tag:blogger.com,1999:blog-24636421866281770122024-03-13T01:27:47.943-07:00Pediatric Preclinical Testing InitiativePPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.comBlogger22125tag:blogger.com,1999:blog-2463642186628177012.post-46336428573399467072014-12-21T22:34:00.001-08:002014-12-21T22:34:20.989-08:00updates & more<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Please continue to check the dipg preclinical consortium blog entry below for regular updates. Also stay tuned for our upcoming announcement about <a href="http://www.cc-tdi.org/">cc-TDI</a> ... which, like the dipg preclinical consortium effort, will directly bring discoveries about childhood cancer biology to the initiation of clinical trials. </span>PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com1tag:blogger.com,1999:blog-2463642186628177012.post-65977477713868462692012-04-01T09:53:00.001-07:002013-02-07T19:53:37.258-08:00Rally Foundation funds 'Next Steps' Undifferentiated Sarcoma Research<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhouCRlnZYkFFOv3Y9FzILWzIYjS2yjDYC3N7oAjV7GoPpg6W_BzzkdykuCX9u9t7_BVyx2wAnuaES8ywBH-CfdWXX5aDq8iLkUbJsrWcJkKxthamwp0e0wETJ4ucp6yFCrBJJPbcPH1dI/s1600/PPTI-KellerLab.png" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="198" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhouCRlnZYkFFOv3Y9FzILWzIYjS2yjDYC3N7oAjV7GoPpg6W_BzzkdykuCX9u9t7_BVyx2wAnuaES8ywBH-CfdWXX5aDq8iLkUbJsrWcJkKxthamwp0e0wETJ4ucp6yFCrBJJPbcPH1dI/s200/PPTI-KellerLab.png" width="200" /></a></div>
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">We are grateful to the Rally Foundation for new $40,000 award for the grant entitled, <i>The Next Step in Defining Targeted Therapies for Undifferentiated Sarcoma</i>. This award follows a prior grant for <i>in vitro</i> studies of tumor cells from undifferentiated sarcoma mouse models, and allows Elaine and Jinu to proceed with preclinical studies in mice that will test whether our best drug(s) from a screen of 60 agents would be worth pursuing in a clinical trial. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">This award is in memory of a little 4 year old girl named Ava Sentell whose life was interrupted by this same cancer, and in honor of Brady Wolfe and Aidyn Reid. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">[update 2/7/2013: Please see the Rally Foundation webpage for <i><a href="http://rallyfoundation.org/kids/avas_angels_research_fund">Ava's Angels Research Fund</a>! ]</i></span></div>
PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com2tag:blogger.com,1999:blog-2463642186628177012.post-64186394168975289422012-01-26T17:04:00.000-08:002012-01-26T17:05:19.432-08:00Partnership with JAX creates new childhood cancer models<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgpYqr8gKm4B5IOG1-HrY8fcvG9RlbJPc1PmtuAGskXC0f2ABzsGI-gDX-KXqW3sWf5lxFHicg7MnluStGDeYtep9GMsCWmUG7kuxYCsPegnaTMjxLZmuFMbPG2osYGuQpUubL6D7YqH80/s1600/ERMS-PCC.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="150" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgpYqr8gKm4B5IOG1-HrY8fcvG9RlbJPc1PmtuAGskXC0f2ABzsGI-gDX-KXqW3sWf5lxFHicg7MnluStGDeYtep9GMsCWmUG7kuxYCsPegnaTMjxLZmuFMbPG2osYGuQpUubL6D7YqH80/s200/ERMS-PCC.jpg" width="200" /></a>We are excited to partner with Jackson Laboratory on the creation of a series of mouse models of childhood cancers. Our first successful patient-derived xenograft model is now established for an embryonal rhabdomyosarcoma, with many more models in development. The sample came from an autopsy-derived <a href="http://kellerlabblog.blogspot.com/2011/10/leaving-legacy-value-of-tumor-tissue.html">Legacy Gift</a>. This model accompanied by the creation of a primary cell culture model (pictured), with <a href="http://pcb-ohsu.blogspot.com/2011/04/personalized-medicine-on-horizon.html">genetic characterization</a>. These resources are intended to be broadly available to all laboratories in North America and beyond.<br />
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Because pediatric cancers are rare, few established cell lines are available and many of these cell lines are very old. For embryonal rhabdomyosarcoma, the RD cell line was established in 1968 and <a href="http://www.ncbi.nlm.nih.gov/pubmed?term=4241949%5Buid%5D">reported in the literature in 1969</a>. We are grateful to the family that made their child's Legacy Gift possible in order to advance the field. PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com3tag:blogger.com,1999:blog-2463642186628177012.post-35704922672901634462011-12-22T20:01:00.000-08:002011-12-22T20:01:03.046-08:00Moving the field, One cell line at a time<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">An interesting idea of the Chordoma Foundation is to create a <a href="http://www.chordomafoundation.org/research/panel.aspx#Prize">$10,000 prize</a> for new chordoma cell lines. Not sure what chordoma is? It wouldn't be surprising... this is a very rare cancer of the cranial base and spinal column. Few cell lines or tissue resources existed before the Chordoma Foundation initiatives. Now, though, a great deal is known and the path towards treatment is ever closer. </span>PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com1tag:blogger.com,1999:blog-2463642186628177012.post-72860902240652560062011-12-03T19:02:00.009-08:002015-05-18T15:23:05.840-07:00Open Science Forum: DIPG Preclinical Consortium<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Check back frequently to this blog post, which gives a week to week account of the project entitled, "Rapid Preclinical Development of a Targeted Therapy Combination for DIPG" described <a href="http://kellerlabblog.blogspot.com/2011/11/thecurestartsnow-funds-dipg.html">here</a> and <a href="http://kellerlabblog.blogspot.com/2011/11/lyla-nsouli-foundation-funds-supplement.html">here</a>. This study is made possible by a $100,000 grant from</span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">. An additional $28,000 supplement from The Lyla Nsouli Foundation for Children’s Brain Cancer Research has allowed our project to expand to our 2 participating European collaborators.</span><br />
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">The full international team is:</span><br />
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Charles Keller MD at the Children's Cancer Therapy Development Institute (<a href="http://www.cc-TDI.org/">www.cc-TDI.org</a>) with: </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Kellie Nazemi MD, Nate Selden MD, PhD, Dan Guillaume MD, PhD Catie Grasso PhD and Paul Spellman PhD at the Oregon Health & Science University</span><br />
<span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">(cell lines: OHSU-DIPG#1 <i>now senescent</i>, OHSU-DIPG#2 <i>now senescent</i>) </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Oren Becher MD, Duke University Medical Center</span><br />
<span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">(cell line, <i>from mouse</i>: 11.1003.2, which is GFAP tva:floxed PDGF p53) </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Michelle Monje MD, PhD, Stanford University</span><br />
<span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">(cell lines: SU-DIPG-I, SU-DIPG-II, SU-DIPG-III, <b>SU-DIPG-IV</b>, SU-DIPG-V, <b>SU-DIPG-VI</b></span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">, </span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;"><b>SU-DIPG-XIII</b></span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">)</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Maryam Fouladi MD, Cincinnati Children’s Hospital Medical Center</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Cynthia Hawkins, MD, PhD, University of Toronto</span><br />
<span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">(cell lines: HSC-DIPG27, HSC-DIPG58)</span><br />
<span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;"> </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Xiao-Nan Li MD, PhD, Baylor College of Medicine</span><br />
<span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">(cell lines: IBs-1215DIPG(<b>Li-A</b>), IBs-A1204DIPG, IBs-AB10206DIPG, IBs-C1220DIPG, IBs-J1204DIPG, IBs-W0128DIPG(<b>Li-F</b>))</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Dannis G. van Vuurden MD, MSc, & Esther Hulleman, VU Cancer Center Amsterdam, </span><br />
<span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">(cell lines: <b>VUMC-DIPG-B</b>, </span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;"><b>VUMC-DIPG-A</b></span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">,</span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;"> </span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">VU-10170)</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Jacques Grill, Institut Gustave-Roussy, Villejuif, France</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span class="Apple-style-span" style="color: #990000;">(</span></span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">Nem144, Nem145, <b>Nem157</b>, <b>Nem163</b>, <b>Nem165</b>, <b>Nem168</b>, <b>Nem175</b>, Nem181, <b>Nem186</b> and Nem198; <b>Nem215</b> and Nem226</span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">) </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><br /></span>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">and </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><br /></span>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Eric H. Raabe, Johns Hopkins University, Baltimore, MD; Katherine Warren, Paul Meltzer and Martha Quezado, NIH, Bethesda, MD</span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"></span><br />
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span class="Apple-style-span" style="color: #990000;">(cell line: <b>JHH-DIPG1</b>)</span></span></span></div>
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Mariko DeWire, Nationwide Children's Hospital, Columbus, OH</span></span></div>
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span class="Apple-style-span" style="color: #990000;">(<strike>cell line name TBA</strike>)</span></span></span></div>
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Dennis Steindler, University of Florida, Gainesville, FL</span></div>
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span class="Apple-style-span" style="color: #990000;">(hDIPG-L1(?))</span></span></span></div>
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Marta Alonso, University of Navarra, Madrid, Spain</span></div>
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span class="Apple-style-span" style="color: #990000;">(<strike>pedNav-1</strike>)</span></span></span></div>
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><b>The ultimate goal is to move the most effective single agent or combination therapy forward to early phase clinical trials in the next 18-24 months.</b> The clinical trial would be available from the Children's Oncology Group, and/or collaborating institutions. This is the first time that a group of basic and translational scientists and physicians from eight institutions throughout North America and Europe have come together as a consortium to focus on DIPGs and to focus on a bench-to-bedside approach to rationally target therapy for children with DIPGs.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><br />
</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Project Progress:</span><br />
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<a href="http://2.bp.blogspot.com/-RhPSNrgUiX8/TvZUIzPisTI/AAAAAAAAARI/LBqrRTj_ecA/s1600/CSN.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><img border="0" height="28" src="http://2.bp.blogspot.com/-RhPSNrgUiX8/TvZUIzPisTI/AAAAAAAAARI/LBqrRTj_ecA/s200/CSN.jpg" width="200" /></span></a></div>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11/01/2011: <a href="http://www.thecurestartsnow.org/">The CureStartsNow</a> and affiliated foundations provide $100,000 for project for labs in North America.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11/21/2011: Prototype drug plates sent to Becher, Li and Monje labs (shipping to Hawkins lab tba).</span><br />
<a href="http://2.bp.blogspot.com/-RvvS0x2BzA8/TvZTy2K3lSI/AAAAAAAAAQ8/QDHXiJTGGgE/s1600/LNF.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><img border="0" height="76" src="http://2.bp.blogspot.com/-RvvS0x2BzA8/TvZTy2K3lSI/AAAAAAAAAQ8/QDHXiJTGGgE/s200/LNF.jpg" width="200" /></span></a><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11/23/2011: The <a href="http://www.lylansoulifoundation.org//">Lyla Nsouli Foundation</a> provides $28,000 to add participating European labs. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11/23/2011: Prototype drug plates sent to Grill and Hulleman labs.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11/28/2011: Concept of exon sequencing of paired cell lines, primary tumors and normal DNA (via tertiary funding source) considered.</span><br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhPsp7YtJh0K8X4L44IxeyYSxhlGGRk7SdhHWAmAj9Tm_YAj6pOSqAriQ2JKSI7nCXRZK8CtoBuAUHd26FD8_B5sMwP004ELcdC-efTVyKWRaTEEoBbP1sVbGMRrrvcQq-DHdIn2YqmhL4/s1600/OHSU-DIPG-1_40x_2011_1209.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><img border="0" height="150" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhPsp7YtJh0K8X4L44IxeyYSxhlGGRk7SdhHWAmAj9Tm_YAj6pOSqAriQ2JKSI7nCXRZK8CtoBuAUHd26FD8_B5sMwP004ELcdC-efTVyKWRaTEEoBbP1sVbGMRrrvcQq-DHdIn2YqmhL4/s200/OHSU-DIPG-1_40x_2011_1209.jpg" width="200" /></span></a><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/08/2011: Subcontract paperwork to each site has been initiated.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/08/2011: Plastic tips for robotic drug plating on order (needed to create more plates).</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/08/2011: (Keller lab) Plan initiated for biomarker characterization of OHSU-DIPG#1 cell culture.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/08/2011: (Keller lab) Sequenom MassArray screen completed for OHSU-DIPG#1 cell culture.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/15/2011: Plastic tips for drug plating were backorder from Eppendorf but may arrive in the coming days. Plan to create/send 384-well drug plates to Cynthia Hawkins group once tips are in. Also sending additional plates to Oren Becher lab at that time. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/15/2011: After extensive review, a generation #2 drug plate set has been designed. 60 agents across 3 plates, dozens of molecular targets. Incorporates the consensus preferred compounds from labs of Jim Olson, Maryam Fouladi, Robin Jones, Darren Hargrave, Jacques Grill and Esther Hulleman. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/21/2011: Plastic tips were received this week and new drug plates have been printed and will ship to the Li lab and Hawkins lab soon. Experience with the plates thus far (Becher lab) suggests that a new plate types (non-clear/black plastic) with or without gelatin undercoating may be needed. Assessment will be made once each of the other labs has experience with the generation #1 plates.</span><br />
