Wed Poster #5 Dr. Timothy Wai Ho Shuen 孫傳豪
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NPC stage IVb patients → 抽300-400 ml blood → 一部分加B95-8 養成LCL → 養成的LCL與病人自己PBL aliquot co-culture → mapping 出effective CTL → expand → 打回去病人身上 (response rate還蠻不錯的! 整個時程約1-2個月)
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Wed Poster #9
University of Malaya
Velapasamy, Sharmila … LF Yap
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SB-431542 10 uM, a TGFBRI inhibitor. Adding of this inhibitor in NP550 or NP361 infected Akata-GFP EBV, maintain cells with higher proliferative potential!
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Wed Poster #11
Whitehurst, Christopher B
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BPLF1 DUB in Tegument → PCNA → interferes with Pol eta → impaired in DNA repair
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Hong Zheng (The University of Hong Kong, Hong Kong SAR China)
“Identification of Genetic Susceptibility Genes in Nasopharyngeal Carcinoma by Next-Generation Sequencing”
- 67 FH (family history mean age 40), 39 EAO (early-age onset mean age 17), 59 sporadic NPC (mean age 55), 895 controls
- Analysis pipeline (KEGG Seq and ANNOVAR)
- Only 19 genes were overlapped between FH and EAO group
- In the EAO group highly mutated genes (n= 157) are distributed in the following pathway: ECM, ABC, Ligand-receptor, proteoglycans, DNA replication (eg. COL17A1, MST1R, PTPRG, ITAG9)
- Single variant association test (MST1R) Dai et al PNAS 2016 (Dai et al., Proc Natl Acad Sci U S A, 2016)
From Ming-Han
- Phd Candidate
- Compare three groups:
- Family NPC (>= 2 generations have NPC cancers) Ave yr: 40 yrs.
- Sporadic NPC (random) Ave yr: 55 yrs
- Early-onset NPC (around 20 yr?)
- Compare the genomic sequencing.
- Highly mutated ones: ERCC2, FaNCA, FANCI, POLE, LIG33): all involved in DNA repair.
- HIGHLY OVERLAY GENE WITH MUTATION: ITGA9
- BY RARE VARIANCE? RASSF1, TLR9, ATXN7, MST1R (Dai et al., Proc Natl Acad Sci U S A, 2016)
- MSTR1 damage can cause tissue-specific macrophage mobility impair.
Question: If MST1R mutated: whether they have also problem with Cilia symptoms?
Question: Whether MST1R mutation cause microbe flora changes?
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Honglin Chen (University of Hong Kong, Hong Kong SAR China)
“EBV BART miRNA and Serological Biomarkers for NPC”
- EBV BART Ist paper by Griffn BE EMBO journal
- 2004 Science 304, p734
- 40 mature miRNA
- Extracellular miR BARTs in NPC cells extracellular BART 3, 7, 13 JV 2014 plasma is better than serum but only miBART7 and 13 associated with NPC (not BART3)
- Patient with metastatic NPC have high-level of BART7
- Higher BART 7 > 5000 can distinguish outcomes
From Ming-Han
- Current biomarker of NPC: EBER, BARTmiRNA, EBVab, plasmid EBV DNA level.
- EBV miRNAs and EBV promoters can be regulated?
- @CP/LP: by EBNA2; LCL/PTLD
- @QP of EBNA1 by STAT3/NFKB
- @p1 p2 of BARTs by CEBP/NFKB
- Method: extracellular BART miRNAS (only some BART miRNAs can be highly detective)
- BART7 and 13: highly in NPC
- Plasma qPCR is more sensitivity to Serum qPCR; for miRNA.
- EBVDNA or EBV-mirBART7 which is better to predict? BART7 is better.
- Further: whether can apply serological BART-7 miRNA as an early predictive thing to guess NPC incidence? need long term research.
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Brigette Ma (Chinese University of Hong Kong, Hong Kong SAR China)
“Novel Targets for NPC Treatment”
- 與KW Lo, Broad Inst, UCSF, Pittsburgh U, Soul University 都有合作
- Ref: CCR 22 1865,2016
- Ref: Bruce JCO Review EBV infection
- Potential NOTCH1
- PDR001 NORVARTIS
From Ming-Han
- To study the effects of chemotherapy after tumor recurrence.
- Select targets->exome sequence
- NPC: few copy number change;
- NPC: PD1 and PDL1 level (Hegde Clin Cancer research 22(8) 1865-74 2016 AACR) discuss microenvironment.
- PDL1 is up regulated in EBV+NPC (>80%).
- EBV infection elevate PDL1 in vitro; LMP1 activate PDL1.
Three drugs to test EBV:
- Pembrolizumab (phase I): specific testing for PDL1 positive tumors
- Nivolumab (phase II); this ab not cause ADCC
- PDR001 (Phase III)
Results:
- Pembrolizumab: all PDL1+ positive solid tumor; 37% not keratinized; 22% Keratining NPC
- in 67% tumor became smaller; still testing.
- Nivolumab: test only in 2 cases: tumor disappear.
Question: how to check “recurrence” after primary tumours?
1. Endoscopy; 2. MRI, 3: blood EBV DNA level But in recurrence: 60% can detect high EBV DNA whereas 40% can’t. So local SWAP might be better.
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Wei Dai (The University of Hong Kong, Hong Kong SAR China) “Methylation Biomarkers in NPC”
- Aberrant methylation markers in NPC
- 450 K illumination hardshi (Chin Clin Oncol. 2016 Apr (Dai et al., Chin Clin Oncol, 2016)
- MS-HRM Int J Cancer 2014, Yang et al, a qualitative assays, needs to use positive purpose for quantification
- Illumina make this assumption when designing their array probes, ie that all CpGs in the 50bp probe sequence are co-methylated. (Eckhardt et al., Nat Genet, 2006)
- Regional analysis showed that 6p21.3 is more frequently hypermethylated.
- HLA- L TRIM31 IER3 FLIT
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提前返台、未聽到下面六個talk
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