GRC NPC - Liu, Fei-Fei

Fei-Fei Liu (Princess Margaret Hospital, Canada)
"Prognostic Significance of miRNA Signatures for Detection of Metastatic NPC"

• metastatic NPC, metastamirs   let-7  miR9
• Nanostring 654 miRNA + 34 EBV mi RNA +   mi RNA from other viruses on 124 patients
• Bruce Oncotarget , 2015 miRNAS 154 + miRNA 449 - MENA 140 - MIRNA 34c (Bruce et al., Oncotarget, 2015)
• N stage coefficient 0.3 p - value very significant
• Adding LN status to miRNA signature
• However, no miRNA signatures overlaps with those in Liu et al (Liu et al., Lancet Oncol, 2012 馬駿group)  
• -----------以下未發表
• Cell line data NP69 NP460 C666-1     miR-499  pops out
• KO of more 499  73 downregulated ones top 1 is TGFBI
• CO-IP OF ITGB3 and TGFBI (also expressed into media)
• miRNA in TME!!
• Also exsomal miRNA in metastatic niche
• CD9, FLOT1

From Ming-Han

• @Some miRNA levels highly associated to tumorigenesis (white et al, Nature review clinical oncology 8:75 2014)
• @FFPE->microdissection-> RNA kit-> sequence.
• @654 hmiRNA; 34EBV miRNAs had been detect
• @normal NPE cell as control.
• @use combined calculation to calculate:
• miR154*0.147+mir449b*0.28-mir34C*0.311-miR140*0.653 (if value is high: high risk of relapse!!)
• (Bruce et al: oncotarget 6: 4537 2015yr).
• Especially mir449b and miR34C highly expressed in EBV+ NPC cell line.
• @Mechanisms: KD of miR34C or mir449b can make C666 sensitive to Cisplatin. (C666 doesn't affair Cisplatin!)
• What's the target?? TGFBI
• 
  
• Tumor repression
• Low TFGBI consistent to promoter methylation
• TGFBI KO mice: no tumor.
• tf TGFBI into C666: become sensitive to cisplatin.
• KD TGFBI into NP69: resistant to cisplatin.
• Use 293 IP-> flag TGFBI-> pull down ITGB3.
• TGFBI is secreting protein.
• Model: TGFBI bind to ITGB3-> Block PTEN
• TGFB-> induce PI3K---> PI3Kp-> resistant to cisplatin

	C666	NP460
pAKTser473	+++++	-
TGFBI	-	++++

They found exosomes have huge amount of miRNAs.

	Exosome	Supernatant	cell
CD9	+++++	-	+	exosome
FLOT1	+++	+	+++
GRP94	-	-	++++	ER marker

GRC NPC - Lu, Xin

Xin Lu (Ludwig Institute for Cancer Research, United Kingdom) 
"p53, a Key Regulator of Genomic Stability in Cancer"

• Discovery of p53: 1979 about the same time “tumor antigen” by Lloyd and Old, PNAS.
• Binding partner of large T antigen of SV40 (A Larid and David Lane)
• p53 mutation in 30–40% BL, why only 9 % in NPC 
• A review paper in 2008 (Murray-Zmijewski et al., Nat Rev Mol Cell Biol, 2008)
• P53: a guardian of cellular plasticity (ability to change for one state to another)
• KLF4/SOX2/OCT4/MYC → iPS. In this setting, get rid of p53 (or p16) enhances iPS.
• Over 80% melanoma cell harbor structurally wild type but functionally defective p53, why?
• Synthetic suppression (B-RAF 50%, p53 <20 150="" been="" cellular="" have="" identified="" interact="" li="" over="" p53="" protein="" to="" with="">
• ASPP (ankyrin-repeat, (Zta also has this motif?), SH3-domain)
• ASPP1, ASPP2, iASPP
• ASPP1 and 2 (陰, which activate p53/p63/p73)
• iASPP (陽, which inactivate p53/p63/p73)
• JNJ-7706621 CCNB/CDK1 inhibitor can be used as an iASPP inhibitor since iASPP inactivates p53 via phosphrylating CCNB1/CDK1. (+Nutlin to suppress MDM2)
• RaDAR (RanGDP/Ankyrin repeat binding) code (Lu et al., Cell, 2014)
• Hyrdophobic 13th residue (Notch, Ankyrin 1, 2, NF-KB etc)
• Altering RaDAR code can change cellular location of ARPs.
• CDKN2A (p16) M53I & R87P both are 13th residue of ankyrin repeats
• ARPs are enriched in the nucleus and many RaDAR code containing ARPs are regulators of NFKB & p53
• Many cytoplasmic-nuclear shuttling proteins cannot bind DNA but are able to influence transcript (MRTF → binds actin in the cytoplasm, b-catenin, ASPP, YAP etc) (Lu et al., Nat Rev Mol Cell Biol, 2016)
• 好像聽到她提到 Zta 有ankyrin motif, CYLD/BCL3/NFKB blablabla