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<a href="http://3.bp.blogspot.com/-wpR9ADBh0eY/TvZTArELa7I/AAAAAAAAAQw/15UZdrW1MaQ/s1600/ABC2-CureSearch.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><img border="0" height="52" src="http://3.bp.blogspot.com/-wpR9ADBh0eY/TvZTArELa7I/AAAAAAAAAQw/15UZdrW1MaQ/s200/ABC2-CureSearch.jpg" width="200" /></span></a></div>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/23/2011: In an <a href="http://kellerlabblog.blogspot.com/2011/12/sincere-thanks-to-abc2-and-curesearch.html">amazing development</a>, ABC2 and CureSearch for Children's Cancer have jointly funded a supplement to the Preclinical Consortium project (with $76,000 and $25,000, respectively). This new supplement will allow us to exon sequencing of all 16 cell lines, their primary tumor and paired normal DNA via the functional genomics laboratory of Dr. Paul Spellman (OHSU). From this data we will prioritize combination drug testing on the most clinically ‘representative’ samples <i>(i.e.</i>, samples that have classical DIPG findings which are in order: c‐MET amplification, p53 deletion, PDGFRA amplification, IGF1R/IGF2 amplification, CDK4/CDK6 gain or Shh pathway mutation, EGFR amplification or KRAS/NRAS mutation) or cell lines that are most similar overall to one another (<i>i.e.</i>, not outliers).</span><br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgid0tIbv4gdPDfsWi1Lxp17VhANPcFRZiFoxnANSHF_rkP62mpaP2lH74Wxb1rEIDujHiUP4uVWf8two7xul9njsVca8sCawyjBNdHgyOfoSkk-0scxr8Kik0W6bCCLN1gXikrgthoQhE/s1600/11.1003.2.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="150" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgid0tIbv4gdPDfsWi1Lxp17VhANPcFRZiFoxnANSHF_rkP62mpaP2lH74Wxb1rEIDujHiUP4uVWf8two7xul9njsVca8sCawyjBNdHgyOfoSkk-0scxr8Kik0W6bCCLN1gXikrgthoQhE/s200/11.1003.2.jpg" width="200" /></a><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">01/05/2012: Each lab was requested to organize samples for DNA sequencing; correspondence from Stanford and Amsterdam was received; further more active correspondence expected as the new year ensues.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">01/12/2012: Most of the cell cultures from participating centers are now verified by name, and in some cases new cell cultures are available. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">01/12/2012: The first drug screen on a generation#1 drug plate set has been performed by the Becher lab using a mouse DIPG culture. A logistical success, and at least 8 interesting cytocidal drugs have been identified. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">01/19/2012: Our first <a href="http://kellerlabblog.blogspot.com/2011/10/our-approach-to-personalized-cancer.html">probabilistic boolean model</a> (PBM) of the data above is from the mouse DIPG cells is being generated by our collaborators at Texas Tech, Dr. Ranadip Pal and graduate student Noah Berlow. </span><br />
<span style="font-family: Arial;">01/26/2012: PBM data still pending (results soon); DNA or RNA samples from DIPG cultures yet to be received from each institution (for sequencing; target date to receive all samples is Feb 9); 24 new sets of generation#1 plates printed for sending out tomorrow to Toronto (for use with potential new primary culture) and other sites; interesting spherical cell culture beads with different coatings being explored at OHSU as a potential way to accelerate DIPG cell culture growth ;official press release now available <a href="http://www.abc2.org/article/patient-groups-and-researchers-join-forces-speed-treatments-rare-pediatric-brain-tumor">here</a>. </span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgMr6MHEE-sbFA1EcG8xjykzluz7vG3yP6G2KQl6cbJmS6Z1KDsG2m1mIOhI0RhsNeAhSWAuWJF4oVGJRViYi9_1D-ZXTFpJdO1hfJGWCu_wZh1-pn8qWYbjtQJiJ8dvNnei7vxjFuPxjw/s1600/anonymized-Mouse+DIPG+PKIM+Circuit.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="163" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgMr6MHEE-sbFA1EcG8xjykzluz7vG3yP6G2KQl6cbJmS6Z1KDsG2m1mIOhI0RhsNeAhSWAuWJF4oVGJRViYi9_1D-ZXTFpJdO1hfJGWCu_wZh1-pn8qWYbjtQJiJ8dvNnei7vxjFuPxjw/s320/anonymized-Mouse+DIPG+PKIM+Circuit.jpg" width="320" /></a></div>
<span style="font-family: Arial;">01/28/2012: First (draft) PBM tumor maintenance circuit now created for mouse DIPG cells. Thank you, Noah! Many known targets were affirmed, but new ones were found, and co-dependencies were identified. Validation experiments will follow. </span><br />
<span style="font-family: Arial;">02/02/2012: New generation#1 drug plates sent to Toronto and Duke; orders submitted for 55 of the 60 drugs to be used to create generation#2 drug plates; DNA/RNA samples received from Stanford and Toronto. Many public questions asked about the bioinformatics approach. For clarification of PBM tumor circuits a movie is available <a href="http://kellerlabblog.blogspot.com/2011/10/our-approach-to-personalized-cancer.html">here</a>. </span><br />
<span style="font-family: Arial;">02/09/2012: samples for deep sequencing received from Amsterdam, Stanford and Toronto. Additional samples from Stanford and Baylor to arrive today. Second run of raw data for mouse DIPG culture drug plates received from Duke, with analysis now underway. </span><br />
<span style="font-family: Arial;">02/16/2012: Second run of drug screen from Duke mouse model consistent with first run; Partial data for 30 drugs screened received for </span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">SU-DIPG-II </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">from Stanford. One strong drug 'hit' found in common with Duke mouse model</span><span class="Apple-style-span" style="font-family: Arial;">; DNA and RNA sequencing of samples is to start shortly. </span><br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhCVQeRlCbq0WfrPmF8IevnhgakhrSOCUnN72xdvxCaYRl22mAgUyzxnY2L9k1f9XYVIEnrQ7IzWJ5JJul0i8RGaAyZbt8QuHThH9dT1BDlAPs-TDK7Isf1is_Xm5wgbZCQwY3z-lwuOtE/s1600/TJF.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="13" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhCVQeRlCbq0WfrPmF8IevnhgakhrSOCUnN72xdvxCaYRl22mAgUyzxnY2L9k1f9XYVIEnrQ7IzWJ5JJul0i8RGaAyZbt8QuHThH9dT1BDlAPs-TDK7Isf1is_Xm5wgbZCQwY3z-lwuOtE/s200/TJF.jpg" width="200" /></a><span class="Apple-style-span" style="font-family: Arial;"><b><span class="Apple-style-span" style="color: blue;">IMPORTANT UPDATE:</span> </b> Another cell line has been added as an with an new affiliate investigator & participating institution. A DIPG primary cell culture being studied at Nationwide Children's Hospital in Columbus, OH, by Dr. Mariko DeWire. Characterization will include focused genetic characterization and drug screening. This additional affiliate is being made possible by the generous $8800 sponsorship of the <a href="http://www.teamjulianfoundation.com/">Team Julian Foundation</a>. </span><br />
<span class="Apple-style-span" style="font-family: Arial;">02/23/2012: DNA and RNA for sequencing can be summarized as: we have samples related to 19 independent cultures:</span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">DNA from the primary tumor from 5; </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">RNA from the primary tumor from 0;</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">DNA from normal tissue from 12;</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">RNA from normal tissue from 5;</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">DNA from xenograft tissue for 7;</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">RNA from xenograft tissue for 0;</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">DNA from tumor cell cultures from 12;</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">RNA from tumor cell cultures from 8.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Complete sets of DNA & RNA from tumor cultures, the original primary tumor and normal tissue were not available from all samples; however, we are moving forward in the interest of time (and the goal of getting the clinical trial designed in the near term).</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">02/23/2012: The results for the second half of the first SU-DIPG-I drug screen are received and are being processed. Many thanks to Michelle (and Oren) for being among the best and most proactive members of the consortium early on. </span><br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjJrcxeoUViHWcCtzeB6D6joC_CeoWgQCdniq3MK9g4XGHqDWlDlhlPZt3dUFLdornf11VcHltmcNOHli08bo4zMZ2MMnf840EYo2ZHSbajyh02Am17KaPPTfNbdKSkcEfyWVbLjMQLNZw/s1600/2012_0305-PBTC.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="150" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjJrcxeoUViHWcCtzeB6D6joC_CeoWgQCdniq3MK9g4XGHqDWlDlhlPZt3dUFLdornf11VcHltmcNOHli08bo4zMZ2MMnf840EYo2ZHSbajyh02Am17KaPPTfNbdKSkcEfyWVbLjMQLNZw/s200/2012_0305-PBTC.jpg" width="200" /></a><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">03/01/2012: Common target(s) found in human </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">SU-DIPG-I cell line and mouse </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11.1003.2 cell line </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">drug screens; preliminary results to be presented Monday March 5 at PBTC meeting. Results of </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">SU-DIPG-II cell line now being analyzed.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">03/05/2012: Organization and early results of the Consortium presented at the Pediatric Brain Tumor Consortium (PBTC) closed meeting in Dallas. Very well received. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">03/08/2012: In processing RNA and DNA for sequencing, some samples were not of sufficient quantity. We have contacted each collaborator to send new aliquots for these samples. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">03/14/2012: Please see our guest blog entry from Nettie <a href="http://kellerlabblog.blogspot.com/2012/03/guest-entry-our-hope-no-curative.html">here</a>. </span><br />
<span style="font-family: Arial;">03/15/2012: The DNA and RNA sequencing continues to be delayed. Each lab is actively creating supplemental DNA or RNA so that we can begin sequencing April 1 (our new deadline). </span><br />
<span style="font-family: Arial;">03/22/2012: there is nothing new to report this week (sadly). We are just waiting for the replacement DNA's and RNA's to be sent in from the consortium members. </span><br />
<span style="font-family: Arial;">03/29/2012: Preliminary results (similar to those presented at the PBTC meeting) were presented at the COG Brain Tumor committee meeting in Minneapolis. Discussions were active to extend the same approach to other pediatric brain tumors, including high risk medulloblastoma, high grade gliomas, and intracranial germ cell tumors. </span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjwby4uSNXmPCiBh-uV9Chxgrdq-R1TcB3_aZSRaCcPC4yYIbFThVghhEnSMvVJCT-Ya0a9zZkf5dO9wrdgxiVRXyZvD9_1CS0VXQvsGFjl6y-oWSmUShIMrf85zla8SZ5fCxun4Rnt3cA/s1600/RaabeLab.JPG" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="150" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjwby4uSNXmPCiBh-uV9Chxgrdq-R1TcB3_aZSRaCcPC4yYIbFThVghhEnSMvVJCT-Ya0a9zZkf5dO9wrdgxiVRXyZvD9_1CS0VXQvsGFjl6y-oWSmUShIMrf85zla8SZ5fCxun4Rnt3cA/s200/RaabeLab.JPG" width="200" /></a></div>
<span style="font-family: Arial;">04/02/2012: </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">At AACR a</span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><a href="http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=5eccf257-1e78-44ad-a11d-0cb24040c222&cKey=c6e7a032-873e-4aea-a5af-1b3374b5b338&mKey=%7b2D8C569E-B72C-4E7D-AB3B-070BEC7EB280%7d">key new presentation</a></span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> from the Raabe lab was today, "High-level activation of the Notch pathway in diffuse intrinsic pontine glioma" by Hutt</span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><i>et al </i></span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">(a Johns Hopkins - NCI collaboration that generated a new cell line/mouse model of DIPG). Also presented by Dr. Ian Pollack are the</span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><a href="http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=b83a260c-41db-47f8-b1c1-8c14e4f32b1f&cKey=159c5f60-d2de-4197-aaf5-65356dbdab2c&mKey=%7b2D8C569E-B72C-4E7D-AB3B-070BEC7EB280%7d">promising early results of a DIPG vaccine trial</a></span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> (caveats not withstanding). Photo to right is Dr. Eric Raabe and staff scientist, Marianne Hutt. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">04/05/2012: subcontract financial paperwork now in place (completed) for <i><span lang="FR">Institut de Cancérologie Gustave Roussy. </span></i></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">04/12/2012 (late entry): DNA samples still be processed for sequencing.</span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhYw9OTnYiAAWLXfsC9Gzig7ZrYEyyaj1Iczc0Y8Hf0t8D5Ypq5pAwj7T7oeV2PCu6V1gE_to2TlUtP3WkGSsYAruG4ZCIVoK1Dwxv8aUk4vjJTXF0C4r5u7M9oQ76KgotjOZHnTmraIl0/s1600/DIPG-DNA-Summary_2012_0419.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhYw9OTnYiAAWLXfsC9Gzig7ZrYEyyaj1Iczc0Y8Hf0t8D5Ypq5pAwj7T7oeV2PCu6V1gE_to2TlUtP3WkGSsYAruG4ZCIVoK1Dwxv8aUk4vjJTXF0C4r5u7M9oQ76KgotjOZHnTmraIl0/s320/DIPG-DNA-Summary_2012_0419.jpg" width="244" /></a></div>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">04/19/2012: Most samples submitted pass quality control to move on to DNA exon sequencing (see table to right). Only 2 samples overall failed, and these were the normal tissue controls. We are thus moving on to exon sequencing. <u>However</u>, our OHSU sequencing core has an 8-10 week backlog. Therefore we are looking at sending out the samples for sequencing elsewhere. <u>In addition</u>, RNA from the samples have not been fully processed/analyzed because the manufacturer of a key reagent are backlogged at least several weeks. There appears to be no way around this reagent backlog. Meanwhile, "version 2.1" drug plates are nearing ready for printing on the robot. We have 5 of the 60 ordered drugs yet to receive before we start printing.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">ps. a special thanks to Keith Desserich for organizing yesterday's DIPG Collaborative webinar. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">04/26/2012: Manufacturer kits to pre-process RNA for sequencing came in this week, and the samples will be prepared next week. We are weighing options of sending DNA samples for sequencing at OHSU (a longer wait but cost will decrease in that period) versus a secondary service provider outside of OHSU. We also have an informal participant in the Raabe laboratory, who received v1.0 drug plates for their new DIPG primary cell culture. This participant and the related expenses are unfunded, and we would welcome a community gift to bring this work more formally into the Consortium.</span><br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEik9Jzy_HQVa8maNiW2iG2jqlVqZ7vr2Sjc6-iphijRbRTtSOSSvEF4XTnA-LBbIiELJQEMddYXBxz1UZHecqkctT7CbYR6YQ8I9iYq-KoAEf9Co2R01X_NwPyZuGZ5zmliZCLfBLuF1As/s1600/OHSU-DIPG-2.