Mills:Challenges and need for functional genomics. Are aberrations in genes drivers? Bioinformatic annotation not enough #AACR14
3:10pm April 8th 2014 via Hootsuite
Mills: Starting another trial in '14, AKTi and Olaparib funded by AZ and their SPORE grant, working downstream. #AACR14
3:09pm April 8th 2014 via Hootsuite
Mills:Leveraging SU2C to convince Novartis & AZ to combine PI3Ki and PARPi, started in '12 and results will be announced at ASCO #AACR14
Mills: p53 driven, HR defects and CN change, PI3KCA targeted: with the SU2C program using a Parp inhibitor #AACR14
3:07pm April 8th 2014 via Hootsuite
Mills: TCGA are high-grade serous ov ca samples, something to keep in mind when designing a study #AACR14
3:01pm April 8th 2014 via Hootsuite
Mills: HGSEOC primarily driven by DNA CNV - but ov ca has multiple diff. forms, many are lethal. 8 ov ca genes - % of TCGA v theirs #AACR14
Mills: Great opening slides of kits and gophers with guns. "Capitalizing on the vulnerabilities of cancer" #AACR14
2:59pm April 8th 2014 via Hootsuite
Next: Gordon Mills, MD Anderson. "Mutation Driven View of Ovarian Cancer" #AACR14
2:58pm April 8th 2014 via Hootsuite
Haber: Pts with lots of CTC-clusters fare much worse (br ca) than with fewer. Staining for plakoglobin - helps tether CTCs together #AACR14
2:40pm April 8th 2014 via Hootsuite
Haber: One gene - plakoglobin 200x overexpressed in clusters. shRNA knockdown expt's show metasis suppressed #AACR14
2:39pm April 8th 2014 via Hootsuite
Haber: Br ca did RNA-Seq to cp single vs. clustered CTCs; within each individual sample, single vs clusters were distinct #AACR14
2:37pm April 8th 2014 via Hootsuite
Haber: Mechanism: tested clustered cells proliferate better than single ones; clusters showed less apoptosis #AACR14
2:36pm April 8th 2014 via Hootsuite
Haber: Clusters are rare but 'bad actors'. Lung mets are 'primarily derived from one tumor (92%)' #AACR14
2:35pm April 8th 2014 via Hootsuite
Haber: CTC's from a mouse - vast majority were groups of CTCs together. "CTC-clusters are 50x metastasis competent' cp to single CTC #AACR14
2:33pm April 8th 2014 via Hootsuite
Haber: Can do std IHC on these cells. Clusters are a problem.Ref Stott et al Sci Trans Med 2010 http://t.co/P9RzjQdU0n #AACR14
2:32pm April 8th 2014 via Hootsuite
Haber: Looks like a polycarbonate CD with fluidic channels, may be commercialized by J&J as a replacement to their CellSearch #AACR14
2:30pm April 8th 2014 via Hootsuite
Haber: Single-stream of cells, are able to separate out WBCs from the CTCs. 2013 Ozkumur Sci Trans Med ref: http://t.co/05ga9DrlR5 #AACR14
Haber: 3rd gen - i-chip, using magnetic deflection, get rid of normal white cells. A negative selection - Ab against WBCs #AACR14
2:29pm April 8th 2014 via Hootsuite
Haber: Challenge - in 10mL had 50B RBC's, perhaps 100 CTC's. Microfluidic - alpha-EpCAM coated microposts at MGH. Then surfaces #AACR14
2:28pm April 8th 2014 via Hootsuite
Oops, next up is Daniel Haber, Mass Gen Hosp. "Molecular characterization of single circulating tumor cells"
2:25pm April 8th 2014 via Hootsuite
Next: David Ting, Mass Gen. "Diversity of circ. tumor cells in a mouse pancreatic cancer model identified by single-cell RNA seq" #AACR14
Nolan: Expect to move CyTOF from 45 to 60-70 param. Can measure mRNA long with Abs (down to 5 copies/cell) #AACR14
2:22pm April 8th 2014 via Hootsuite
Nolan: MIBI-TOF is down to 1 day turn; comparison chart displayed. Scalable, resolution 10nm - 1 um; 6mos will build instrument #AACR14
2:21pm April 8th 2014 via Hootsuite
Nolan: Movie of MIBI - multiple sccan enabled over 40 times; 3D reconstructions are feasible #AACR14
2:19pm April 8th 2014 via Hootsuite
Nolan: Now can do high dimensional epigenetics using this method. Mass-labled IHC - what kind of specification? #AACR14
2:18pm April 8th 2014 via Hootsuite
