation of gene signatures<div class="panel-pane pane-highwire-article-citation" style="-webkit-font-smoothing: antialiased; background-color: white; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: 14px; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px 0px 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
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<div class="highwire-article-citation highwire-citation-type-highwire-article" data-apath="/biorxiv/early/2017/10/16/203729.atom" data-hw-author-tooltip-instance="highwire_author_tooltip" data-node-nid="62065" data-pisa-master="biorxiv;203729" data-pisa="biorxiv;203729v1" id="node62065" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
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<h1 class="highwire-cite-title" id="page-title" style="-webkit-font-smoothing: antialiased; border: 0px; color: #131313; font-size: 1.33rem; font-stretch: normal; letter-spacing: -0.03em; line-height: 1.9rem; margin: 0px 0px 20px; outline: 0px; padding: 16px 0px 0px; vertical-align: baseline;">
sigQC: A procedural approach for standardising the evaluation of gene signatures</h1>
<div class="highwire-cite-authors" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-citation-authors" style="border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="highwire-citation-author first has-tooltip hasTooltip" data-delta="0" data-hasqtip="3" style="border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Andrew</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Dhawan</span></span>, <span class="highwire-citation-author" data-delta="1" style="border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Alessandro</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Barberis</span></span>, <span class="highwire-citation-author" data-delta="2" style="border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Wei-Chen</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Cheng</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="3" data-hasqtip="1" style="border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Enric</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Domingo</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="4" data-hasqtip="2" style="border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Catharine</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">West</span></span>, <span class="highwire-citation-author" data-delta="5" style="border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Tim</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Maughan</span></span>, <span class="highwire-citation-author" data-delta="6" style="border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Jacob</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Scott</span></span>, <span class="highwire-citation-author" data-delta="7" style="border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Adrian L</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Harris</span></span>, <span aria-describedby="qtip-0" class="highwire-citation-author has-tooltip hasTooltip" data-delta="8" data-hasqtip="0" style="border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Francesca M</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Buffa</span></span></span></div>
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<span class="highwire-cite-metadata-doi highwire-cite-metadata" style="border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="label" style="border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: bold; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">doi:</span> https://doi.org/10.1101/203729</span><br />
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This article is a preprint and has not been peer-reviewed [<a href="https://www.biorxiv.org/content/what-unrefereed-preprint" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank">what does this mean?</a>].</div>
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<li style="-webkit-font-smoothing: antialiased; background: transparent; border: 0px; display: inline; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.5em; list-style: none; margin: 0px; outline: 0px; padding: 0px; text-align: left; vertical-align: baseline;"><a class="panels-ajax-tab-tab panels-ajax-tabs-once-processed hw-panels-ajax-tabs-once-processed" data-entity-context="node:62065" data-panel-name="biorxiv_tab_info" data-target-id="highwire_article_tabs" data-trigger="article-info" data-url-enabled="1" href="https://www.biorxiv.org/content/early/2017/10/16/203729.article-info" style="-webkit-background-clip: padding-box; -webkit-font-smoothing: antialiased; background: transparent; border-bottom-color: initial; border-bottom-style: initial; border-image: initial; border-left-color: transparent; border-left-style: solid; border-radius: 0px; border-right-color: transparent; border-right-style: solid; border-top-color: transparent; border-top-style: solid; border-width: 1px 1px 0px; color: grey; cursor: pointer; display: inline-block; font-family: inherit; font-size: 1em; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: 1.17em; margin: 0px 10px 0px 0px; outline: 0px; padding: 6px 8px; text-align: center; text-decoration-line: none; transition: background-color 200ms ease-in, color 200ms ease-in; vertical-align: baseline; width: auto; zoom: 1;">Info/History</a></li>
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Abstract</h2>
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With the increase in next generation sequencing generating large amounts of genomic data, gene expression signatures are becoming critically important tools, poised to make a large impact on the diagnosis, management and prognosis for a number of diseases. Increasingly, it is becoming necessary to determine whether a gene expression signature may apply to a dataset, but no standard quality control methodology exists. In this work, we introduce the first protocol, implemented in an R package sigQC, enabling a streamlined methodological and standardised approach for the quality control validation of gene signatures on independent data sets. The emphasis in this work is in showing the critical quality control steps involved in the generation of a clinically and biologically useful, transportable gene signature, including ensuring sufficient expression, variability, and autocorrelation of a signature. We demonstrate the application of the protocol in this work, showing how the outputs created from sigQC may be used for the evaluation of gene signatures on large-scale gene expression data in cancer.</div>
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<span style="color: #191919; font-family: "lucida sans" , "helvetica" , "arial" , sans-serif;"><span style="font-size: 16.8px;">https://www.biorxiv.org/content/early/2017/10/16/203729</span></span></div>
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Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.com3tag:blogger.com,1999:blog-1481440158840549455.post-35012990430817360202017-10-12T06:02:00.002-07:002017-10-12T06:02:16.890-07:00Optimal Therapy Scheduling Based on a Pair of Collaterally Sensitive Drugs<div class="panel-pane pane-highwire-article-citation" style="-webkit-font-smoothing: antialiased; background-color: white; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: 14px; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px 0px 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
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Optimal Therapy Scheduling Based on a Pair of Collaterally Sensitive Drugs</h1>
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<span class="highwire-citation-authors" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="highwire-citation-author first hw-author-orcid-logo-wrapper has-tooltip hasTooltip" data-delta="0" data-hasqtip="1" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0001-8937-4196" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Nara</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Yoon</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" data-hasqtip="0" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Robert</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Vander Velde</span></span>, <span class="highwire-citation-author" data-delta="2" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Andriy</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Marusyk</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="3" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0003-2971-7673" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Jacob</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Scott</span></span></span></div>
<div class="highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 0.82rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-cite-metadata-doi highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="label" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: bold; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">doi:</span> https://doi.org/10.1101/196824</span><div class="pub_jnl" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: 10pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25em; margin: 0px; outline: 0px; padding: 8px 0px 0px; vertical-align: baseline;">
This article is a preprint and has not been peer-reviewed [<a href="https://www.biorxiv.org/content/what-unrefereed-preprint" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank">what does this mean?</a>].</div>
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Abstract</h2>
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Despite major strides in the treatment of cancer, the development of drug resistance remains a major hurdle. To address this issue, researchers have proposed sequential drug therapies with which the resistance developed by a previous drug can be relieved by the next one, a concept called collateral sensitivity. The optimal times of these switches, however, remains unknown. We therefore developed a dynamical model and study the effect of sequential therapy on heterogeneous tumors comprised of resistant and sensitivity cells. A pair of drugs (DrugA, DrugB) are utilized and switched in turn within the therapy schedule. Assuming that they are collaterally sensitive to each other, we classified cancer cells into two groups, and explored their population dynamics: A_R and B_R, each of which is subpopulation of cells resistant to the indicated drug and concurrently sensitive to the other. Based on a system of ordinary differential equations for A_R and B_R, we determined that the optimal treatment strategy consists of two stages: initial stage in which a chosen better drug is utilised until a specific time point, T, and afterward; a combination of the two drugs with relative durations (i.e. f Δt-long for DrugA and (1-f)Δt-long for DrugB with 0≤f≤1 and Δt≥0). Of note, we prove that the initial period, in which the first drug is administered, T, is shorter than the period in which it remains effective in lowing total population, contrary to current clinical intuition. We further analyzed the relationship between population makeup, ApB=A_R/B_R, and effect of each drug. We determine a specific makeup, ApB*, at which the two drugs are equally effective. While the optimal strategy is applied, ApB is changing monotonically to ApB* and then remains at ApB* thereafter. Beyond our analytic results, we explored an individual based stochastic model and presented the distribution of extinction times for the classes of solutions found. Taken together, our results suggest opportunities to improve therapy scheduling in clinical oncology.</div>
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<span style="color: #191919; font-family: Lucida Sans, Helvetica, Arial, sans-serif;"><span style="font-size: 16.8px;">https://www.biorxiv.org/content/early/2017/10/11/196824</span></span></div>
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Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.com2tag:blogger.com,1999:blog-1481440158840549455.post-31728744419149585302017-09-14T12:11:00.003-07:002017-09-14T12:11:45.697-07:00Complexity of evolutionary equilibria in static fitness landscapes<div class="panel-pane pane-highwire-article-citation" style="-webkit-font-smoothing: antialiased; background-color: white; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: 14px; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px 0px 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
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Complexity of evolutionary equilibria in static fitness landscapes</h1>
<div class="highwire-cite-authors" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-citation-authors" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="highwire-citation-author first has-tooltip hasTooltip" data-delta="0" data-hasqtip="0" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Artem</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Kaznatcheev</span></span></span></div>
<div class="highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 0.82rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-cite-metadata-doi highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="label" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: bold; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">doi:</span> https://doi.org/10.1101/187682</span><div class="pub_jnl" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: 10pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25em; margin: 0px; outline: 0px; padding: 8px 0px 0px; vertical-align: baseline;">
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<li style="-webkit-font-smoothing: antialiased; background: transparent; border: 0px; display: inline; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.5em; list-style: none; margin: 0px; outline: 0px; padding: 0px; text-align: left; vertical-align: baseline;"><a class="panels-ajax-tab-tab panels-ajax-tabs-once-processed hw-panels-ajax-tabs-once-processed" data-entity-context="node:56782" data-panel-name="biorxiv_tab_info" data-target-id="highwire_article_tabs" data-trigger="article-info" data-url-enabled="1" href="http://www.biorxiv.org/content/early/2017/09/12/187682.article-info" style="-webkit-background-clip: padding-box; -webkit-font-smoothing: antialiased; background: transparent; border-bottom-color: initial; border-bottom-style: initial; border-image: initial; border-left-color: transparent; border-left-style: solid; border-radius: 0px; border-right-color: transparent; border-right-style: solid; border-top-color: transparent; border-top-style: solid; border-width: 1px 1px 0px; color: grey; cursor: pointer; display: inline-block; font-family: inherit; font-size: 1em; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: 1.17em; margin: 0px 10px 0px 0px; outline: 0px; padding: 6px 8px; text-align: center; text-decoration-line: none; transition: background-color 200ms ease-in, color 200ms ease-in; vertical-align: baseline; width: auto; zoom: 1;">Info/History</a></li>
<li style="-webkit-font-smoothing: antialiased; background: transparent; border: 0px; display: inline; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.5em; list-style: none; margin: 0px; outline: 0px; padding: 0px; text-align: left; vertical-align: baseline;"><a class="panels-ajax-tab-tab panels-ajax-tabs-once-processed hw-panels-ajax-tabs-once-processed" data-entity-context="node:56782" data-panel-name="article_tab_metrics" data-target-id="highwire_article_tabs" data-trigger="article-metrics" data-url-enabled="1" href="http://www.biorxiv.org/content/early/2017/09/12/187682.article-metrics" style="-webkit-background-clip: padding-box; -webkit-font-smoothing: antialiased; background: transparent; border-bottom-color: initial; border-bottom-style: initial; border-image: initial; border-left-color: transparent; border-left-style: solid; border-radius: 0px; border-right-color: transparent; border-right-style: solid; border-top-color: transparent; border-top-style: solid; border-width: 1px 1px 0px; color: grey; cursor: pointer; display: inline-block; font-family: inherit; font-size: 1em; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: 1.17em; margin: 0px 10px 0px 0px; outline: 0px; padding: 6px 8px; text-align: center; text-decoration-line: none; transition: background-color 200ms ease-in, color 200ms ease-in; vertical-align: baseline; width: auto; zoom: 1;">Metrics</a></li>
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Abstract</h2>