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="150" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEik9Jzy_HQVa8maNiW2iG2jqlVqZ7vr2Sjc6-iphijRbRTtSOSSvEF4XTnA-LBbIiELJQEMddYXBxz1UZHecqkctT7CbYR6YQ8I9iYq-KoAEf9Co2R01X_NwPyZuGZ5zmliZCLfBLuF1As/s200/OHSU-DIPG-2.jpg" width="200" /></a><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><i>nb. </i>Another new DIPG primary cell culture has been established at OHSU, but not in time for sequencing. Thanks as always to Michelle Monje for the culturing advice that makes this possible for OHSU and other institutions to successfully grow this type of tumor cells. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">05/05/2012: DNA samples now submitted for sequencing at OHSU core facility. If we were a regular customer, it might take 2 months. We've been moved up the queue somewhat with the understanding that our project is time-sensitive. RNA sample pre-processing is still not performed, but might be in the next 1-2 weeks, with sequencing results likely to follow in another ~ 2 weeks. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">05/10/12: DNA sequencing *might* get run in the next week if we are lucky. There is no change in status of RNA sequencing. No progress on drug testing pilot from Toronto thus far. Amsterdam labs are working out how to evenly plate spheres into drug plates (this is an issue for all labs; breaking apart cells leads to poor survival, but quantifying cells in an intact sphere for even plating is not easy). Villejuif lab has several cell lines, but has requested more plates. The prior shipment of plates was held in customs and thawed out too long, which may have impacted the usefulness of the first set of plates that were sent. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">05/17/2012: RNA processing for sequencing to be done in the coming week. DNA final quality check shows that 3 formalin-fixed, paraffin-embedded samples failed (38 of 41 samples passed). Raw DNA sequencing data may be available as early as 5/27. Dr. Monje sent (yet) another set of drug screen results from a human DIPG culture (SU-DIPG-VI)... overall similar to past results with other cultures, which is good to see. Also, Dr. Kristin Schroeder's abstract from the Becher lab has been accepted for an oral presentation at the ISPNO meeting in Toronto next month. Finally, we may have (accidentally) identified a way to improve propagation of early DIPG cultures. Validation experiments are ongoing. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">05/24/2012: No new news about DNA or RNA sequencing. The lab of Esther Hulleman succeeded in screening a new DIPG cell line, VU-10170. Results were similar to all other screens, with a special sensitivity only seen in one other cell line. The lab of Jacques Grille is making a strong late-breaking showing in a cadre of 10 DIPG primary cell cultures for DNA and RNA sequencing, as well as drug testing. Brian Rivera from Eppendorf made a service visit recently to improve the efficiency of our robot, which will be very helpful in creating version 2.1 drug plates (to be distributed after analysis of the main batch of DNA and RNA sequencing is analyzed by Catie Grasso in the OHSU Spellman lab. Another good week. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">05/31/2012: The first (large) batch of DNA sequencing data is done! Analysis is ongoing by Catie Grasso in the Spellman lab. No new news on the RNA sequencing samples. We're waiting for a new large batch of DNA's and RNA's from the Grille lab, as well as the ok to ship additional drug plates to them. Special note: Maryam Fouladi as new head of the PBTC is organizing <i>High Risk Medulloblastoma</i> and <i>High Grade Glioma</i> preclinical consortia based on the COG Preclinical Consortium for DIPG. These other initiatives are also very worthwhile, but have no funding (and cannot move forward without it). Please spread the word! </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">06/07/2012: The only new news is that the set of 10 drug plates safely arrived in the Grille laboratory this week, and that replacement DNA's have also arrived from the Li lab. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">06/14/2012: no new news. I'm sorry. The batch#1 genomic DNA is still actively being analyzed, and the batch#1 RNA is still in the queue for sequencing. No new drug testing results. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">06/21/2012: no report on account of being out of office. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">06/28/2012: Genomic DNA still in analysis. RNA libraries (prepared material) will be sent to the OHSU core facility for sequencing next week. Grille laboratory DNA and RNA samples (many new ones) still expectant to arrive. </span><br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgSBgRRO9szjCq32hxUYQST-Bqh1Ru9-ZFv7k8BVItnwbI9v8beWgC5qwIwZmqhN0I783JoMj70NfZBt8zf9JgqIFpPAlvaCfZKBNJXo9FkE5DwA8VB4wfH1vXNhwTEUdCaAn7r0Y-Smqg/s1600/dipg-seq-update_2012_0707.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgSBgRRO9szjCq32hxUYQST-Bqh1Ru9-ZFv7k8BVItnwbI9v8beWgC5qwIwZmqhN0I783JoMj70NfZBt8zf9JgqIFpPAlvaCfZKBNJXo9FkE5DwA8VB4wfH1vXNhwTEUdCaAn7r0Y-Smqg/s320/dipg-seq-update_2012_0707.jpg" width="182" /></a><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">07/05/2012: new drug screen data now available from Grille laboratory for Nem145. This is a total of 7 cell lines that have been drug screened (one mouse, 6 human). Partial DNA sequencing analysis is ongoing. DNA sequencing is partially complete (click on updated table to right). We are waiting for the core facility to have enough samples to go with our samples for a full sequencing "run". We are conscious of the need to move to combination testing and<i> in vivo</i> testing very soon if we are to create the drug combination clinical trial that was the main purpose of this preclinical consortium. Thankfully, too, a leader from the community has offered to fund the participation of the Raabe lab to incorporate cell line JHH-DIPG1 into our studies. More officially on that very important grant soon. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">07/13/2012: RNA samples are at the sequencing core awaiting run when space on the instrument is available. Interim drug screen data is in the hands of clinical trial leaders. Drug screen 2.0 plates may be printed in the next 14 days. Nothing is more important than to integrate existing data and move to experiments in mice before the September COG meeting.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">07/20/2012: Li lab drug screen performed, consistent with other 7 cell line screens. Heuristic combinations being tested ad hoc per request of Cincinnati collaborator. Project is being accelerated towards September COG meeting date.</span><br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhItgh8bSjevb4qGuDrtXMyqACr8o_JHNliedWi3uQcz9kubTlpFQ3RKtm1zTew6LXc-77x0h-upPxcUc4ONtOQKPbUAe3wvHfj5vt0KURMje2Q8cR1dEx0eWp26DiFbYKofxXjtXTKmFU/s1600/ISBN+978-94-6191-323-4.JPG" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="200" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhItgh8bSjevb4qGuDrtXMyqACr8o_JHNliedWi3uQcz9kubTlpFQ3RKtm1zTew6LXc-77x0h-upPxcUc4ONtOQKPbUAe3wvHfj5vt0KURMje2Q8cR1dEx0eWp26DiFbYKofxXjtXTKmFU/s200/ISBN+978-94-6191-323-4.JPG" width="149" /></a><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">07/20/2012: No news on sequencing. Balance between immediacy of data for planning trials at cooperative groups is intersecting with due diligence of scientific process (delicate balance). Note, too, the recent thoughtful thesis publication of Viola Caretti, <i>Pioneering Preclinical Research in Diffuse Intrinsic Pontine Glioma: Towards New Treatment Strategies" </i>(ISBN 978-94-6191-323-4, publisher www.ipskampdrukkers.nl). </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">08/02/2012: No news on sequencing. In anticipation of 7 DIPG parents being at the Pediatric Cancer Nanocourse next week, we're creating an action plan for a Sept 10 "best available" analysis to present to the COG brain tumor cmte.</span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhbW-HBd2i-cXZfBJ5YGAgje0McxfTxLAO_9cyCsAmxFbwbjY1kBgihHCbSsyzWsiMNSzhM2J2oyoqjoe3DcjyL_ML5Rg8J47sGEJQFLOr4B85qfqXIdazak6FRiGMap5EAgO0YJKDG8jI/s1600/NC-Attendees-with-Paul.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="135" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhbW-HBd2i-cXZfBJ5YGAgje0McxfTxLAO_9cyCsAmxFbwbjY1kBgihHCbSsyzWsiMNSzhM2J2oyoqjoe3DcjyL_ML5Rg8J47sGEJQFLOr4B85qfqXIdazak6FRiGMap5EAgO0YJKDG8jI/s320/NC-Attendees-with-Paul.jpg" style="cursor: move;" width="320" /></a></div>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">08/09/2012: 4 new DNA samples have been sequenced. <i>excitingly</i>, Nathalene Truffaux from the Grille lab just shipped 20 new DNA and RNA samples from DIPG primary cell cultures (DHL en route). In addition, an action plan is in place, catalyzed by our Nanocourse attendees (picture above). Under the leadership of Paul Spellman and Catie Grasso, sequencing will be accelerated and analysis performed for drug-responsive DNA and RNA biomarkers <u>by September 10</u>. Our thanks to these amazing genomic biology scientists! </span><br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgGB3xWXknh8FRy5DV8npiydnJpcHAPWRfbOQ0JbAqprOU9oX0jun8xZ59osiFOSwk38o-CuKnl185B6I-_oWiRm55jESn2WW7OfK6ajH-ih2DT1dJB8AoPTkTaKGRpcr6eXc5_DLJM4WA/s1600/DIPG-RNA-Sequencing-2012_0829.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgGB3xWXknh8FRy5DV8npiydnJpcHAPWRfbOQ0JbAqprOU9oX0jun8xZ59osiFOSwk38o-CuKnl185B6I-_oWiRm55jESn2WW7OfK6ajH-ih2DT1dJB8AoPTkTaKGRpcr6eXc5_DLJM4WA/s320/DIPG-RNA-Sequencing-2012_0829.jpg" width="134" /></a><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">08/16/2012: The Pediatric Cancer Nanocourse parent alumni (now faculty) are finalizing the manuscript on overcoming barriers to cure for DIPG. For the consortium project, Grille lab DNA and RNA samples are being pre-processed. Data from two Baylor DIPG culture drug screens are being repeated for thoroughness. Version 2.0 drug screen plates began being printed today. Validation is forthcoming. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">08/23/2012: Version 2.0 plates have low error/high reproducibility. Time pressure exists to get results to COG and PBTC for a feasible drug combination based on v1 and v2 plate results.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">08/23/2012: Catie in the Spellman is making great strides to get the following questions answered before the COG meeting on Sept 11:</span><br />
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">- of the
DIPG cell lines studied, samples are outliers? (vs which are more similar)</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">- are
there any driver mutations? (new or known)</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">-<span style="mso-tab-count: 1;"> w</span>hat
gene expression or copy number abnormalities correlate with drug sensitivities?</span></div>
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><br /></span>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">A summary of RNA samples pre-processed (ie, a library was made) and then sequenced is to the right. Those not yet sequenced in time for the COG meeting will be used as a validation set. </span></div>
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<i><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"></span></i><br />
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<i><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">about Catie:</span></i></div>
<i><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">" My career in genomics began in 1999 when I did
the data analysis for the first whole human genome annotations of alternative
splicing, which is the regulated editing of genes before they are made into
proteins.<span style="mso-spacerun: yes;"> </span>More recently, my research has
focused on cancer genomics:<span style="mso-spacerun: yes;"> </span>I just finished
leading the largest sequencing effort of metastatic prostate cancer to date, an
effort that was recently published in Nature.<span style="mso-spacerun: yes;">
</span>We are using the methodology from this study in the context of DIPG in
the hopes of making similar breakthroughs." </span></i><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><i> </i></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">09/06/2012: DNA mutations, amplifications and deletions will be known in 1-2 days for a lead set of samples associated with the drug screens. Xenograft results will follow soon thereafter (requires special care to subtract mouse sequences from human sequences). Plates for v2.0 drug screen, and a compound related to a v1.0 drug screen lead go out on Monday or Tuesday. </span><br />
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">09/13/2012: Jacques Grille and his lab team member, Nathalène Truffaux, have contributed 2 additional DIPG cultures: </span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">Nem215 and Nem226. </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">In addition, </span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">Nem175 </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">cell culture drug screen v1.0 results are now available. </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Nathalène and Jacques (pictured to the right) have added a great deal of depth to our consortium - we are grateful for their participation;</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">in addition, interim results were presented at the COG meeting today (including exome sequencing result for 8 tumors)... well received some very good suggestions to incorporate. Drug screen v2.0 plates delayed in shipping out to other labs until Monday. </span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;"> </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">09/20/2012: The COG brain tumor committee presentation of the DIPG preclinical consortium results (including preliminary dna sequencing - drug sensitivity correlations) was well received in Atlanta. Goal is now to complete dna & rna sequencing and drug plate v2.0 screens before December. Also, <a href="http://dipgregistry.org/">the International DIPG Registry has announced its launch</a>. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">09/27/2012: Seeking additional tumor samples (even without cultures) from collaborators to get better statistical power on the sequencing analysis. v2.0 drug plates now distributed (to N. American institutions... need to print many more plates for European sites).</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">10/04/2012: Results from v2.0 drug plate of mouse DIPG primary cultures are very encouraging... new agents on these plates (chosen by the international neuro-oncology community) do appear to have interesting activity against (at least) the mouse dipg cells.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">10/11/2012: Results of screens now in from VUMC and Baylor labs (1 dipg culture each, including</span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;"> IBs-1215DIPG</span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">). Paul & Catie continuing to analyze DNA sequencing data.