Project 04: Molecular Carcinogenesis and Chemoprevention (MCC)

项目摘要-分子致癌和化学预防（MCC） 俄亥俄州州立大学的分子致癌和化学预防（MCC）项目 综合癌症中心（OSUCCC），由史蒂芬克林顿，医学博士，博士和理查德费舍尔，博士领导， 48名成员来自22个部门和8个俄勒冈州立大学学院（艺术和科学，牙科，教育和人类 生态学、食品、农业和环境科学、医学、药学、公共卫生和兽医 医学）。MCC项目将癌症作为一个综合的动态过程进行研究， 关注遗传学和环境之间的界面，共同影响致癌作用 级联。这种方法为化学预防和饮食干预提供了基础， 癌症的发病率、死亡率和发病率， 我们的俄亥俄州集水区（CA）和全国。我们的专业知识延伸到定义基因筛查标准， 咨询以及通过国家公共政策制定影响癌症风险的饮食和营养指南 和全球范围内。MCC计划的具体目标是：1）致癌作用：为了表征遗传， 由生殖系、化学、物理、激素或微生物介质诱导的分子和细胞变化 导致肿瘤转化和多阶段癌变; 2）化学预防：发展和 表征新型癌症化学预防剂，并确定其有效性、安全性和作用机制 使用最终导致早期人类研究的生物化学、细胞和临床前模型;和，3）饮食， 营养与代谢：确定饮食模式、营养成分和生活方式变量， 增强或抑制贯穿癌症进展连续体的致癌级联。MCC计划 成员们在2014年12月1日至2019年11月30日期间发表了547篇与癌症相关的手稿。其中，14%是内部- 程序性（多位作者来自MCC计划），31%是跨程序性（多位OSUCCC作者） 程序），72%是多机构（作者来自CC和其他机构）。全面合作 出版物占83%。MCC计划的资金总额为790万美元，用于直接治疗癌症，其中 700万美元是同行评审的，其中包括来自NIH的680万美元直接资助（来自NCI的340万美元）。在过去的五年里，MCC 计划成员已累计1，487名参与者参加试验; 670名参与干预性试验，817名参与非干预性试验 审判MCC成员担任俄亥俄州结直肠癌预防计划的领导人，该计划涉及3651名 参与者（3，310例结直肠癌和341例子宫内膜癌）和ORIEN Total Cancer Care，登记人数为50，683人。 MCC计划与OSUCCC的高优先级交叉研究计划和未来计划完全整合 补充和加强计划目标，同时促进与其他研究计划和重点的互动 1）致癌和预防中的代谢特征; 2）微生物组和免疫学接口， Pelotonia免疫肿瘤学研究所倡议;和3）与癌症工程中心的合作努力。

PROJECT SUMMARY – MOLECULAR CARCINOGENESIS AND CHEMOPREVENTION (MCC) The Molecular Carcinogenesis and Chemoprevention (MCC) Program at The Ohio State University Comprehensive Cancer Center (OSUCCC), led by Steven Clinton, MD, PhD, and Richard Fishel, PhD, has 48 members from 22 Departments and 8 OSU Colleges (Arts and Sciences, Dentistry, Education and Human Ecology, Food, Agriculture and Environmental Science, Medicine, Pharmacy, Public Health, and Veterinary Medicine). The MCC Program examines cancer as an integrated and dynamic process over time, with a major focus on the interface between genetics and the environment that collectively impacts the carcinogenesis cascade. This approach provides a foundation for chemoprevention and dietary interventions to reduce the burden of cancer in high-risk individuals as well as to decrease the incidence, mortality and morbidity of cancer in our Ohio catchment area (CA) and the nation. Our expertise extends to defining standards for genetic screening and counselling as well defining dietary and nutritional guidelines that impact cancer risk through public policy, nationally and globally. The Specific Aims of the MCC Program are: 1) Carcinogenesis: To characterize the genetic, molecular and cellular changes induced by germline, chemical, physical, hormonal or microbiological mediators that contribute to neoplastic transformation and multistage carcinogenesis; 2) Chemoprevention: To develop and characterize novel cancer chemopreventive agents and define their efficacy, safety, and mechanisms of action using biochemical, cellular and preclinical models that ultimately lead to early phase human studies; and, 3) Diet, Nutrition and Metabolism: To identify dietary patterns, nutritional components, and lifestyle variables that enhance or inhibit the carcinogenesis cascade across the continuum of cancer progression. MCC Program members published 547 cancer-relevant manuscripts between 12/01/14 and 11/30/19. Of these, 14% were intra- programmatic (multiple authors from MCC Program), 31% were inter-programmatic (authors from multiple OSUCCC Programs), and 72% were multi-institutional (authors from both CC and another institution). The total collaborative publications is 83%. MCC Program funding stands at $7.9M in overall direct, cancer-focused funding, of which $7.0M is peer-reviewed, including $6.8M direct funding from NIH ($3.4M from NCI). Over the last five years, MCC Program members have accrued 1,487 participants to trials; 670 to interventional trials and 817 to non-interventional trials. MCC members serve as leaders of the Ohio Colorectal Cancer Prevention Initiative involving 3,651 participants (3,310 colorectal and 341 endometrial) and ORIEN Total Cancer Care with enrollment of 50,683.The MCC program is fully integrated with the high priority crosscutting research initiatives of the OSUCCC and future plans complement and enhance programmatic aims while promoting interactions with the other research Programs and focus on 1) metabolic signatures in carcinogenesis and prevention; 2) the microbiome and immunology interface with Pelotonia Institute for Immuno-Oncology initiatives; and 3) collaborative efforts with the Center for Cancer Engineering.