CANCER CHEMOPREVENTION--ROLE OF INFECTION/IMMUNITY

在过去的十年中，积累了大量的数据，表明人类乳头瘤病毒（hpv）与上皮性癌症，特别是宫颈癌有关。最近，在皮肤癌中发现了一个新的家族HPV，该家族HPV与最初在遗传性皮肤癌易感性（疣状表皮发育不良）患者中发现的HPV有关。随着针对这些癌症类型的新化学预防策略的出现，开发新的次要终点生物标志物（seb）似乎是谨慎的。因此，本项目的中心主题是在两种新的化学预防策略的背景下开发HPV相关的seb，其中一种是明确针对HPV感染的。计划在梅奥诊所和中北部癌症治疗小组（NCCTG）成员机构进行两项二期化学预防临床试验，主要由NCCTG cccop资助（即研究基地和个别机构资助）支持方案制定、数据管理和统计分析。首先是对局部咪喹莫特和免疫调节剂的随机试验评估，免疫调节剂已被证明对治疗生殖器疣是安全有效的。该试验将在复发和/或高度宫颈上皮内瘤变（CIN）患者中进行。治疗皮肤癌。该试验将试图重现并进一步证实先前的一项随机试验，该试验证明了治疗效果。广谱PCR技术将用于监测在咪喹莫特治疗后宫颈标本中HPV的类型特异性持久性。类似的技术将用于表征HPV在皮肤癌中的潜在作用，还将制定策略来确定HPV特异性免疫反应是否可以用作CIN相关基因表达的SEBs，并将为皮肤癌化学预防项目开发AP-1的表达/活性。

Over the past decade, a substantial body of data has accumulated which implicates the human papillomaviruses (HPVs) in epithelial cancers, especially cervical cancer. More recently, a new family HPV has been identified in skin cancers that are related to those found originally in patients with heritable skin cancer prone condition, epidermodysplasia verruciformis. With the advent of new chemoprevention strategies directed against each of these cancer types, it appears prudent to develop novel secondary endpoint biomarkers (SEBs). Accordingly, a central Theme of this project is to develop HPV-related SEBs in the context of two novel chemoprevention strategies, one of which is expressly directed against HPV infection. Two Phase II chemoprevention clinical trials are planned at the Mayo Clinic and in the North Central Cancer Treatment Group (NCCTG) member institutions, with support for protocol development, data management, and statistical analysis deriving primarily from NCCTG CCOP grants ( i.e. research base and individual institution grants). The first is a randomized pilot evaluation of topical imiquimod, and immunomodulatory agent which has proven to be safe and effective for the treatment of genital warts. This trial will be conducted on patients with recurrent and/or high-grade cervical intraepithelial neoplasia (CIN). For skin cancers. This trial will attempt to reproduce and further substantiate a previous randomized trial in the which a treatment benefit was demonstrated. Broad-range PCR techniques will be used to monitor the type-specific persistence of HPV in cervical specimens after imiquimod therapy. Similar techniques will be used to characterize the potential role of HPV in skin cancers, strategies will also be developed to determine if HPV - specific immune responses can be used as SEBs in CIN related gene expression and AP-1 expression/activity will be developed for the skin cancer chemoprevention project.