Ideker: Systems biology between g-type/p-type - will be talking about the construction of 'Cytoscape' network http://t.co/pGI4X3GKoq #AACR14
5:13pm April 6th 2014 via Hootsuite
Up next: Trey Ideker, UCSD "Network based stratification of tumor mutations". #AACR14
5:11pm April 6th 2014 via Hootsuite
Califano:Q:Looked at indiv differences? A:Every sample treated independently, all 'N of 1' protocol. But networks only change ¬5%. #AACR14
5:09pm April 6th 2014 via Hootsuite
Califano:Q:Do MRs populate super enhancers? A:Disregulation of myc or others can occur in many ways. #AACR14
5:06pm April 6th 2014 via Hootsuite
Califano: Alterations of genes and affect MRs? Using EGFR as example, can associate spec mutations to master regulators #AACR14
5:04pm April 6th 2014 via Hootsuite
Califano: Across 5.4K TCGA samples, can look at master regulators across subtypes. #AACR14
5:01pm April 6th 2014 via Hootsuite
Califano: Looking now at mutations that may affect master regulators.10K var, 3.5k samples, 12 tumor types, 5K regulators each ass'd #AACR14
4:57pm April 6th 2014 via Hootsuite
Califano: Looking at Foxm1, Cenpf as master regulators, combination of observed compounds, model shown to work as expected #AACR14
4:54pm April 6th 2014 via Hootsuite
Califano: Prostate ca, 13 transgenic mice, hit with 28 compounds, 364 matrix. Of top 20 regulators, 6 from mouse intersect w/ human #AACR14
4:49pm April 6th 2014 via Hootsuite
Califano: A phenotype of interest - what genes regulated the genes that changed? So they can rank the regulators #AACR14
4:45pm April 6th 2014 via Hootsuite
Califano: Types of big data - transcr. interactions, post-transl. interactoins, post-transcriptional interactions, master regulators #AACR14
4:44pm April 6th 2014 via Hootsuite
Califano: Looking at 3-5 regulatory proteins that cause a 'cancer bottleneck' - oncogene-induced dependencies #AACR14
4:42pm April 6th 2014 via Hootsuite
Califano: 'Black Box' (colored in green!) - open it up and look at the 'ridiculomes' with cellular context of regulatory models #AACR14
4:40pm April 6th 2014 via Hootsuite
Califano: But events are complex: Trastuzumab 70% response, then 70% relapse in br ca #AACR14
4:39pm April 6th 2014 via Hootsuite
Califano: Linking a gene or var to phenotypic outcome. SOD1 in ALS (not targetable), BRC/Abl fusion resulted in Imatinib, Nolotinib #AACR14
4:38pm April 6th 2014 via Hootsuite
Next: Andrea Califano, Columbia "De novo assembly... of regulatory networks reveals mechanism of tumorigenesis and chemosensitivity" #AACR14
4:37pm April 6th 2014 via Hootsuite
Sanford Simon: 'Encourage kids to ask questions about the world around them' 'Now I come home and discuss the science we're doing' #AACR14
4:32pm April 6th 2014 via Hootsuite
Elana Simon from AM (connection probs): 'Parents have emailed me about their kids' interest in science. I encourage them.' #AACR14
4:30pm April 6th 2014 via Hootsuite
Elana Simon: 'Publishing in Science still hasn't hit me'.'So many people around the world do not know about these (pt) communities' #AACR14
4:29pm April 6th 2014 via Hootsuite
From this morning: "I was amazed to see how much data was available." "Such a collaborative open project like this." Elana Simon #AACR14
4:27pm April 6th 2014 via Hootsuite
Permutter: Looking at TCGA mutational freq. data - can revisit the concept of immune surveillance. Immune response ‘sculpts’ tumors #AACR14
3:43pm April 6th 2014 via Hootsuite
Permutter: ‘We are encourage and intimidates sat the se time’ - so many agonists and antagonists on The T-cell surface #AACR14
3:39pm April 6th 2014 via Hootsuite
Permutter:Work on PD1 published in JCO Topalian et al. Last month, although not randomized study #AACR14
3:35pm April 6th 2014 via Hootsuite
Permutter: PD-1 an activation antigen on T and B cells; cancers can ‘hijack’ the PD1 pathway. Nivolumab targets PD1. #AACR14
3:33pm April 6th 2014 via Hootsuite