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Experiments show that fitness landscapes can have a rich combinatorial structure due to epistasis and yet theory assumes that local peaks can be reached quickly. I introduce a distinction between easy landscapes where local fitness peaks can be found in a moderate number of steps and hard landscapes where finding evolutionary equilibria requires an infeasible amount of time. Hard examples exist even among landscapes with no reciprocal sign epistasis; on these, strong selection weak mutation dynamics cannot find the unique peak in polynomial time. On hard rugged fitness landscapes, no evolutionary dynamics -- even ones that do not follow adaptive paths -- can find a local fitness peak quickly; and the fitness advantage of nearby mutants cannot drop off exponentially fast but has to follow a power-law that long term evolution experiments have associated with unbounded growth in fitness. I present candidates for hard landscapes at scales from singles genes, to microbes, to complex organisms with costly learning (Baldwin effect). Even though hard landscapes are static and finite, local evolutionary equilibrium cannot be assumed.</div>
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<span style="color: #191919; font-family: Lucida Sans, Helvetica, Arial, sans-serif;"><span style="font-size: 16.8px;">http://www.biorxiv.org/content/early/2017/09/12/187682</span></span></div>
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Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-88499586852624179032017-09-07T21:14:00.001-07:002017-09-07T21:14:25.235-07:00Collateral sensitivity is contingent on the repeatability of evolution<div class="panel-pane pane-highwire-article-citation" style="-webkit-font-smoothing: antialiased; background-color: white; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: 14px; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px 0px 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
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Collateral sensitivity is contingent on the repeatability of evolution</h1>
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outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Daniel</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Nichol</span></span>, <span aria-describedby="qtip-0" class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" data-hasqtip="0" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; 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border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Christopher</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Bryant</span></span>, <span class="highwire-citation-author" data-delta="3" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Peter</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Jeavons</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="4" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0002-2536-4383" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Alexander</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Anderson</span></span>, <span class="highwire-citation-author" data-delta="5" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Robert</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Bonomo</span></span>, <span class="highwire-citation-author" data-delta="6" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Jacob</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Scott</span></span></span></div>
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<span class="highwire-cite-metadata-doi highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="label" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: bold; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">doi:</span> https://doi.org/10.1101/185892</span><div class="pub_jnl" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: 10pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25em; margin: 0px; outline: 0px; padding: 8px 0px 0px; vertical-align: baseline;">
This article is a preprint and has not been peer-reviewed [<a href="http://www.biorxiv.org/content/what-unrefereed-preprint" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank">what does this mean?</a>].</div>
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Abstract</h2>
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Antibiotic resistance represents a growing health crisis that necessitates the immediate discovery of novel treatment strategies. One such strategy is the identification of sequences of drugs exhibiting collateral sensitivity, wherein the evolution of resistance to a first drug renders a population more susceptible to a second. Here, we demonstrate that sequential multi-drug therapies derived from in vitro evolution experiments can have overstated therapeutic benefit - potentially suggesting a collaterally sensitive response where cross resistance ultimately occurs. The evolution of drug resistance need not be genetically or phenotypically convergent, and where resistance arises through divergent mechanisms, the efficacy of a second drug can vary substantially. We first quantify the likelihood of this occurring by use of a mathematical model parametrised by a set of small combinatorially complete fitness landscapes for Escherichia coli. We then verify, through in vitro experimental evolution, that a second-line drug can indeed stochastically exhibit either increased susceptibility or increased resistance when following a first. Genetic divergence is confirmed as the driver of this differential response through targeted sequencing. These results indicate that the present methodology of designing drug regimens through experimental collateral sensitivity analysis may be flawed under certain ecological conditions. Further, these results suggest the need for a more rigorous probabilistic understanding of the contingencies that can arise during the evolution of drug resistance.</div>
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<span style="color: #191919; font-family: Lucida Sans, Helvetica, Arial, sans-serif;"><span style="font-size: 16.8px;">http://www.biorxiv.org/content/early/2017/09/07/185892</span></span></div>
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Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-59608666663110627892017-09-04T06:25:00.002-07:002017-09-04T06:26:09.349-07:00Temporally-Feathered Intensity Modulated Radiation Therapy: A technique to reduce normal tissue toxicity<div class="panel-pane pane-highwire-article-citation" style="-webkit-font-smoothing: antialiased; background-color: white; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: 14px; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px 0px 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
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<div class="highwire-article-citation highwire-citation-type-highwire-article" data-apath="/biorxiv/early/2017/09/03/184044.atom" data-hw-author-tooltip-instance="highwire_author_tooltip" data-node-nid="55698" data-pisa-master="biorxiv;184044" data-pisa="biorxiv;184044v1" id="node55698" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
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Temporally-Feathered Intensity Modulated Radiation Therapy: A technique to reduce normal tissue toxicity</h1>
<div class="highwire-cite-authors" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-citation-authors" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="highwire-citation-author first hw-author-orcid-logo-wrapper" data-delta="0" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0003-2432-5953" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">J. C. L.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Alfonso</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" data-hasqtip="0" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">S.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Parsai</span></span>, <span class="highwire-citation-author" data-delta="2" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">N.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Joshi</span></span>, <span class="highwire-citation-author" data-delta="3" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">A.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Godley</span></span>, <span class="highwire-citation-author" data-delta="4" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">S. A.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Koyfman</span></span>, <span class="highwire-citation-author" data-delta="5" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">J. J.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Caudell</span></span>, <span class="highwire-citation-author" data-delta="6" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">C. D.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Fuller</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="7" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0002-9696-6410" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">H.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Enderling</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper has-tooltip hasTooltip" data-delta="8" data-hasqtip="1" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0003-2971-7673" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Jacob</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Scott</span></span></span></div>
<div class="highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 0.82rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-cite-metadata-doi highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="label" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: bold; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">doi:</span> https://doi.org/10.1101/184044</span><div class="pub_jnl" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: 10pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25em; margin: 0px; outline: 0px; padding: 8px 0px 0px; vertical-align: baseline;">
This article is a preprint and has not been peer-reviewed [<a href="http://www.biorxiv.org/content/what-unrefereed-preprint" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank">what does this mean?</a>].</div>
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<li style="-webkit-font-smoothing: antialiased; background: transparent; border: 0px; display: inline; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.5em; list-style: none; margin: 0px; outline: 0px; padding: 0px; text-align: left; vertical-align: baseline;"><a class="panels-ajax-tab-tab panels-ajax-tabs-once-processed hw-panels-ajax-tabs-once-processed" data-entity-context="node:55698" data-panel-name="biorxiv_tab_info" data-target-id="highwire_article_tabs" data-trigger="article-info" data-url-enabled="1" href="http://www.biorxiv.org/content/early/2017/09/03/184044.article-info" style="-webkit-background-clip: padding-box; -webkit-font-smoothing: antialiased; background: transparent; border-bottom-color: initial; border-bottom-style: initial; border-image: initial; border-left-color: transparent; border-left-style: solid; border-radius: 0px; border-right-color: transparent; border-right-style: solid; border-top-color: transparent; border-top-style: solid; border-width: 1px 1px 0px; color: grey; cursor: pointer; display: inline-block; font-family: inherit; font-size: 1em; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: 1.17em; margin: 0px 10px 0px 0px; outline: 0px; padding: 6px 8px; text-align: center; text-decoration-line: none; transition: background-color 200ms ease-in, color 200ms ease-in; vertical-align: baseline; width: auto; zoom: 1;">Info/History</a></li>
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<span style="font-family: inherit;"><span class="highwire-journal-article-marker-start" style="-webkit-font-smoothing: antialiased; border-color: initial; border-image: initial; border-style: initial; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-stretch: inherit; font-style: inherit; font-style: inherit; font-variant: inherit; font-variant: inherit; font-weight: inherit; font-weight: inherit; line-height: inherit; line-height: inherit; margin: 0px; outline-color: initial; outline-style: initial; outline: 0px; padding: 0px; vertical-align: baseline;"></span></span><div class="section abstract" id="abstract-1" style="-webkit-font-smoothing: antialiased; border: 0px; clear: both; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
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Abstract</h2>
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Purpose/Objective: We introduce a novel strategy of radiation therapy planning using canonical radiobiology principles and leveraging time to further decrease normal tissue complication probability (NTCP). Temporally feathered radiation therapy (TFRT) is presented as a strategy to reduce radiation-induced toxicity, and is compared with conventionally fractionated radiotherapy an in silico model of normal tissue radiation response. Material/Methods: As a first choice to compare conventional and temporally feathered plans, we consider the biologically equivalent dose (BED), which is the most common model used to compare different fractionation schemes in radiotherapy. We formulated a mathematical model to simulate normal tissue radiation-induced damage and recovery induced by different fractionation regimens. This model considers tissue recovery as a dynamic process rather than a static probability. Radiation response is determined by the Linear-Quadratic (LQ) model, which is widely used in radiobiology. Results: TFRT is shown to be beneficial in reducing radiation-induced toxicity to normal tissues compared to conventional treatment schedules. BED is not suitable to evaluate the success potential of TFRT because of its static nature in time, the proposed dynamical NTCP model however, demonstrates that there exists a window of opportunity for temporally feathering organs at risk whereby toxicity can be reduced without affecting tumor dosing. The high and low fractional doses delivered by temporally feathered plans to organs at risk allow increased damage recovery despite higher total doses compared to standard plans. The clinical benefit of temporally feathered plans not only depends on the combination of fractional doses considered, but also on the organ-specific recovery rate of radiation damage. In particular, we found that when comparing temporally feathered and standard plans, for each recovery rate a certain range of standard fractional doses exists in which TFRT reduces toxicity. Although the potential benefit of TFRT over conventionally fractionated radiotherapy is always higher in those ranges, there exists an optimal standard fractional dose in which toxicity induced by the temporally feathered plan is minimum. Conclusions: Our novel TFRT methodology opens a yet unexplored avenue for planning optimization in radiotherapy. Application of this technique to carefully selected cases will not only potentially allow reduction in normal tissue toxicity, but also allow dose escalation to the tumor thereby enhancing the therapeutic ratio.</div>
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<span style="color: #191919; font-family: Lucida Sans, Helvetica, Arial, sans-serif;"><span style="font-size: 16.8px;">http://www.biorxiv.org/content/early/2017/09/03/184044</span></span></div>
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Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-76678809177842943632017-08-22T08:54:00.002-07:002017-08-22T08:54:41.811-07:00Cancer associated fibroblasts and alectinib switch the evolutionary games that non-small cell lung cancer plays<div class="panel-pane pane-highwire-article-citation" style="-webkit-font-smoothing: antialiased; background-color: white; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: 14px; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px 0px 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
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Cancer associated fibroblasts and alectinib switch the evolutionary games that non-small cell lung cancer plays</h1>
<div class="highwire-cite-authors" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-citation-authors" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="highwire-citation-author first has-tooltip hasTooltip" data-delta="0" data-hasqtip="3" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Artem</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Kaznatcheev</span></span>, <span class="highwire-citation-author" data-delta="1" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Jeffrey</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Peacock</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="2" data-hasqtip="0" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">David</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Basanta</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="3" data-hasqtip="2" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Andriy</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Marusyk</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="4" data-hasqtip="1" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Jacob G.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Scott</span></span></span></div>
