IMPROVED MRNA DISPLAY FOR DETECTING METASTASES

改进 mRNA 显示以检测转移

• 批准号: 2101960
• 负责人: ARTHUR B PARDEE
• 金额: $ 23.91万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2101960
• 关键词: antisense nucleic acid; breast neoplasm /cancer diagnosis; breast neoplasms; gene expression; genetic markers; messenger RNA; metastasis; molecular cloning; neoplasm /cancer genetics; neoplasm /cancer immunodiagnosis; neoplasm /cancer immunology; neoplasm /cancer pharmacology; northern blottings; nucleic acid probes; nucleic acid sequence; oncogenes; polymerase chain reaction; prognosis; subtraction hybridization; tumor suppressor genes

This Grant is one of three, submitted in response to an RFA for an interdisciplinary approach to breast cancer. The overall aims of our three Grants are: (i) to develop novel methods for identifying and cloning genes that are differentially expressed in cancer vs. normal cells, positively as for oncogenes or negatively as for tumor suppressor genes; (ii) to investigate properties of these genes, and to select a subset useful for diagnosis, prognosis and therapy; (iii) to apply these findings to clinical samples. The approaches include cell biology and molecular genetics, and bridge the basic science-- clinical interface. Collaborations have been arranged in later years with Dr. Lloyd Old on applications of immunology, with Dr. Alan Sartorelli on pharmacology, and with Dr. Paul Zamecnik on antisense constructs. From what is already known, a large number of genes involved in the regulation of diseases, proliferation, aging, differentiation, DNA repair, chromosome function and cell-cell interaction will be shown to have suppressor or activator functions. These will provide important pieces of the cancer puzzle. Their identification will allow many researchers to integrate their studies into the entire picture. However, as yet only a small fraction of such genes have been identified (1), in part owing to the difficulty of methods for their selection. This Grant application is based upon the powerful Differential Display technique developed by Dr. Pardee, which provides a novel approach to this problem of gene selection. We propose to improve it in several important ways. In our collaborative effort with Drs. Sager, Smith and Thor, a selected subset of these genes will be cloned, sequenced and compared with data banks. We will prepare immunological (with Dr. Lloyd Old) and hybridization probes for diagnosis/prognosis, and their functions investigated for designing therapies including antisense constructs (with Dr. Paul Zamecnik) and drugs (with Dr. Alan Sartorelli) for treatment of breast cancers and other solid tumors. I will apply our results to develop methods for finding rare metastatic cells in early breast cancer patients.

这笔赠款是为回应RFA申请而提交的三项拨款之一 乳腺癌的跨学科治疗方法。我们的总体目标是 三项赠款是：(I)开发新的方法来识别和 克隆癌症与正常组织差异表达的基因 癌基因阳性或肿瘤阴性的细胞 抑制基因；(Ii)研究这些基因的性质，以及 选择对诊断、预后和治疗有用的子集； 将这些发现应用于临床样本。这些方法包括 细胞生物学和分子遗传学，并架起基础科学的桥梁-- 临床界面。合作安排在以后的几年里 与劳埃德·奥尔德博士讨论免疫学的应用，与艾伦博士 Sartorelli谈药理学，与Paul Zamecnik博士谈反义 构造。 从已知的情况来看，大量的基因参与了 疾病、增殖、衰老、分化、DNA的调控 修复，染色体功能和细胞与细胞的相互作用将被展示 具有抑制器或激活器功能。这些将提供重要的 癌症之谜的碎片。他们的身份将允许许多人 研究人员将他们的研究整合到整个图景中。 然而，到目前为止，只有一小部分这样的基因被 确定(1)，部分原因是他们的方法很困难 选择。此Grant应用程序基于功能强大的 Pardee博士开发的差异显示技术，它提供了 解决这个基因选择问题的一种新方法。我们建议 在几个重要方面改进它。在我们与 Sager，Smith和Thor博士，这些基因的一个精选子集将是 克隆、测序，并与数据库进行比较。我们会做好准备 免疫学(与劳埃德·奥尔德博士合作)和杂交探针 诊断/预后及其为设计而研究的功能 包括反义构建的治疗(与Paul Zamecnik博士合作)和 治疗乳腺癌的药物(与艾伦·萨托雷利博士合作)和 其他实体瘤。我将应用我们的结果来开发方法 在早期乳腺癌患者中发现罕见的转移细胞。