MOLECULAR CYTOLOGY IN HUMAN PANCRETIC CANCER

人类胰腺癌的分子细胞学

• 批准号: 3191224
• 负责人: JAMES Douglas JAMIESON
• 金额: $ 16.93万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-05-10 至 1991-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3191224
• 关键词: adenocarcinoma; antitumor antibody; biopsy; cell differentiation; cellular oncology; electron microscopy; enzyme substrate; genetic manipulation; genetic transcription; genetic translation; hormone receptor; human subject; immunochemistry; immunocytochemistry; laboratory rat; messenger RNA; molecular oncology; neoplasm /cancer genetics; neoplasm /cancer immunodiagnosis; nucleic acid hybridization; pancreas neoplasms; protein kinase; tumor antigens

Pancreatic cancer continues to present a major cause of cancer mortality in this country in that of the -25,000 new cases diagnosed each year, nearly all will succumb within a few months of detection. This bleak outlook is due to the absence of specific and sensitive diagnostic markers for the early stages of the disease and the lack of decisive means of tumor eradication at the later stages of progression and metastasis. The long range goal of this proposal is to utilize a battery of molecular probes that recognize normal human exocrine pancreatic cell constituents, several of which may be expressed specifically by subsets of pancreatic tumor cells of similar morphology. Poorly- differentiated and moderately-well differentiated pancreatic adenocarcinomas, for example, may be found to resemble several phases of normal tissue differentiation or a number of forms of transformed cells deriving from a particular normal cell type. Several lines of evidence indicate that pancreatic tumors can exhibit phenotypes that correspond to stages of the normal differentiation program. In these studies we plan to use riboprobes for several classes of mRNA: major cell structural components, enzymes involved in metabolism and secretion, hormone receptors, and protein kinases and substrates; antibodies specific for protein kinases and their substrates will be used in consort with gene probes for these molecules. Freshly fixed and snap-frozen pancreatic adenocarcinoma resections and biopsies and normal tissue will be analyzed using the techniques of Northern analysis of tissue extracts and in situ hybridization of tissue sections, as well as light microscopic immunocytochemistry for proteins of interest. Electron microscopy of sections of Epon- embedded fixed tissues will be done for refined morphological analysis. These specimens will be classified pathologically and the patients' clinical course correlated with the data. Sections of pathologic specimens embedded in paraffin from patients with pancreatic adenocarcinoma previously treated in our institution will be similarly examined in order to provide a retrospective clinical-pathologic correlation with new information gained in this study. At the same time, we plan to examine the normal embryonic rat pancreas with the same gene probes and immunologic probes in order to compare the human tumors with an accessible pancreatic developmental system. This analytical scheme should enable us to test the hypothesis that human pancreatic neoplasms reflect aberrant stages in the normal differentiation process and should allow us to identify potential cells of origin and developmental stages that may be the targets of the carcinogenic process in the pancreas.

胰腺癌仍然是癌症的主要原因 在这个国家的25,000个新病例中 几乎所有人都会在几个月内死亡 检测。 这种暗淡的前景是由于缺乏具体的 和敏感的早期诊断标志物 疾病和缺乏决定性的手段，消除肿瘤， 晚期进展和转移。 长期目标是 该建议是利用一组分子探针， 识别正常人外分泌胰腺细胞成分， 其中的几个可以通过以下子集来具体表达： 形态相似的胰腺肿瘤细胞。 可怜的- 分化和中高分化胰腺癌 例如，可以发现腺癌类似于几种 正常组织分化的阶段或许多形式的 从特定的正常细胞类型衍生的转化细胞。 一些证据表明胰腺肿瘤可以 表现出对应于正常的阶段的表型 差异化方案 在这些研究中，我们计划使用 几类mRNA的核糖核酸探针：主要细胞结构 参与代谢和分泌的酶， 激素受体、蛋白激酶和底物;抗体 对蛋白激酶及其底物具有特异性， 与这些分子的基因探针结合。 刚修好的， 速冻胰腺癌切除和活检 和正常组织将使用以下技术进行分析 组织提取物的北方分析和 组织切片以及光镜免疫细胞化学 for proteins蛋白of interest感兴趣. Epon-1细胞切片的电镜观察 将进行包埋固定组织以进行精细形态学 分析. 这些标本将进行病理分类， 患者的临床过程与数据相关。 路段 石蜡包埋的病理标本， 既往在我院治疗过的胰腺癌 将进行类似的审查，以提供一个回顾 临床病理相关性与本研究中获得的新信息 study. 同时，我们计划检查正常的 胚胎大鼠胰腺与相同的基因探针， 免疫探针，以比较人类肿瘤与 胰腺发育系统 该分析 该计划应该使我们能够测试假设，人类 胰腺肿瘤反映了正常胰腺的异常分期， 差异化过程，并应使我们能够识别潜力 可能是靶的起源和发育阶段的细胞 胰腺的致癌过程。