<div class="highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 0.82rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-cite-metadata-doi highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="label" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: bold; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">doi:</span> https://doi.org/10.1101/179259</span><div class="pub_jnl" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: 10pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25em; margin: 0px; outline: 0px; padding: 8px 0px 0px; vertical-align: baseline;">
This article is a preprint and has not been peer-reviewed [<a href="http://www.biorxiv.org/content/what-unrefereed-preprint" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank">what does this mean?</a>].</div>
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Abstract</h2>
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Tumors are heterogeneous, evolving ecosystems, composed of sub-populations of neoplastic cells that follow distinct strategies for survival and propagation. The success of a strategy defining any single neoplastic sub-population is dependent on the distribution of other strategies, and on various components of the tumour microenvironment like cancer associated fibroblasts (CAFs). The rules mapping the population's strategy distribution to the fitness of individual strategies can be represented as an evolutionary game. In four different environments, we measure the games between treatment naive (Alectinib therapy sensitive) cells and a derivative line in which resistance was previously evolved. We find that the games are not only qualitatively different between different environments, but that targeted therapy and the presence of CAFs qualitatively switch the type of game being played. This provides the first empirical confirmation for the theoretical postulate of evolutionary game theory (EGT) in mathematical oncology that we can treat not just the player, but also the game. Although we concentrate on measuring games played by cancer cells, the measurement methodology we develop can be used to advance the study of games in other microscopic systems.</div>
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<span style="color: #191919; font-family: Lucida Sans, Helvetica, Arial, sans-serif;"><span style="font-size: 16.8px;">http://www.biorxiv.org/content/early/2017/08/21/179259</span></span></div>
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Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-83236302571143608952017-08-21T12:34:00.000-07:002017-08-21T12:34:19.357-07:00Stromal Reactivity Differentially Drives Tumor Cell Evolution and Prostate Cancer Progression<div class="panel-pane pane-highwire-article-citation" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px 0px 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
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Stromal Reactivity Differentially Drives Tumor Cell Evolution and Prostate Cancer Progression</h1>
<span class="biorxiv-article-type" style="-webkit-font-smoothing: antialiased; border: 0px; color: #222222; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant-alternates: inherit; font-variant-caps: inherit; font-variant-east-asian: inherit; font-variant-ligatures: inherit; font-variant-numeric: inherit; font-variant-position: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">New Results</span><div class="highwire-cite-authors" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 1.05rem; font-style: inherit; font-variant-caps: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
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<span class="highwire-citation-authors" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="highwire-citation-author first" data-delta="0" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Ziv</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Frankenstein</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="1" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0002-8527-0776" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-variant-east-asian: normal; font-variant-ligatures: normal; font-variant-position: normal; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px, 1px, 1px, 1px); font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">David</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Basanta</span></span>, <span class="highwire-citation-author" data-delta="2" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Omar E.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Franco</span></span>, <span class="highwire-citation-author" data-delta="3" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Yan</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Gao</span></span>, <span class="highwire-citation-author" data-delta="4" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Rodrigo A.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Javier</span></span>, <span class="highwire-citation-author" data-delta="5" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Douglas W.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Strand</span></span>, <span class="highwire-citation-author" data-delta="6" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">MinJae</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Lee</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="7" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0002-6059-6550" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-variant-east-asian: normal; font-variant-ligatures: normal; font-variant-position: normal; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px, 1px, 1px, 1px); font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Simon W.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Hayward</span></span>, <span class="highwire-citation-author" data-delta="8" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Gustavo</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Ayala</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="9" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0002-2536-4383" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-variant-east-asian: normal; font-variant-ligatures: normal; font-variant-position: normal; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px, 1px, 1px, 1px); font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Alexander R. A.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, 'Gill Sans MT', 'Gill Sans', Helvetica, Arial, sans-serif; font-size: inherit; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Anderson</span></span></span></div>
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<span class="highwire-cite-metadata-doi highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-style: inherit; font-variant-caps: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="label" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-style: inherit; font-variant-caps: inherit; font-weight: bold; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">doi:</span> https://doi.org/10.1101/159616 </span></div>
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Abstract</h2>
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We implemented a hybrid multiscale model of carcinogenesis that merges data from biology and pathology on the microenvironmental regulation of prostate cancer (PCa) cell behavior. It recapitulates the biology of stromal influence in prostate cancer progression. Our data indicate that the interactions between the tumor cells and reactive stroma shape the evolutionary dynamics of PCa cells and explain overall tumor aggressiveness. We show that the degree of stromal reactivity, when coupled with the current clinical biomarkers, significantly improves PCa prognostication, both for death and recurrence, that may alter treatment decisions. We also show that stromal reactivity correlates directly with tumor growth but inversely modulates tumor evolution. This suggests that the aggressive stromal independent PCa may be an inevitable evolutionary result of poor stromal reactivity. It also suggests that purely tumor centric metrics of aggressiveness may be misleading in terms on clinical outcome.</div>
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http://www.biorxiv.org/content/early/2017/08/21/159616</div>
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Anonymoushttp://www.blogger.com/profile/06336532069057637717noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-33349631292361456752017-07-28T10:27:00.003-07:002017-07-28T10:27:38.179-07:00Recasting the cancer stem cell hypothesis: unification using a continuum model of microenvironmental forces<div class="panel-pane pane-highwire-article-citation" style="-webkit-font-smoothing: antialiased; background-color: white; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: 14px; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px 0px 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
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<div class="highwire-article-citation highwire-citation-type-highwire-article" data-apath="/biorxiv/early/2017/07/28/169615.atom" data-hw-author-tooltip-instance="highwire_author_tooltip" data-node-nid="50693" data-pisa-master="biorxiv;169615" data-pisa="biorxiv;169615v1" id="node50693" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<div class="highwire-cite highwire-cite-highwire-article highwire-citation-biorxiv-article-top clearfix has-author-tooltip" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; zoom: 1;">
<span class="biorxiv-article-type" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">New Results</span><h1 class="highwire-cite-title" id="page-title" style="-webkit-font-smoothing: antialiased; border: 0px; color: #131313; font-size: 1.33rem; font-stretch: normal; letter-spacing: -0.03em; line-height: 1.9rem; margin: 0px 0px 20px; outline: 0px; padding: 16px 0px 0px; vertical-align: baseline;">
Recasting the cancer stem cell hypothesis: unification using a continuum model of microenvironmental forces</h1>
<div class="highwire-cite-authors" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-citation-authors" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="highwire-citation-author first" data-delta="0" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Jacob G.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Scott</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="1" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0002-5027-1277" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Andrew</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Dhawan</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper has-tooltip hasTooltip" data-delta="2" data-hasqtip="1" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0003-2200-3248" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Anita</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Hjelmeland</span></span>, <span aria-describedby="qtip-0" class="highwire-citation-author hw-author-orcid-logo-wrapper has-tooltip hasTooltip" data-delta="3" data-hasqtip="0" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0003-3168-7290" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Justin</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Lathia</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="4" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0002-0937-6640" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Masahiro</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Hitomi</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper has-tooltip hasTooltip" data-delta="5" data-hasqtip="3" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0003-0525-4336" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Alexander G.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Fletcher</span></span>, <span class="highwire-citation-author" data-delta="6" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Philip K.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Maini</span></span>, <span aria-describedby="qtip-2" class="highwire-citation-author has-tooltip hasTooltip" data-delta="7" data-hasqtip="2" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Alexander R. A.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Anderson</span></span></span></div>
<div class="highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 0.82rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-cite-metadata-doi highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="label" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: bold; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">doi:</span> https://doi.org/10.1101/169615</span><div class="pub_jnl" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: 10pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25em; margin: 0px; outline: 0px; padding: 8px 0px 0px; vertical-align: baseline;">
This article is a preprint and has not been peer-reviewed [<a href="http://www.biorxiv.org/content/what-unrefereed-preprint" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank">what does this mean?</a>].</div>
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<li class="first active" style="-webkit-font-smoothing: antialiased; background-attachment: initial; background-clip: initial; background-image: initial; background-origin: initial; background-position: initial; background-repeat: initial; background-size: initial; border: 0px rgb(169, 169, 169); color: #565656; display: inline; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: bold; line-height: 1.5em; list-style: none; margin: 0px; outline: 0px; padding: 0px; text-align: left; vertical-align: baseline;"><a class="panels-ajax-tab-tab panels-ajax-tabs-once-processed panels-ajax-tabs-first-loaded hw-panels-ajax-tabs-once-processed" data-entity-context="node:50693" data-panel-name="biorxiv_tab_art" data-target-id="highwire_article_tabs" data-trigger="" data-url-enabled="1" href="http://www.biorxiv.org/content/early/2017/07/28/169615" style="-webkit-background-clip: padding-box; -webkit-font-smoothing: antialiased; background-attachment: initial; background-clip: initial; background-image: initial; background-origin: initial; background-position: initial; background-repeat: initial; background-size: initial; border-bottom-style: initial; border-color: rgb(169, 169, 169); border-image: initial; border-left-style: solid; border-radius: 0px; border-right-style: solid; border-top-style: solid; border-width: 1px 1px 0px; color: #565656; cursor: pointer; display: inline-block; font-family: inherit; font-size: 1em; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: 1.17em; margin: 0px 10px -1px 0px; outline: 0px; padding: 6px 8px; text-align: center; text-decoration-line: none; transition: background-color 200ms ease-in, color 200ms ease-in; vertical-align: baseline; width: auto; zoom: 1;">Abstract</a></li>
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Abstract</h2>
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Since the first evidence for cancer stem cells in leukemia, experimentalists have sought to identify tumorigenic subpopulations in solid tumors. In parallel, scientists have argued over the implications of the existence of this subpopulation. On one side, the cancer stem cell hypothesis posits that a small subset of cells within a tumor are responsible for tumorigenesis and are capable of recapitulating the entire tumor on their own. Under this hypothesis, a tumor may be conceptualized as a series of coupled compartments, representing populations of progressively differentiated cell types, starting from stem cells. The allure of this model is that it elegantly explains our therapeutic failures: we have been targeting the wrong cells. Alternatively, the stochastic model states that all cells in a tumor can have stem-like properties, and have an equally small capability of forming a tumor. As tumors are, by nature, heterogeneous, there is ample evidence to support both hypotheses. We propose a mechanistic mathematical description that integrates these two theories, settling the dissonance between the schools of thought and providing a road map for integrating disparate experimental results into a single theoretical framework. We present experimental results from clonogenic assays that demonstrate the importance of defining this novel formulation, and the clarity that is provided when interpreting these results through the lens of this formulation.</div>
