CANCER CHEMOPREVENTION & MENTORING CLINICAL RESEARCHERS

不断发展的卫生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在缓慢减少；从而造成潜在的危机。这场危机将对社会和卫生保健系统产生多重影响。解决这一危机的一个办法是支持年轻、活跃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。Mack T. Ruffin博士代表了这些成功的医生之一，拥有15年的专业培训，并致力于指导下一代临床研究人员。此申请是为了响应以患者为导向的研究的职业中期研究者奖（PA-98-053）。该项目的活动领域是Ruffin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：(三个项目已经获得了外部支持。这项资助将允许Ruffin博士在这些项目上进一步开展工作)：宫颈类维生素a应用评估（CARE）项目(1)在160-180名CIN II或III型女性中，确定外用全转维甲酸是否减少每个细胞HPV病毒基因组拷贝数和/或抑制HPV E6/E7基因表达。富含类胡萝卜素的饮食逆转CIN I和CIN II的试验（CAPRE研究）(1)在一项随机对照研究中，确定在326名女性中给予富含类胡萝卜素的高水果和蔬菜饮食是否会显著增加CIN I和CIN II的回归率。姜黄素作为化学预防剂(1)确定姜黄素作为营养补充剂口服“Cyclox”微粉制剂的人体药代动力学。另外三个项目将在未来五年内直接得到该基金的支持：COX-2特异性抑制剂（塞来昔布）和散发性结肠息肉(1)，以确定塞来昔布是否能减少人类腺瘤性结肠息肉的复发。HPV感染与饮食(1)确定富含类胡萝卜素的高水果和蔬菜饮食是否会显著降低女大学生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.