缺口計畫相關資訊

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由 sufang 在 六, 07/05/2014 – 17:12 發表 Pre-published Arecoline COE (Cancer of Excellence) OPMD Potentially malignant disorder

10/05/2014 (SUN) PK大賽
第二期癌症研究缺口補強計畫評選會議議程
開會時間：103年10月5日（星期日）上午10時
開會地點：本部204會議室
壹、主席致詞

貳、報告



時間 報告事項 報告單位及時間
10:05-10:20 一、科技發展組會議說明  
  二、簡報及委員問與答(報告10分鐘、問與答5分鐘)  
10:20-10:35  (一)三陰性乳癌缺口補強研究計畫: 聚焦生物特性，個人化治療及新治療策略 (1100萬) 國立台灣大學醫學院附設醫院  
10:35-10:50  (二)以基因體學方法找尋台灣早發性乳癌相關基因及生物標記 國家衛生研究院   
10:50-11:05  (三)大腸直腸癌早期篩檢高準確率之生物指標開發 臺北醫學大學   
11:05-11:20  (四)合併使用血清生物標計與糞便潛血反應於大腸直腸癌的篩檢效益(280萬) 國立台灣大學醫學院附設醫院       
11:20-11:35  (五)大腸直腸癌免疫基因體檢測與人源化腫瘤(PDX)動物模式之開發(600萬) 國家衛生研究院        
11:35-11:50  (六)吲哚胺-2,3-雙加氧酶在大腸直腸癌腫瘤進展與臨床預後之分子剖析: 以其為標靶之新穎免疫治療藥物研發 國家衛生研究院
11:50-12:30  中場休息         
12:30-12:45  (七)預防口腔癌前病變患者的復發與惡性轉化 中國醫藥大學附設醫院  
12:45-13:00  (八)發展早期偵測口腔潛在惡性病症之診斷平台以降低惡性轉變率(1100萬) 高雄醫學大學附設中和紀念醫院    
13:00-13:15  (九)針對台灣口腔癌前病變惡性轉化開發快速診斷與有效化學預防之整合研究 國家衛生研究院        
13:15-14:00 三、委員討論  
  四、散會  
 
10/6/2014 (Monday) SFL notes:
According to David and Janelle: 審查委員有劉扶東、周玉山、陳瑞華、梁賡義、劉宗正、陳全木。
 
10/21/2014 (Tuesday) SFL notes: 收到衛福部核可函、審查意見。(共通過六件, 上表中藍字加畫底線者)
Janelle Kuo  2:05 PM (13 hours ago) 09/23/2014  to Dr. 陳立宗, Dr. 劉滄梧, Dr. 劉柯俊, me, Dr. 陳雅雯, Dr. 夏興國, Dr. 李岳倫, Dr. 江士昇, 林佩瑩
Dear all
根據昨天的討論，訂定口腔癌缺口計畫含四個子計畫與一個支援中心 (supporting core)，總計畫名稱與子計畫名稱如下：
總計畫：(Frozen, 因為要發函給其他單位申請IRB，題目不能再變更了)
針對台灣口腔癌前病變惡性轉化開發快速診斷與有效化學預防之整合研究
Rapid diagnosis and effective chemoprevention for malignant transformation of oral potentially malignant disorders in Taiwan
 
子計畫一：
以遺傳與表觀遺傳因子鑑定口腔癌前病變惡性轉化：臨床應用為導向  (取代利基)   
Identification of malignant transformation of oral potentially malignant disorders by (epi)genetic factors: a clinically oriented approach
(取代focus on clinical niche)
PI: 張憶壽研究員 (國家衛生研究院癌症研究所)
 
子計畫二：(中山醫/交大團隊)
發展以血漿微核醣核酸作為口腔癌前病變惡性轉化之快速診斷工具
Development of plasma circulating microRNA as biomarker for quick diagnosis of malignant transformation of oral potentially malignant disorders
PI: 黃建寧院長 (中山醫大附醫 總院長)  Co-PI: 鐘育志院長 (國立交通大學 生物科技學院 生物科技系所 所長)
 