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http://www.biorxiv.org/content/early/2017/07/28/169615Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-47926659638896119962017-07-03T19:27:00.002-07:002017-07-03T19:27:15.248-07:00The effects of mutational process and selection on driver mutations across cancer types<div class="panel-pane pane-highwire-article-citation" style="-webkit-font-smoothing: antialiased; background-color: white; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: 14px; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px 0px 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
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<div class="highwire-article-citation highwire-citation-type-highwire-article" data-apath="/biorxiv/early/2017/06/12/149096.atom" data-hw-author-tooltip-instance="highwire_author_tooltip" data-node-nid="44270" data-pisa-master="biorxiv;149096" data-pisa="biorxiv;149096v1" id="node44270" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<div class="highwire-cite highwire-cite-highwire-article highwire-citation-biorxiv-article-top clearfix has-author-tooltip" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; zoom: 1;">
<span class="biorxiv-article-type" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">New Results</span><h1 class="highwire-cite-title" id="page-title" style="-webkit-font-smoothing: antialiased; border: 0px; color: #131313; font-size: 1.33rem; font-stretch: normal; letter-spacing: -0.03em; line-height: 1.9rem; margin: 0px 0px 20px; outline: 0px; padding: 16px 0px 0px; vertical-align: baseline;">
The effects of mutational process and selection on driver mutations across cancer types</h1>
<div class="highwire-cite-authors" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-citation-authors" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span aria-describedby="qtip-1" class="highwire-citation-author first hw-author-orcid-logo-wrapper has-tooltip hasTooltip" data-delta="0" data-hasqtip="1" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0002-0165-292X" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Daniel</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Temko</span></span>, <span class="highwire-citation-author" data-delta="1" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Ian</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Tomlinson</span></span>, <span class="highwire-citation-author" data-delta="2" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Simone</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Severini</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="3" data-hasqtip="0" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Benjamin</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Schuster-Boeckler</span></span>, <span class="highwire-citation-author" data-delta="4" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Trevor</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Graham</span></span></span></div>
<div class="highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 0.82rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-cite-metadata-doi highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="label" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: bold; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">doi:</span> https://doi.org/10.1101/149096</span><div class="pub_jnl" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: 10pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25em; margin: 0px; outline: 0px; padding: 8px 0px 0px; vertical-align: baseline;">
This article is a preprint and has not been peer-reviewed [<a href="http://www.biorxiv.org/content/what-unrefereed-preprint" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank">what does this mean?</a>].</div>
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Abstract</h2>
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Epidemiological evidence has long associated environmental mutagens with increased cancer risk. However, links between specific mutation-causing processes and the acquisition of individual driver mutations have remained obscure. Here we have used public cancer sequencing data to infer the independent effects of mutation and selection on driver mutation complement. First, we detect associations between a range of mutational processes, including those linked to smoking, ageing, APOBEC and DNA mismatch repair (MMR) and the presence of key driver mutations across cancer types. Second, we quantify differential selection between well-known alternative driver mutations, including differences in selection between distinct mutant residues in the same gene. These results show that while mutational processes play a large role in determining which driver mutations are present in a cancer, the role of selection frequently dominates.</div>
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<span style="color: #191919; font-family: Lucida Sans, Helvetica, Arial, sans-serif;"><span style="font-size: 16.8px;">http://www.biorxiv.org/content/early/2017/06/12/149096</span></span></div>
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Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-43142757757385169332017-05-11T14:19:00.002-07:002017-05-11T14:19:12.509-07:00Extinction Times In Tumor Public Goods Games<div class="panel-pane pane-highwire-article-citation" style="-webkit-font-smoothing: antialiased; background-color: white; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: 14px; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px 0px 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
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<div class="highwire-article-citation highwire-citation-type-highwire-article" data-apath="/biorxiv/early/2017/05/04/134361.atom" data-hw-author-tooltip-instance="highwire_author_tooltip" data-node-nid="39428" data-pisa-master="biorxiv;134361" data-pisa="biorxiv;134361v1" id="node39428" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<div class="highwire-cite highwire-cite-highwire-article highwire-citation-biorxiv-article-top clearfix has-author-tooltip" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; zoom: 1;">
<h1 class="highwire-cite-title" id="page-title" style="-webkit-font-smoothing: antialiased; border: 0px; color: #131313; font-size: 1.33rem; font-stretch: normal; letter-spacing: -0.03em; line-height: 1.9rem; margin: 0px 0px 20px; outline: 0px; padding: 16px 0px 0px; vertical-align: baseline;">
Extinction Times In Tumor Public Goods Games</h1>
<div class="highwire-cite-authors" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-citation-authors" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="highwire-citation-author first has-tooltip hasTooltip" data-delta="0" data-hasqtip="0" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Philip</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Gerlee</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="1" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0001-7731-3345" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Philipp M.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Altrock</span></span></span></div>
<div class="highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 0.82rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-cite-metadata-doi highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="label" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: bold; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">doi:</span> https://doi.org/10.1101/134361</span><div class="pub_jnl" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: 10pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25em; margin: 0px; outline: 0px; padding: 8px 0px 0px; vertical-align: baseline;">
This article is a preprint and has not been peer-reviewed [<a href="http://biorxiv.org/content/what-unrefereed-preprint" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" target="_blank">what does this mean?</a>].</div>
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<div data-highwire-cite-ref-tooltip-instance="highwire_reflinks_tooltip" id="content-block-markup" style="-webkit-font-smoothing: antialiased; border: 0px; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;" xmlns:xhtml="http://www.w3.org/1999/xhtml" xmlns="http://www.w3.org/1999/xhtml">
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<span style="font-family: inherit;"><span class="highwire-journal-article-marker-start" style="-webkit-font-smoothing: antialiased; border-color: initial; border-image: initial; border-style: initial; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-stretch: inherit; font-style: inherit; font-style: inherit; font-variant: inherit; font-variant: inherit; font-weight: inherit; font-weight: inherit; line-height: inherit; line-height: inherit; margin: 0px; outline-color: initial; outline-style: initial; outline: 0px; padding: 0px; vertical-align: baseline;"></span></span><div class="section abstract" id="abstract-1" style="-webkit-font-smoothing: antialiased; border: 0px; clear: both; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<h2 style="-webkit-font-smoothing: antialiased; border: 0px; color: #121212; font-family: Helvetica, Arial, sans-serif; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; letter-spacing: 0px; line-height: 1.43em; margin: 15px 0px 15px -15px; outline: 0px; padding: 0px; vertical-align: baseline;">
Abstract</h2>
<div id="p-2" style="-webkit-font-smoothing: antialiased; border: 0px; color: #191919; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin-bottom: 15px; outline: 0px; padding: 0px; vertical-align: baseline; word-wrap: break-word;">
Cancer evolution and progression are shaped by Darwinian selection and cell-to-cell interactions. Evolutionary game theory incorporates both of these principles, and has been recently as a framework to describe tumor cell population dynamics. A cornerstone of evolutionary dynamics is the replicator equation, which describes changes in the relative abundance of different cell types, and is able to predict evolutionary equilibria. Typically, the replicator equation focuses on differences in relative fitness. We here show that this framework might not be sufficient under all circumstances, as it neglects important aspects of population growth. Standard replicator dynamics might miss critical differences in the time it takes to reach an equilibrium, as this time also depends on cellular birth and death rates in growing but bounded populations. As the system reaches a stable manifold, the time to reach equilibrium depends on cellular death and birth rates. These rates shape evolutionary timescales, in particular in competitive co-evolutionary dynamics of growth factor producers and free-riders. Replicator dynamics might be an appropriate framework only when birth and death rates are of comparable magnitude. Otherwise, population growth effects cannot be neglected when predicting the time to reach an equilibrium, and cellular events have to be accounted for explicitly.</div>
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<span style="color: #191919; font-family: Lucida Sans, Helvetica, Arial, sans-serif;"><span style="font-size: 16.8px;">http://biorxiv.org/content/early/2017/05/04/134361</span></span></div>
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Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-31422962964362054082017-05-10T14:25:00.000-07:002017-05-10T14:25:05.296-07:00Mechanistic Modeling Quantifies The Influence Of Tumor Growth Kinetics On The Response To Anti-Angiogenic Treatment<h1 class="highwire-cite-title" id="page-title">
Mechanistic Modeling Quantifies The Influence Of Tumor Growth Kinetics On The Response To Anti-Angiogenic Treatment</h1>
<div>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span aria-describedby="qtip-1" class="highwire-citation-author first has-tooltip hasTooltip author-popup-hover" data-delta="0" data-hasqtip="1"><span class="nlm-given-names">Thomas D.</span> <span class="nlm-surname">Gaddy</span></span>, <span aria-describedby="qtip-0" class="highwire-citation-author hw-author-orcid-logo-wrapper has-tooltip hasTooltip" data-delta="1" data-hasqtip="0"><span class="nlm-given-names">Stacey D.</span> <span class="nlm-surname">Finley</span></span></span></div>
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<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span aria-describedby="qtip-0" class="highwire-citation-author hw-author-orcid-logo-wrapper has-tooltip hasTooltip" data-delta="1" data-hasqtip="0"><span class="nlm-surname"><br /></span></span></span></div>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span aria-describedby="qtip-0" class="highwire-citation-author hw-author-orcid-logo-wrapper has-tooltip hasTooltip" data-delta="1" data-hasqtip="0"><span class="nlm-surname"><div class="section abstract" id="abstract-1">
<h2>
Abstract</h2>
<div id="p-2">
Tumors
exploit angiogenesis, the formation of new blood vessels from
pre-existing vasculature, in order to obtain nutrients required for
continued growth and proliferation. Targeting factors that regulate
angiogenesis, including the potent promoter vascular endothelial growth
factor (VEGF), is therefore an attractive strategy for inhibiting tumor
growth. Systems biology modeling enables us to identify tumor-specific
properties that influence the response to those anti-angiogenic
strategies. Here, we build on our previous systems biology model of VEGF
transport and kinetics in tumor-bearing mice to include a tumor
compartment whose volume depends on the “angiogenic signal” produced
when VEGF binds to its receptors on tumor endothelial cells. We trained
and validated the model using in vivo measurements of xenograft tumor
volume to produce a model that accurately predicts the tumor's response
to anti-angiogenic treatment. We applied the model to investigate how
tumor growth kinetics influence the response to anti-angiogenic
treatment targeting VEGF. Based on multivariate regression analysis, we
found that certain intrinsic kinetic parameters that characterize the
growth of tumors could successfully predict response to anti-VEGF
treatment. This model is a useful tool for predicting which tumors will
respond to anti-VEGF treatment, complementing pre-clinical in vivo
studies.</div>
<div id="p-2">
<br /></div>
<div id="p-2">
Link: <a href="http://biorxiv.org/content/early/2017/05/10/136531">http://biorxiv.org/content/early/2017/05/10/136531</a></div>
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David Basantahttp://www.blogger.com/profile/15504719079207200602noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-89405087576498133562017-03-14T06:12:00.000-07:002017-03-14T06:12:01.812-07:00Stochastic model of contact inhibition and the proliferation of melanoma in situ<div class="panel-pane pane-highwire-article-citation" style="-webkit-font-smoothing: antialiased; background-color: white; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: 14px; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px 0px 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
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<div class="highwire-article-citation highwire-citation-type-highwire-article" data-apath="/biorxiv/early/2017/03/02/110007.atom" data-hw-author-tooltip-instance="highwire_author_tooltip" data-node-nid="32731" data-pisa-master="biorxiv;110007" data-pisa="biorxiv;110007v2" id="node32731" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
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<h1 class="highwire-cite-title" id="page-title" style="-webkit-font-smoothing: antialiased; border: 0px; color: #131313; font-size: 1.33rem; font-stretch: normal; letter-spacing: -0.03em; line-height: 1.9rem; margin: 0px 0px 20px; outline: 0px; padding: 16px 0px 0px; vertical-align: baseline;">
Stochastic model of contact inhibition and the proliferation of melanoma <em style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">in situ</em></h1>