Nolan:Dynamic SIMS or MIBI Angelo et al Nature Med 2014 ref http://t.co/529dKS1FYV Quantitative (relative to IHC) #AACR14
Nolan: Observed that stereotypical signaling responses are decoupled from surface markers. A non-coordinated movement in AML #AACR14
2:14pm April 8th 2014 via Hootsuite
Nolan: Using this bounded map - all the 'typical' AML markers map very similarly; a few unique phenotypes obsv'd. #AACR14
2:11pm April 8th 2014 via Hootsuite
Nolan:Graphing - to t-SNE space (high-dimensional clustering) across 20 samples, still a bounded set of phenotypes for AML #AACR14
2:09pm April 8th 2014 via Hootsuite
Nolan: To what extent is surface phenotype coupled to. intracellular signalling? Used AML, 17 stimulations, 15 Fn markers, 16 surf #AACR14
2:07pm April 8th 2014 via Hootsuite
Noland: In press word (Bendall et al, Cell) looking at the derivative of the change in signal, looking at coord. points #AACR14
2:06pm April 8th 2014 via Hootsuite
Nolan: Refer to Bendall et al Science 2010 http://t.co/wYB8gUE9cE Referred to Dana Pe'er's work for analysis 'Wanderlust' tool #AACR14
2:05pm April 8th 2014 via Hootsuite
Nolan:"Let no good anomaly go unloved". 45-dimension single-cell MS: 76k MS scans/s. It's just mass; no minimum comp. like w/ flow #AACR14
2:03pm April 8th 2014 via Hootsuite
Nolan: Called 'Cy-TOF' - decorated cells are passed through 7500K ionizer, detects lanthanides, 1K cells/s, correlated to bound Ab #AACR14
2:00pm April 8th 2014 via Hootsuite
Nolan: A new type of flow cytometry - using isotopes (60-80), use 'compressed sensing' up to 200-300 parameters on a per-cell basis #AACR14
1:59pm April 8th 2014 via Hootsuite
Next: Garry Nolan, Stanford. "A single cell systems-structuredview of immunity and cancer" #AACR14
1:58pm April 8th 2014 via Hootsuite
Hicks:When bulk is used it's a very confusing picture; single-cell is very clear distinction between different types #AACR14
1:52pm April 8th 2014 via Hootsuite
Hicks: For aggressive prostate ca? Can get normal adj. along with tumor; Looking at 5 regions by Gleason 9, clear differences #AACR14
Hicks: Looking at bulk DNA baseline and post-treatment bulk / post-trtmt single cells have chr20 amplifications #AACR14
1:47pm April 8th 2014 via Hootsuite
Hicks: Example stories on breast ca: observe CCND1 CNV from one cell; another cell has androgen receptor (?!?); another CCNE1... #AACR14
1:46pm April 8th 2014 via Hootsuite
Hicks: Shown data from 2011 Navin et al Nature paper http://t.co/5psWYTgo3N to follow tumor dev over time; CNVs as a marker #AACR14
1:39pm April 8th 2014 via Hootsuite
Hicks: Using nuclei, using low-coverage CNV, good comparison to million's of cells; can detect 10x and 11x integer CN's clearly #AACR14
1:38pm April 8th 2014 via Hootsuite
Hicks: One way is to use FLDM's C1 Autoprep; do sparse NGS for CNV, or targeted for SNV #AACR14
1:36pm April 8th 2014 via Hootsuite
Hicks:Single-cell techniques labeled 'Method of the Year' in 2013. Nature Methods ref: http://t.co/g4VVAOmQee #AACR14
Next: James Hicks, CSHL "Single-cell genomic and clonal anlaysis of breast and prostate" #AACR14
1:34pm April 8th 2014 via Hootsuite
.@MsStephKayB You are welcome! Shame that there weren't more in attendance - it is the 3rd day at 7am - I certainly did enjoy it! #AACR14
12:40pm April 8th 2014 via Hootsuite in reply to
Janne: Showing combinations in EGFR TKI naive pts was not very effective for lung adenocarcinoma #AACR14
11:49am April 8th 2014 via Hootsuite
Janne: Lung adenocarcinoma pie chart of known genotypes - went from ~75% unk in '03 to ~45% unk in 2014 #AACR14
11:46am April 8th 2014 via Hootsuite
Next: Pasi Janne, Dana Farber Cancer Inst. "Combination therapies for lung cancer: Opportunities and challenges" #AACR14
11:44am April 8th 2014 via Hootsuite
Nowak: Mapped cell growth in a 3D model over time, with effect of treatment as a video movie #AACR14
11:43am April 8th 2014 via Hootsuite