子計畫三：
探討口腔微生物在口腔癌前病變惡性轉化所扮演之角色
Investigating the roles of oral microorganisms for malignant transformation of oral potentially malignant disorders
 
子計畫四：
針對台灣口腔癌前病變惡性轉化建立有效之化學預防策略
Development of effective chemoprevention strategy for malignant transformation of oral potentially malignant disorders in Taiwan
PI: 張俊彥院長 (國立成功大學醫學院) Co-PI: 楊順發主任 (中山醫大附醫 臨床研究中心主任)
 
支援中心
PI: 劉滄梧副所長 (國家衛生研究院癌症研究所)
From MOHW:
(三)    申請方式：
1.    計畫徵求說明書及相關附件請至本部www.mohw.gov.tw網頁「公告訊息」處下載。
2.    申請機構應於計畫申請書截止期限前提出詳細計畫申請書一式八份(其中一份不裝訂)及一份含word格式的計畫申請書電子檔光碟片(信封及光碟正面需註明「衛生福利部第二期癌症研究缺口補強研究計畫申請案」及「申請機構名稱」)，函送衛生福利部科技發展組（11558 台北市南港區忠孝東路6段488號），逾期本部將不受理。
3.    申請計畫書應包括103年及104年的工作內容。
4.    計畫申請書請以掛號、快遞或宅急便等方式寄達、截止時限以郵戳或收執聯為憑；如有以專人送達者，請送本部科技發展組收、其截止時限以本部科技發展組之簽收日期(當日下午5時前)為準。
(四)    審查方式：
1.    由本部依計畫內容遴聘相關專家進行書面及會議審核。
2.    由各審查委員依據各申請機構所提計畫申請書，按本案所列審查項目及配分，評定得分。
評  審  項  目    配分
一、    是否符合徵求重點。10分
二、    過去計畫執行成效    5
三、    計畫可行性(針對其計畫之方法、步驟及人力配置等內容)。30分
四、    計畫之預期效益。    25分
五、    跨中心的研究合作及整合。10分
六、    經費編列合理性。    20分
3.    各計畫申請書經審查委員依評審項目完成評分後，總平均分數達75分（含）以上者為合格；總平均分數未達75分者為不合格。總平均分數最高者為第一優勝序位機構，次低者為第二優勝序位機構，依此類推，實際補助計畫件數視預算而定；惟經評定為不合格者，不得作為補助對象。
09/21/2014 version
總計畫
針對台灣口腔潛在惡性病症(口潛惡症)開發快速診斷與有效化學防護策略之整合研究
Rapid diagnosis and effective chemoprevention of oral potentially malignant disorders (OPMD) in Taiwanese population
 
子計畫ㄧ
遺傳與表觀遺傳因子鑑定口潛惡症高危險群: 以臨床利基為導向
Identification of high-risk OPMD patients by (epi)genetic factors: a clinically oriented approach
 
子計畫二
血漿微核醣核酸作為口潛惡症高危險群快速診斷工具之研究
Investigating the utility of diagnostic plasma microRNAs for high-risk OPMD patients
 
子計畫三
針對口潛惡症病人之復發與惡性轉化開發與臨床接軌之化學防護策略
Chemoprevention of recurrence and malignant transformation in OPMD patients

09/17/2014
附件1、衛生福利部第二期癌症研究缺口補強計畫研究議題  (103.08.05版)
 