------------------------------------------------------------------------
From Ming-Han

• P53 problem in 70% of BL; most of NPC cell line but only 9% of the PRIMARY NPC TUMOR. It seems p53 functions totally different in different cell line.
• ie: P53+53bp1: DNA repair
•     P53+53BP2; p53+BCLXL, P53+ASSP+DNA…. many different functions.
• @By ips (KLH4, Sox2, myc, Oct4); we found P53 or p16 can block the differentiation of ups cells.
• @RaDarCode (interestingly the protein that regulate p53 are more often by using this way than NLS)
• Why some proteins has no NLS but can anyway move to the nucleus?
• -example: RanGDP/Ankynin repeats binding code.
• NLS binding to importin-> RanGTP to GDP-> bring NLSprotein to nucleus  -> NES code move outside.
• Example: EBV CYLD: (CYLD+BCL3) to nucleus that can elevate p53 level But if CYLD mutant then can't move to nucleus; even if p53 is intact but similar to p53 mutation.
• 聽到有點恍神這個

GRC NPC - Futreal, Andrew

Andrew Futreal (University of Texas MD Anderson Cancer Center, USA) 
"Cancer Genomics and Evolution"

• tumors heterogeneous from one patient to another
• intratumor heterogeneity—a state where subclonal subpopulations within the same tumor accumulate different kinds of mutations over time (65% heterogeneity in RCC)
• 1 mutation/wk, 40 mutations / year
• APOLLO platform  https://goo.gl/uRmjHX
• Moon shot platform
• 40% subclonal mutation vs 17% no subclonal mutation
• Immune signature mapping (n=54) → anti-CTLA4 --responder (n=8)  and progressor (all sent to PCR-seq check for clonality), for progressors → anti-PD1 blockade → responder (n=17) progressor (n=29)
• TCR beta chain-seq for neoantigen
• Only individual biomarkers are predictive
• Mutation load and neoantigen and common drivers: gene mutations do not predict response to immune checkpoint blockade, but TCR clonality is seen in responders to anti-PD1
• Genome-wide copy loss correlates with responder (KEGG/immune response pathway loss) 這個結論與 Science 2015 這一篇一樣  (LA Garraway group (Van Allen et al., Science, 2015)
• Subclonal evolution under immune pressure (CLL & transplant), multiple rounds of chemotherapy driver genes
• Driver genes : ERG2 appears at later time / p53 also emerges after many years
• Clone T cells → do single cell seq → any special T cells responsible for eliminate some portions of tumor cells

----------------------------------------------------------------

From Ming-Han

Goal: Germline genomic vs extrinsic factors (microbe, chemical, environment) vs tumor heterogeneity

General: they separate cancer patients with many groups; whether they are response to anti-CTLA4 or anti-PDL1

@melanoma:

Before treatment (biopsy)-> treat with CTLA4 -> replies (biopsy) -> antiPDL1 -> relapse (biopsy) ---> sequence tumor genomic and blood components

Conclusion:

• Patients response to PDL1: high CD8+T cells, tumor express PDL1 at high level.
• If patients' clonality of T cells is higher: response to PD1 better.
• If genomic copy number tends to "loss": both CTLA4 and PDL1 work well. If genomic tends to "gain" copy: no response. 
• Loss of copy number in cancer genome tends to have the reduced immune response.

@CLL treatment: transfusion allogenic donor's T cells? (FCR treatment, DLI? WES windows?)

-allosct? DLI?

@TRA framework: the Apollo TRA team:

Try to combine the clinical and genomic and whatever together for the more specific treatment in the future.

