Brown: Hormone-dep cancer questions about acquired resistance (clonal evol. or differentiation of cancer stem cell), other epi Q's #AACR14
2:06pm April 7th 2014 via Hootsuite
Next: Myles Brown, Dana-Farber Cancer Inst. "Genetic and epigenetic mechanisms of resistance to endocrine therapy" #AACR14
2:04pm April 7th 2014 via Hootsuite
Next: Myles Brown, Dana-Farber Cancer Inst. "Genetic and epigenetic mechanisms of resistance to endocrine therapy"
Stam.:Q:What if DHS were replaced with methylation, other states? A:With gene exp, can't get a lineage tree. A memory compartment #AACR14
2:01pm April 7th 2014 via Hootsuite
Stam.:Q:Involvement of superenhancers? A:The top group of DHSs, yes have TFs but further work needed. #AACR14
1:57pm April 7th 2014 via Hootsuite
Stam.:Q:(Bernstein) TF sites shared, is it way off? A:More than a 3D landscape, more like 100D. How far off? Depends on the tumor #AACR14
1:55pm April 7th 2014 via Hootsuite
Stam.: Ectopic regulatory landscape - dys-differentiation. Reactivation ES cell DHSs, loss/gain of TF's of oncogenes / suppressors #AACR14
1:54pm April 7th 2014 via Hootsuite
Stam.: 'Cancer is like Waddington's ball meet Tiger Woods' #AACR14
1:53pm April 7th 2014 via Hootsuite
Stam.: TFs: oncogenes key drivers of this regulatory transformation. FOXA1, ELF5, ER, GL12 etc. Suppressor TF's in turn are lost #AACR14
1:51pm April 7th 2014 via Hootsuite
Stam.: In br ca, T-cell leukemia, same basic pattern of ~80% reactivated from other cell-type development #AACR14
1:50pm April 7th 2014 via Hootsuite
Stam.: But in melanoma: "73% reactivated DHSs from other lineages', 24% from ES DHSs - disordered reactivation #AACR14
1:49pm April 7th 2014 via Hootsuite
Stam.: Regulatory landscape retrograde remodeling - from ES to melanocytes to melanoma: 257K to 171K to 163K DHSs #AACR14
1:48pm April 7th 2014 via Hootsuite
Stam.: Back to PCoA chart: cancer cells move toward the hESCs in the center of the plot. A 'retrograde remodeling' of landscape #AACR14
1:47pm April 7th 2014 via Hootsuite
Stam.: (abbrev. for Stamatoyannopoulos): The normal state: hESCs move down the 'valleys'. Can det which TF's involved ea step #AACR14
1:46pm April 7th 2014 via Hootsuite
Stamatoyannopoulos: DHS gains/losses highlight key regulatory factors; Ref 2013 Cell Stergachis et al http://t.co/Fe701Vbhhf #AACR14
1:44pm April 7th 2014 via Hootsuite
Stamatoyannopoulos: hESC w/ 257K DHSs, Hematopoeitc progenitors, gain 83K, lose 202K DHSs. ~40% of hESC DHSs' preserved #AACR14
1:42pm April 7th 2014 via Hootsuite
Stamatoyannopoulos: PCoA of DNAseI hypersensitivity (3D plot) - orbiting around hESC's #AACR14
1:41pm April 7th 2014 via Hootsuite
Stamatoyannopoulos: Extensive memory (chromatin, TF's) preserved in terminally differentiated cells #AACR14
1:40pm April 7th 2014 via Hootsuite
Stamatoyannopoulos: hESC's sit at the top - derivatives of primitive mesoderm. 'Lineage memory' encoded in cellular reg DNA #AACR14
Stamatoyannopoulos: Introducing the epigenetic landscape via ENCODE project http://t.co/sNzMQfeWoT #AACR14
1:38pm April 7th 2014 via Hootsuite
Up first: John Stamatoyannopoulos, Univ Washington: "Reactivationn of early developmental programs during oncogenesis" #AACR14
1:37pm April 7th 2014 via Hootsuite
Symposium: "Functional regulation of the cancer genome". Chair: Brad Bernstein, Broad Institute. #AACR14
Rosenberg: Determined that 26.9% of the TIL's from an individual tumor were specific to the tumor mutated antigen #AACR14
12:44pm April 7th 2014 via Hootsuite
Rosenberg: Now looking at TCR clonotypes that recognize individual's mutations. Most abundant (fresh tumor) is spec to that cancer #AACR14
12:42pm April 7th 2014 via Hootsuite
Rosenberg: ID ERBB2IP gene (the single antigen), used for adoptive therapy. The 'ultimate "personalized therapy" ' In ~6 wk time #AACR14
