DES ASSOC CCA OF VAGINA/CERVIX--COLLABORATIVE STUDIES

阴道/子宫颈 DES ASSOC CCA——合作研究

• 批准号: 2763887
• 负责人: ARTHUR L HERBST
• 金额: $ 11.33万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2763887
• 关键词: DNA repair; adenocarcinoma; adult human (21+); age difference; athymic mouse; cancer information system; cancer registry /resource; cell line; cervix neoplasms; clinical research; cooperative study; diethylstilbestrol; drug related neoplasm /cancer; embryo /fetus toxicology; female; gene expression; hormone related neoplasm /cancer; human subject; neoplasm /cancer epidemiology; neoplasm /cancer relapse /recurrence; questionnaires; smoking; vagina neoplasms; women's health; xenotransplantation

The data collected and analyzed in the Registry provide the sole comprehensive series of cases of DES-associated clear cell adenocarcinoma (CCA) of the vagina and/or cervix in women born after 1948 for comparative and collaborative study. Both DES-exposed and unexposed patients are accessioned. The Tissue Bank of fixed specimens from patients treated for CCA along with fresh tissue from newly diagnosed and/or recurrent cases will be maintained and expanded. An established Advisory Board of external investigators will meet regularly with to oversee the distribution of these rare tissues to qualified investigators for molecular studies. The success of these initial efforts has led to a new collaborative project with Dr. G. Cunha of UCSF, who, using fresh CCA tissue supplied by Registry patients, has established a human CCA transplant cell line. His laboratory will evaluate growth and differentiation requirements of CCA as well as identify the role of the stroma in these processes and test the response of CCA to estrogen with the goals of gaining a better understanding of the molecular regulations of these malignancies and the potential development of new therapeutic strategies. Collaborative work regarding the induction of microsatellite instability and down-regulation of DNA mismatch repair gene expression with Dr. Jeff Boyd, of MKSCC, is also being proposed. The hypothesis is that the induction of microsatellite instability represents a critical component of the molecular mechanism through which DES initiates carcinogenesis. Preliminary data indicate there may be a secondary rise in the age incidence curve developing in DES-exposed patients over the age of 40 years, similar to what is observed in the unexposed population. The possible early detection of such a rise will be tested. If detected, this would provide important public health information to the DES-exposed population since many physicians have erroneously assumed that patients over age 30 years are not at risk for CCA. With Dr. J. Palmer of the Boston University School of Medicine, epidemiologic studies will be performed to evaluate factors that contribute to the development of the disease in older DES-exposed (over age 35 years) and also the reasons for late recurrences of CCA (beyond 5 years).

登记处收集和分析的数据提供了 1948 年之后出生的女性阴道和/或子宫颈 DES 相关透明细胞腺癌 (CCA) 的唯一综合系列病例，用于比较和合作研究。 暴露于 DES 和未暴露于 DES 的患者均已加入。 来自接受 CCA 治疗的患者的固定标本以及来自新诊断和/或复发病例的新鲜组织的组织库将得到维护和扩大。 一个由外部研究人员组成的咨询委员会将定期召开会议，监督这些稀有组织向合格的研究人员进行分子研究的分配。 这些初步努力的成功促成了与加州大学旧金山分校 (UCSF) 的 G. Cunha 博士的一个新合作项目，该项目使用登记处患者提供的新鲜 CCA 组织，建立了人类 CCA 移植细胞系。 他的实验室将评估 CCA 的生长和分化要求，并确定基质在这些过程中的作用，并测试 CCA 对雌激素的反应，目的是更好地了解这些恶性肿瘤的分子调控和潜在的发展新的治疗策略。 还提议与 MKSCC 的 Jeff Boyd 博士就诱导微卫星不稳定性和下调 DNA 错配修复基因表达进行合作。 假设认为，微卫星不稳定性的诱导代表了 DES 引发癌变分子机制的关键组成部分。初步数据表明，40 岁以上暴露于 DES 的患者的年龄发病率曲线可能会出现二次上升，与未暴露人群中观察到的情况类似。 能否及早发现这种上涨将受到考验。 如果检测到，这将为 DES 暴露人群提供重要的公共卫生信息，因为许多医生错误地认为 30 岁以上的患者没有 CCA 的风险。 波士顿大学医学院的 J. Palmer 博士将进行流行病学研究，以评估老年 DES 暴露者（35 岁以上）中导致疾病发展的因素以及 CCA 晚期复发的原因（超过 5 年）。