議題：口腔癌癌前病變致癌危險因子之鑑定及應用 （包含配合之診斷工具或預防及治療策略）
說明：
口腔癌為少數能早期掌握癌前病變階段之癌症，缺口補強研究計畫應為多中心之大規模整合型研究，應強調病患篩選，檢體收集，檢測方法及資料分析之一致性及資源共享原則，並經由系統化追蹤病患資料，尋找出有具體臨床價值之癌化高危險因子及早期化學預防之分子標靶，建立危險因子評估指標及因應治療方案。從而對屬於罹患口腔癌高風險之國人，有效提高早期診斷率及降低口腔癌發生率。
預期成果：
  1. 找出 2項 有具體臨床應用價值、可預測口腔癌前病變轉化為癌症之癌化高危險因子。此癌化高危險因子，在下一階段計畫中，應可開發出診斷試劑，以配合國民健康署推動之口腔癌篩檢計畫，有效提高早期診斷率。
  2. 找出 2項 可作為口腔癌早期化學預防 (初級預防及 次級預防) 之分子標靶，以進行口腔癌防癌化學藥物之開發，有效降低口腔癌發生率。透過有效提高早期診斷率及有效降低口腔癌發生率，來達成降低國人口腔癌死亡率之目標。
07/05/2014 SFL wrote:
2007年起我們所謂的口腔癌前病變(白斑、紅斑、口腔黏膜下纖維化、扁平苔蘚等等)統一被正名為 oral potentially malignant disorders, 下面列出幾篇近期發表文獻供大家參考:
  1.  Warnakulasuriya S, Johnson NW, van der Waal I (2007) Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 36: 575-580.
  2. van der Waal I (2009) Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. Oral Oncol 45: 317-323.
  3. Amarasinghe HK, Usgodaarachchi US, Johnson NW, Lalloo R, Warnakulasuriya S (2010) Betel-quid chewing with or without tobacco is a major risk factor for oral potentially malignant disorders in Sri Lanka: a case-control study. Oral Oncol 46: 297-301
  4. van der Waal I (2010) Potentially malignant disorders of the oral and oropharyngeal mucosa; present concepts of management. Oral Oncol 46: 423-425.
  5. Syrjanen S, Lodi G, von Bultzingslowen I, Aliko A, Arduino P, et al. (2011) Human papillomaviruses in oral carcinoma and oral potentially malignant disorders: a systematic review. Oral diseases 17 Suppl 1: 58-72.
  6. van der Waal I, Scully C (2011) Oral cancer: comprehending the condition, causes, controversies, control and consequences. 4. Potentially malignant disorders of the oral and oropharyngeal mucosa. Dental update 38: 138-140.
  7. Chang MC, Chen YJ, Chang HH, Chan CP, Yeh CY, et al. (2014) Areca Nut Components Affect COX-2, Cyclin B1/cdc25C and Keratin Expression, PGE2 Production in Keratinocyte Is Related to Reactive Oxygen Species, CYP1A1, Src, EGFR and Ras Signaling. PLoS One 9: e101959. (台大牙醫系研究群組)
  8. Lian Ie, B., Y. T. Tseng, C. C. Su, and K. Y. Tsai. Progression of precancerous lesions to oral cancer: results based on the Taiwan National Health Insurance Database. (2013). Oral Oncol. 49: 427-30. (PubMed Link) (referred by YWC)
 
OPMD (oral potentially malignant disorders):
#高醫陳中和教授、中國醫大葛應親教授均翻譯為 「口腔潛在惡性病症(變)」。
#OPMD在台灣的轉癌率究竟有多高?
#Chemoprevention of oral cancer for OPMD patients 可幫忙節省多少健保費? 有多少經濟效應?
#### referred by Ya-Wen: oral lichen planus 口腔扁平苔蘚
名詞解釋：  是臨床上常會遇到的。病患除了抱怨口腔內有白色網狀病灶外，潰瘍型的扁平苔蘚更因表皮破壞而造成口腔不適、疼痛、容易出血等問題，扁平苔蘚有出現在口腔中、也有出現在皮膚上的病灶，後者通常在一、兩年之間會自行緩解或癒合，然而口腔中的病灶時常會持續較久，甚至終生相隨。
 


