CLINICAL TRIAL: BOWMAN-BIRK INHIBITOR CONCENTRATE AND ORAL LEUKOPLAKIA: PHASE I

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 具体目标 我们工作的总体目标是确定化学预防是否可以预防人类癌症。口腔白斑(OL)是一种易于评估、临床可识别的头颈癌先兆，是研究化学预防的极佳模型系统，也是研究人员所熟悉的模型系统。 流行病学和实验数据都有力地表明，蛋白酶抑制剂在提供预防癌症形成的保护作用方面具有广泛的作用。临床前毒理学研究表明，这些药物非常没有副作用，而且是安全的。研究人员已经按照FDA的要求进行了大豆衍生的Bowman-Birk抑制剂浓缩物(BBIC)的I期试验，并已获准进行更长期的研究。BBIC对口腔黏膜细胞(BMC)的影响将从以下中间标记终点(IME)方面进行研究：1)白斑的临床和组织学状态，2)使用蛋白酶底物Boc-Val-Pro-Arg-MCA和GH-Gly-Arg-MCA的蛋白分解活性(PA)水平，以及3)RNA表达水平(c-erb-B)。这些研究将在两个连续的临床化学预防试验的背景下进行。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aims The overall objective of our work is to determine whether chemoprevention can prevent cancer in humans. Oral leukoplakia (OL) is an easily assessable, clinically identifiable precursor to head and neck cancer represents an excellent model system in which to study chemoprevention, and one with which the investigators are familiar. Both epidemiologic and experimental data strongly suggest a broad role for protease inhibitors in providing a protective effect against cancer formation. Preclinical toxicology studies indicate that these agents are remarkably free of side effects and safe. The investigators have conducted an FDA-required phase I trial of the soybean-derived Bowman-Birk Inhibitor Concentrate (BBIC) as the prototype agent and have been approved to do longer term studies. The effect of BBIC on buccal mucosa cells (BMC) will be investigated with respect to the following intermediate marker endpoints (IME): 1) clinical and histologic status of leukoplakia, 2) level of proteolytic activity (PA) using the protease substrates Boc-Val-Pro-Arg-MCA and GH-Gly-Arg-MCA, and 3) level of RNA expression (c-erb-B). These studies will be performed in the context of two sequential clinical chemoprevention trials.