Permutter: Tumors have a way to inactivate T-cells. Illustrates immune checkpt regulation. #AACR14
3:31pm April 6th 2014 via Hootsuite
Permutter: at here must have been local T-cells that were recruited by the VTEC-induced antigen #AACR14
3:30pm April 6th 2014 via Hootsuite
Permutter: Showed efficacy of their viral vector with engineered antigen, incl ‘action at a distance’ #AACR14
3:28pm April 6th 2014 via Hootsuite
Permutter: Process of immunization: APC’s recruited, can increase amount of antigen ‘and it works’ #AACR14
3:24pm April 6th 2014 via Hootsuite
Permutter: Another option to expand CD19-reactive chimeric TCR-bearing T-cell clones that persist #AACR14
3:22pm April 6th 2014 via Hootsuite
Permutter: Bispecific Ab reagents to activate T-cells, other against tumor-assoc’d antigen. Redirected lysis #AACR14
3:19pm April 6th 2014 via Hootsuite
Permutter: Timeline include 2010 1st cellular immuno therapy (Provenge, prostate ca), 2011 anti-CTLA-4 #AACR14
3:16pm April 6th 2014 via Hootsuite
Permutter: An old field: 40y ago he looked at cell-mediated immunity. Timeline: enthusiasm (78-85), skepticism (85-97), renaissance #AACR14
3:14pm April 6th 2014 via Hootsuite
Up next: Roger Perlmutter, Merck. “Tumor-specific immune activation: immuno-oncology comes of age” #AACR14
3:09pm April 6th 2014 via Hootsuite
Willett: Weight gain as high a risk factor as for smoking for breast cancer in women. #AACR14
2:56pm April 6th 2014 via Hootsuite
Prives: ~1K genes affected by mut p53: is there a common mechanism? Do diff mutants affect invasion, migration, metastasis? #AACR14
1:17pm April 6th 2014 via Hootsuite
Prives: Suggests that mutant p53 drives expression of sterol biosynthesis enzymes SREBPs Ref from 2007: http://t.co/BxO5MKzpyD #AACR14
1:14pm April 6th 2014 via Hootsuite
Prives: Mevalonate pathway - affected by statins. Affect br ca cell growth? Showed morphology changes of disrupted p53 cells #AACR14
1:11pm April 6th 2014 via Hootsuite
Prives: Depletion of mutant p53 also down-regulated mevalonate pathway (cholesterol synthesis) #AACR14
1:08pm April 6th 2014 via Hootsuite
Prives: Using hu mammary MCF10A cells in 3D culture; induce shRNA-mediated knock-down the mutant p53; morphology became more normal #AACR14
1:07pm April 6th 2014 via Hootsuite
RT @BertGold4: Here is Young's NIH talk from a few months ago on super enhancers: http://t.co/cAF7yfczkx … #AACR14 from far away..
1:03pm April 6th 2014 via Hootsuite
Prives: Tumor-derived missense mutated p53, led to the idea of mutant p53 confer gain-of-function #AACR14
1:00pm April 6th 2014 via Hootsuite
Prives: Extent of p53 mutations, refers to her Cell 2009 review: http://t.co/udCNnd8SoQ #AACR14
12:58pm April 6th 2014 via Hootsuite
Prives: p53 one of the most extensively-studied proteins. MdmX & Mdm2 supress it; multiple cellular outcomes once activated #AACR14
12:55pm April 6th 2014 via Hootsuite
Up next: Carol Prives, Columbia. “The two faces of p53: Tumor suppressor and oncogene” #AACR14
12:54pm April 6th 2014 via Hootsuite
.@teamoncology In yesterday's session Rosenfeld (UCSD) suggested Pit1 R27W mutation could become a target #AACR14
12:52pm April 6th 2014 via Hootsuite in reply to
RT @GenomeNathan: Young: cMyc saturation of enhancers drives promiscuous expression of relevant genes. #aacr14
12:48pm April 6th 2014 via Hootsuite
Young: Binding cooperativity on xcr - super enh ultra-sens. +JQ1 treatment impact on BRD4 2013 Cell ref: http://t.co/R6eBVOe1VP #AACR14
12:47pm April 6th 2014 via Hootsuite
Young: Super-enhancers suggest high c-Myc help recruit for pause-release 2012 Cell paper: http://t.co/Jrm4YBAmSN #AACR14
12:44pm April 6th 2014 via Hootsuite
Young: Super-anhancers haven't been noticed before as they drive mRNA with short half-life at a high level #AACR14
12:40pm April 6th 2014 via Hootsuite
Young: Tumor super-enhancers are at key genes (MYC, IGLL5) and acquired by oncogenes. Their 2013 Cell review http://t.co/DunSdVWJTW #AACR14
12:39pm April 6th 2014 via Hootsuite