12:38pm April 7th 2014 via Hootsuite
Rosenberg: WES of lung metastasis - found 26 nsSNVs, did tandem minigenes of all 26, only 1 / 3 TMG, identified single antigen #AACR14
12:36pm April 7th 2014 via Hootsuite
Rosenberg: Now with 25 samples; each with a unique mutation. #AACR14
12:35pm April 7th 2014 via Hootsuite
Rosenberg: Constructing a tandem minigene - to express all the mutated peptides, all tested against TIL of complete regress'n #AACR14
12:33pm April 7th 2014 via Hootsuite
Rosenberg: Illustrates examples of very low-likelihood binders that have been shown to be the spec peptide antigen #AACR14
12:32pm April 7th 2014 via Hootsuite
Rosenberg: Then screen for invitro recognition by TIL cells that mediate complete regression #AACR14
12:29pm April 7th 2014 via Hootsuite
Rosenberg: For a mut to be a cancer antigen - 9- or 10-mer peptide ID'd, synthesize 20-40 candidate peptides with high MHC affinity #AACR14
Rosenberg: The puzzle of melanoma immunogenicity - unique in susceptibility to cytokins. From WES, looking at wide # of nsSNV #AACR14
12:28pm April 7th 2014 via Hootsuite
Rosenberg: Success rates are irrespective of prior melanoma treatment regimen #AACR14
12:26pm April 7th 2014 via Hootsuite
Rosenberg: "TIL appear to eliminate the last cancer cell' with such long time-frame of complete regressions #AACR14
Rosenberg: Photo of a nasty melanoma: 8y on now disease-free; only one to require 2nd treatment #AACR14
12:25pm April 7th 2014 via Hootsuite
Rosenberg: 8.8y followup: Of 93, 22% have a complete response, 19/20 CRs ongoing at 80-120 months #AACR14
12:23pm April 7th 2014 via Hootsuite
Rosenberg: From decades ago: adoptive transfer of TIL - tumor removed, IL-2 stim, select, expand, administer #AACR14
12:22pm April 7th 2014 via Hootsuite
Rosenberg: To use lymphocytes for treatment. Chart of advantages: large #'s, activated ex-vivo, ID cell subpops, can manipulate host #AACR14
12:21pm April 7th 2014 via Hootsuite
Next: Steven Rosenberg, Chief of Surgery, NCI. "The curative potential of T cell transfer therapy for patients with cancer" #AACR14
12:19pm April 7th 2014 via Hootsuite
Weissman: 5F9g4 humanized Ab is headed to AML trial. $20M CIRM grant for 'an all comers solid tumor' trial #AACR14
12:16pm April 7th 2014 via Hootsuite
Weissman: Targeting CD47 "Every human cancer we see has CD47'. Can get statis but not removal. #AACR14
12:13pm April 7th 2014 via Hootsuite
Weissman: Young cells ++exp CD47 to evade phagocytosis; 'in 3 mos the smartest (new) person becomes the stupidest' thinking alike! #AACR14
12:04pm April 7th 2014 via Hootsuite
Weissman: If prog. in HSC clone for AML is true, 'it is probably true for all cancers' in tissues that regen. from tiss. stem cells #AACR14
12:01pm April 7th 2014 via Hootsuite
Weissman: Looking at NGS exomes to ID somatic mut's in AML. List of ~25 genes; determined order of mutations. Single HSC analysis #AACR14
12:00pm April 7th 2014 via Hootsuite
Weissman: Looking at GSK3-beta expression by blast crisis CML progenitors. But for epigenetics need specific subsets #AACR14
11:58am April 7th 2014 via Hootsuite
RT @00livier: Weissman: no overlap of interest between academia and industry in stem cell therapy #AACR14
11:55am April 7th 2014 via Hootsuite
Weissman: Figure of hematopoeitc pathway. Ref Miyamoto 2000 PNAS ref http://t.co/ifX4HibY1l #AACR14
11:54am April 7th 2014 via Hootsuite
Weissman: Cancer-free stem-cell grafts improves survival - fig. from 2011 Muller et al ref: http://t.co/Au2ciR7vkf #AACR14
11:52am April 7th 2014 via Hootsuite
Weissman: Can remove contam. cancer and T-cell from stem cell grafts #AACR14
11:49am April 7th 2014 via Hootsuite
Next: I. Weissman Stanford. "Investigating inhibition of the CD47 'don't eat me' signal to enable tumor phagocytic removal..." #AACR14
11:48am April 7th 2014 via Hootsuite