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">10/18/2012: ongoing support to Monje lab regarding potential combinations; additional v2.0 drug screen from Li lab (on </span><span class="Apple-style-span" style="color: #990000; font-family: Arial, Helvetica, sans-serif;">IBs-W0128DIPG</span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">) looks very promising. Catie still working on DNA and RNA sequencing data as they continue to be generated.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><br /></span>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">10/25/2012: Sequencing Facility openings make it possible that 17 additional samples will be run in the next 1-2 weeks.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><br /></span>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11/01/2012: Meeting with bioinformatics team, it appears that about 3 of 7 xenograft samples will have a human:mouse DNA content balance that will allow useful information to be gained. Met with Sequencing Facility director earlier this week with assurances that our project is felt to be important and prioritized. (note: no RNA sequencing data has yet been generated, though it is highly anticipated). Still gathering important sample characteristics from collaborators with which to make bioinformatics analysis. Additional v2.0 drug plates go to Grille and Hulleman labs on Monday. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11/08/2012: More v2.0 plates sent to Hulleman and Grille labs. RNA sequencing data very close to being performed. Thanks to Catie Grasso for kindly integrating mixtures of multiple types of data. ABC2 introduction made to industry-associated community group that could assist with data storage and perhaps analysis. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11/15/2012: Sequence analysis ongoing. no other new results.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11/22/2012: Holiday (no progress this week).</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11/29/2012: Four additional samples sequenced. Bioinformatics analysis of probable mutations in DNA sequenced sample is well underway. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/06/2012: Preliminary DNA sequencing analysis complete, with confirmation of known mutations and identification of potential new targets. French DNA samples are sequenced, but need to be added to the analysis.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><br /></span>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/13/2012: DNA sequence analysis ongoing; RNA sequencing done! and analysis also underway. The Grille laboratory has sent a large number of new version 2.0 drug screen results for integration. The bioinformatics team from the Spellman (OHSU) and Pal (TTU) laboratories are now working together to integrate sequencing and drug sensitivity results. This is an exciting week!</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/20/2012: Sequence analysis ongoing; final batch of v2 drug plates need to be printed to send out to 2 participants. Funds spending down appropriately as grants end. We're grateful to Catie, Noah and Ranadip for all their hard work on analysis, as well as Eric, Jacques and Nathalene who are working so diligently to get the final experimental data. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/27/2012: New batch of v2 drug plates printed (thank you, Mat!). Will not ship out until after holidays. No other updates.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">01/03/2013: Happy New Year. getting back on track in preparing shipments of plates. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">01/10/2013: thanks to Catie, the DNA and RNA sequencing analysis is mostly complete. Exciting expected and unexpected findings. Version 2 plates shipped to Raabe and Grille labs. Pal lab is awaiting drug screen results to cross-correlate genomic findings with drug sensitivities. Chances are good of designing useful 2-drug combination, but we'll see. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif; font-size: x-small;">* if any foundations are willing, we could use ~ 25k USD to bring together all preclinical consortia investigators for a first face-to-face consortium and data analysis working meeting.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">01/17/2013: RNA sequences not previously incorporated bring that count up to almost 30 (controls and replicates are included in this tally). NEM-215 and NEM-226 still need to be processed & sequenced in the coming few weeks. JHH-DIPG1 cell pellets received today (thank you, Eric and team) for DNA and RNA sequencing with NEM-215 and NEM-226. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">01/24/2013: Many thanks to Elaine who has compiled the drug screen results to date in a single summary file (including absolute and relative IC50's). All other analysis are ongoing. Collaborators have begun adding dipg biology knowledge to Catie's sequence analysis results. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">01/31/2013: NEM-215 drug screen data from Grille lab looks very good. De-identified tumor features (age, histology, survival) from samples being integrated into bioinformatics analysis. All consortium members working to expedite last final experiments to be completed.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">02/07/2013: All final sample experiments and analysis still ongoing. In addition, we have opened discussions with Dan Silver and his mentor, Dennis Steindler, at the University of Florida, to participate in the consortium. Our thanks to David Sandak at ABC2 for making this introduction.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">02/14/2013: Interesting drug screen results for JHH-DIPG1. DNA and RNA sequencing pre-processing (libraries) done for </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">JHH-DIPG1, NEM215 and NEM226. Drug screen plates sent to Steindler lab. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">02/21/2013: Catie will be working on RNA sequencing outlier analysis so that Pal lab (Noah!) can complete probabilistic boolean modeling correlations with the sequencing data. These are critical elements of the project now. The last few (straggler) DNA and RNA libraries submitted to sequencing core. Very constructive comments and new data from Grille lab. April 10 COG meeting is a hard deadline for manuscript answer and selection of combined targeted agents for next testing with in vivo preclinical testing. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><br /></span>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">02/28/2013: Catie has completed outlier analysis for RNA sequencing. </span><br />
<br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">03/07/2013: 34 days to go! until COG meeting and presentation of results. Here is the rundown thus far:</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">- DNA sequencing on tumors, cell lines and/or paired normal samples x 33 independent tumors </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><i>with 2 more pending.</i></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">- RNA sequencing on 25 independent tumors <i>with 2 more pending.</i></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">- Drug screens (v1, v2 or v2.1) on 21 samples (5 tumors run more than once on different versions) <i>plus 4 additional drug screens just in from the Grille research group </i>(thank you, Ludivine!)</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">- Integrate of sequencing and drug sensitivities underway with Ranadip and Noah.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Thanks, too, to J.D. and Myron for creating the FTP sharesite and compressing the sequencing data to a size that can easily be exchanged back to the originating labs (respectively). </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">03/14/2013: Becher, Monje, Hulleman and Grille labs each working on aspects of project interpretation. Catie leading manuscript write-up. Our continued thanks to Paul Spellman for his team's incredible support of the genomics studies (including the tenacity of team member Nick Wang). </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">03/22/2013: Final samples for sequencing were submitted 2/19 and 3/21. They are: </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">DNA (JHH-DIPG1, NEM-215, <span style="color: black;">NEM-226,</span> <span style="color: black;">OHSU-DIPG#2 Normal, </span><span style="color: black;">OHSU-DIPG#2<span style="mso-spacerun: yes;"> </span>TUMOR) and </span>RNA (<span style="color: black;">JHH-DIPG1, </span><span style="color: black;">NEM-215, </span><span style="color: black;">NEM-226). Ludivine submitted NEM-157 v1 drug screen results. Noah completed the individualized tumor cell survival circuits (that he calls PTIM's) just today. Catie and others across the consortium are busy analyzing data and writing up results. </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="color: black;"> </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="color: black;">03/28/2013: Last library samples sent for sequencing. </span></span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">NEM-157 v1 drug screen were fruitful. Noah, Catie, Michelle, Oren, Jacques and Michelle have all been very actively working on analysis this week.</span><br />
<span style="font-family: Arial;"> </span><br />
<span style="font-family: Arial;">04/04/2013: Preparations for COG ongoing, very actively. Catie in full swing, but contributions from Monje, Grille, Hulleman and Becher labs are very strong. </span><br />
<span style="font-family: Arial;"> </span><br />
<span style="font-family: Arial;">04/11/2013: It all seems worth the work from everyone. We have a clear direction from the data for 2, if not 3 drugs. The CNS committee gave valuable input, and now we are working towards in vitro (petri dish) validation of drug synergies, then mouse models. Unexpected targets were revealed, and we hope all this work will make a tangible difference. What a great team across so many labs. </span><br />
<span style="font-family: Arial;"> </span><br />
<span style="font-family: Arial;">04/18/2013: lab teams in Europe and U.S. working towards the goal of validating drug combinations (in comparison to agents in COG dipg phase I/II pipeline). contributions and insights of Kathy Warren and Esther Hulleman particularly appreciated. Monje lab working to get new DIPG-IX drug screen results; Becher lab screening 2-4 additional mouse TVA cultures. Catie integrating last few DNA and RNA sequencing results. Michelle Monje to present briefly preliminary studies at The Cure Starts Now meeting next week. </span><br />
<span style="font-family: Arial;"><br /></span>
<span style="font-family: Arial;">04/25/2013: Additional data in process of being generated by Steindler lab, as well as Monje lab. Sequencing of DNA and/or RNA for last few samples from Grille, Keller and Raabe labs now done. Catie and others working on manuscript. Dr. William Weiss (UCSF) will join consortium for <i>in vivo</i> testing phase. </span><br />
<span style="font-family: Arial;"> </span><br />
<span style="font-family: Arial;">05/02/2013: Michelle Monje presents update of preclinical consortium collaborative work at TheCureStartsNow symposium in Cincinnati, Ohio. Lots of discussion on how best to present drug screen data (what format) for manuscript. Brief <i>logistical</i> summary of this COG-related consortium work to be presented by Dr. Oren Becher at Pediatric SNO meeting. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">05/09/2013: Additional Becher lab mouse dipg cell culture cultures examining the impact of histone mutations have been tested on the drug screen. Experiments still underway in the Steindler lab. Manuscript writing by Catie in progress. Jacques Grille will present selected results at the upcoming June 2013 SIOP meeting in Warsaw (our thanks to the SIOP investigators for reaching out to collaborate!)</span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">05/16/2013: New dipg and comparative pediatric HHG culture drug screen results now in. Manuscript writing by Catie in progress. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">05/22/2013: </span><span class="Apple-style-span" style="font-family: Arial;">Manuscript writing by Catie in progress. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">05/30/2013: A lot of email traffic preparing figures & tables with collaborators!</span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">06/06/2013: Exploring novel mutations found in dataset. Interestingly, these are pharmacologically amenable. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">06/13/2013: We gratefully welcome Dr. Marta Alonso from the University Hospital of Navarra to the DIPG Preclinical Consortium. Marta's role will be in in vivo validation of drug screen combinations, alongside complementary studies in the Monje, Becher and Raabe laboratories.</span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">06/20/2013: Preliminary in vitro drug combination validation data are encouraging. Hulleman lab to also participate in animal validation studies. Congratulations to the Lyla Nsouli Foundation on their recent Gala. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">06/27/2013: "Next step" in vivo (mouse) preclinical projects are firmly outlined by consortia members, with funding requests to follow.</span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">07/03/2013: Ongoing manuscript writing in progress. Additional samples from Grille lab to be sequenced. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">07/10/2013: New experiments explore the transcriptional changes attributable to an effective drug. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">07/17/2013: Manuscript maturing... the goal is to get this data public as early as possible. Will focus on 2 classes of drugs and 3 interesting gene mutations. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">07/23/2013: Next steps of in vivo validation of drug targets in mice is still dependent upon funding, decisions on which are pending. Three of 4 funding agencies are considering our request. CureSearch passed on funding the dipg preclinical consortium in order to prioritize their Grand Challenge initiatives. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">For the manuscript of existing data, a new set of supplemental data by the Grille lab has been created that describes minor but sometimes interesting differences in the way in which tumor cell growth is measured (and is probably worth sharing with the field). </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">08/01/2013: Data on pre/post drug treatment (and gene expression changes as a result) is pending runs of the sequencing. Catie has matured the manuscript, with extensive help and input from Michelle, Ranadip and Jacques (and kind assistance of Lining). Noah continues to integrate sequencing and drug screening data. A unifying explanation for how the 2 different drug classes found to be effective might interact is slowly coming to light. Dennis is temporarily taking a leave of absence from the Consortium, with the intention of future active collaborations. A manuscript submission by the end of the month is the goal (give or take a week), so that the data can be especially freely shared at the September DIPG Trials meeting in Paris, and the October Fall COG meeting. </span><br />
