CANCER CHEMOPREVENTION--ROLE OF INFECTION/IMMUNITY

在过去的十年中，积累了大量的数据，这些数据涉及上皮癌，特别是宫颈癌中的人乳头瘤病毒（HPV）。 最近，在皮肤癌中发现了一个新的家族HPV，该家族HPV与最初在具有遗传性皮肤癌倾向的疾病疣状表皮发育不良的患者中发现的那些相关。 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）似乎是明智的。 因此，该项目的中心主题是在两种新型化学预防策略的背景下开发HPV相关SEB，其中一种明确针对HPV感染。计划在马约诊所和中北部癌症治疗小组（NCCTG）成员机构开展两项II期化学预防临床试验，方案制定、数据管理和统计分析的支持主要来自NCCTG CCOP赠款（即研究基地和单个机构赠款）。 第一个是局部咪喹莫特和免疫调节剂的随机试点评估，已被证明是安全和有效的治疗生殖器疣。 本试验将在复发性和/或高度宫颈上皮内瘤变（CIN）患者中进行。 治疗皮肤癌 本试验将尝试重现并进一步证实先前的随机试验，该试验证明了治疗获益。 将使用大范围PCR技术监测咪喹莫特治疗后宫颈标本中HPV的类型特异性持续性。 类似的技术将用于表征HPV在皮肤癌中的潜在作用，还将开发策略以确定HPV特异性免疫应答是否可用作CIN相关基因表达中的SEB，并且将开发用于皮肤癌化学预防项目的AP-1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.