至目前為止各家醫院想做的東西 計畫列表：原始excel檔按我下載

#1由 jeffery 在 二, 10/14/2014 – 14:06 發表。

我是Janelle

劉宗正、陳全木．

#2由 sufang 在 四, 10/09/2014 – 16:00 發表。

Genome TV 觀後筆記

FFPE for methylation anslysis : https://www.youtube.com/watch?v=QAW6Tr2kp34&list=PL1ay9ko4A8sk4l9pbggl5A… (Illumina FFPE restoration method)
  • SNP 6.0: 不行
  • mRNA-seq: 大部分okay, 但有些基因與frozen tissue完全相反
  • miRNA: good
  • Mutaion calling: C->T bias
Head and Neck Cancer: TP53-loss of 3p/miR-548K  https://www.youtube.com/watch?v=i1ZQLNd9Jrs&list=PL1ay9ko4A8sk4l9pbggl5A…
#3由 sufang 在 三, 10/01/2014 – 15:29 發表。
09/20/2014 二期COE第三次進度報告 (台大兒醫中心) before 缺口計劃討論
臺北榮民總醫院/楊醫師報告
高壽延
miR-31
C/EBP
EGFR
Keratinocyte immortalization
 
Ku-80
 
Tumor recurrence
mTOR- activation
OSCC CSC OCT4
 
朱本元教授
recurrence/second primary
 
Yang MH. Acetylation of Snail
ARID3B is regulated by let7
 
吳國瑞
Twist BMI1 KLF4
——————————
中國醫大/葛教授報告
成癮
 
缺口計劃
—188個sample precancer lesions 送中研院
—epigenetic regulation of DNMT1…
-Celecoxib 抑制 cell model and
  • 4NQO mouse 不是檳榔癌? (he said that!!!)
—————————————
高醫/報告
—Photodynamics (Metvix)
–DNA repair protein
NF-KB
b-catennin
IL8
—————————————
成大蕭醫師/報告
ALDH1A
ADH1B slow
UADT mucosa
 
國內HPV感染與HNSCC之關聯
hypopharynx maybe is related to HPV infection in Taiwan
pRb/E7
GeneChip
——————————————-
中山醫大黃憲達/報告
metagenomics
metablomics
來源: saliva, blood, plasma,
 
Nessiea and Stropococcis
 
MMP11 (楊順發主任)
miRNA NGS and
miRNA-204 and OSCC CSC SOX4 （余成佳老師)
Profiling Ig diversity
——————————————-
中榮/報告
陳萬宜主任（？）報告十項子計劃的進度．
 
——————————————-
 
檢體部分
 
缺口計劃/劉博士報告
10/4 Review
10/7 公告
 
Blood
Pool 5 persons / sample      
               oral cancer vs precancer vs normal
15 miRNAs markers
 
delvelop GeneChip for diagnosis
 
收血例子 1000-2000例．
  中山、高醫大、交大
 
 
Methylation.
北榮 defines dysplasia
 
miR155
miR10b
miR9-1, 9-3,
#4由 EVKVLIN 在 二, 09/16/2014 – 11:34 發表。
美國的SPORE/HNSCC-他山之石 可以攻錯
美國NCI也有一個類似我們cancer of excellence的program (或許是我們效法他們的 – 嘻)，叫SPORE (specialized programs of research excellence) 網站地址: http://trp.cancer.gov/
這個program是專做translational medicine, 立意有夠感人: 我copy兩段在回應中與大家分享 。
目前有六個機構得到 HNSCC/SPORE, 其中Texas/MD Anderson的研究主題有部份也是針對precancer lesion (有說要收350個檢體, which is “unprecedented opportunity”) 值得我們效法!
 
