GRC NPC – Unclassified


Wed Poster #5 Dr. Timothy Wai Ho Shuen 孫傳豪
Singapore TESSA therapeutics (http://goo.gl/zdbYpA)

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)
Wed Poster #9
University of Malaya
Velapasamy, Sharmila … LF Yap
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!
Wed Poster #11
Whitehurst, Christopher B
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”

  1. 67 FH (family history mean age 40), 39 EAO (early-age onset mean age 17), 59 sporadic NPC (mean age 55), 895 controls
  2. Analysis pipeline (KEGG Seq and ANNOVAR)
  3. Only 19 genes were overlapped between FH and EAO group
  4. 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)
  5. Single variant association test (MST1R) Dai et al PNAS 2016 (Dai et al., Proc Natl Acad Sci U S A, 2016)
From Ming-Han
  1. Phd Candidate
  2. Compare three groups:
  3. Family NPC (>= 2 generations have NPC cancers) Ave yr: 40 yrs.
  4. Sporadic NPC (random) Ave yr: 55 yrs
  5. Early-onset NPC (around 20 yr?)
  6. Compare the genomic sequencing.
  7. Highly mutated ones: ERCC2, FaNCA, FANCI, POLE, LIG33): all involved in DNA repair.
  8. HIGHLY OVERLAY GENE WITH MUTATION: ITGA9
  9. BY RARE VARIANCE?   RASSF1, TLR9, ATXN7, MST1R (Dai et al., Proc Natl Acad Sci U S A, 2016)
  10. 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”
  1. EBV BART  Ist paper by Griffn BE EMBO journal 
  2. 2004 Science 304, p734
  3. 40 mature miRNA 
  4. 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)
  5. Patient with metastatic NPC have high-level of BART7
  6. 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”
  1. 與KW Lo, Broad Inst, UCSF, Pittsburgh U, Soul University 都有合作
  2. Ref: CCR 22 1865,2016
  3. Ref: Bruce  JCO Review EBV infection 
  4. Potential NOTCH1
  5. 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
  1. William Wei (Hong Kong Sanatorium & Hospital, Hong Kong SAR China) “Challenges for Surgical Management of Recurrent NPC”
  2. Raymond Ng (University of Toronto, Canada) “Detection and Screening for NPC with Trans-Oral Brushing and Determination of EBV DNA”
  3. Troy Messick (The Wistar Institute, USA) “Development of Small Molecule Inhibitors of EBNA1 for the Treatment of Nasopharyngeal Carcinoma” (Tuesday Poster # 18)
  4. Mhairi Morris (Faculty of Health and Life Sciences, De Montfort University, United Kingdom) “EBV-Encoded LMP1 Induces a Myofibroblast-Like Phenotype in Epithelial Cells via Epithelial-to-Mesenchymal Transition” (Monday Poster # 10, 二個小女生一人講一半)
  5. Alan Rickinson (University of Birmingham, United Kingdom) “Future Focus for Basic NPC and EBV Studies”
  6. Quynh Le (Stanford University, USA) “Future Personalised Clinical Care for NPC Patients”

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