GRC NPC - Hildesheim, Allan

Allan Hildesheim (National Cancer Institute, NIH, USA) 
"Use of Viral and Genetic Markers for Risk Stratification for Development of Screening Programs for the Early Detection of NPC"

1. 1987 Use of viral and genetic markers for NPC risk stratification.
2. 16% cancers are caused by infectious agents (Lancet Oncol 2012, de Martel)
3. EBV vaccination: EBV gp350 (Coghill et al., Clin Cancer Res, 2016 High Levels of Antibody that Neutralize B-cell Infection of Epstein-Barr Virus and that Bind EBV gp350 Are Associated with a Lower Risk of Nasopharyngeal Carcinoma)
4. Screening for NPC: (Chien et al., N Engl J Med, 2001 Serologic markers of Epstein-Barr virus infection and nasopharyngeal carcinoma in Taiwanese men)
5. Individuals positive for anti-VCA IgA or anti-EBV DNase antibodies have a much higher risk for NPC (Yu et al., Clin Cancer Res, 2011 Prognostic utility of anti-EBV antibody testing for defining NPC risk among individuals from high-risk NPC families.)
6. For those unaffected families (members from NPC multiplex families) anti-EBV IgA-VCA and IgA-EBNA1 are the best (Hildesheim, Am J Epidemiol, 2013 Invited commentary: Epstein-Barr virus-based screening for the early detection of nasopharyngeal carcinoma: a new frontier)
7. Protein array (EBV1 chip Muta, B95-8, Akata strains, Middledorf), Cohort design: NPC array project strategy. Screen for promising candidate markers using case-control design → evaluate top hits in population-based screening
8. Special notes for case-control design: estimate sensitivity and specificity, but not positivity and negativity
9. LF2 (IgG), BGLF2(IgG), Rta(IgG), BMRF1-EAD(IgA), BXLF1-TK(IgA) | two or three of them achieve highest SE and SP
10. EBV DNA viral load in plasma (insensitive for early stage NPC)
11. EBV DNA in nasopharynx swab (high specificity and sensitivity, combined with miRNA and DNA variants)
12. Host genetic risk factors: only ~7–9 % NPC is familial, which has 5-10 fold increased risk
13. Also comments on EBV lytic cycle replication in differentiated

有人踢館: 一方面anti-VCA是NPC高危險群，一方面說病人體內有anti-VCA似可neuturalize病毒、降低罹患NPC風險 這...    Allan: OOXXOOXXOOXX

From Ming-Han

• Martel; lacent oncol 2012: each pathogen and cancer: good reference!!
• EBV Vaccine (gp350 vaccine) against NPC?
• Yes this antibody can block clinical diseases of IM but not infection?
• Vaccine and childhood?
• Some data said might be work for treatment of NPC?
• The facts:
• People with NPC have higher level ab against VCA and DNase; and vice versa.
• People with NPC with much lower ab against gp350 "at the time they have NPC"; and without NPC people with high level ab against gp350. (level of anti-gp350 study not like VCA and DNase have long-term predictable results).
• If people/patient have high level anti-VCA anti DNase ab; will also have high level anti-EBNA1 abs. (Yu, Taiwan group).
• @EBV protein microarray (sensitivity; specificity problem…? It seems he has a special but correct way to determine that).
• -Use patient's serum to the microarray that had been coated with different EBV proteins to detect the antibody level.

Results:
High level of IgA against EBV-> associated to NPC
High level of IgG against EBV-> associated to lymphoma.

Top markers of antibodies in NPC high-risk or NPC patients: (all IgA)
LF2,
BGLF2,
BRLF1
BMRF1
BXLF1 (TK).

Now applying this array to BL, NKT, EBVaGC…etc.

In Aug EBV Meeting Session 10: Nasopharyngeal carcinoma and other epithelial cell tumors
Whole Exome Sequencing of NPC Multiplex Families Identifies Variants potentially Involved in EBV Control
Allan Hildesheim, National Cancer Institute, Rockville, USA

GRC NPC - zur Hausen

Harald zur Hausen (German Cancer Research Center, Germany) 
"Discovery and Early Studies of EBV in Burkitt's Lymphoma and NPC"

1. EBV provides a step in the malignization of pre-malignant NPC lesion (methylation of p16)
2. Endemic multiple sclerosis
3. TGFb is an inducing agent for EBV lytic replication
4. Vit D deficiency -> TGFb increase -> EBV reactivation
5. EBV enhances TT virus replication
6. In dually infected BL or LCL cells, EBV and BMV  bovine milk factor  --> low sun exposure/Vit D deficiency --> TGFb increases  -->  EBV reactivation --> inflammation → tissue destruction --> multiple sclerosis