Head & Neck SPOREs
SPOREs in Head and Neck (H&N) cancer support translational research on cancers of the upper aero-digestive tract and on thyroid cancer. An estimated 53,640 patients will be diagnosed for cancers of the oral cavity, pharynx, or larynx in the year 2013. Another 60,220 patients will be diagnosed with thyroid cancer. The incidence for the first group of cancers is 2 to 3 times higher in men compared to women, whereas thyroid cancer is three times more common in women than in men. By estimates of the American Cancer Society, 11,520 people will die of cancers of the oral cavity, pharynx, or larynx and 1,850 of thyroid cancer in 2013. The first three SPOREs in H&N Cancers were established in 2002 and the current (2013) number of H&N SPOREs is six, including the first Thyroid Cancer SPORE introduced this year.  Head and Neck Cancer SPOREs are co-funded by the National Cancer Institute and the National Institute of Dental and Craniofacial Research.
Johns Hopkins University   (有Immunothearpy, TGF-b, and Dr. 吳子丑)
  • Project 1: Augmentation of immune response to head&neck squamous cell carcinoma via phosphodiesterase type 5 inhibition
  • Project 2: HNSCC from cancer genomics to personalized biomarkers
  • Project 3: Improving epidermal growth factor receptor-targeted therapy of HNSCC by inhibition of TGF-b
  • Project 4: HPV vaccine and correlates of response
  • Project 5: Etiologic heterogeneity in head and neck squamous cell carcinoma
  • Core A: Adminstrative core
  • Core B: Biostatistics and bioinformatics core
  • Core C: Career development core
  • Core D: Development Project core
  • Core E: Tissue core
University of Michigan (有一個chemoprevention project:大豆異黃酮reverse hypermethylation)
  • Project 1: Metronomic Small Molecule Inhibitors of Bcl2 in Head And Neck Cancer Therapy
  • Project 2: Therapeutic Potential and Mechanism of Action of Potent, Small Molecule Inhibitors of the p53-MDM2 Interaction for the treatment of Head and Neck Cancer
  • Project 3: Smoking Abstinence, Molecular Markers and Soy Isoflavone Chemoprevention in Head and Neck Cancer
  • Project 4: Integration of EGFR Inhibitors with Radiochemotherapy
  • Core A: Administration and transliational trials
  • Core B: Biostatistics
  • Core C: Tissue and histopathology
  • Career development program
  • Developmental research program
University of Pittsburg   (Jennifer the woman!)
  • Project 1: Pathway and GWAS SNPs: Role in SCCHN Risk, Outcome and Treatment Response
  • Project 2: Inhibition of the STAT3 Signaling Network
  • Project 3: Cellular Immunity and Immune Escape from EGFR Antibody Therapy
  • Project 4: Therapeutic Mechanisms of Co-Targeting of EGFR and Src Family Kinases
  • Core A: Administrative
  • Core B: Tissue/Histology
  • Core C: Biostatistics/Bioinformatics
University of Texas/MD Anderson  (有high risk screening of oral premalignant lesions, 3p/9p)
  • Project 1: Intrinsic apoptosis phenotype and susceptibility to squamous cell carcinoma of the oral cavity
  • Project 2: Cancer risk assessment in patients with oral premalignant lesions: an integrative approach
  • Project 3: Predictors of resistance to dual VEGFR/EGFR targeted therapy of head and neck cancer
  • Project 4: Targeting EGFR and the IGF axis for therapy of head and neck squamous cell carcinoma
  • Core A: Administrative core
  • Core B: Biostatistics and data management core
  • Core C: Pathology core
  • Developmental research program
  • Career development program
Ohio State University  (first thyroid SPORE)
  • Project 1: Low-penetrance genes in the predisposition to papillary thyroid carcinoma
  • Project 2: Biomarker discovery and personalized intervention of radioiodine induced salivary gland damage in thyroid cancer patients
  • Project 3: Developing combination therapies for medullary thyroid cancer
  • Project 4: Development and validation of novel circulating medullary thyroid cancer markers
  • Core A: Integrated clinicopathology and biorepository core
  • Core B: Biostatistics core
  • Core C: Adminstrative core
  • Developmental research program
  • Career development program

第一期SPORE/HNSCC還有這個學校

Emory Winship Cancer Institute:
  • Project 1: Chemoprevention with green tea polyphenon E (PPE) and EGFR-TKIs in head and neck cancer 
  • Project 2: Targeting death receptor-mediated apoptosis for head and neck cancer
  • Project 3: Developing novel small model of curcumin analog for  head and neck cancer
  • Project 4: Biodegradable nanoparticle formulated taxol for targeted therapy of head and neck cancer
  • Core 1: Adminstrative core
  • Core 2: Specimen resources, proteomics, and bioinformatics Core
  • Core 3: Biostatistics & data management core
  • Career development program
  • Developmental research program