<div class="highwire-cite-authors" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-citation-authors" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span aria-describedby="qtip-5" class="highwire-citation-author first has-tooltip hasTooltip" data-delta="0" data-hasqtip="5" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Mauro Cesar C</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Morais</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" data-hasqtip="0" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Izabella</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Stuhl</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="2" data-hasqtip="2" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Alan U</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Sabino</span></span>, <span aria-describedby="qtip-3" class="highwire-citation-author has-tooltip hasTooltip" data-delta="3" data-hasqtip="3" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Willian W</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Lautenschlager</span></span>, <span class="highwire-citation-author" data-delta="4" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Alexandre S</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Queiroga</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="5" data-hasqtip="6" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Tharcisio C</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Tortelli</span></span>, <span class="highwire-citation-author" data-delta="6" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Roger</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Chammas</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="7" data-hasqtip="1" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Yuri</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Suhov</span></span>, <span aria-describedby="qtip-4" class="highwire-citation-author has-tooltip hasTooltip" data-delta="8" data-hasqtip="4" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; cursor: pointer; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Alexandre F</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Ramos</span></span></span></div>
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<span class="highwire-cite-metadata-doi highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="label" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: bold; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">doi:</span> https://doi.org/10.1101/110007</span><div class="pub_jnl" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: 10pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25em; margin: 0px; outline: 0px; padding: 8px 0px 0px; vertical-align: baseline;">
This article is a preprint and has not been peer-reviewed [<a href="http://biorxiv.org/content/what-unrefereed-preprint" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration: none; vertical-align: baseline;" target="_blank">what does this mean?</a>].</div>
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<li style="-webkit-font-smoothing: antialiased; background: transparent; border: 0px; display: inline; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.5em; list-style: none; margin: 0px; outline: 0px; padding: 0px; text-align: left; vertical-align: baseline;"><a class="panels-ajax-tab-tab panels-ajax-tabs-once-processed hw-panels-ajax-tabs-once-processed" data-entity-context="node:32731" data-panel-name="biorxiv_tab_info" data-target-id="highwire_article_tabs" data-trigger="article-info" data-url-enabled="1" href="http://biorxiv.org/content/early/2017/03/02/110007.article-info" style="-webkit-background-clip: padding-box; -webkit-font-smoothing: antialiased; background: transparent; border-bottom-color: initial; border-bottom-style: initial; border-image: initial; border-left-color: transparent; border-left-style: solid; border-radius: 0px; border-right-color: transparent; border-right-style: solid; border-top-color: transparent; border-top-style: solid; border-width: 1px 1px 0px; color: grey; cursor: pointer; display: inline-block; font-family: inherit; font-size: 1em; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: 1.17em; margin: 0px 10px 0px 0px; outline: 0px; padding: 6px 8px; text-align: center; text-decoration: none; transition: background-color 200ms ease-in, color 200ms ease-in; vertical-align: baseline; width: auto; zoom: 1;">Info/History</a></li>
<li style="-webkit-font-smoothing: antialiased; background: transparent; border: 0px; display: inline; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.5em; list-style: none; margin: 0px; outline: 0px; padding: 0px; text-align: left; vertical-align: baseline;"><a class="panels-ajax-tab-tab panels-ajax-tabs-once-processed hw-panels-ajax-tabs-once-processed" data-entity-context="node:32731" data-panel-name="article_tab_metrics" data-target-id="highwire_article_tabs" data-trigger="article-metrics" data-url-enabled="1" href="http://biorxiv.org/content/early/2017/03/02/110007.article-metrics" style="-webkit-background-clip: padding-box; -webkit-font-smoothing: antialiased; background: transparent; border-bottom-color: initial; border-bottom-style: initial; border-image: initial; border-left-color: transparent; border-left-style: solid; border-radius: 0px; border-right-color: transparent; border-right-style: solid; border-top-color: transparent; border-top-style: solid; border-width: 1px 1px 0px; color: grey; cursor: pointer; display: inline-block; font-family: inherit; font-size: 1em; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: 1.17em; margin: 0px 10px 0px 0px; outline: 0px; padding: 6px 8px; text-align: center; text-decoration: none; transition: background-color 200ms ease-in, color 200ms ease-in; vertical-align: baseline; width: auto; zoom: 1;">Metrics</a></li>
<li style="-webkit-font-smoothing: antialiased; background: transparent; border: 0px; display: inline; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.5em; list-style: none; margin: 0px; outline: 0px; padding: 0px; text-align: left; vertical-align: baseline;"><a class="panels-ajax-tab-tab panels-ajax-tabs-once-processed hw-panels-ajax-tabs-once-processed" data-entity-context="node:32731" data-panel-name="biorxiv_tab_data" data-target-id="highwire_article_tabs" data-trigger="figures-only" data-url-enabled="1" href="http://biorxiv.org/content/early/2017/03/02/110007.figures-only" style="-webkit-background-clip: padding-box; -webkit-font-smoothing: antialiased; background: transparent; border-bottom-color: initial; border-bottom-style: initial; border-image: initial; border-left-color: transparent; border-left-style: solid; border-radius: 0px; border-right-color: transparent; border-right-style: solid; border-top-color: transparent; border-top-style: solid; border-width: 1px 1px 0px; color: grey; cursor: pointer; display: inline-block; font-family: inherit; font-size: 1em; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: 1.17em; margin: 0px 10px 0px 0px; outline: 0px; padding: 6px 8px; text-align: center; text-decoration: none; transition: background-color 200ms ease-in, color 200ms ease-in; vertical-align: baseline; width: auto; zoom: 1;">Supplementary material</a></li>
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Abstract</h2>
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Contact inhibition is a central feature orchestrating cell proliferation in culture experiments with its loss being associated with malignant transformation and tumorigenesis. We performed a co-culture experiment with human metastatic melanoma cell line (SK-MEL-147) and immortalized keratinocyte cells (HaCaT). After 8 days a spatial pattern was detected, characterized by the formation of clusters of melanoma cells surrounded by keratinocytes constraining their proliferation. In addition, we observed that the proportion of melanoma cells within the total population has increased. To explain our results we propose a spatial stochastic model (following a philosophy of the Widom-Rowlinson model from Statistical Physics and Molecular Chemistry) where we consider cell proliferation, death, migration, and cell-to-cell interaction through contact inhibition. Our numerical simulations demonstrate that loss of contact inhibition is a sufficient mechanism, appropriate for an explanation of the increase in the proportion of tumor cells and generation of spatial patterns established in conducted experiments.</div>
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<span style="color: #191919; font-family: Lucida Sans, Helvetica, Arial, sans-serif;"><span style="font-size: 16.8px;">http://biorxiv.org/content/early/2017/03/02/110007</span></span></div>
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Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-32088457158878376982017-03-14T06:07:00.001-07:002017-03-14T06:07:48.837-07:00A cautionary tale on using tumour growth rate to predict survival<div class="panel-pane pane-highwire-article-citation" style="-webkit-font-smoothing: antialiased; background-color: white; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: 14px; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px 0px 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
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A cautionary tale on using tumour growth rate to predict survival</h1>
<div class="highwire-cite-authors" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-citation-authors" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="highwire-citation-author first hw-author-orcid-logo-wrapper" data-delta="0" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0002-9683-1903" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Hitesh</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Mistry</span></span>, <span class="highwire-citation-author" data-delta="1" style="-webkit-font-smoothing: antialiased; border-bottom-color: transparent; border-bottom-style: dotted; border-image: initial; border-left-color: initial; border-left-style: initial; border-right-color: initial; border-right-style: initial; border-top-color: initial; border-top-style: initial; border-width: 0px 0px 1px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; white-space: nowrap;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Fernando</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Ortega</span></span></span></div>
<div class="highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 0.82rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-cite-metadata-doi highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="label" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 1.05rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: bold; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">doi:</span> https://doi.org/10.1101/109934</span><div class="pub_jnl" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: 10pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25em; margin: 0px; outline: 0px; padding: 8px 0px 0px; vertical-align: baseline;">
This article is a preprint and has not been peer-reviewed [<a href="http://biorxiv.org/content/what-unrefereed-preprint" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration: none; vertical-align: baseline;" target="_blank">what does this mean?</a>].</div>
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<li style="-webkit-font-smoothing: antialiased; background: transparent; border: 0px; display: inline; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.5em; list-style: none; margin: 0px; outline: 0px; padding: 0px; text-align: left; vertical-align: baseline;"><a class="panels-ajax-tab-tab panels-ajax-tabs-once-processed hw-panels-ajax-tabs-once-processed" data-entity-context="node:31738" data-panel-name="biorxiv_tab_info" data-target-id="highwire_article_tabs" data-trigger="article-info" data-url-enabled="1" href="http://biorxiv.org/content/early/2017/02/20/109934.article-info" style="-webkit-background-clip: padding-box; -webkit-font-smoothing: antialiased; background: transparent; border-bottom-color: initial; border-bottom-style: initial; border-image: initial; border-left-color: transparent; border-left-style: solid; border-radius: 0px; border-right-color: transparent; border-right-style: solid; border-top-color: transparent; border-top-style: solid; border-width: 1px 1px 0px; color: grey; cursor: pointer; display: inline-block; font-family: inherit; font-size: 1em; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: 1.17em; margin: 0px 10px 0px 0px; outline: 0px; padding: 6px 8px; text-align: center; text-decoration: none; transition: background-color 200ms ease-in, color 200ms ease-in; vertical-align: baseline; width: auto; zoom: 1;">Info/History</a></li>
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<span style="font-family: inherit;"><span class="highwire-journal-article-marker-start" style="-webkit-font-smoothing: antialiased; border-color: initial; border-image: initial; border-style: initial; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-stretch: inherit; font-style: inherit; font-style: inherit; font-variant: inherit; font-variant: inherit; font-weight: inherit; font-weight: inherit; line-height: inherit; line-height: inherit; margin: 0px; outline-color: initial; outline-style: initial; outline: 0px; padding: 0px; vertical-align: baseline;"></span></span><div class="section abstract" id="abstract-1" style="-webkit-font-smoothing: antialiased; border: 0px; clear: both; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
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Abstract</h2>
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A recurrent question within oncology drug development is predicting phase III outcome for a new treatment using early clinical data. One approach to tackle this problem has been to derive metrics from mathematical models that describe tumour size dynamics termed re-growth rate and time to tumour re-growth. They have shown to be strong predictors of overall survival in numerous studies but there is debate about how these metrics are derived and if they are more predictive than empirical end-points. This work explores the issues raised in using model-derived metric as predictors for survival analyses. Re-growth rate and time to tumour re-growth were calculated for three large clinical studies by forward and reverse alignment. The latter involves re-aligning patients to their time of progression. Hence it accounts for the time taken to estimate re-growth rate and time to tumour re-growth but also assesses if these predictors correlate to survival from the time of progression. We found that neither re-growth rate nor time to tumour re-growth correlated to survival using reverse alignment. This suggests that the dynamics of tumours up until disease progression has no relationship to survival post progression. For prediction of a phase III trial we found the metrics performed no better than empirical end-points. These results highlight that care must be taken when relating dynamics of tumour imaging to survival and that bench-marking new approaches to existing ones is essential.</div>
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<span style="color: #191919; font-family: Lucida Sans, Helvetica, Arial, sans-serif;"><span style="font-size: 16.8px;">http://biorxiv.org/content/early/2017/02/20/109934</span></span></div>
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Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-86417067413867383222017-01-31T17:03:00.000-08:002017-01-31T17:03:36.588-08:00Allele Frequency Spectrum in a Cancer Cell Population<h1 class="highwire-cite-title" id="page-title">
Allele Frequency Spectrum in a Cancer Cell Population</h1>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author first has-tooltip hasTooltip author-popup-hover" data-delta="0" data-hasqtip="1"><span class="nlm-given-names">Hisashi</span> <span class="nlm-surname">Ohtsuki</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" data-hasqtip="0"><span class="nlm-given-names">Hideki</span> <span class="nlm-surname">Innan</span></span></span></div>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" data-hasqtip="0"><span class="nlm-surname"> </span></span></span></div>
<div class="highwire-cite-authors">
<div class="section abstract" id="abstract-1">
<h2>
Abstract</h2>
<div id="p-2">
A
cancer grows from a single cell, thereby constituting a large cell
population. In this work, we are interested in how mutations accumulate
in a cancer cell population. We provide a theoretical framework of the
stochastic process in a cancer cell population and obtain near exact
expressions of allele frequency spectrum or AFS (only continuous
approximation is involved) from both forward and backward treatments
under a simple setting; all cells undergo cell division and die at
constant rates, b and d, respectively, such that the entire population
grows exponentially. This setting means that once a parental cancer cell
is established, in the following growth phase, all mutations are
assumed to have no effect on b or d (i.e., neutral or passengers). Our
theoretical results show that the difference from organismal population
genetics is mainly in the coalescent time scale, and the mutation rate
is defined per cell division, not per time unit (e.g., generation).