<br />
<span class="Apple-style-span" style="font-family: Arial;">08/07/2013: Catie continues to hone the genomic analysis (the manuscript is to be focused on drug screening results as the genomic changes that correlate them; however, the genomic analysis itself has revealed some rather interesting genes not otherwise on the field's radar). No other new news at this time. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">08/14/2013: We are moving towards trans-Atlantic clinical trials collaboration that would have complementary, non-overlapping approaches. Our thanks to Jacques Grille and Darren Hargrave for reaching out in this regard. Please also see <a href="http://www.lylansoulifoundation.org/events">the videos from the Lyla Nsouli Foundation</a>, one of this project's key sponsors. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">08/22/2013: No progress to report this week (on account of Summer holidays).</span><br />
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<iframe allowfullscreen='allowfullscreen' webkitallowfullscreen='webkitallowfullscreen' mozallowfullscreen='mozallowfullscreen' width='320' height='266' src='https://www.blogger.com/video.g?token=AD6v5dw3Rr7E5nBjwrdlKcDLACo0kEeeWBvYVh4u5jcfbxwklredDLO7ba_VNL0kOvcCthybj63Jrb1g3mcXOcwrGw' class='b-hbp-video b-uploaded' frameborder='0'></iframe></div>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">08/28/2013: Jacques Grill to present results of preclinical consortium at the Sept 2013 NDDS meeting in Paris (organized by Dr. Darren Hargrave). ps. This video from the laboratory of Jacques Grille shows how DIPG cells invade a strip of matrigel
(mimicking the extracellular matrix seen in a tissue) within a short time frame
of less than one day. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> 09/05/13: We were pleasantly surprised with the additional RNA expression studies following treatment with a particular drug in 2 dipg cultures. There are consistencies with effects of other efficacious drugs... making us feel we might be onto something from multiple lines of evidence. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">09/12/2013: Catie, Nathalene and Marie-Anne continue to work on finalizing figures. A framework for data sharing and complementary COG, PBTC and SIOP dipg clinical trials is coming together.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">09/19/2013: Promising correlation seen between drug effects on gene expression and targets of the original chemical screen. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">09/26/2013: A few normal brain RNA samples found to have contamination with tumor cells to some degree. Not unexpected, but the process of making figures is now re-started. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">10/03/2013: Awaiting decisions on funding for our 'next steps' proposal for preclinical studies.</span><br />
<span style="font-family: Arial;"> </span><br />
<span style="font-family: Arial;">10/11/2013: Results presented yesterday at the Children's Oncology Group meeting in Dallas, Texas. Very well received, and remarkably complementary to current approaches. A new dipg clinical trial concept, based in part on our consortium's results, was proposed within the group. Validation experiments in mouse models will be key... and complementarity & transparency with PBTC and SIOP clinical trial groups was again reiterated. please stay tuned for an exciting funding announcement from our colleagues at a particularly progressive Foundation. </span><br />
<span style="font-family: Arial;"> </span><br />
<span style="font-family: Arial;">10/18/2013: Manuscript writing continues, as we try to distill the most interesting details of the consortium project. The 'next steps' funding to be announced soon, once paperwork is completed with each participating institution. </span><br />
<span style="font-family: Arial;"> </span><br />
<span style="font-family: Arial;">10/25/2013: This week begins the big push on manuscript finalization. A lot of discussions have ensued how best to present the interesting RNAseq data. Funding announcements on next steps are also still pending. Details of important pharmacokinetics and pharmacodynamics studies in the next step studies are being worked out. </span><br />
<span style="font-family: Arial;"> </span><br />
<span style="font-family: Arial;">11/01/2013: Manuscript writing and figure finalization rapidly underway. A journal has agreed to review our initial manuscript submission, but a long list of little things (from data finalization to formatting) is still being done. </span><br />
<span style="font-family: Arial;"> </span><br />
<span style="font-family: Arial;">11/08/2013: More manuscript writing is being done. Version control has gone back and forth across the Atlantic. </span><br />
<span style="font-family: Arial;"> </span><br />
<span style="font-family: Arial;">11/15/2013: Preparations for the Society of Neuro-Oncology (SNO) meeting presentation are being done for Catie's talk on our results thus far. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">11/21-22/2013: On Wednesday Charles attended a National Brain Tumor Society sponsored special summit at SNO on Availability of Drugs for Pediatric Brain Tumor and Pediatric Cancer Research. Attendees included industry, parent groups, academic researchers, government regulatory agencies... it was truly a productive meeting, and we hope that great new approaches come to making novel drugs available to children with brain tumors via timely clinical trials. There remains much work to be done, but the conversation itself was the beginning of this progress. </span><br />
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<span class="Apple-style-span" style="font-family: Arial;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiLGse5F8UJjlt6ikVwsQwWmpHtLKALXAasoYCAIFvlZ-Ph1OmGY8lMK-OOlnMa7yXcewIShbYKfU-HqhovkT76u_h4EqtiyukQ-p4n-XoZeB71Yh94VtgrYELlc1_2LcLzNwoY0RTqAr0/s1600/Catie-SNO-Talk.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="131" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiLGse5F8UJjlt6ikVwsQwWmpHtLKALXAasoYCAIFvlZ-Ph1OmGY8lMK-OOlnMa7yXcewIShbYKfU-HqhovkT76u_h4EqtiyukQ-p4n-XoZeB71Yh94VtgrYELlc1_2LcLzNwoY0RTqAr0/s200/Catie-SNO-Talk.jpg" width="200" /></a></span></div>
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<span class="Apple-style-span" style="font-family: Arial;">Catie also presented our dipg preclinical consortium results thus far. Her talk was well received, and we appreciate the comments afterwards. Particularly the suggestion to show how dipg cultures responded relative to tumors of other types tested in the same way. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">For the 'next steps' funding announcement, now that we have all but one set of paperwork for participating institutions we should be able to make a formal announcement soon. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">11/29/2013: paperwork at all sites now complete so that we can proceed with 'next steps' funding and grant agreement. manuscript nearly final, but additional validation studies are being done by our European colleagues to ensure differences in culture generation still allow inter-comparison. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">12/05/2013: we still are running additional cell culture validation.</span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">12/12/2013: for one of the drug hits, we now have promising brain pharmacokinetic data.</span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">12/19/2013: for the drug hit, we now have promising <i>in vivo</i> anti-tumor results (likely to be included in manuscript).</span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">12/26/2013: no progress this week (holidays).</span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial;">01/02/2014: Catie and Michelle are moving forward to finalize the manuscript. As you might have noticed, manuscript writing has been ongoing in parallel with validation experiments to refine our results since April '13, but this is on par for the kind of study here. </span><br />
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<span class="Apple-style-span" style="font-family: Arial;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgOGa3RzkQ_Wyg067fVkfVLI_6sjjmMXEEpIdZ1bWzqk0Aja1_HeuDq86s-dn6UM4wi71ZSPYSVpdyFXIEvBAUtg1O-_M_hcwSxA9NJxaUNccojKLbVTT0awijcko6Uptek7ACFbAB2Iwk/s1600/LylaNsouliFdtn.png" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="67" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgOGa3RzkQ_Wyg067fVkfVLI_6sjjmMXEEpIdZ1bWzqk0Aja1_HeuDq86s-dn6UM4wi71ZSPYSVpdyFXIEvBAUtg1O-_M_hcwSxA9NJxaUNccojKLbVTT0awijcko6Uptek7ACFbAB2Iwk/s1600/LylaNsouliFdtn.png" width="200" /></a></span></div>
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<span class="Apple-style-span" style="font-family: Arial;">01/09/2014: Please see the <a href="http://kellerlabblog.blogspot.com/2014/01/international-group-of-pediatric-brain.html">press release</a> on our 'Next Steps' funding, generously provided by the Lyla Nsouli Foundation. </span><br />
<span class="Apple-style-span" style="font-family: Arial;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">01/16/2014: Discussions between all labs on harmonization of methods is taking place (thank you Esther, Michelle, Marta and Eric). Manuscript near-final draft circulated to all authors. New culture model being investigated (thank you, Dennis). </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><br /></span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">01/24/2014: Manuscript is submitted and in review at a high impact journal. Everyone in the consortium deserves acknowledgement for making this possible, especially Catie, Nathalene, Noah, Jacques and Michelle. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">01/30/2014: New DNAs sent from Stanford for sequencin<i>g </i>(<i>new samples are really helpful for follow-on informatics studies</i>). </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">02/06/2014: ISPNO meeting abstract to be submitted this week. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">02/14/2014: Preliminary discussions started for trans-Atlantic coordinated partnership to determine clinical availability of a promising preclinical agent. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">02/20/2014: New samples/culture to be sent from Steindler lab (Univ. of Florida) to Stanford once material transfer agreement is in place. Additional experimental samples sent from Monje lab to OHSU for sequencing. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg0m1skA5NTuKKhJD282_AYwo9-nYLzhm4CcMfNYsIR_JSICVsB3xQ_ei7EsWHisSg2h1gvSymEucNKBlogaRhfAp80iM5BJq5jmcHNkmU7L_I62fHr71ZzeLPeqT-l1DPM5VBVXe_l4bQ/s1600/Nazarian+Lab+2014.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="128" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg0m1skA5NTuKKhJD282_AYwo9-nYLzhm4CcMfNYsIR_JSICVsB3xQ_ei7EsWHisSg2h1gvSymEucNKBlogaRhfAp80iM5BJq5jmcHNkmU7L_I62fHr71ZzeLPeqT-l1DPM5VBVXe_l4bQ/s1600/Nazarian+Lab+2014.jpg" width="200" /></a><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">02/27/2014: We are excited to announce a new, valued collaborator, Dr. Javad Nazarian, at Children's National Medical Center! [pictured, from left to right: </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Sridevi Yadavilli, MD, PhD (postdoctoral fellow); </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Madhury Kambhampati, MS (technician); </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Jamila Gittens, MS (technician); </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Elizabeth Wells, MD (Neurologist); </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Javad Nazarian (P.I.)] </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">03/06/2014: Manuscript will need revisions, including additional experiments, prior to submission to a new journal. those experiments have been planned amongst the participants. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">03/13/2014: See the <a href="http://kellerlabblog.blogspot.com/2014/03/nbts-working-group-meeting.html">NBTS blog post</a>. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">03/20/2014: from the OHSU group (Keller): we have received more than expected new samples for sequencing (16 new samples from our new consortium collaborator Dr. Javad Nazarian at The George Washington University; 3 new samples from OHSU; and 3 new samples from Stanford). Coordination of projects across the sites is ongoing.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">03/27/2014: from the VUMC group (Hulleman): Initial in vitro HDAC/Wee1 inhibitor studies completed. Now examining influence of common DIPG mutations on response. From the JHU group (Raabe): mouse innoculations performed so that preclinical studies can be conducted. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">04/03/2014: from the Navarra group (Alonso): in vivo model characterized recently completed. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">04/10/2014: from the Stanford group (Monje): key CNS pharmacokinetic parameters of selected drugs completed... very promising, looking at it from a given point of view. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">04/17/2014: from the Baylor group (Li): model expansion and preparations for MRI imaging in progress. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">04/25/2014: preparing for the next batch of tumor DNAs and RNAs for sequencing; synergy studies in biologically distinct cell cultures may be promising for a specific combination. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">05/01/2014: Baylor group to start new preclinical trials soon. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">05/08/2014: adding roughly 25-30 new samples for functional genomics studies to complement preclinical trial analysis</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">05/15/2014: promising conversations with pharma regarding trial concept with implicated 'hit' from our studies (nothing final); Stanford validation studies of combinations ongoing.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">05/21/2014: JHMI group gearing for in vivo studies (multi-week process). </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">05/28/2014: One of the combination studies is nearing completion at the Alonso laboratory, with pharmacodynamic studies underway. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">06/05/2014: update from the Baylor team: a large scale preclinical study of drug A, drug B, or the combination is initiated (will be a multi-week study). Pharmacodynamic and resistance studies to be incorporated. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">06/12/2014: from the Stanford team: additional drug combination validations underway using chemical and genetic approaches. Early results expected in ~2 weeks. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">06/19/2014: Univ. of Navarra update: dose finding done so that near-final in vivo studies with drug combinations can be conducted. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">06/26/2014: OHSU update: via consortium sites, an additional 49 new dipg samples for potential DNA exome sequencing and 42 new samples for potential RNA deep sequencing have been collected. We are grateful to the families who have made this possible, many having come from legacy gifts (research autopsies). </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">07/03/2014: We very, very much appreciate the <b>$85,000</b> in supplemental research funding from The Lyla Nsouli Foundation, which makes possible sequencing the above 49 new dipg DNA samples and 42 new dipg RNA samples. These data significantly improve the impact of our ongoing studies, and move us significantly closer to the development of a 2-drug combination for clinical trials of dipg. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">07/31/2014: samples for DNA exome sequencing will be submitted Monday. RNA samples still undergoing QC, but are also hoped to be submitted next week. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><br /></span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">08/08/2014: all DNA samples submitted for sequencing on Tuesday! Also, Charles gave lectures at the DIPG Nanocourse at Stanford University (the follow-up to the <a href="http://kellerlabblog.blogspot.com/2012/08/pediatric-cancer-nanocourse-2012.html">2012 Nanocourse</a>). This year's Nanocourse was hosted by the Monje laboratory. See associated links below. Charles & Michelle met to review preclinical validation studies... all very encouraging. A plan for manuscript submission to a scientific journal was put in place. </span><br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhQq_z7rjuK8aiQ8-fvbVC4VlbibjQsO3sSHppz98pBf9rRZlpvgQqmTACy5_QZen16asR5TMRjale8x00WEA1b11N2498UYtpT7M9FyKMg_hboWm2__i_KmICcbOW78TcgmzrFdUynaVg/s1600/PCN2014Group.JPG" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="105" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhQq_z7rjuK8aiQ8-fvbVC4VlbibjQsO3sSHppz98pBf9rRZlpvgQqmTACy5_QZen16asR5TMRjale8x00WEA1b11N2498UYtpT7M9FyKMg_hboWm2__i_KmICcbOW78TcgmzrFdUynaVg/s1600/PCN2014Group.JPG" width="200" /></a><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><i>about the Nanocourse:</i></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><i> </i></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><a href="http://unravelpediatriccancer.org/nanocourse/" target="_blank">nano
course | Unravel Pediatric Cancer</a></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><o:p></o:p></span><br />
<div style="margin-bottom: 0px; margin-left: 0px; margin-right: 0px; margin-top: 0px;">
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><a href="http://youtu.be/9XQLS9J5vXs" target="_blank">Elsa Visits the 2014 Pediatric Cancer Nanocourse</a> (it's good there's a bit of humor to an otherwise difficult topic)</span></div>
<div style="margin-bottom: 0px; margin-left: 0px; margin-right: 0px; margin-top: 0px;">
</div>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">08/15/2014: single agent activity of one of our lead drug hits seen with Baylor team members. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">08/21/2014: the same single agent activity seen with Baylor studies also seen in Stanford group studies. Another agent appears not well tolerated, and not effective. Backup combinations (heuristic choices) not as effective in vitro as hoped. The data is what it is - better to know now.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">08/27/2014: very nice pharmacodynamic studies developed by team in Spain.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">09/04/2014: JHU group studies in vitro for the high-activity single agent also look promising. Animal studies in progress. Consortium members considering additional 2nd agents for combination studies going forward.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">09/11/2014: 3rd quarter progress report submitted. All RNA samples submitted for deep sequencing. ** very exciting news: preclinical studies of high-activity single agent (above) have led to approval by a major pharma to make the drug available for a cooperative group trial! The trial proposal still needs to be finalized... but we are hopeful that this agent is worth studying in children with dipg.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">09/17/2014: JHMI in vivo studies underway (drug combination). Strong preclinical results from Baylor group. Complementary studies completed at Stanford group's lab. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">09/24/2014: Very nice pharmacodynamic assays developed in Alonso lab (will be a central reference for us). Results presented at the COG semi-annual meeting in Dallas. Well-received. One agent selection is justified by preclinical studies. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">10/02/2014: Still waiting for OHSU sequencing results. The product is always good, at a good price; however, in future studies we will opt for the turnaround efficiency of a commercial service. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">10/09/2014: no new news. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">10/16/2014: single agent study (trial) in development with PBTC (pharma company agrees/will provide agent; actual trial still in development/not yet approved). </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">10/24/2014: sequencing core facility awaiting arrival of backordered library preparation kits. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">10/31/2014: journal editors have invited submission of our consortium study</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11/06/2014: backordered library preparation kits now received by sequencing core facility (thank you, Bob!)</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11/13/2014: manuscript now in mature draft form, awaiting addition of final sequencing data. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11/20/2014: more manuscript preparations.</span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">11/27/2014: yet more manuscript preparations. still awaiting sequencing data.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/04/2014: final manuscript formating in progress. working with Villejuif group to include as much data as possible within the text and figure limit of the journal. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/11/2014: manuscript submitted! Batch 1 of 4 of RNAseq data now available.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/18/2014: </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">Batch 2 of 4 of RNAseq data now available. Project move to <a href="http://www.cc-TDI.org/">cc-TDI</a> now in progress. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">12/31/2014: on short term
hold pending transfer of grant from OHSU to our new, bold adventure at
<a href="http://www.cc-tdi.org/">cc-TDI</a>.<span style="mso-spacerun: yes;"> </span></span><br />
<div class="MsoNormal">
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
<div class="MsoNormal">
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;">01/12/2015: manuscript generally well received by Reviewers at journal. Key questions of the Reviewers will need to be addressed by both clarifications, different methods of analysis, and new experiments. The turnaround time for resubmission (6 weeks) is relatively short, but all members of the consortium are actively working to make this happen. </span></span></div>
<div class="MsoNormal">
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"> </span></span></div>
<div class="MsoNormal">
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;">01/27/2015: our thanks to Bob Searles, Amy Carlos and Chenwei Lin at the OHSU DNA sequencing core for prioritizing our new sequencing samples. Results anticipated for early in the second week of February. </span></span></div>
<div class="MsoNormal">
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"> </span></span></div>
<div class="MsoNormal">
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;">02/07/2015: still awaiting transfer of funds from OHSU, back to foundation, then to </span></span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><a href="http://www.cc-tdi.org/">cc-TDI</a>. Meanwhile, TTU team has completed their revisions/reanalysis. </span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"> </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"><br /></span></span>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;">02/14/2015: still compiling and analyzing new data!</span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"> </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;">02/23/2015: manuscript was submitted today! We're very excited about the findings, the added value of the new experiments requested by the Reviewers ... we'll see how it is received. Nonetheless, the consortium's preclinical studies are very supportive of moving a particular clinical investigation agent (drug) to a pediatric dipg phase I clinical trial. more soon on the latter!</span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"> </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;">02/27/2015: our team is actively planning the search for a second drug to combine with the one featured in our manuscript. Our thanks to <a href="http://www.cc-tdi.org/#!Welcome-to-the-Founders-Circle-With-Purpose/c218l/43E06D84-87C0-4E77-AD3E-614004DEA03B">withpurpose</a> whose gift made possible sending "version 3" drug plates to our Stanford consortium members (as well as the plates we'll send shortly to our team in Spain). </span></span></div>
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<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"> </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;">03/05/2015: process started to share all DNA and RNA deep sequencing results on dbGaP. </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"> </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;">03/12/2015: VUMC group has performed highly informative studies of key small molecule inhibitors with radiotherapy. </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"> </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;">03/19/2015: One dipg culture has dropped out for study; another 2 added.</span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"> </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;">03/26/2015: JHMI, Stanford and Baylor groups have framed the tolerable vs too-high doses to use of agents for our experimental studies in mice.</span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"> </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;">04/02/2015: Baylor group continues robust preclinical modeling, giving insights into drug combinations originally envisioned. </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"> </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;">04/09/2015: Stay tuned for potential near-term publication and related clinical trial concepts in the works. Thank you, <a href="http://www.lylansoulifoundation.org/">Lyla Nsouli Foundation</a>, for bringing us to this point!</span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"> </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;">05/04/2015: See our blog regarding the DIPG Preclinical Consortium publication in <i>Nature Medicine</i> <a href="http://www.cc-tdi.org/#!Scientists-from-13-institutions-worldwide-collaborate-to-discover-promising-therapy-for-DIPG/c218l/55479d6d0cf24874170c1eef">here</a>. </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"> </span></span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;">05/07/2015: Follow-on studies are now to be performed on a </span>large number of sequencing results from samples not
included in the paper, but of great value to the DIPG research community. </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;">05/14/2015: Some more good news about DIPG tumor sequences for the research community: we are rounding up the
remaining data (not otherwise included in the Nature Medicine paper) and performing sequence-level QC and SNP fingerprinting. There are 29 additional RNA samples (15 tumor and 14 normal) and 23 additional DNA samples (13 tumor and 10 normal), on top of the 75 samples that were in the paper and uploaded to dbGaP.</span><br />
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><span style="mso-spacerun: yes;"><br /></span>
<span style="mso-spacerun: yes;"> </span></span><span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"> </span></div>
<span class="Apple-style-span" style="font-family: Arial, Helvetica, sans-serif;"><br /></span></div>
PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com15tag:blogger.com,1999:blog-2463642186628177012.post-70721075916639092752011-10-28T11:00:00.000-07:002011-10-28T11:00:03.073-07:00Children's Cause Cancer Advocacy and SurvivorshipExciting news comes from the CCCA for the quality of life for childhood cancer survivors! The excerpt below comes directly from the CCCA's recent news feed, <a href="http://www.childrenscause.org/press-release-survivorship-bill-112thCongress">click here</a> to read more.<br />
<br />
<b>CCCA Supports Introduction of Childhood Cancer Survivorship Legislation</b><br />
<br />
On September 22, 2011, Senators Jack Reed (D-RI) and Kay Bailey Hutchison (R-TX) and Representatives Jackie Speier (D-CA) and Michael McCaul (R-TX) introduced bipartisan legislation to improve the care and quality of life of childhood cancer survivors. The Pediatric, Adolescent and Young Adult Cancer Survivorship Research and Quality of Life Act of 2011 marks a critical step forward in the delivery of medical and psychosocial care to survivors of childhood cancer.PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com1tag:blogger.com,1999:blog-2463642186628177012.post-64786275772647443372011-10-22T10:00:00.000-07:002011-10-22T10:00:01.837-07:00Free podcast!Highlighting: Solving Kids’ Cancer – FREE podcast!<br />
<br />
We would like to introduce you to the This Week in Pediatric Oncology podcast (thanks to the ped-onc-surv for the hat tip!)<br />
<br />
<a href="http://solvingkidscancer.org/podcasts/">Solving Kids' Cancer</a> is a website that hosts podcasts and so far 17 episodes have been published:<br />
<br />
1. 4/11/2011 Epidemiology of Childhood Cancer (landmark paper)<br />
2. 4/13/2011 Interview with Greg Reaman (outgoing chair of COG)<br />
3. 4/25/2011 Vincristine Pharmacogenetics, Irinotecan/Temozolomide for Relapsed Neuroblastoma<br />
4. 5/8/2011 Meetings Recap and Immunotherapy for Synovial Cell Sarcoma<br />
5. 5/19/2011 Hedgehog Signaling and Itraconazole<br />
6. 5/26/2011 Interview with Dr Archie Bleyer (was head of Children's Cancer Group for 10 years)<br />
7. 6/2/2011 Interview with E. Anders Kolb and Andrew Napper on drug development<br />
8. 7/9/2011 Seneca Valley virus and medulloblastoma<br />
9.7/16/11 Interview with Dr Peter Adamson<br />
10. 7/7/2011 Interview with Dr Robert Seeger<br />
11.7/12/2011 BuMel SIOP results and MIBG transplant with Dr Brian Weiss<br />
