PATHOGENESIS OF KAPOSI'S SARCOMA

该提案的目的是阐明卡波西的发病机制 肉瘤（KS）在存在或不存在IEV感染，基于 假设糖皮质激素和某些细胞因子/单核因子（IL-1， TNF、IL-6、新型生长因子）直接和间接地诱导 并促进KS的生长。将采用病例对照研究， 免疫功能相对完整的男性同性恋者中HIV相关KS 系统（CD 4），200/dl，无AMS定义的机会性感染）。例 将从LAC/USC医疗中心的KS诊所累积 （N=160）。每例病例将确定3例年龄匹配的对照。组I 对照组将是EIV阳性的无临床症状的同性恋朋友 对照组;第2组对照将是HIV阴性的同性恋朋友 对照组;第3组对照组为HIV阴性异性恋 邻里控制。经典的KS病例将从洛杉矶 Angeles County population based cancer registry（CSP）（n=272）。控制 对于这些病例，将确定年龄匹配的邻居对照， 使用预定的算法。流行病学调查问卷，血液 并采集所有受试者的尿液样本。此外，KS 将从所有A.MS-KS病例和临床样本中获得组织 KS案件。我们将测定（1）血浆ACTH、血清皮质醇和 KS患者尿游离皮质醇水平高于对照组;（2） 如果血清和短期血液单核细胞/巨噬细胞培养上清液 细胞因子/单核因子水平（TNF、EL-1、EL-6）和尿IL-6水平是 与对照组相比，病例中存在较高水平;（3）如果某些 流行病学特征是KS风险因素，例如使用 类固醇，某些性传播疾病史， 改变免疫功能等。该提案的第二个目的是 建立一个血清和组织库，以供将来的研究使用。

The goal of this proposal is to elucidate the pathogenesis of Kaposi sarcoma (KS) in the presence or absence of IEV infection, based on the hypothesis that glucocorticoids and certain cytokines/monokines (IL-l, TNF, IL-6, novel growth factors) act directly and indirectly to induce and enhance the growth of KS. A case-control study will be employed for HIV-related KS among homosexual men with a relatively intact immune system (CD4),200/dl, no AMS-defining opportunistic infections). Cases will be accrued from the KS clinics at the LAC/USC Medical Center (N=160). Three age-matched controls will be identified per case. Group I controls will be EIV-positive clinically asymptomatic homosexual friend controls; Group 2 controls will be HIV-negative homosexual friend controls; Group 3 controls will be HIV-negative heterosexual neighborhood controls. Classic KS cases will be identified from the Los Angeles County population based cancer registry (CSP) (n=272). Controls for these cases will be age-matched neighborhood controls identified using a predetermined algorithm. An epidemiologic questionnaire, blood and urine specimens will be obtained on all participants. In addition KS tissue will be obtained on all A.MS-KS cases and on a sample of clinic KS cases. We will determine (1) if plasma ACTH, serum cortisol and urinary free cortisol are elevated in KS cases compared to controls; (2) if serum and short term blood monocyte/macrophage culture supernatant cytokine/monokine levels (TNF, EL-1, EL-6) and urinary IL-6 levels are present at higher levels in cases compared to controls; (3) if certain epidemiologic characteristics are KS risk factors, such as use of steroids, history of certain sexually transmitted diseases, indices of altered immune function, etc. A secondary objective of the proposal is to establish a serum and tissue bank for use in future studies.