Manne: Biomarkers need relevant outcomes, and demonstrate clinical utility in different cohorts https://t.co/ifStfc1C8Y #NGDx17
2:44pm August 18th 2017 via Hootsuite
Upender Manne (Univ AL Birmingham) miRNAs as biomarkers of colorectal cancer disparity: current status and perspective #NGDx17
2:41pm August 18th 2017 via Hootsuite
Fabbri: #NGDx17 A few reviews he's written: https://t.co/ehhfVUgM6j And this one looks interesting: https://t.co/07novdj3fQ
2:32pm August 18th 2017 via Hootsuite
Fabbri: For neuroblastoma, MYC-N ampl is stratifying. Shows data of MYC up-reg in NB-TAM co-cultures despite MYC-N status #NGDx17
2:27pm August 18th 2017 via Hootsuite
Fabbri: 1^o neuroblastoma samples able to be divided into high/low CD163 expr, and co-culture how TERP1 in tumor assoc'd macrophages #NGDx17
2:26pm August 18th 2017 via Hootsuite
Fabbri: miR-21 is transferred from neuroblastoma to monocytes via exosomes. Co-cultured cells' supernatant - plenty of data #NGDx17
2:23pm August 18th 2017 via Hootsuite
Fabbri: Thought the immune cells were helping eradicate cancer, instead induce secretion of cytokines promotiong tumorigenesis #NGDx17
2:17pm August 18th 2017 via Hootsuite
Fabbri: Illustrates with miR-21/29a, taken in macrophage, activation of TLR8 which is NF-kB promoting tumor growth, met potential #NGDx17
2:16pm August 18th 2017 via Hootsuite
Fabbri: Shows co-localization experiment results, showing in NSCLC the interaction between TLR and mIR in endosome, in macrophages #NGDx17
2:15pm August 18th 2017 via Hootsuite
Fabbri: (What is fun about this presentation is he's asking the research question, and then walks you through the answer.) #NGDx17
2:13pm August 18th 2017 via Hootsuite
Fabbri: Exo miR-21 and -29a bind to Toll Like Receptor 7/8, what if they bind to uRNA in the endosome where the receptor is located #NGDx17
2:12pm August 18th 2017 via Hootsuite
Fabbri: Isolated vesicles, uRNAchar via @nanostringtech and 9 candidates, validated via qPCR ended w/4. mIR-16/21/27b/29a #NGDx17
2:10pm August 18th 2017 via Hootsuite
Fabbri: Think of microRNAs as hormones: then what receptor and downstream signaling is utilized? #NGDx17
2:09pm August 18th 2017 via Hootsuite
Fabbri: Shown that supernatants from one cell target can target a second cell type affecting the distant cell's GEX, like hormones #NGDx17
2:08pm August 18th 2017 via Hootsuite
Fabbri: And specific markers assoc'd with each. His work started with EVs and miRNAs, released by NSCLC cell lines #NGDx17
2:06pm August 18th 2017 via Hootsuite
Fabbri: 3 types - exosomes, microvesicles, apoptotic bodies: 40-120nm, 50-1000nm, 500-2000nm in size #NGDx17
2:05pm August 18th 2017 via Hootsuite
Fabbri: Long list of historical naming of EVs: Ectosomes Microparticles Prostatosome Cardiosomes Vexosomes Texosomes Oncosomes #NGDx17
2:04pm August 18th 2017 via Hootsuite
Muller Fabbri (Univ Southern CA) Exosomal microRNAs regulate the biology of the tumor microenvironment #NGDx17
2:03pm August 18th 2017 via Hootsuite
Rosenbaum: Shows chart cp FFPE FISH, IHC, NGS: TAT is days, hours to days, and weeks. Pluses and minuses covered #NGDx17
12:22pm August 18th 2017 via Hootsuite
Rosenbaum: And shows significant survival differences. 3 cases w/inter-assay discordance and/or complex rearr's #NGDx17
12:20pm August 18th 2017 via Hootsuite
Rosenbaum: The issue: do pts respond to Rx. Shows n=20 OS for ALK FISH+, and others w/non-canonical or no evidence of rearr #NGDx17
12:19pm August 18th 2017 via Hootsuite
Rosenbaum: 2/4 novel: "Non-productive rearrs": ALK is inverted. #NGDx17
12:14pm August 18th 2017 via Hootsuite
Rosenbaum: 21/33 had EML4/ALK, 64% (similar to 60% radiographic response rate). 1 case of KIF5B/ALK, 1 of PRKAR1A/ALK, 4 novel #NGDx17
12:12pm August 18th 2017 via Hootsuite
Rosenbaum: Shows split reads and unmatched pairs in IGV, and EML4 rearr. WashU and Univ WA provided 33 NSCLC as FISH+ also NGS #NGDx17