From Ming-Han

• In Henle's lab before and identify EBV is specific to IM and BL (JV 1967; 1: 1174-85) and Identify abnormal ch 12. Whether EBV cause chromosome instability?
• Prove EBV associated to BL and NPC (ISH)
• NPC: epidemiological factors of NPC?
• p16 inactivation (Tsang et al) and Cyclin D1 activation (Tsang et al, PNAS 2012).
• Hypothesis: whether EBV cause NPC for the prp-malignant NP cells???
• BL: cMyc translocation is important (RAG1/2; NEHJ)
• Current research: Streker and de villiers: TT-like particles (23: 11-2006)
• Whether EBV stimulate TT virus replication? For example: CMV, Herpesvirus, adenovirus infected cells can cause lytic replication in the non-permissing cells. 
• 概念：人類的病毒在人類不會lytic但是人類病毒在動物細胞可以。反之亦然。是否動物的病毒感染人類造成chronic infection而導致MS?
• ＠發現：HSV infected HL secrete small viral particles? (Lacent 2001, 257: 381-384).
• @May animal viruses DO NOT replicate in Human but do lytic cycle in animals can cause human diseases? On the other hand, is that possible that human virus cause tumor in animals?

Model: He used milk cow viruses (episomal type; DNA virus) to test his hypothesis

• These viruses can infect human cells (RNA, protein, replication).
• Correlation: children drink milk is associating to the deficiency of VitD later, Reactivation of latent HSV infection (EBV, HHV6, VZV also), and also the high MS factor. On the other hand, if children drink mother milk>6 month and live in tropical regions may have fish factor. Importantly, the reduced of VitD is associating to the elevated MS factor.
• Why VitD and MS?
• elevated VitD3 receptor is associating to lower TGFB secretion
• TGFB elevate EBV lytic cycle.
• Whether low vitD-> big TGFB-> high EBV activation?

Result:

• EBV infection can elevate cellular small DNA virus activation!! whether these small viral particle causes chronic inflammation?
• Model: many cells infected by milk virus and many cell infected by EBV: few cells with both. these cells stimulate viral reactivation.

Q: what EBV protein cause these milk viruses from cows super replication? UNKNOWN!!!

Q: Whether these small viruses alter human immune responses? UNKNOWN and ongoing.

Q: by Rickonson: connection between infection and cancer?

A: HPV and smoker and lung cancer: actually people found 20-50% lung cancer actually not smoker.

A: Vaccine against virus: like VSV and rebulla and HPV: nearly 100% protective.

Q: EBV vaccine and NPC?

A: problem: since EBV mostly do replication in oral epithelial cells, that means the vaccine need to produce high level of AB in Saliva...

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

---------------------------------------------------------------------------------------------------
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?

---------------------------------------------------------------------------------------------------

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.

---------------------------------------------------------------------------------------------------

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.


---------------------------------------------------------------------------------------------------

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

-----------------------------------------------------------------------------------------

提前返台、未聽到下面六個talk William Wei (Hong Kong Sanatorium & Hospital, Hong Kong SAR China) "Challenges for Surgical Management of Recurrent NPC" Raymond Ng (University of Toronto, Canada) "Detection and Screening for NPC with Trans-Oral Brushing and Determination of EBV DNA" Troy Messick (The Wistar Institute, USA) "Development of Small Molecule Inhibitors of EBNA1 for the Treatment of Nasopharyngeal Carcinoma" (Tuesday Poster # 18) 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) Alan Rickinson (University of Birmingham, United Kingdom) "Future Focus for Basic NPC and EBV Studies" Quynh Le (Stanford University, USA) "Future Personalised Clinical Care for NPC Patients"

LabLog-SFL

LogID	Title	Initial	Date
AF001	Codebook for GA341 (= YJC AE538 = YMU RNA-seq on OKB2/S1F/THP1)	SFL	10/21/15
AF002	Experimental sheme for AE592 (YMU RNA-seq GA416 and GA417)	SFL	10/23/15
AF003	Codebook for GA417	SFL	11/3/15
AF004	Codebook for GA416	SFL	11/4/15
AF005	Codebook for Po-Ting	SFL	11/5/15
AF006	Codebook for tidy 40T/N raw data (2015_1110_11SVA_40TN_raw = 40TNRaw)	SFL	11/10/15
AF007		SFL

The history of primary infection of EBV in keratinocytes

2006/10

Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase (the link to NCBI)

