MOLECULAR CYTOLOGY IN HUMAN PANCRETIC CANCER

胰腺癌仍然是癌症的主要原因。 这个国家的死亡率为-25,000新病例 每年确诊后，几乎所有人都会在几个月内死亡。 关于侦测的问题。这种黯淡的前景是由于缺乏具体的 和敏感的早期诊断标记物 疾病和缺乏根治肿瘤的决定性手段 进展和转移的后期阶段。的长期目标 这项提议是利用一组分子探测器， 识别正常的人外分泌胰腺细胞成分， 其中几个可能具体地由以下子集表示 形态相似的胰腺肿瘤细胞。糟糕的- 分化和中高分化的胰腺 例如，腺癌可能被发现类似于几种 正常组织分化的阶段或多种形式的 来源于特定正常细胞类型的转化细胞。 有几条证据表明胰腺肿瘤可以 表现出与正常阶段相对应的表型 差异化计划。在这些研究中，我们计划使用 几类信使核糖核酸探针：主要细胞结构 成分，参与新陈代谢和分泌的酶， 激素受体、蛋白激酶和底物；抗体 特定的蛋白激酶及其底物将用于 与这些分子的基因探针相结合。刚修好的和 快速冷冻胰腺癌切除和活检 和正常组织将使用技术分析 组织提取液的Northern分析和原位杂交 组织切片以及光镜下的免疫细胞化学 寻找感兴趣的蛋白质。EPON切片的电子显微镜观察 嵌入固定组织将进行精细的形态观察 分析。这些标本将被病理分类，并 患者的临床病程与数据相关。部分内容 石蜡包埋患者的病理标本 曾在我所接受治疗的胰腺癌 将进行类似的检查，以便提供回顾 临床病理与新信息的相关性 学习。同时，我们计划检查正常的 具有相同基因探针的胚胎大鼠胰腺和 免疫学探针，以比较人类肿瘤与 一个可接近的胰腺发育系统。这份分析报告 方案应该使我们能够检验人类 胰腺肿瘤反映正常的异常分期 差异化过程，并应使我们能够发现潜力 可能是靶标的起源和发育阶段的细胞 胰腺的致癌过程。

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.