Except for these two factors, the basic logic are very similar between
organismal and cancer population genetics, indicating that a number of
well established theories of organismal population genetics could be
translated to cancer population genetics with simple modifications.</div>
<div id="p-2">
<br /></div>
<div id="p-2">
<span class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">doi:</span> <a href="http://biorxiv.org/content/early/2017/01/30/104158">http://biorxiv.org/content/early/2017/01/30/104158</a> </span></div>
</div>
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" data-hasqtip="0"><span class="nlm-surname"> </span></span></span></div>
<h1 class="highwire-cite-title" id="page-title">
</h1>
David Basantahttp://www.blogger.com/profile/15504719079207200602noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-82266948651668286742017-01-26T19:55:00.003-08:002017-01-26T19:55:45.463-08:00Heterogeneity in the tumour size dynamics differentiates Vemurafenib, Dabrafenib and Trametinib in metastatic melanoma<h1 class="highwire-cite-title" id="page-title">
Heterogeneity in the tumour size dynamics differentiates Vemurafenib, Dabrafenib and Trametinib in metastatic melanoma</h1>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author first has-tooltip hasTooltip author-popup-hover" data-delta="0" data-hasqtip="2"><span class="nlm-given-names">Hitesh</span> <span class="nlm-surname">Mistry</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" data-hasqtip="1"><span class="nlm-given-names">David</span> <span class="nlm-surname">Orrell</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="2" data-hasqtip="0"><span class="nlm-given-names">Raluca</span> <span class="nlm-surname">Eftimie</span></span></span></div>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="2" data-hasqtip="0"><span class="nlm-surname"> </span></span></span></div>
<div class="highwire-cite-authors">
<div class="section abstract" id="abstract-1">
<h2>
Abstract</h2>
<div id="p-2">
Molecular
heterogeneity in tumours leads to variability in drug response both
between patients and across lesions within a patient. These sources of
variability could be explored through analysis of routinely collected
clinical trial imaging data. We applied a mathematical model of tumour
growth to analyse both within and between patient variability in tumour
size dynamics to clinical data from three drugs, Vemurafenib, Dabrafenib
and Trametinib, used in the treatment of metastatic melanoma. The
analysis revealed: 1) existence of homogeneity in drug response and
resistance development within a patient; 2) tumour shrinkage rate does
not relate to rate of resistance development; 3) Vemurafenib and
Dabrafenib, two BRAF inhibitors, have different variability in tumour
shrinkage rates. Overall these results show how analysis of the dynamics
of individual lesions can shed light on the within and between patient
differences in tumour shrinkage and resistance rates, which could be
used to gain a macroscopic understanding of tumour heterogeneity.</div>
<div id="p-2">
<br /></div>
<div id="p-2">
Keywords: heterogeneity, vemurafenib, dabrafenib, trametinib, melanoma, metastasis </div>
<div id="p-2">
<br /></div>
<div id="p-2">
doi: <a href="http://biorxiv.org/content/early/2017/01/26/103366"><span class="highwire-cite-metadata-doi highwire-cite-metadata">http://biorxiv.org/content/early/2017/01/26/103366</span></a></div>
</div>
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="2" data-hasqtip="0"><span class="nlm-surname"> </span></span></span></div>
<h1 class="highwire-cite-title" id="page-title">
</h1>
David Basantahttp://www.blogger.com/profile/15504719079207200602noreply@blogger.com1tag:blogger.com,1999:blog-1481440158840549455.post-70753553394450204172017-01-25T16:54:00.002-08:002017-01-25T16:56:03.283-08:00Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype<h1 class="title mathjax" style="background-color: white; font-family: "Lucida Grande", helvetica, arial, verdana, sans-serif; font-size: x-large; line-height: 28.8px; margin: 0.5em 0px 0.5em 20px;">
Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype</h1>
<div class="authors" style="background-color: white; font-family: "Lucida Grande", helvetica, arial, verdana, sans-serif; line-height: 24px; margin: 0.5em 0px 0.5em 20px;">
<a href="https://arxiv.org/find/q-bio/1/au:+Fernandez_de_Cossio_Diaz_J/0/1/0/all/0/1" style="text-decoration: none;">Jorge Fernandez-de-Cossio-Diaz</a>, <a href="https://arxiv.org/find/q-bio/1/au:+Martino_A/0/1/0/all/0/1" style="text-decoration: none;">Andrea De Martino</a>, <a href="https://arxiv.org/find/q-bio/1/au:+Mulet_R/0/1/0/all/0/1" style="text-decoration: none;">Roberto Mulet</a></div>
<div class="dateline" style="background-color: white; font-family: "Lucida Grande", helvetica, arial, verdana, sans-serif; font-size: small; font-style: italic; margin: 0.5em 0px 0.5em 20px;">
(Submitted on 24 Jan 2017)</div>
<blockquote class="abstract mathjax" style="background-color: white; font-family: "Lucida Grande", helvetica, arial, verdana, sans-serif; font-size: 14.4px; line-height: 20.16px; margin-bottom: 1.5em;">
We introduce an in silico model for the initial spread of an aberrant phenotype with Warburg-like overflow metabolism within a healthy homeostatic tissue in contact with a nutrient reservoir (the blood), aimed at characterizing the role of the microenvironment for aberrant growth. Accounting for cellular metabolic activity, competition for nutrients, spatial diffusion and their feedbacks on aberrant replication and death rates, we obtain a phase portrait where distinct asymptotic whole-tissue states are found upon varying the tissue-blood turnover rate and the level of blood-borne primary nutrient. Over a broad range of parameters, the spreading dynamics is bistable as random fluctuations can impact the final state of the tissue. Such a behaviour turns out to be linked to the re-cycling of overflow products by non-aberrant cells. Quantitative insight on the overall emerging picture is provided by a spatially homogeneous version of the model.</blockquote>
<br />
link: <a href="https://arxiv.org/abs/1701.06781">https://arxiv.org/abs/1701.06781</a>Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-61378611696820328302016-11-13T16:25:00.000-08:002016-11-13T16:25:49.196-08:00Novel computational method for predicting polytherapy switching strategies to overcome tumor heterogeneity and evolution<h1 class="highwire-cite-title" id="page-title">
Novel computational method for predicting polytherapy switching strategies to overcome tumor heterogeneity and evolution</h1>
<h1 class="highwire-cite-title" id="page-title">
</h1>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author first has-tooltip hasTooltip" data-delta="0" rel="#hw-article-author-popups-node24158 .author-tooltip-0" title=""><span class="nlm-given-names">Vanessa D</span> <span class="nlm-surname">Jonsson</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper has-tooltip hasTooltip" data-delta="1" rel="#hw-article-author-popups-node24158 .author-tooltip-1" title=""><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0003-2760-9513" target="_blank"></a><span class="nlm-given-names">Colin M</span> <span class="nlm-surname">Blakely</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="2" rel="#hw-article-author-popups-node24158 .author-tooltip-2" title=""><span class="nlm-given-names">Luping</span> <span class="nlm-surname">Lin</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="3" rel="#hw-article-author-popups-node24158 .author-tooltip-3" title=""><span class="nlm-given-names">Saurabh</span> <span class="nlm-surname">Asthana</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Victor</span> <span class="nlm-surname">Olivas</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Matthew A</span> <span class="nlm-surname">Gubens</span></span>,<span class="highwire-citation-author hw-author-orcid-logo-wrapper has-tooltip hasTooltip" data-delta="6" rel="#hw-article-author-popups-node24158 .author-tooltip-6" title=""><span class="nlm-given-names"> Nikolai</span> <span class="nlm-surname">Matni</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="7" rel="#hw-article-author-popups-node24158 .author-tooltip-7" title=""><span class="nlm-given-names">Boris C</span> <span class="nlm-surname">Bastian</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">Barry S</span> <span class="nlm-surname">Taylor</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="9" rel="#hw-article-author-popups-node24158 .author-tooltip-9" title=""><span class="nlm-given-names">John C</span> <span class="nlm-surname">Doyle</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="10" rel="#hw-article-author-popups-node24158 .author-tooltip-10" title=""><span class="nlm-given-names">Trever G</span> <span class="nlm-surname">Bivona</span></span></span></div>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="10" rel="#hw-article-author-popups-node24158 .author-tooltip-10" title=""><span class="nlm-surname"> </span></span></span></div>
<div class="highwire-cite-authors">
<div class="section abstract" id="abstract-1">
<h2>
Abstract</h2>
<div id="p-2">
The
success of targeted cancer therapy is limited by drug resistance that
can result from tumor genetic heterogeneity. The current approach to
address resistance typically involves initiating a new treatment after
clinical/radiographic disease progression, ultimately resulting in
futility in most patients. Towards a potential alternative solution, we
developed a novel computational framework that uses human cancer
profiling data to systematically identify dynamic, pre-emptive, and
sometimes non-intuitive treatment strategies that can better control
tumors in real-time. By studying lung adenocarcinoma clinical specimens
and preclinical models, our computational analyses revealed that the
best anti-cancer strategies addressed existing resistant subpopulations
as they emerged dynamically during treatment. In some cases, the best
computed treatment strategy used unconventional therapy switching while
the bulk tumor was responding, a prediction we confirmed in vitro. The
new framework presented here could guide the principled implementation
of dynamic molecular monitoring and treatment strategies to improve
cancer control.</div>
<div id="p-2">
<br /></div>
<div id="p-2">
Link: <a href="http://dx.doi.org/10.1101/086553"><span class="highwire-cite-metadata-doi highwire-cite-metadata">http://dx.doi.org/10.1101/086553</span></a> </div>
</div>
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="10" rel="#hw-article-author-popups-node24158 .author-tooltip-10" title=""><span class="nlm-surname"> </span></span></span></div>
<h1 class="highwire-cite-title" id="page-title">
</h1>
David Basantahttp://www.blogger.com/profile/15504719079207200602noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-55907434288709603502016-10-24T19:46:00.002-07:002016-10-24T19:46:52.910-07:00Optimal structure of heterogeneous stem cell niche: The importance of cell migration in delaying tumorigenesis<div class="panel-pane pane-highwire-article-citation" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px 0px 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
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<div class="highwire-article-citation highwire-citation-type-highwire-article" data-apath="/biorxiv/early/2016/10/24/082982.atom" data-node-nid="23109" data-pisa-master="biorxiv;082982" data-pisa="biorxiv;082982v1" id="node23109" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<div class="highwire-cite highwire-cite-highwire-article highwire-citation-biorxiv-article-top clearfix has-author-tooltip" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline; zoom: 1;">
<h1 class="highwire-cite-title" id="page-title" style="-webkit-font-smoothing: antialiased; border: 0px; color: #131313; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: 14pt; font-stretch: normal; letter-spacing: -0.03em; line-height: 20pt; margin: 0px 0px 20px; outline: 0px; padding: 16px 0px 0px; vertical-align: baseline;">
Optimal structure of heterogeneous stem cell niche: The importance of cell migration in delaying tumorigenesis</h1>
<div class="highwire-cite-authors" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 11pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-citation-authors" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 11pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="highwire-citation-author first has-tooltip hasTooltip" data-delta="0" rel="#hw-article-author-popups-node23109 .author-tooltip-0" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;" title=""><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Leili</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Shahriyari</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" rel="#hw-article-author-popups-node23109 .author-tooltip-1" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;" title=""><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Ali</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Mahdipour Shirayeh</span></span></span></div>
<div class="highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; color: #333333; font-family: inherit; font-size: 0.82rem; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25; margin: 5px 0px 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span class="highwire-cite-metadata-doi highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 11pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="label" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 11pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: bold; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">doi:</span> http://dx.doi.org/10.1101/082982</span><div class="pub_jnl" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: 10pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25em; margin: 0px; outline: 0px; padding: 8px 0px 0px; vertical-align: baseline;">
This article is a preprint and has not been peer-reviewed [<a href="http://biorxiv.org/content/what-unrefereed-preprint" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration: none; vertical-align: baseline;" target="_blank">what does this mean?</a>].</div>
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Abstract</h2>
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Studying the stem cell niche architecture is a crucial step for investigating the process of oncogenesis and obtaining an effective stem cell therapy for various cancers. Recently, it has been observed that there are two groups of stem cells in the stem cell niche collaborating with each other to maintain tissue homeostasis. One group comprises the border stem cells, which is responsible to control the number of non-stem cells as well as stem cells. The other group, central stem cells, regulates the stem cell niche. In the present study, we develop a bi-compartmental stochastic model for the stem cell niche to study the spread of mutants within the niche. The analytic calculations and numeric simulations, which are in perfect agreement, reveal that in order to delay the spread of mutants in the stem cell niche, a small but non-zero number of stem cell proliferations must occur in the central stem cell compartment. Moreover, the migration of border stem cells to the central stem cell compartment delays the spread of mutants. Furthermore, the fixation probability of mutants in the stem cell niche is independent of types of stem cell division as long as all stem cells do not divide fully asymmetrically. Additionally, the progeny of central stem cells have a much higher chance than the progeny of border stem cells to take over the entire niche.</div>