12:11pm August 18th 2017 via Hootsuite
Rosenbaum: Use Paired-Ends, able to look for mis-matched pair. Illustrates unmapped cognate pairs, where split reads occur #NGDx17
12:10pm August 18th 2017 via Hootsuite
Rosenbaum: Shows an IGV plot, needed entire coding region (including introns) to know where rearr took place #NGDx17
12:09pm August 18th 2017 via Hootsuite
Rosenbaum: Why so low? FISH you know ALK is broken, not whether there will be response to Rx #NGDx17
12:08pm August 18th 2017 via Hootsuite
Rosenbaum: A first CDx - in 2011, w/Xalcori. Soon joined in '15 with IHC. Only 60% radiographic objective response rate #NGDx17
Rosenbaurm: Std tech was break-apart FISH to see whether ALK is broken, agnostic regarding translocation partner #NGDx17
12:07pm August 18th 2017 via Hootsuite
Rosenbaurm: ALK is consistent, not a lot of variability. In EML4 - dimerization domain always there but heterogeneous #NGDx17
12:06pm August 18th 2017 via Hootsuite
Rosenbaurm: ALK-EML4 translocation shown. ALK normally in neuroendocrine cells in development. In lung - constitutively dimerized #NGDx17
Jason Rosenbaum (U Penn) NGS reveals genomic heterogeneity of ALK fusion breakpoints in NSCLC #NGDx17
12:04pm August 18th 2017 via Hootsuite
Q: Done 'omics on the captured EVs? Hu: Yes, but here only using exosomes for the readout #NGDx17
11:59am August 18th 2017 via Hootsuite
Hu: Working on taking it from a microscope (fluorimetry) to a cellphone (!!) #NGDx17
11:55am August 18th 2017 via Hootsuite
Hu: PNAS manuscript (in press) for TB diagnosis as a detection platform. Shows data from that paper, showing HIV+TB+ v normal #NGDx17
11:54am August 18th 2017 via Hootsuite
Hu: This work published this year in Nature Biomed Eng https://t.co/GYuZZOy9o7 #NGDx17
11:52am August 18th 2017 via Hootsuite
Hu: NCI's EDRN is now sending samples for additional validation of their approach #NGDx17
11:49am August 18th 2017 via Hootsuite
Hu: Showed CA19-9 ELISA data for PancCa and their EV detection paltform. AUC curves look very favorable. 91%/85% sens/spec #NGDx17
Hu: nPES cost /1000wells is ~$1200 cp to ~$1650 for ELISA. 0.2 ng/uL cp to 30-77 ng/uL. 4-5 logs cp to 2 logs dyn range #NGDx17
11:43am August 18th 2017 via Hootsuite
Hu: Shows 1000-fold sensitivity compared to ELISA. Sample vol is also 1/100th (1uL input). At higher vol nPES signal too high #NGDx17
11:42am August 18th 2017 via Hootsuite
Hu: Glass slide coated w/anti-CD81 ab, EV-capture, detected by AuS-anti-CD63 and AuR-anti-CD9. Two different particles #NGDx17
11:39am August 18th 2017 via Hootsuite
Hu: Other methods w/polymers, antibody mag beads, ELISAs. Problem is unable to directly detect tumor EVs. Sample excludes mouse #NGDx17
11:37am August 18th 2017 via Hootsuite
Hu: Shows great video of exosome release from cells into the blood. Exosomes still depend on size-exclusion by ultracentrifugation #NGDx17
11:36am August 18th 2017 via Hootsuite
Tony Hu (Arizona State Univ) Nanoplasmonic quantification of tumor-derived extracellular vesicles in plasma microsamples #NGDx17
11:34am August 18th 2017 via Hootsuite
Q: Looking at cell-free? Murphy: Yes #NGDx17
11:33am August 18th 2017 via Hootsuite
Q: Can this be applied to RNA? Murphy: Hard to do along a few dimensions #NGDx17
Q: Easy to implement? Murphy: There are concerns by others for WGA, but have shown data is consistent #NGDx17
11:31am August 18th 2017 via Hootsuite
Q: Picking up rearr - how prevalent in the core? Murphy: Showing less conservative filtering. More noise - but low amt of sample #NGDx17
11:28am August 18th 2017 via Hootsuite
Murphy: Not only FNAs but also other cases where small samples are impt - bile brushes etc #NGDx17
11:26am August 18th 2017 via Hootsuite
Murphy: Touch Prep already in the clinic. (FYI here's a '12 ref that describes method w/MatePair NGS https://t.co/AHciyh4FyV ) #NGDx17
11:23am August 18th 2017 via Hootsuite