SPORE精神

1. Mechanism of Support
A SPORE is supported through the NIH specialized center (P50) grant mechanism.  Applicants are solely responsible for planning, directing, and executing the proposed project.  This mechanism provides funding for a broad range of research and developmental activities, from basic to human intervention studies.  These grants are intended to promote multidisciplinary research focused upon a specific cancer (or related cancer) site(s).  SPORE grants differ from traditional program project (P01) grants in that they also provide support for pilot research projects and a career development program, as well as enable investigators more flexibility to modify their research activities when new opportunities arise.
This funding opportunity uses just-in-time concepts.  It also uses the non-modular budget format described in the PHS 398 application instructions.  A detailed categorical budget for the “Initial Budget Period” and the “Entire Proposed Period of Support” is to be submitted with the application.
2. Funds Available
The NCI policy for SPORE grants establishes the following limits to the requested budgets: new or competing renewal P50 SPORE applications may each request a maximum annual total cost of $2.3 million.  The facilities and administrative (F&A) costs related to subcontracts to other institutions or organizations are included in the total cost cap of $2.3 million.  Applications can exceed this cap in subsequent years as a result of standard cost-of-living increases or special supplements approved by NCI.
A SPORE grant application may be submitted for up to 5 years of funding.
Up to approximately 8-12 SPORE awards per each of the 2 years of this FOA are anticipated.
Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary.  Although the financial plans of the NCI provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.
 
For the SPORE program, the NCI defines translational research as follows:
“Translational research uses knowledge of human biology to develop and test the feasibility of cancer-relevant interventions in humans and/or determines the biological basis for observations made in individuals with cancer or in populations at risk for cancer.”
The term “interventions” is used in its broadest sense to include molecular assays, imaging techniques, drugs, biological agents, and/or other methodologies applicable to the prevention, early detection, diagnosis, prognosis, and/or treatment of cancer. SPORE translational research projects may involve the use of any cellular, molecular, structural, biochemical, and/or genetic experimental approaches.
The SPORE program fosters highly interactive translational research based on a unique approach with the following characteristics:
  • Focuses solely on translational research with at least four scientific projects, each reaching a human end-point within 5 years.
  • Requires that each project include both basic and applied/clinical scientist co-leaders in a team science approach.
  • Requires an administrative core; requires a biospecimen/pathology core that collects and shares biospecimens among the scientific community.
  • Requires a Developmental Research Program which promotes the exploration of innovative ideas through the funding of pilot projects and encourages collaboration, and requires a Career Development Program which supports investigators in pursuing careers in organ-based translational cancer research.
  • In addition to translational research that involves basic research discoveries being applied in the clinic, the SPORE program encourages translational research projects that start with a clinical observation and return to the laboratory to explore the underlying biological mechanisms.
  • Allows flexibility to change research directions during the grant period in order to pursue the most promising projects; research projects that demonstrate little or no translational progress may be terminated and replaced with new projects that have greater translational potential.
  • Requires a project on early detection, prevention or population science in breast, prostate, lung and GI SPOREs, and encourages the inclusion of this type of project in all other organ site SPORE applications.
  • Requires a strong research base in the respective cancer type, reliable access to patient populations and strong institutional commitment to promote SPORE activities.
  • Requires collaborations among individual SPORE awardees (inter-SPORE collaborations) and/or collaborations between individual SPOREs and other NIH programs.
  • Encourages early phase clinical trials and handing off later trials to other mechanisms including industry and other governmental and non-governmental mechanisms.
  • Expects each individual SPORE awardee and the “network” of SPOREs to conduct research that will have the most immediate impact possible on reducing incidence and mortality of human cancer.  
Inherent in this process is the interdependence between investigators conducting basic and applied research. Clinical and/or epidemiological research that does not include a laboratory component or capitalize upon a biological discovery relevant to human cancer is not considered translational for the SPORE.
#5由 sufang 在 日, 07/27/2014 – 10:41 發表。
中榮黃穰基主任 is a 港仔?
無意中看到2009年他在陽明的合聘教授資料，發現他做口腔癌methylation, microarray, 口腔疑似癌前病症與幹細胞已經很久了。

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