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<span style="color: #191919; font-family: Lucida Sans, Helvetica, Arial, sans-serif;"><span style="font-size: 14.6667px;"><a href="http://biorxiv.org/content/early/2016/10/24/082982">http://biorxiv.org/content/early/2016/10/24/082982</a></span></span></div>
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Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-80405774501874080402016-10-13T05:52:00.001-07:002016-10-13T05:52:48.171-07:003D Hybrid Modelling of Vascular Network Formation<br />
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3D hybrid modeling of vascular network formation</h1>
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<a href="https://arxiv.org/find/q-bio/1/au:+Perfahl_H/0/1/0/all/0/1" style="text-decoration: none;">Holger Perfahl</a>, <a href="https://arxiv.org/find/q-bio/1/au:+Hughes_B/0/1/0/all/0/1" style="text-decoration: none;">Barry D Hughes</a>, <a href="https://arxiv.org/find/q-bio/1/au:+Alaracon_T/0/1/0/all/0/1" style="text-decoration: none;">Tomas Alaracon</a>, <a href="https://arxiv.org/find/q-bio/1/au:+Maini_P/0/1/0/all/0/1" style="text-decoration: none;">Philip K Maini</a>, <a href="https://arxiv.org/find/q-bio/1/au:+Lloyd_M/0/1/0/all/0/1" style="text-decoration: none;">Mark C Lloyd</a>, <a href="https://arxiv.org/find/q-bio/1/au:+Reuss_M/0/1/0/all/0/1" style="text-decoration: none;">Matthias Reuss</a>, <a href="https://arxiv.org/find/q-bio/1/au:+Byrne_H/0/1/0/all/0/1" style="text-decoration: none;">Helen M Byrne</a></div>
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<b><span style="font-size: large;">Abstract</span></b></div>
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<span style="font-size: 14px;">We develop an agent-based model of vasculogenesis, the de novo formation of blood vessels. Endothelial cells in the vessel network are viewed as linearly elastic spheres and are of two types: vessel elements are contained within the network; tip cells are located at endpoints. Tip cells move in response to forces due to interactions with neighbouring vessel elements, the local tissue environment, chemotaxis and a persistence force modeling their tendency to continue moving in the same direction. Vessel elements experience similar forces but not chemotaxis. An angular persistence force representing local tissue interactions stabilises buckling instabilities due to proliferation. Vessel elements proliferate, at rates that depend on their degree of stretch: elongated elements proliferate more rapidly than compressed elements. Following division, new cells are more likely to form new sprouts if the parent vessel is highly compressed and to be incorporated into the parent vessel if it is stretched. </span></div>
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<span style="font-size: 14px;">Model simulations reproduce key features of vasculogenesis. Parameter sensitivity analyses reveal significant changes in network size and morphology on varying the chemotactic sensitivity of tip cells, and the sensitivities of the proliferation rate and sprouting probability to mechanical stretch. Varying chemotactic sensitivity also affects network directionality. Branching and network density are influenced by the sprouting probability. Glyphs depicting multiple network properties show how network quantities change over time and as model parameters vary. We also show how glyphs constructed from in vivo data could be used to discriminate between normal and tumour vasculature and, ultimately, for model validation. We conclude that our biomechanical hybrid model generates vascular networks similar to those generated from in vitro and in vivo experiments.</span></div>
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<tr><td class="tablecell label" style="padding: 0.1em 0.5em 0em 0em; vertical-align: top;"><span style="font-size: large;">Link:</span></td><td class="tablecell arxivid" style="font-weight: bold; padding: 0.1em 0.5em 0em 0em; vertical-align: top;"><span style="font-size: large;"><a href="https://arxiv.org/abs/1610.00661" style="text-decoration: none;">arXiv:1610.00661</a> [q-bio.QM]</span></td></tr>
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Anonymoushttp://www.blogger.com/profile/06336532069057637717noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-7444710334858395722016-09-19T10:46:00.003-07:002016-09-19T10:48:15.844-07:00Collateral sensitivity networks reveal evolutionary instability and novel treatment strategies in ALK mutated non-small cell lung cancer.<div class="panel-pane pane-highwire-article-citation" style="-webkit-font-smoothing: antialiased; background-color: white; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: 14px; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px 0px 20px; outline: 0px; padding: 0px; vertical-align: baseline;">
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Collateral sensitivity networks reveal evolutionary instability and novel treatment strategies in ALK mutated non-small cell lung cancer.</h1>
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height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Andrew</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Dhawan</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" rel="#hw-article-author-popups-node20936 .author-tooltip-1" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;" title=""><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Daniel</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Nichol</span></span>, <span class="highwire-citation-author" data-delta="2" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Fumi</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Kinose</span></span>, <span class="highwire-citation-author hw-icon-author-orcid" data-delta="3" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0002-6614-4440" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Mohamed E.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Abazeed</span></span>, <span class="highwire-citation-author hw-icon-author-orcid" data-delta="4" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0002-0087-9575" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Andriy</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Marusyk</span></span>, <span class="highwire-citation-author hw-icon-author-orcid" data-delta="5" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0003-3114-1909" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Eric B.</span><span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Haura</span></span>, <span class="highwire-citation-author hw-icon-author-orcid" data-delta="6" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; display: inline; font-family: hwicons !important; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"><a class="hw-author-orcid-logo link-icon-only link-icon" href="http://orcid.org/0000-0003-2971-7673" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration: none; vertical-align: baseline;" target="_blank"><span class="hw-icon-orcid hw-icon-color-orcid" style="-webkit-font-smoothing: antialiased; background-image: none; background-position: 0px 0px; background-repeat: repeat; border: 0px; color: #a6ce39; display: inline; font-size: inherit; font-stretch: inherit; font-variant-numeric: inherit; height: auto; line-height: 1; margin: 0px; outline: 0px; padding: 0px; speak: none; vertical-align: baseline; width: auto;"></span> <span class="title element-invisible" style="-webkit-font-smoothing: antialiased; border: 0px; clip: rect(1px 1px 1px 1px); font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; height: 1px; line-height: inherit; margin: 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute !important; vertical-align: baseline; width: 1px;">View ORCID Profile</span></a><span class="nlm-given-names" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Jacob G.</span> <span class="nlm-surname" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: GillSansRegular, "Gill Sans MT", "Gill Sans", Helvetica, Arial, sans-serif; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">Scott</span></span></span></div>
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<span class="highwire-cite-metadata-doi highwire-cite-metadata" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 11pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;"><span class="label" style="-webkit-font-smoothing: antialiased; border: 0px; font-family: inherit; font-size: 11pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: bold; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">doi:</span> http://dx.doi.org/10.1101/075846</span><div class="pub_jnl" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: 10pt; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.25em; margin: 0px; outline: 0px; padding: 8px 0px 0px; vertical-align: baseline;">
This article is a preprint and has not been peer-reviewed [<a href="http://biorxiv.org/content/what-unrefereed-preprint" style="-webkit-font-smoothing: antialiased; border: 0px; color: grey; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; text-decoration: none; vertical-align: baseline;" target="_blank">what does this mean?</a>].</div>
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<li class="" style="-webkit-font-smoothing: antialiased; background: transparent; border: 0px; display: inline; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.5em; list-style: none; margin: 0px; outline: 0px; padding: 0px; text-align: left; vertical-align: baseline;"><a class="panels-ajax-tab-tab panels-ajax-tabs-once-processed panels-ajax-tabs-first-loaded hw-panels-ajax-tabs-once-processed" data-entity-context="node:20936" data-panel-name="biorxiv_tab_info" data-target-id="highwire_article_tabs" data-trigger="article-info" data-url-enabled="1" href="http://biorxiv.org/content/early/2016/09/19/075846.article-info" style="-webkit-background-clip: padding-box; -webkit-font-smoothing: antialiased; background: transparent; border-bottom-color: initial; border-bottom-style: initial; border-image: initial; border-left-color: transparent; border-left-style: solid; border-radius: 0px; border-right-color: transparent; border-right-style: solid; border-top-color: transparent; border-top-style: solid; border-width: 1px 1px 0px; color: grey; cursor: pointer; display: inline-block; font-family: inherit; font-size: 1em; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: 1.17em; margin: 0px 10px 0px 0px; outline: 0px; padding: 6px 8px; text-align: center; text-decoration: none; transition: background-color 200ms ease-in, color 200ms ease-in; vertical-align: baseline; width: auto; zoom: 1;">Info/History</a></li>
<li class="" style="-webkit-font-smoothing: antialiased; background: transparent; border: 0px; display: inline; font-family: inherit; font-size: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 1.5em; list-style: none; margin: 0px; outline: 0px; padding: 0px; text-align: left; vertical-align: baseline;"><a class="panels-ajax-tab-tab panels-ajax-tabs-once-processed hw-panels-ajax-tabs-once-processed" data-entity-context="node:20936" data-panel-name="article_tab_metrics" data-target-id="highwire_article_tabs" data-trigger="article-metrics" data-url-enabled="1" href="http://biorxiv.org/content/early/2016/09/19/075846.article-metrics" style="-webkit-background-clip: padding-box; -webkit-font-smoothing: antialiased; background: transparent; border-bottom-color: initial; border-bottom-style: initial; border-image: initial; border-left-color: transparent; border-left-style: solid; border-radius: 0px; border-right-color: transparent; border-right-style: solid; border-top-color: transparent; border-top-style: solid; border-width: 1px 1px 0px; color: grey; cursor: pointer; display: inline-block; font-family: inherit; font-size: 1em; font-stretch: inherit; font-style: inherit; font-variant: inherit; line-height: 1.17em; margin: 0px 10px 0px 0px; outline: 0px; padding: 6px 8px; text-align: center; text-decoration: none; transition: background-color 200ms ease-in, color 200ms ease-in; vertical-align: baseline; width: auto; zoom: 1;">Metrics</a></li>
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<span style="font-family: inherit;"><span class="highwire-journal-article-marker-start" style="-webkit-font-smoothing: antialiased; border-color: initial; border-image: initial; border-style: initial; border: 0px; font-family: inherit; font-size: inherit; font-stretch: inherit; font-stretch: inherit; font-style: inherit; font-style: inherit; font-variant: inherit; font-variant: inherit; font-weight: inherit; font-weight: inherit; line-height: inherit; line-height: inherit; margin: 0px; outline-color: initial; outline-style: initial; outline: 0px; padding: 0px; vertical-align: baseline;"></span></span><div class="section abstract" id="abstract-1" style="-webkit-font-smoothing: antialiased; border: 0px; clear: both; font-stretch: inherit; font-variant-numeric: inherit; line-height: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
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Abstract</h2>
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Drug resistance remains an elusive problem in cancer therapy, particularly with novel targeted therapy approaches. Much work is currently focused upon the development of an increasing arsenal of targeted therapies, towards oncogenic driver genes such as ALK-EML4, to overcome the inevitable resistance that develops as therapies are continued over time. The current clinical paradigm after failure of first line ALK TKI is to administer another drug in the same class. As to which drug however, the answer is uncertain, as clinical evidence is lacking. To address this shortcoming, we evolved resistance in an ALK rearranged non-small cell lung cancer line (H3122) to a panel of 4 ALK tyrosine kinase inhibitors used in clinic, and performed a collateral sensitivity analysis to each of the other drugs. We found that all of the ALK inhibitor resistant cell lines displayed a significant cross-resistance to all other ALK inhibitors. To test for the stability of the resistance phenotypes, we evaluated the ALK-inhibitor sensitivities after drug holidays of varying length (1, 3, 7, 14, and 21 days). We found the resistance patterns to be stochastic and dynamic, with few conserved patterns. This unpredictability led us to an expanded search for treatment options for resistant cells. In this expansion, we tested a panel of 6 more anti-cancer agents for collateral sensitivity among the resistant cells, uncovering a multitude of possibilities for further treatment, including cross-sensitivity to several standard cytotoxic therapies as well as the HSP-90 inhibitors. Taken together, these results imply that resistance to targeted therapy in non-small cell lung cancer is truly a moving target; but also one where there are many opportunities to re-establish sensitivities where there was once resistance.</div>
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<span style="color: #191919; font-family: Lucida Sans, Helvetica, Arial, sans-serif;"><span style="font-size: 14.6667px;"><a href="http://biorxiv.org/content/early/2016/09/19/075846">http://biorxiv.org/content/early/2016/09/19/075846</a></span></span></div>
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Jacob Scotthttp://www.blogger.com/profile/12788368243256158841noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-22874849230152757182016-09-15T01:12:00.000-07:002016-09-15T01:12:05.200-07:00Reconstructing phylogenies of metastatic cancers<h1 class="highwire-cite-title" id="page-title">
Reconstructing phylogenies of metastatic cancers</h1>
<div>