2008/10/10

根據這一篇, 那送EBV進入NP460h-hTERT不就等同於把EBV關禁閉? 另外Dr.George Miller有篇在J.Virol.Methods(2006)的文章,看起來像是一位MD/PhD的學生做的。他以兩位IM病人血清(富含各種anti-EBV抗體)去分離經NaB處理過的P3HR1(HH514)細胞。分什麼呢?分那些在走lytic cycle和不被NaB活化的HH514。分下來後的細胞再送回去petri-dish養。結果發現走lytic cycle的細胞無一存活、而沒有induce的細胞可以再被養回來,而且induction rate隨著時間增加而增加。很有意思的一篇文章。George大學是學歷史的,非常會寫文章,邏輯性很強而且要言不贅,讀他的paper總覺得能做science真好。

LabLog-柏廷篇

LogID	Title	Initial	Date
AE801	Compare Serum folate concn in OPMD patient and summary MAF in SNPs of folate-mediated one carbon metabolism	PTL	2015/11/9
AE802	Calculate and compare the MAF of rs1801133 and rs1801131 from sample	PTL	2015/11/13
AE803	Calculate and compare the MAF of rs2274976, rs1805087, rs1801394 and rs1979277 from sample	PTL	2015/11/17
AE804		PTL
AE805		PTL

#1由 poting 在 三, 11/11/2015 - 09:14 發表。

修改完畢

老師 我已經修改完畢了

#2由 poting 在 一, 11/09/2015 - 12:06 發表。

AE801 result

•FTEST=0.039 < 0.05      Variance between control and OPMD

•P=0.067 > 0.05               No significant difference  

IRB 問與答 2014年題庫

IRB 問與答 2014年題庫 由 sufang 在 二, 06/09/2015 - 09:09 發表  Oral Cancer   IRB   Oral Cancer

Su-Fang Lin <sflin1@gmail.com> Jun 5 Reply to 張書銘, 陳雅雯, 江士昇, 夏興國 
Dear All,

我PP計畫的IRB審查回來了, 兩個reviewer都有一點問題. 總評皆為「修正後推薦」。想請問大家先前有沒有碰到類似的問題, 其正解為何? 先謝謝大家的幫忙!  之後如果大家不介意的話, 我們是不是把各自的問題集合在一起、弄成一本題庫? 具IRB同仁說 送出去的審委不一樣、同樣的申請件, 碰到的問題都不一樣。  Thanks again!  Su-Fang (ext 35107)   (餘刪, 見下6/8回覆)

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Ya-Wen Chen Jun 5 Reply to me, 張書銘, 江士昇, 夏興國 

以下是我遇到的問題及回答, 素芳的問題與我的問題有相似, 重點是(簡易審查核對表)提及使用合法生物資料庫..
簡易審查核對表我更改成接續前階段研究之後續資料分析(湘如建議).
 

EBV and NGS

由 sufang 在 四, 06/04/2015 - 13:38 發表  Pre-published   EVKV   NGS

3552_2012_12_Whole genome sequencing of the Akata and Mutu Epstein-Barr virus (EBV) strains.pdf

3577_2011_11_Direct sequencing and characterization of a clinical isolate of Epstein-Barr virus from nasopharyngeal carcinoma tissue by using next-generation sequencing technology

3964_2014_02_Integrated mRNA and microRNA transcriptome sequencing characterizes sequence variants and mRNA–microRNA regulatory network in nasopharyngeal carcinoma model systems

2015/05 Methylation Marker Paper from JAMA Oncology

Correlation of Smoking-Associated DNA Methylation Changes in Buccal Cells With DNA Methylation Changes in Epithelial Cancer JAMA Oncol. Published online May 14, 2015. doi:10.1001/jamaoncol.2015.1053

Andrew E. Teschendorff, PhD^1,2; Zhen Yang, PhD²; Andrew Wong, PhD^3; Christodoulos P. Pipinikas, PhD⁴; Yinming Jiao, MSc²; Allison Jones, BSc⁵; Shahzia Anjum, PhD⁵; Rebecca Hardy, PhD³; Helga B. Salvesen, MD⁶; Christina Thirlwell, PhD⁴; Samuel M. Janes, PhD⁷; Diana Kuh, PhD³; Martin Widschwendter, MD⁵

---

At a Glance

¶ The purpose of the research was to assess the suitability of buccal cells as an epithelial source of tissue to examine the effects of smoking on the epigenome, and to test whether these effects are also seen in smoke-related epithelial cancers.

¶ Smoking is associated with widespread changes in the DNA methylation landscape of buccal cells.

¶ Some smoking-associated DNA methylation changes are common to buccal and blood tissue, but buccal cells exhibit significantly more changes than blood cells.

¶ Smoking-associated DNA methylation changes in buccal cells correlate with DNA methylation changes in epithelial cancers and do so most strongly in smoke-related epithelial cancer.