12. 8/5/2011 ALL: Anti-CD19 BiTE and Genetic Risk Groups<br />
13.8/19/2011 Updates, epidemiology of CNS tumors, birth order, and cell phone risks<br />
14.8/24/2011 Interview with Dr. Kate Matthay<br />
15.9/28/2011 MicroRNAs and hereditary cancer<br />
16.10/7/2011 Genetic Underpinnings of Ewing Sarcomas: Interview with Dr. Stephen L. Lessnick<br />
17.10/13/2011 Personalized medicine: Interview with Giselle Sholler<br />
<br />
You can subscribe by email, RSS or iTunes on the SKC site (see the right side of their webpage)!PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0tag:blogger.com,1999:blog-2463642186628177012.post-61941484680871858472011-10-17T12:15:00.000-07:002011-10-17T12:15:28.781-07:00The FDA and rare disease researchLast month we read about a move by the FDA to increase its rare disease efforts. The impact on pediatric sarcoma research remains to be seen, but we are hopeful! <br />
<br />
<b><a href="http://the-scientist.com/2011/09/12/fda-to-revamp-rare-disease-efforts/">FDA to Revamp Rare Disease Efforts<br />
<br />
The US government agency vows to improve the way it facilitates the development and approval of drugs for orphan diseases.<br />
By Bob Grant | September 12, 2011</a></b>PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0tag:blogger.com,1999:blog-2463642186628177012.post-37709625118399649652011-08-15T11:00:00.000-07:002011-08-15T11:00:01.069-07:00Websites we like!Here is a list of websites that have caught our attention - they will begin appearing on our sidebar, so be sure to come back and see what gets added!<br />
<br />
<table border="1"><tr> <td><b>Site name</b></td> <td><b>Why we like it</b></td> <td><b>shares data with <a href="http://clinicaltrials.gov">clinicaltrails.gov</a>?</b></td> </tr>
<tr> <td><a href="http://www.pbtc.org/">Pediatric Brain Tumor Consortium</a></td> <td>The PBTC’s goal is to find “superior treatment strategies for children with brain cancers”</td> <td>yes</td> </tr>
<tr> <td><a href="http://www.nant.org/">New Approaches to Neuroblastoma Therapy</a></td> <td>NANT wants to “develop and test new therapies that will be targeted specifically to neuroblastoma cells”</td> <td>yes</td> </tr>
<tr> <td><a href="https://ipcr-chla.usc.edu/tacl/">Therapeutic Advances in Childhood Leukemia and Lymphoma</a></td> <td>TACL “was established to provide a means for carrying out early studies of new drugs in children with recurrent leukemia or lymphoma”</td> <td>yes</td> </tr>
<tr> <td><a href="http://poeticphase1.org/">Pediatric Oncology Experimental Therapeutics Investigators’ Consortium</a></td> <td>POETIC “promotes the early clinical development of promising therapies for the treatment of children, adolescents and young adults with cancer and related disorders.”</td> <td>yes</td> </tr>
<tr> <td><a href="http://drugpath.org">DrugPath</a></td> <td>DrugPath aims to provide a free online resource for academic researchers that details developmental drugs in industry in order to accelerate the application of these drugs.</td> <td>n/a</td> </tr>
<tr> <td><a href="http://www.broadinstitute.org/ccle/home">The Broad-Novartis Cancer Cell Line Encyclopedia</a></td> <td>The CCLE’s goal is to develop a comprehensive and detailed bank of information of human cancer cell for public use.</td> <td>n/a</td> </tr>
</table>PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0tag:blogger.com,1999:blog-2463642186628177012.post-72966648386956531962011-08-09T14:43:00.000-07:002011-08-09T14:43:00.460-07:00The Long Road to Immunotherapy<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj6fu52pen7Qs2namrivgTwWq6dUB_KNzRmp3IkFmcGOJi_DVjt-RlZQR7aiYB8tACVIv1IOI6FSlmMx9kvTzMluBC5Bp8C6m9GW8KHnD_TShlWjbQJaAOKyXR4gkfLWJAfuWMxGYau_Mo/s1600/14+point+Bold.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="207" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj6fu52pen7Qs2namrivgTwWq6dUB_KNzRmp3IkFmcGOJi_DVjt-RlZQR7aiYB8tACVIv1IOI6FSlmMx9kvTzMluBC5Bp8C6m9GW8KHnD_TShlWjbQJaAOKyXR4gkfLWJAfuWMxGYau_Mo/s320/14+point+Bold.jpg" width="320" /></a></div><div class="MsoNoSpacing">Be sure to check out the recent publication by Elaine from the PPTI and the Keller lab about the trials and tribulations of immunotherapies in cancer in<a href="http://onlinelibrary.wiley.com/doi/10.1002/pbc.23136/full"> Pediatric Blood and Cancer</a>! </div>PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0tag:blogger.com,1999:blog-2463642186628177012.post-68004276641234797172011-08-05T12:00:00.000-07:002011-08-05T12:00:03.054-07:00Welcome, Melanie!<!--[if !mso]> <style>
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<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhq01sLr1OnOXjkDFlF8DhX-hf7TmCt26wn000Ohc8EesD4ga24PcmdZ5uWxuauQQHqQjhfUIaht3iR7lNChWM1XNzkDjIOUcqRLlqxYov-rs52-NLsN1X1MNb51j3o3e71FZKqpgU69LY/s1600/Melanie_Honduras+%25282%2529.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="212" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhq01sLr1OnOXjkDFlF8DhX-hf7TmCt26wn000Ohc8EesD4ga24PcmdZ5uWxuauQQHqQjhfUIaht3iR7lNChWM1XNzkDjIOUcqRLlqxYov-rs52-NLsN1X1MNb51j3o3e71FZKqpgU69LY/s320/Melanie_Honduras+%25282%2529.jpg" width="320" /></a></div><div class="MsoNormal">The <a href="http://www.stbaldricks.org/">St. Baldrick’sFoundation</a> funds childhood cancer research grants throughout the United States and may be best known for their lighthearted fundraising efforts where donors get to shave their heads in solidarity with cancer patients!<span style="mso-spacerun: yes;"> </span><span style="mso-spacerun: yes;"> </span>The money goes to research labs, first year medical students, new doctors, young researchers and clinical trials amongst many other things.<span style="mso-spacerun: yes;"> </span>We are fortunate this year to have a medical student participate in our lab work through collaboration with the Department of Pediatrics Summer Internship Program directed by Dr. Amy Skinner under the auspices of the St. Baldrick’s Foundation Summer Fellowship.<span style="mso-spacerun: yes;"> </span></div><div class="MsoNormal"><br />
</div><div class="MsoNormal">Melanie Jackson is a (soon-to-be) second year medical student here at Oregon Health and Science University with basic research experience in skeletal biology.<span style="mso-spacerun: yes;"> </span>Her primary goal is a career in academic medicine where she will create a much needed link between research findings and clinical practice.<span style="mso-spacerun: yes;"> </span></div>PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0tag:blogger.com,1999:blog-2463642186628177012.post-35612661035180839762011-08-03T14:00:00.000-07:002011-08-03T14:00:12.264-07:00Words from Charles<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiBYYhbNcc_aosVqPcih93pes2BfrMemPNCwvfVaCRvmcvB4yRz1k7v6pcWT-ovft2MjRZ7l3pR0fxLH8Nb9rGGnbZVlKJtM6sp-woZoytN0l3AUyu3pfggZxjYhNx8QTNEsy4nSbHOwpU/s1600/OHSU+062211+-692.jpg" imageanchor="1" style="clear:left; float:left;margin-right:1em; margin-bottom:1em"><img border="0" height="214" width="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiBYYhbNcc_aosVqPcih93pes2BfrMemPNCwvfVaCRvmcvB4yRz1k7v6pcWT-ovft2MjRZ7l3pR0fxLH8Nb9rGGnbZVlKJtM6sp-woZoytN0l3AUyu3pfggZxjYhNx8QTNEsy4nSbHOwpU/s320/OHSU+062211+-692.jpg" /></a></div><br />
<b>One would like to think that tangibly better treatments for rhabdomyosarcoma, medulloblastoma and other childhood cancers can be found in a matter of years, instead of tens of years.</b> Finding new treatments starts with research, perhaps even a new research approach to identifying effective new treatments. The Pediatric Preclinical Testing Initiative (at the Pediatric Cancer Biology Program, Pape' Family Pediatric Research Institute, Oregon Health & Science University) focuses on finding molecules in childhood cancers that can be directly turned off or on by drugs so that the tumor stops growing. Behind our novel approach is the use of genetically-engineered mice. Our Pediatric Preclinical Testing Initiative uses mice modified from before birth so that at a certain age, and in a certain tissue, the same mutations found in a child’s cancer are activated in the mouse. These special mouse models of childhood cancer can be used to test a treatment to see whether the tumor growth and spread (metastasis) can be reversed. The specific aspect of these mice having normal immune systems is a real plus, too, because white blood cells play an important role in how tumors evolve and respond to therapy.PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0tag:blogger.com,1999:blog-2463642186628177012.post-33343966221852910132011-08-01T14:40:00.000-07:002011-08-01T14:40:28.076-07:00CMTRA Conference<!--[if !mso]> <style>
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<div class="MsoNoSpacing">A lot of things have been going on and keeping up with them all on the blog has been a challenge, as I’m sure you’ve noticed!<span style="mso-spacerun: yes;"> </span></div><div class="MsoNoSpacing"><br />
</div><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj3xG6w9INbBxhclo9vJAmvB4Pe-bQjonIWJLOWwrT1CEVXG3MYZ1s1o1U47Rpvl3HRSCJFHGfW9k674-MW0hyphenhyphenU4j1ppDmTug_wJwy4C8pTN9x4-QCPMOLeQy8klHHRjwI-WDB2fy8zEkw/s1600/asilomar.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="240" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj3xG6w9INbBxhclo9vJAmvB4Pe-bQjonIWJLOWwrT1CEVXG3MYZ1s1o1U47Rpvl3HRSCJFHGfW9k674-MW0hyphenhyphenU4j1ppDmTug_wJwy4C8pTN9x4-QCPMOLeQy8klHHRjwI-WDB2fy8zEkw/s320/asilomar.jpg" width="320" /></a></div><div class="MsoNoSpacing">Recently Elaine was sent to the 2011<a href="http://www.blogger.com/%20http://www.cancermoleculartherapeutics.org/index.html"> MolecularTherapeutics of Cancer Research Conference</a> where she got the chance to hear top scientists discuss cutting edge research at the Asilomar Conference Center in Pacific Grove, CA.<span style="mso-spacerun: yes;"> </span>Talks covered topics ranging from the challenges of gaining government approval for clinical research to the minute details of manipulating signaling pathways in novel ways to treat a wide variety of cancers.<span style="mso-spacerun: yes;"> </span>Participants came from both industry and academia to discuss the near and long-ranging future of molecular therapeutics.<span style="mso-spacerun: yes;"> </span></div>PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0tag:blogger.com,1999:blog-2463642186628177012.post-91558850998234072952011-04-13T10:37:00.001-07:002011-05-18T10:04:07.619-07:00Tools for Pediatric Cancer Drug Discovery<div class="MsoNormal">Finding a cure for cancer means knowing what drugs are available and how they are currently performing on the market. There are any number of sources for this information including personal networking, publications and databases of current research aims and goals. <a href="http://drugpath.org/">Drugpath.org</a> is an online database that lists cancer drugs that are currently being developed. The drugs are listed by a variety of characteristics that allows scientists to search for particulars that are relevant to their interests. </div><div class="MsoNormal"><br />
</div><div class="MsoNormal">The database is maintained by a research team of faculty and students at Texas Tech University System and collaborates with the National Center for Integrative Biomedical Informatics (NCIBI). Both researchers and members of industry can join in order to maximize exposure to new drugs and new applications for both groups. </div>PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com1tag:blogger.com,1999:blog-2463642186628177012.post-48536697057597579392011-02-04T10:41:00.000-08:002011-05-18T10:10:38.751-07:00Valuing our Colleagues<div class="MsoNormal"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjin2QW6gE-obSpFruoREqu9oCRULmL5tTyJl-vaiA3zUzZzqeQoki7hKjiT-E4Nv01gFS2O7yrK83aljmDJcQsbeEBOsud71xNJtKj0SiaNRiaBhIJR0opMMjXt-rnbnXSHO0y5GHQWOc/s1600/respect+LAT+poster.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="200" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjin2QW6gE-obSpFruoREqu9oCRULmL5tTyJl-vaiA3zUzZzqeQoki7hKjiT-E4Nv01gFS2O7yrK83aljmDJcQsbeEBOsud71xNJtKj0SiaNRiaBhIJR0opMMjXt-rnbnXSHO0y5GHQWOc/s200/respect+LAT+poster.jpg" width="130" /></a><span style="font-size: small;">As we mentioned last time, the core of the PPTI is the mouse colony. Thanks to the hard work and diligence of the laboratory animal technicians of OHSU’s Department of Comparative Medicine, we know that our mice will always have the best care any one of them could ask for. While we rely on the talented and dedicated staff as a whole, we would like to take the time during International Laboratory Animal Technician Week to thank the two primary caregivers of our rooms.</span></div><br />
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</div><div class="MsoNormal"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhUx8Tx5dL5eNLbSd_hLjkF-iHOyXVBLm6WtN5e7-AxUa6bRrlQFEXEeAoqtUQdemScPr-NfuLrwJJv1mBbq3y0MFFc7Sz46PEHyrXB_nxUec0bOuh46DJciPwQukBaetm4tOMqDMuFRiA/s1600/Larry.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="173" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhUx8Tx5dL5eNLbSd_hLjkF-iHOyXVBLm6WtN5e7-AxUa6bRrlQFEXEeAoqtUQdemScPr-NfuLrwJJv1mBbq3y0MFFc7Sz46PEHyrXB_nxUec0bOuh46DJciPwQukBaetm4tOMqDMuFRiA/s200/Larry.jpg" width="200" /></a><span style="font-size: small;">Larry Belle manages our barrier room where we keep the bulk of our mouse colony. His attention to detail means that we can maintain complex mouse strains without any worries. Larry’s sense of humor makes the trials of such a full room much more fun than they have a right to be!</span></div><div class="MsoNormal"><span style="font-size: small;"><br />
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</div><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhHCM0e-CC7Ww6I4esdQ3mXqYUqMejK7TcNxowPnW83j1P3F3j0BbP96grUG3hyidJqMQ3F_RxL5eZz7HjEGpP7y0e-u8rMPVqMnzCtztujYjLUN6JRXaXeSl13xwDqIMozCaUD3yNypRs/s1600/Freian.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="200" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhHCM0e-CC7Ww6I4esdQ3mXqYUqMejK7TcNxowPnW83j1P3F3j0BbP96grUG3hyidJqMQ3F_RxL5eZz7HjEGpP7y0e-u8rMPVqMnzCtztujYjLUN6JRXaXeSl13xwDqIMozCaUD3yNypRs/s200/Freian.jpg" width="195" /></a></div><div class="MsoNormal"><span style="font-size: small;">Freian Valbuena has only recently been introduced to our mice in a more conventional room. These experimental mice form the backbone of our data collection and are critical to Keller lab members and PPTI projects alike. Freian’s great communication skills have made the establishment of this room smooth and problem free. We are looking forward to getting to know him better.</span></div><div class="MsoNormal"><span style="font-size: small;"><br />
</span></div>PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0tag:blogger.com,1999:blog-2463642186628177012.post-15822819243396448402010-12-14T10:32:00.000-08:002011-05-18T10:09:17.303-07:00Mouse Models<div class="separator" style="clear: both; text-align: center;"></div><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEilxEwfGgtipFG8DvtWQEfqU3ZhZRSn290U9ewDOmvbIhGoIkJsj70k48FQEq1VhX931kLPKOraz9nvMt6VljQv8CjeM-wMDlL5eYCsc9fHBG_fcwGazfhPoFccZjGaJdvApWWPhCgYtVo/s1600/GEMMs.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="150" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEilxEwfGgtipFG8DvtWQEfqU3ZhZRSn290U9ewDOmvbIhGoIkJsj70k48FQEq1VhX931kLPKOraz9nvMt6VljQv8CjeM-wMDlL5eYCsc9fHBG_fcwGazfhPoFccZjGaJdvApWWPhCgYtVo/s200/GEMMs.jpg" width="200" /></a></div><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgoI6DYjmXDytObjngcVkyqKOn82NOcM4xDgbhpH3E6gKuuMyxQ2JFkGoppTdoHWHNnsKyvJdstKnlW_Lkd94tTlROJCZfijtKPbUvor3a2dBYGp07D-5EucQOWOZX0349VLZ5neisVFXk/s1600/models.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><br />
