CANCER CHEMOPREVENTION--ROLE OF INFECTION/IMMUNITY

在过去的十年里，积累了大量的数据，这些数据表明人乳头瘤病毒(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HPV家族，这种皮肤癌与最初在遗传性皮肤癌易发疾病--疣状表皮发育不良症患者中发现的皮肤癌有关。随着针对这些癌症类型的新的化学预防策略的出现，开发新的次要终点生物标记物(SEB)似乎是谨慎的。因此，该项目的一个中心主题是在两种新的化学预防战略的背景下开发与HPV相关的SEB，其中一种明确针对HPV感染。梅奥诊所和北中癌症治疗集团(NCCTG)成员机构计划进行两项第二阶段化学预防临床试验，以支持方案制定、数据管理和统计分析，这些支持主要来自NCCTG CCOP赠款(即研究基地和个别机构赠款)。第一项是外用咪喹莫特和免疫调节剂的随机试点评估，已被证明是治疗生殖器尖锐湿疣安全有效的药物。这项试验将在复发和/或高度分级的宫颈上皮内瘤变(CIN)患者身上进行。治疗皮肤癌。这项试验将试图重现并进一步证实先前的随机试验，在该试验中证明了治疗的益处。广谱聚合酶链式反应技术将被用来监测咪喹莫特治疗后宫颈标本中HPV的特定类型的持续时间。类似的技术将被用来表征HPV在皮肤癌中的潜在作用，还将开发策略来确定HPV特异性免疫反应是否可以用作CIN相关基因表达的SEB，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.