CANCER CHEMOPREVENTION & MENTORING CLINICAL RESEARCHERS

不断发展的医疗保健系统给医生带来了许多新的障碍和负担，以至于临床研究人员的数量似乎正在缓慢减少，从而造成了一种潜在的危机。这场危机将对社会和医疗保健系统产生多重影响。这场危机的一个解决方案是支持年轻、积极和成功的临床研究人员，以克服以患者为导向的研究的一些主要障碍：时间、资源和指导。马克·T·鲁芬博士代表了这些成功的医生之一，他们接受了15年的专业培训，并致力于指导下一代临床研究人员。这项申请是对以患者为中心的研究的职业生涯中期奖(PA-98-053)的响应。该项目的活动领域是鲁芬博士的研究计划，重点是宫颈癌和结直肠癌的癌症化学预防，以及他指导初级临床研究人员的计划。研究项目的具体目标是：(三个项目已获得外部支持。这笔赠款将使鲁芬博士能够在这些项目上进一步开展工作。)：维甲酸颈部应用评估(CARE)项目(1)，以确定局部应用全反式维甲酸是否减少了160-180名CIN II或III女性中HPV E6/E7基因的表达和/或减少每个细胞的HPV基因组拷贝数。富含胡萝卜素的饮食试验逆转CIN I和CIN II(CAPRE研究)(1)确定在随机和对照研究中给予富含胡萝卜素的饮食是否会导致326名女性CIN I和CIN II的消退率显著增加。姜黄素作为化学预防药物(1)，以确定在用作营养补充剂的“环磷酰胺”微粉化制剂中口服姜黄素的人体药代动力学。在接下来的五年里，将在这笔赠款的直接支持下开发另外三个项目：环氧合酶-2特异性抑制剂(Celecoxib)和散发性大肠息肉(1)，以确定塞来昔布是否可以减少人类腺瘤性结肠息肉的复发。HPV感染和饮食(1)确定富含胡萝卜素的水果和蔬菜饮食是否会显著降低大学女性HPV感染的发生率。最后，CARE项目和CAPRE研究的结果将用于进一步研究其他潜在的宫颈癌化学预防药物。

The evolving health care system has placed many new barriers and burdens on physicians such that there appears to be slowly decreasing the numbers of clinical investigators; thereby creating a potential crisis. This crisis will have multiple impacts on society and the health care system. One answer to this crisis is to support young, active and successful clinical investigators in order to overcome some of the major barriers to patient-oriented research: time, resources, and mentoring. Dr. Mack T. Ruffin represents one of these successful physicians with 15 years of specialty training and a commitment to mentoring the next generations of clinical investigators. This application is in response to the Midcareer Investigator Award in Patient-Oriented Research (PA-98-053). The areas of activity of this project are Dr. Ruffin's research plan focused on cancer chemoprevention in cervical and colorectal cancer along with his plan for mentoring beginning clinical investigators. The specific aims of the research projects are: (Three projects already have external support. This grant will allow further work by Dr. Ruffin on these projects.): Cervical Application of Retinoids Evaluation (CARE) Project (1) To determine if topical all-transretinoic acid reduces the number of viral genome copies of HPV per cell and/or inhibits HPV E6/E7 gene expression among 160-180 women with CIN II or III. Carotenoid-Rich Diet Trial to Reverse CIN I and II (CAPRE Study) (1) To determine if a carotenoid-rich diet high in fruits and vegetables given in a randomized and controlled study will cause significant increase in the regression rate of CIN I and CIN II among 326 women. Curcumin as a Chemopreventive Agent (1) To define the human pharmacokinetics of curcumin administered orally in the "Cyclox" micronized formulation for use as a nutritional supplement. Three additional projects will be developed in direct support from this grant over the next five years: COX-2 Specific Inhibitor (Celecoxib) and Sporadic Colorectal Polyps (1) To determine whether celecoxib reduces the recurrence of human adenomatous colonic polyps. HPV Infection and Diet (1) To determine if a carotenoid-rich diet high in fruits and vegetables will significantly reduce the incidence of HPV infection among college women. Finally, the findings of CARE Project and CAPRE Study will be used to further study other potential chemopreventive agents for cervical cancer.