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<div class="MsoNormal" style="line-height: 150%;">The strength of the PPTI is its use of genetically engineered mouse models to study the effect of drugs on particular kinds of cancer. In the past, cancer models used mice with weakened or missing immune systems that added in cancer cells to watch their growth (xenografts). This method has yielded many great results but we know that cancer interacts heavily with the immune system interact so this is a major drawback of the model to consider. Another concern is the location of the tumors that grow – the cancer cells are added in places that are easy to get to and are not necessarily the natural site of development. </div><div class="MsoNormal" style="line-height: 150%;"></div><div class="MsoNormal" style="line-height: 150%;"><br />
</div><div class="MsoNormal" style="line-height: 150%;">Both of these issues are addressed in the PPTI models of cancer in that the mice have normal immune systems and are genetically modified so that their tumors begin and expand in the places that are found in patients. Combined with other changes that allow us to “see” these tumors as they develop we believe that we have a unique opportunity to find effective treatments faster than ever before.</div>PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0tag:blogger.com,1999:blog-2463642186628177012.post-30815546229155392042010-10-29T11:57:00.000-07:002011-05-18T10:03:27.105-07:00A Word from Charles<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh88REfWDah2a6Tc9GKPkoYzljNlZaT2c3y_xfAf63AdHMfb7jK94E_IlE7hiEafewK_4WdSzI1O_9a2m7N8hapf2SMX_FTHTriU1MwzXA0_zXfISmOOKYwMPC7QqlmoWplz3uUw0VVKnw/s1600/mARMS.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="150" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh88REfWDah2a6Tc9GKPkoYzljNlZaT2c3y_xfAf63AdHMfb7jK94E_IlE7hiEafewK_4WdSzI1O_9a2m7N8hapf2SMX_FTHTriU1MwzXA0_zXfISmOOKYwMPC7QqlmoWplz3uUw0VVKnw/s200/mARMS.jpg" width="200" /></a></div><b></b><br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgsxsPWp9Q44pN8k9ibUMzgaB-mU_iNl_rxkUlrXTly3YO-pysk0OIdy_5yfEWJSaTLxoCogsBZXSuH8tfQR3mRmtOb_SxxUHYMA17zD94gwwHO2Hws5bWkgkHAiGub4gmmH-UbLGL10-w/s1600/DSC_0052.JPG" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"></a><span class="apple-style-span"> As a physician-scientist, my laboratory is devoted to the development of novel molecular therapies for advanced childhood solid tumors associated with high morbidity or mortality. To achieve this goal, my laboratory utilizes physiologically-accurate, genetically-engineered mouse models (GEMMs) of three related pediatric small round blue cell tumors: medulloblastoma, alveolar rhabdomyosarcoma and embryonal rhabdomyosarcoma. Medulloblastoma is a childhood brain tumor with a predilection for leptomeningeal metastasis for which radiation-sparing treatments are needed, whereas alveolar and embryonal rhabdomyosarcoma are aggressive muscle cancers that are difficult to cure if not completely resected or if metastatic. The long-term emphasis of my laboratory’s research is the investigation of tumor progression, since advanced disease remains the greatest challenge in the treatment of children with these cancers. The ultimate goal of my research program is to develop pre-clinically tested, molecularly-targeted therapies to halt progression or induce regression for gross residual disease, metastatic disease and relapsed disease.</span>PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0tag:blogger.com,1999:blog-2463642186628177012.post-76006971417075710802010-10-22T13:07:00.001-07:002011-05-18T10:06:17.796-07:00Accelerating Drug Discovery<div class="separator" style="clear: both; text-align: center;"></div><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh-4HHxOWudGrGMk0hN7Pzwb3HpAnbVbifVEp5HPvbHg_8be1xD-tajXdU2KjHBmU_Wej7ed1UxE7GRhuK3mA5VZErzLOrF5DmHlITT8mx2gPnRTZ_UW1eTX5_gFLCrwQDTL_2xBkJT9QU/s1600/EpMotionandJinu.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="150" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh-4HHxOWudGrGMk0hN7Pzwb3HpAnbVbifVEp5HPvbHg_8be1xD-tajXdU2KjHBmU_Wej7ed1UxE7GRhuK3mA5VZErzLOrF5DmHlITT8mx2gPnRTZ_UW1eTX5_gFLCrwQDTL_2xBkJT9QU/s200/EpMotionandJinu.jpg" width="200" /></a></div><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiO9aQPu65iDb2p8y4cCnjABy6S4pM9Fe1CiqldhKjvazRP1lQJ-ptZWEBvtikX0e-pJCoFX7jDLtBH3HBrMLuJe4KKJYcEoyMODgDTZiHkjKpqnVFJqNEs4iCxBmX81jU1Q5pWeBYs2Dw/s1600/EpMotion.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><br />
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<div style="font-family: inherit;"><span style="font-size: small;">We are very excited to welcome the newest member of our equipment crew: the Eppendorf epMotion 5075! (Shown here with Jinu Abraham, PhD, our Scientific Manager.) This machine will give us high throughput capabilities that will be critical for getting drugs into the testing process and out into trials as fast as possible (with the least amount of human error!) This instrument is also central to the forthcoming Personalized Medicine effort for childhood cancer at OHSU. Check back to see it in action! </span></div>PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0tag:blogger.com,1999:blog-2463642186628177012.post-78264220314950814792010-09-24T17:25:00.000-07:002011-05-18T10:02:40.528-07:00Scientific and Operational Managers: Jinu Abraham and Elaine Huang<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgCGEVWnobI5IeY05VAg1TUZfIs1fZ0ueAMzl1l3H-OQnzAPVSD7sNwsRr52PJPaY1Dix8QvkAWZNayH02NMo6MyUyEKko_x6pYQiDVqmv2wAOICaDICbwl4bXELNLWvJEjNHTVqD2nuPg/s1600/DSC_0006.JPG" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="132" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgCGEVWnobI5IeY05VAg1TUZfIs1fZ0ueAMzl1l3H-OQnzAPVSD7sNwsRr52PJPaY1Dix8QvkAWZNayH02NMo6MyUyEKko_x6pYQiDVqmv2wAOICaDICbwl4bXELNLWvJEjNHTVqD2nuPg/s200/DSC_0006.JPG" width="200" /></a></div><div class="MsoNoSpacing"><br />
</div><div class="MsoNoSpacing"><i>Jinu Abraham, PhD</i> earned his doctoral degree in Molecular and Cellular Biology and as a postdoctoral researcher in the Keller laboratory has been investigating how rhabdomyosarcoma can, over time, begin to develop resistance to treatment by a class of drugs called tyrosine kinase inhibitors. He is the driving force behind the analysis and selection of novel therapeutic agents to be tested by the PPTI. </div><div class="MsoNoSpacing"><br />
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</div><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjNox67u3D6psrFPdLPi6eIufD7_HC_66pwRGPpM1HsHbPgVAmpQUz_4UilMEFP5PyD3PBDu1-NFg3oDekNFl9o3SlP5lkpnT2w_pE7sIVSwCfXCNmKKJRYYiJBRikrLjXkWolxkdZO7jk/s1600/Elaine-in-Culver.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="200" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjNox67u3D6psrFPdLPi6eIufD7_HC_66pwRGPpM1HsHbPgVAmpQUz_4UilMEFP5PyD3PBDu1-NFg3oDekNFl9o3SlP5lkpnT2w_pE7sIVSwCfXCNmKKJRYYiJBRikrLjXkWolxkdZO7jk/s200/Elaine-in-Culver.jpg" width="170" /></a></div><div class="MsoNoSpacing"><i>Elaine Huang, MSc</i> received her M. Sc. in Immunology and begain working <span class="apple-style-span">in an industry-sponsored GLP/GMP clinical cell and vaccine production facility. More recently she has been employed in a facility dedicated to generating genetically modified mice for the research community of OHSU. The PPTI will utilize her experience with animals and familiarity with industry standards to streamline the testing and analysis of drugs.</span></div>PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0tag:blogger.com,1999:blog-2463642186628177012.post-15349253135819334752010-08-27T14:23:00.000-07:002011-05-18T10:01:47.333-07:00Good times with the Papé Family Pediatric Research Institute and the Oregon Stem Cell Center!<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjWzdva8HRN7FVnmb-7BhrO5QjoTL9PsoM24NiTn1oGd_QvZljfAL0zdBJHugZog5I3LZNBDYrXjUO2vWx9AeCi9z2p02JUBXgfVdjyDWdAYb2tWMeZJJe2b3MQ1KrrdD7jxU8bk455jTk/s1600/DSC_0070.JPG" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="133" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjWzdva8HRN7FVnmb-7BhrO5QjoTL9PsoM24NiTn1oGd_QvZljfAL0zdBJHugZog5I3LZNBDYrXjUO2vWx9AeCi9z2p02JUBXgfVdjyDWdAYb2tWMeZJJe2b3MQ1KrrdD7jxU8bk455jTk/s200/DSC_0070.JPG" width="200" /></a></div>Many thanks to the Papé Institute and the OSCC for a fun filled picnic/barbeque/potluck yesterday evening! Laboratory and administration members and their families all gathered to enjoy food, music, games and each others' company in Gabriel Park on a picturesque Portland summer evening. With two grills firing and the loads of homemade treats that were brought in, no one left hungry!PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0tag:blogger.com,1999:blog-2463642186628177012.post-85234988499926077092010-08-23T14:34:00.000-07:002011-05-18T10:01:20.106-07:00Introducing Charles<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhS1ZD6_Wwd9-CYNd6AEiJBHZoNK3ANHOkX_E91LzhK2Ac6F9zPLG27_LMj8y9L1C4d9y16_YCvBvKygXfC86oKwzqkgrmFOF1V5eTNKZPagxxmBq2EMOSNvc5DOT6IXwhJy30sBBFo6dU/s1600/FearlessLeader.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="200" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhS1ZD6_Wwd9-CYNd6AEiJBHZoNK3ANHOkX_E91LzhK2Ac6F9zPLG27_LMj8y9L1C4d9y16_YCvBvKygXfC86oKwzqkgrmFOF1V5eTNKZPagxxmBq2EMOSNvc5DOT6IXwhJy30sBBFo6dU/s200/FearlessLeader.jpg" width="200" /></a></div><br />
Dr. Keller is a board-certified pediatric oncologist and NIH R01-funded investigator specializing in the development of more effective, less toxic therapies for the childhood muscle cancer, rhabdomyosarcoma, and the childhood brain tumor, medulloblastoma. His special interest is advanced disease that has spread beyond the initial location of the cancer. Dr. Keller is investigating whether the genes thought to be responsible for the initial tumors are also important when the disease progresses, thereby identifying targets for new medical therapies. To address these diseases, Dr. Keller's laboratory encompasses a multidisciplinary team with expertise in genetically-engineered mouse models, biochemistry and biomedical engineering. Dr. Keller is a Full Member of the Soft Tissue Sarcoma Committee of the Children's Oncology Group (COG) and a participant in the COG Central Nervous System Biology Committee (groups which identify new opportunities for diagnosis and treatment of childhood sarcomas and brain tumors). Dr. Keller is also a Consultant to the Pediatric Preclinical Testing Program sponsored by the National Cancer Institute. Dr. Keller has authored more than 35 scientific publications. <br />
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Dr. Keller joined the Pape' Family Pediatric Research Institute, Department of Pediatrics, as Leader of the Pediatric Cancer Biology Program in June of 2010 as an Associate Professor and the Tarshis Professor of Pediatric Hematology-Oncology. Dr. Keller also directs the Pediatric Preclinical Testing Initiative in the Pape' Family Pediatric Research Institute. Dr. Keller is also a Member of the Knight Cancer Institute and the Oregon Stem Cell Center. Dr. Keller was previously a Founding Principal Investigator of the Greehey Children's Cancer Research Institute at the University of Texas Health Science Center in San Antonio. For his education, Dr. Keller attended Tulane University where he received a degree in Biomedical Engineering prior to attending Baylor College of Medicine where he received his M.D. degree. After completing his internship and residency in Pediatrics at Texas Children's Hospital Dr. Keller trained in Pediatric Hematology-Oncology at the University of Utah and as a K08-funded postdoctoral fellow in the laboratory of 2007 Nobel laureate, Mario R. Capecchi.<br />
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Strengths<br />
- Expertise in growth factor biology as a therapeutic target in pediatric cancers<br />
- Specialization in the development of state-of-the-art genetically-engineered mouse models of human disease<br />
- Interests in both basic science and therapeutic approaches for childhood cancer (that is, defining the cell of origin of a cancer then developing a treatment approach which best stops growth of a tumor based on this knowledge)<br />
- Firm commitment to training the next generation of physician-scientists and multidisciplinary pediatric cancer biologistsPPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0tag:blogger.com,1999:blog-2463642186628177012.post-20414625174641001242010-08-17T17:08:00.000-07:002010-08-17T17:08:00.798-07:00Welcome<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj6mqqq2un8QmnwG6ga7UZHe8J7ourbfTtaYfcQfK9c4nRykLYtp0CEiEojV5URAEQIgDtGc06Fl35pDFekPNqnPjPp-q_TaV-vXCiSB4-h4Xv2cvmJx32noVnQle3NaWZvRpUxfydP1dQ/s1600/KellerLab-PPTI-logo.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="152" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj6mqqq2un8QmnwG6ga7UZHe8J7ourbfTtaYfcQfK9c4nRykLYtp0CEiEojV5URAEQIgDtGc06Fl35pDFekPNqnPjPp-q_TaV-vXCiSB4-h4Xv2cvmJx32noVnQle3NaWZvRpUxfydP1dQ/s200/KellerLab-PPTI-logo.jpg" width="200" /></a></div><br />
The Pediatric Preclinical Testing Initiative (PPTI) at the <a href="http://www.ohsu.edu/xd/health/services/doernbecher/research-education/research/research-institute/pape.cfm">Papé Family Pediatric Research Institute</a> of the <a href="http://www.ohsu.edu/">Oregon Health and Science University</a> (OHSU) has been established with the <b>mission of identifying novel targeted therapies for childhood cancer and other diseases using genetically-engineered mouse models</b>. For childhood cancers, the PPTI works in partnership with the <a href="http://ctep.cancer.gov/">Cancer Therapy Evaluation Program</a> (CTEP) at the <a href="http://www.cancer.gov/">National Cancer Institute</a> (NCI)to discover new, molecularly-targeted therapies that are more effective and less toxic than traditional chemotherapy. <br />
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We are a team of scientists from diverse backgrounds - biomedical engineering, biochemistry, immunology - who are dedicated to the performance of leading-edge research that will improve the outcomes of children who find themselves battling pediatric illnesses. For the childhood cancers rhabdomyosarcoma and medulloblastoma, the last three to four decades of research have not resulted in a significant improvement in children diagnosed with advanced forms of these cancers despite the earnest efforts of scientists across the globe. The PPTI will directly test the effect of newly developed drugs in these and other childhood diseases in collaboration with other universities and pharmaceutical companies alike in order to identify treatments that have the best chance of making a difference in a child's life.PPTI staffhttp://www.blogger.com/profile/07845939846395889100noreply@blogger.com0