CYTOGENETICS AND BIOCHEMISTRY OF PROSTATE CANCER

前列腺癌的细胞遗传学和生物化学

• 批准号: 2097939
• 负责人: THOMAS G PRETLOW
• 金额: $ 33.77万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-23 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2097939
• 关键词: athymic mouse; cytogenetics; epidermal growth factor; fibroblast growth factor; flow cytometry; gender difference; gene deletion mutation; gene expression; growth factor; growth factor receptors; human tissue; in situ hybridization; karyotype; molecular cloning; molecular oncology; natural gene amplification; neoplasm /cancer transplantation; nucleic acid sequence; phenotype; point mutation; polymerase chain reaction; prognosis; prostate neoplasms; racial /ethnic difference; restriction fragment length polymorphism; tissue /cell culture; tumor suppressor genes

This is a response to RFA CA-91-10 and is a collaboration among cytogenetics, medicine, molecular biology, pathology, and urology. Prostate cancer (PCA) is the most commonly diagnosed invasive cancer and the second most common cause of cancer deaths in US males. It is increased in incidence among blacks and among increasingly aged subjects. Survival is shorter among blacks. The clinical course ranges from rapidly fatal to survival often 10-20 years after diagnosis. Most PCA is discovered only at autopsy. Most PCA diagnosed during life is or becomes symptomatic and may result in severe pain from metastases to bone in up to 70-80% of PCA. Survival may be long, with or without severe symptoms, even many years after the identification of metastases. There is a great need to be able to predict which PCAs will progress slowly and which will progress rapidly, i.e., may be better followed without aggressive therapy. Our goal is the precise identification of biologically different subpopulations. The most commonly recognized predictor of clinical behavior is histopathological differentiation. A more powerful predictor is needed; this may require an approach that is qualitatively different from (hopefully complementary to) the currently employed predictors. We want to identify cytogenetic and molecular genetic aberrations that will be useful as more precise prognostic indicators. An important obstacle to this goal in the past has been the exceptional difficulty encountered in the propagation of PCA cells both in vivo and in vitro. Recently, we reported a method for the propagation of a large proportion of primary PCAs in athymic animals. We have since transplanted xenografts serially. This permits expansion of the available tumor, a useful approach to the procurement of malignant PCA cells free of benign epithelial cells and human stromal cells, and the study of viable PCA cells with many techniques over the course of time. We also have methods that have permitted the short-term culture of PCA adequate for cytogenetic analyses. We shall attempt to correlate several clinical parameters with experimental parameters. Clinical parameters routine in our center include race, age, Gleason grade, ultrasound image, stage of disease, metastatic survey, serum prostate specific antigen before and at intervals after surgery, rate of growth of measurable tumors in patients, time to recurrence of disease, and survival (both total and disease specific). Experimental parameters to be correlated and evaluated as possibly important predictors both as single parameters and as multiple complementary parameters include Gleason patterns (quantified morphometrically), size of tumor (quantified morphometrically), ploidy, cytogenetic aberrations (both conventional and by fluorescence in situ hybridization). rate of growth in immunodeficient animals, the loss and mutation of selected tumor suppressor genes, and the protein expression and gene amplification of selected growth factors and their receptors.

这是对RFA CA-91-10的响应，是 细胞遗传学、医学、分子生物学、病理学和泌尿学。 前列腺癌(PCa)是最常见的浸润性癌症， 是美国男性癌症死亡的第二大常见原因。它是 在黑人和日益老龄化的受试者中发病率增加。 黑人的生存时间更短。临床病程从快速的 通常在确诊后10-20年内对生存是致命的。大多数PCA都是 只有在尸检时才能发现。大多数在生活中诊断出的前列腺癌是或变成了 有症状，可能导致严重疼痛，从UP的骨转移到骨转移 占PCA的70%-80%。存活时间可能很长，无论有没有严重的症状， 即使是在发现转移瘤多年后。有一个很棒的 需要能够预测哪些PCA进展缓慢，哪些将 进展迅速，也就是说，最好不要咄咄逼人地跟在后面 心理治疗。我们的目标是在生物学上精确鉴定 不同的亚群。公认的最常见的预测因子 临床表现为组织病理学分化。一个更强大的 需要预测器；这可能需要一种定性的方法 不同于(希望是对现有雇员的补充) 预测者。我们想要鉴定细胞遗传学和分子遗传学 像差将是有用的更准确的预后指标。 在过去，实现这一目标的一个重要障碍是例外 前列腺癌细胞在体内和体外增殖中遇到的困难 在试管中。最近，我们报道了一种传播大电流的方法 无性系动物初级PCAs的比例。从那以后我们就 连续移植异种移植物。这允许扩展可用的 肿瘤--获取无恶性前列腺癌细胞的有效途径 良性上皮细胞和人类间质细胞的研究 在一段时间内，使用许多技术可以存活的PCA细胞。我们也 是否有足够的方法来进行短期的PCA培养？ 用于细胞遗传学分析。我们将尝试将几个临床病例联系起来 参数与实验参数的关系。临床参数常规在 我们的中心包括种族，年龄，格里森分级，超声图像，分期 疾病、转移调查、治疗前和治疗后血清前列腺特异性抗原 手术后间隔，患者可测量的肿瘤的生长速度， 疾病复发的时间和存活率(包括总和疾病 具体)。要关联和评估的实验参数为 作为单个参数和多个参数的可能重要的预测因素 补充参数包括格里森图案(量化 形态计量学)、肿瘤大小(形态计量学量化)、倍体、 细胞遗传学异常(包括常规的和原位荧光的 杂交)。免疫缺陷动物的生长速度、损失和 肿瘤抑制基因的突变及其蛋白表达 以及选定的生长因子及其受体的基因扩增。