<span class="highwire-citation-authors"><span class="highwire-citation-author first hw-icon-author-orcid has-tooltip hasTooltip" data-delta="0" rel="#hw-article-author-popups-node13058 .author-tooltip-0" title=""><span class="nlm-given-names">Johannes G</span> <span class="nlm-surname">Reiter</span></span>, <span class="highwire-citation-author hw-icon-author-orcid" data-delta="1"><span class="nlm-given-names">Alvin P</span> <span class="nlm-surname">Makohon-Moore</span></span>, <span class="highwire-citation-author hw-icon-author-orcid" data-delta="2"><span class="nlm-given-names">Jeffrey M</span> <span class="nlm-surname">Gerold</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Ivana</span> <span class="nlm-surname">Bozic</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="4" rel="#hw-article-author-popups-node13058 .author-tooltip-4" title=""><span class="nlm-given-names">Krishnendu</span> <span class="nlm-surname">Chatterjee</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Christine A</span> <span class="nlm-surname">Iacobuzio-Donahue</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">Bert</span> <span class="nlm-surname">Vogelstein</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="7" rel="#hw-article-author-popups-node13058 .author-tooltip-7" title=""><span class="nlm-given-names">Martin A</span> <span class="nlm-surname">Nowak</span></span></span></div>
<div>
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="7" rel="#hw-article-author-popups-node13058 .author-tooltip-7" title=""><span class="nlm-surname"><br /></span></span></span></div>
<div>
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="7" rel="#hw-article-author-popups-node13058 .author-tooltip-7" title=""><span class="nlm-surname"><div class="section abstract" id="abstract-1">
<h2>
Abstract</h2>
<div id="p-2">
Reconstructing
the evolutionary history of metastases is critical for understanding
their basic biological principles and has profound clinical
implications. Genome-wide sequencing data has enabled modern
phylogenomic methods to accurately dissect subclones and their
phylogenies from noisy and impure bulk tumor samples at unprecedented
depth. However, existing methods are not designed to infer metastatic
seeding patterns. We have developed a tool, called Treeomics, that
utilizes Bayesian inference and Integer Linear Programming to
reconstruct the phylogeny of metastases. Treeomics allowed us to infer
comprehensive seeding patterns for pancreatic, ovarian, and prostate
cancers. Moreover, Treeomics correctly disambiguated true seeding
patterns from sequencing artifacts; 7% of variants were misclassified by
conventional statistical methods. These artifacts can skew phylogenies
by creating illusory tumor heterogeneity among distinct samples. Last,
we performed in silico benchmarking on simulated tumor phylogenies
across a wide range of sample purities (30-90%) and sequencing depths
(50-800x) to demonstrate the high accuracy of Treeomics compared to
existing methods.</div>
<div id="p-2">
<br /></div>
<div id="p-2">
Link: <a href="http://biorxiv.org/content/early/2016/04/11/048157">http://biorxiv.org/content/early/2016/04/11/048157</a></div>
</div>
</span></span></span></div>
David Basantahttp://www.blogger.com/profile/15504719079207200602noreply@blogger.com0Bielefeld, Germany52.0302285 8.532470800000055551.7175025 7.8870238000000557 52.3429545 9.1779178000000563tag:blogger.com,1999:blog-1481440158840549455.post-44932525213946570182016-08-25T06:38:00.002-07:002016-08-25T06:38:53.343-07:00Ordinary Differential Equations in Cancer Biology<h1 class="highwire-cite-title" id="page-title">
Ordinary Differential Equations in Cancer Biology</h1>
<div>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author first has-tooltip hasTooltip" data-delta="0" rel="#hw-article-author-popups-node19644 .author-tooltip-0" title=""><span class="nlm-given-names">Margaret P</span> <span class="nlm-surname">Chapman</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" rel="#hw-article-author-popups-node19644 .author-tooltip-1" title=""><span class="nlm-given-names">Claire J.</span> <span class="nlm-surname">Tomlin</span></span></span></div>
</div>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" rel="#hw-article-author-popups-node19644 .author-tooltip-1" title=""><span class="nlm-surname"><br /></span></span></span></div>
<h4>
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" rel="#hw-article-author-popups-node19644 .author-tooltip-1" title=""><span class="nlm-surname">Abstract</span></span></span></h4>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" rel="#hw-article-author-popups-node19644 .author-tooltip-1" title=""><span class="nlm-surname"><br /></span></span></span></div>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" rel="#hw-article-author-popups-node19644 .author-tooltip-1" title=""><span class="nlm-surname">Ordinary differential equations (ODEs) provide a classical framework to
model the dynamics of biological systems, given temporal experimental
data. Qualitative analysis of the ODE model can lead to further
biological insight and deeper understanding compared to traditional
experiments alone. Simulation of the model under various perturbations
can generate novel hypotheses and motivate the design of new
experiments. This short paper will provide an overview of the ODE
modeling framework, and present examples of how ODEs can be used to
address problems in cancer biology.</span></span></span></div>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" rel="#hw-article-author-popups-node19644 .author-tooltip-1" title=""><span class="nlm-surname"><br /></span></span></span></div>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" rel="#hw-article-author-popups-node19644 .author-tooltip-1" title=""><span class="nlm-surname">Link: </span></span></span><a href="http://dx.doi.org/10.1101/071134">dx.doi.org/10.1101/071134</a></div>
David Basantahttp://www.blogger.com/profile/15504719079207200602noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-53513748808354271612016-08-08T06:08:00.000-07:002016-08-08T06:08:00.895-07:00Cancer treatment scheduling and dynamic heterogeneity in social dilemmas of tumour acidity and vasculature<h1 class="highwire-cite-title" id="page-title">
Cancer treatment scheduling and dynamic heterogeneity in social dilemmas of tumour acidity and vasculature</h1>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author first has-tooltip hasTooltip" data-delta="0" rel="#hw-article-author-popups-node18543 .author-tooltip-0" title=""><span class="nlm-given-names">Artem</span> <span class="nlm-surname">Kaznatcheev</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Robert</span> <span class="nlm-surname">Vander Velde</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="2" rel="#hw-article-author-popups-node18543 .author-tooltip-2" title=""><span class="nlm-given-names">Jacob G</span> <span class="nlm-surname">Scott</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="3" rel="#hw-article-author-popups-node18543 .author-tooltip-3" title=""><span class="nlm-given-names">David</span> <span class="nlm-surname">Basanta</span></span></span></div>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="3" rel="#hw-article-author-popups-node18543 .author-tooltip-3" title=""><span class="nlm-surname"> </span></span></span></div>
<div class="highwire-cite-authors">
<div class="section abstract" id="abstract-1">
<h2>
Abstract</h2>
<div id="p-2">
Background:
Tumours are diverse ecosystems with persistent heterogeneity in various
cancer hallmarks like self-sufficiency of growth factor production for
angiogenesis and reprogramming of energy-metabolism for aerobic
glycolysis. This heterogeneity has consequences for diagnosis,
treatment, and disease progression.
Methods: We introduce the double goods game to study the dynamics of
these traits using evolutionary game theory. We model glycolytic acid
production as a public good for all tumour cells and oxygen from
vascularization via VEGF production as a club good benefiting
non-glycolytic tumour cells. This results in three viable phenotypic
strategies: glycolytic, angiogenic, and aerobic non-angiogenic.
Results: We classify the dynamics into three qualitatively distinct
regimes: (1) fully glycolytic, (2) fully angiogenic, or (3) polyclonal
in all three cell types. The third regime allows for dynamic
heterogeneity even with linear goods, something that was not possible in
prior public good models that considered glycolysis or growth-factor
production in isolation.
Conclusion: The cyclic dynamics of the polyclonal regime stress the
importance of timing for anti-glycolysis treatments like lonidamine. The
existence of qualitatively different dynamic regimes highlights the
order effects of treatments. In particular, we consider the potential of
vascular renormalization as a neoadjuvant therapy before follow up with
interventions like buffer therapy.</div>
<div id="p-2">
<br /></div>
<div id="p-2">
Link: <a href="http://dx.doi.org/10.1101/067488"><span class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">doi:</span> http://dx.doi.org/10.1101/067488 </span></a> </div>
</div>
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="3" rel="#hw-article-author-popups-node18543 .author-tooltip-3" title=""><span class="nlm-surname"> </span></span></span></div>
<h1 class="highwire-cite-title" id="page-title">
</h1>
David Basantahttp://www.blogger.com/profile/15504719079207200602noreply@blogger.com0Tampa, FL, USA27.950575 -82.45717760000002327.5019215 -83.102624600000027 28.3992285 -81.811730600000018tag:blogger.com,1999:blog-1481440158840549455.post-64764817987000984942016-06-16T07:23:00.002-07:002016-06-16T07:23:25.552-07:00The Evolutionary Trade-off between Stem Cell Niche Size, Aging, and Tumorigenesis<h1 class="highwire-cite-title" id="page-title">
The Evolutionary Trade-off between Stem Cell Niche Size, Aging, and Tumorigenesis</h1>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author first has-tooltip hasTooltip" data-delta="0" rel="#hw-article-author-popups-node16304 .author-tooltip-0" title=""><span class="nlm-given-names">Vincent L.</span> <span class="nlm-surname">Cannataro</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" rel="#hw-article-author-popups-node16304 .author-tooltip-1" title=""><span class="nlm-given-names">Scott A.</span> <span class="nlm-surname">McKinley</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="2" rel="#hw-article-author-popups-node16304 .author-tooltip-2" title=""><span class="nlm-given-names">Colette M.</span> <span class="nlm-surname">St. Mary</span></span></span></div>
<div class="section abstract" id="abstract-1">
<h2>
Abstract</h2>
<div id="p-2">
Many
epithelial tissues within large multicellular organisms are continually
replenished by small independent populations of stem cells. These stem
cells divide within their niches and differentiate into the constituent
cell types of the tissue, and are largely responsible for maintaining
tissue homeostasis. Mutations can accumulate in stem cell niches and
change the rate of stem cell division and differentiation, contributing
to both aging and tumorigenesis. Here, we create a mathematical model of
the intestinal stem cell niche, crypt system, and epithelium. We
calculate the expected effect of fixed mutations in stem cell niches and
their expected effect on tissue homeostasis throughout the intestinal
epithelium over the lifetime of an organism. We find that, due to the
small population size of stem cell niches, fixed mutations are expected
to accumulate via genetic drift and decrease stem cell fitness, leading
to niche and tissue attrition, and contributing to organismal aging. We
also explore mutation accumulation at various stem cell niche sizes, and
demonstrate that an evolutionary trade-off exists between niche size,
tissue aging, and the risk of tumorigenesis; where niches exist at a
size that minimizes the probability of tumorigenesis, at the expense of
accumulating deleterious mutations due to genetic drift. Finally, we
show that the probability of tumorigenesis and the extent of aging
trade-off differently depending on whether mutational effects confer a
selective advantage, or not, in the stem cell niche.</div>
<div id="p-2">
<br /></div>
<div id="p-2">
<a href="http://dx.doi.org/10.1101/059279"><span class="highwire-cite-metadata-doi highwire-cite-metadata">http://dx.doi.org/10.1101/059279</span></a> </div>
</div>
David Basantahttp://www.blogger.com/profile/15504719079207200602noreply@blogger.com0tag:blogger.com,1999:blog-1481440158840549455.post-85244154337975178842016-06-09T07:01:00.000-07:002016-06-09T07:01:27.625-07:00Evolutionary dynamics of CRISPR gene drives<h1 class="highwire-cite-title" id="page-title">
Evolutionary dynamics of CRISPR gene drives</h1>
<div class="highwire-cite-authors">
<span class="highwire-citation-authors"><span class="highwire-citation-author first has-tooltip hasTooltip" data-delta="0" rel="#hw-article-author-popups-node15764 .author-tooltip-0" title=""><span class="nlm-given-names">Charleston</span> <span class="nlm-surname">Noble</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="1" rel="#hw-article-author-popups-node15764 .author-tooltip-1" title=""><span class="nlm-given-names">Jason</span> <span class="nlm-surname">Olejarz</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="2" rel="#hw-article-author-popups-node15764 .author-tooltip-2" title=""><span class="nlm-given-names">Kevin</span> <span class="nlm-surname">Esvelt</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="3" rel="#hw-article-author-popups-node15764 .author-tooltip-3" title=""><span class="nlm-given-names">George</span> <span class="nlm-surname">Church</span></span>, <span class="highwire-citation-author has-tooltip hasTooltip" data-delta="4" rel="#hw-article-author-popups-node15764 .author-tooltip-4" title=""><span class="nlm-given-names">Martin</span> <span class="nlm-surname">Nowak</span></span></span></div>
<div class="highwire-cite-authors">
<div class="section abstract" id="abstract-1">
<h2>
Abstract</h2>
<div id="p-2">
The
alteration of wild populations has been discussed as a solution to a
number of humanity's most pressing ecological and public health
concerns. Enabled by the recent revolution in genome editing, CRISPR
gene drives, selfish genetic elements which can spread through
populations even if they confer no advantage to their host organism, are
rapidly emerging as the most promising approach. But before real-world
applications are considered, it is imperative to develop a clear
understanding of the outcomes of drive release in nature. Toward this
aim, we mathematically study the evolutionary dynamics of CRISPR gene
drives. We demonstrate that the emergence of drive-resistant alleles
presents a major challenge to previously reported constructs, and we
show that an alternative design which selects against resistant alleles
greatly improves evolutionary stability. We discuss all results in the
context of CRISPR technology and provide insights which inform the
engineering of practical gene drive systems.</div>
<div id="p-2">
<br /></div>
<div id="p-2">
<span class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">doi:</span> <a href="doi:%20http://dx.doi.org/10.1101/057281">http://dx.doi.org/10.1101/057281 </a> </span></div>
<div id="p-2">
<span class="highwire-cite-metadata-doi highwire-cite-metadata">link: <a href="http://biorxiv.org/content/early/2016/06/06/057281">http://biorxiv.org/content/early/2016/06/06/057281</a> </span></div>
</div>
<span class="highwire-citation-authors"><span class="highwire-citation-author has-tooltip hasTooltip" data-delta="4" rel="#hw-article-author-popups-node15764 .author-tooltip-4" title=""><span class="nlm-surname"> </span></span></span></div>
<h1 class="highwire-cite-title" id="page-title">
</h1>
David Basantahttp://www.blogger.com/profile/15504719079207200602noreply@blogger.com0