HIRH IN GASTROINTESTINAL MALIGNANCIES

胃肠道恶性肿瘤中的 HIRH

• 批准号: 6124514
• 负责人: GRAHAM F BARNARD
• 金额: $ 10.74万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-16 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6124514
• 关键词: cytokine; gastrointestinal neoplasms; gene expression; guinea pigs; hepatocellular carcinoma; human tissue; laboratory mouse; laboratory rabbit; laboratory rat; neoplasm /cancer genetics; neoplastic growth; polymerase chain reaction; subtraction hybridization

Cytokines include interferons, interleukins, growth factors and other molecules involved in signalling between cells. They play important stimulatory or inhibitory roles in a wide range of normal and pathologic processes such as growth regulation, inflammation, repair, viral and malignant diseases. The long-term objective of this research proposal is to define the role in tumor formation, spread or treatment of a new human cytokine, which we call hIRH, in selected gastrointestinal tissues and malignancies. Subtractive hybridization techniques to compare differences in gene expression at the cDNA level have been used to isolate potentially important genes in malignancy, such as the metastasis suppressor gene nm23. For a more rapid determination of differential gene expression at the cDNA level the technique of differential display has detected new genes, or suggested new roles for known genes in selected malignancies, e.g. maspin and integrins in breast cancer, PTI-1 in prostate cancer. We have isolated, by differential display, a range of new and known genes which we have determined to be differentially expressed in several gastrointestinal malignancies. This proposal focuses on one such gene, hIRH, isolated from differential displays of hepatocellular carcinoma and adjacent non-neoplastic liver, and continues studies to define its potential role in selected gastrointestinal malignancies. The specific aims are to define 1) the genetic structure, and 2) the possible functional role in hepatocellular carcinoma and other tissues, of hIRH which we have determined to be almost uniformly lost from hepatocellular carcinomas, in comparison with the adjacent non-neoplastic livers. Similar cytokines are important either directly, or indirectly via the induction of an inflammatory response, in the inhibition of tumor growth. We plan to assess the activity of hIRH on leukocyte chemotaxis and in growth inhibition, both highly significant processes in tumor biology.

细胞因子包括干扰素、白细胞介素、生长因子和其他细胞因子。 参与细胞间信号传递的分子。起重要 在广泛的正常和病理的刺激或抑制作用 过程，如生长调节、炎症、修复、病毒和 恶性疾病 本研究提案的长期目标是确定 在肿瘤形成、扩散或治疗新的人细胞因子中， 我们称之为hIRH，在特定的胃肠道组织和恶性肿瘤中。 差减杂交技术比较基因差异 在cDNA水平的表达已被用于分离潜在的 恶性肿瘤中的重要基因，如转移抑制基因 nm23。为了更快速地确定不同基因表达， 差异显示技术在cDNA水平上发现了新的 基因，或已知基因在选定的恶性肿瘤中的新作用， 例如乳腺癌中的maspin和整合素，前列腺癌中的PTI-1。我们 通过差异显示，分离出一系列新的和已知的基因 我们已经确定了在几个不同的基因中， 胃肠道恶性肿瘤。这项提议集中在这样一个基因上， hIRH，分离自肝细胞癌的差异显示， 邻近的非肿瘤性肝脏，并继续研究，以确定其 在选定的胃肠道恶性肿瘤中的潜在作用。 具体目标是：1）确定遗传结构; 2）确定 在肝细胞癌和其他组织中可能的功能作用， 我们已经确定，几乎均匀地失去了从hIRH 肝细胞癌，与邻近的非肿瘤性相比 肝脏类似的细胞因子直接或间接地很重要 通过诱导炎症反应，抑制肿瘤， 增长我们计划评估hIRH对白细胞趋化性的活性 和生长抑制，这两个在肿瘤中非常重要的过程 生物学