HUMAN PROSTATE CANCER NUCLEI--STRUCTURE ABNORMALITIES AND NEW MOLECULAR MARKERS

迫切需要新的方法来评估生物 可用于针灸的前列腺癌的性质 活组织检查。这项研究计划将识别新的分子 前列腺癌标志物作为新的诊断和预后指标 临床转化因素对个体预后的影响 病人。这些分子标记将与 前列腺癌的反应和生物学特性，如 结构、生长永生化、侵袭和转移。 研究将集中在细胞结构变化，DNA不稳定性 和端粒酶活性，适用于带状分析 针吸活检。细胞核和细胞形状的变化 长期以来一直被认为是最早和最常见的 与任何类型的致癌有关的细胞事件，这 形态变化涉及到细胞核的变异 形态和染色质图案是区别特征 在癌细胞的细胞病理学鉴定中。我们有 核染色质相关定量形态计量学研究 前列腺癌的预后变化，并在此提出 以确定它们的分子组成，原子核的形状 似乎是由一个内部核脚手架系统定义的 这形成了一个组织框架，我们称之为核 矩阵。核基质提供了组织特异性的3- 决定更高顺序的DNA的次元组织 基因组的结构。基质的蛋白质成分是 组织和肿瘤特异性的，并提供DNA结合位点 定义组织特异性基因表达的空间位置 具有位于核基质上的活跃表达的基因。脱氧核糖核酸 合成发生在位于这些位置附近的固定复制位置 矩阵附件站点。端粒是与细胞紧密相连的 核矩阵。核矩阵是发挥作用的理想位置 在为组织许多组织提供结构性场地方面发挥关键作用 与DNA功能有关的核事件。因此，在 癌症的发生和肿瘤的进展，在 癌核的形状可能在 扰乱在核上组织的正常DNA功能 矩阵。我们观察到了在核领域发生的具体变化 与前列腺癌相关的基质蛋白在人类和 动物。一种新的基质蛋白PC-1出现在人类前列腺中 癌症，而其他基质蛋白，如NBP-4，会消失， 已经针对这些蛋白质产生了抗体，这些抗体将有助于 他们的评价。我们还观察到端粒缩短。 人前列腺癌诱导过程中的长度 端粒酶活性。这些核基质蛋白和端粒酶 活动将应用于针吸活组织检查，并转化为 临床评价。

There is an urgent need for new ways to assess the biological properties of prostate cancers that can be applied to needle biopsies. This research program will identify new molecular markers of human prostate cancer as new diagnostic and prognostic factors for clinical translation to the outcome for individual patients. These molecular markers will be correlated with the response and biological properties of prostate cancer such as structure, growth immortalization, invasion, and metastasis. Studies will focus on cell structural alterations, DNA instability and telomerase activity that are applicable to zonal analysis of needle biopsies. Alterations in nuclear and cellular shapes have long been recognized as one of the very earliest and most common cellular events associated with any type of carcinogenesis, This morphological transformation involves variation in nuclear morphology and chromatin patterns that are distinguishing features in the cytopathological identification of cancer cells. We have correlated quantitative morphometry of nuclear and chromatin changes with prognosis in human prostate cancer, and propose here to identify their molecular components, The shape of the nucleus appears to be defined by an internal nuclear scaffolding system that forms an organizing framework that we termed the nuclear matrix. The nuclear matrix provides a tissue specific 3- dimensional organization of DNA that dictates the higher order structure of the genome. The protein components of the matrix are tissue- and tumor-specific and provide DNA binding sites that define the spatial locations for tissue specific gene expression with actively expressed genes located on the nuclear matrix. DNA synthesis occurs at fixed replicating sites located near these matrix attachment sites. Telomeres are tightly attachments to the nuclear matrix. The nuclear matrix is ideally positioned to play a critical role in providing structural sites for organizing many nuclear events involved in DNA functions. Therefore, in carcinogenesis and tumor progression, the aberrations seen in the shapes of the cancer nuclei may be of prime importance in disturbing normal DNA functions that are organized on the nuclear matrix. We have observed specific changes occurring in nuclear matrix proteins associated with prostate cancer in both humans and animals. A new matrix protein, PC-1, appears in human prostate cancer, while other matrix proteins like NBP-4, disappear, Antibodies have been made to these proteins that will assist in their evaluation. We have also observed shortening in telomere lengths in human prostate cancer that accompanies induction of telomerase activity. These nuclear matrix proteins and telomerase activity will be applied to needle biopsies and translated into clinical evaluation.