HIRH IN GASTROINTESTINAL MALIGNANCIES

胃肠道恶性肿瘤中的 HIRH

• 批准号: 2837699
• 负责人: GRAHAM F BARNARD
• 金额: $ 10.86万
• 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/2837699
• 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、白介素类、生长因子等 参与细胞间信号传递的分子。他们发挥着重要的作用 在广泛的正常和病理状态下的刺激或抑制作用 生长调节、炎症、修复、病毒和 恶性疾病。 这项研究提案的长期目标是确定 在肿瘤的形成、扩散或治疗中，一种新的人类细胞因子 我们称之为HIRH，在选定的胃肠道组织和恶性肿瘤中。 比较基因差异的消减杂交技术 在cdna水平上的表达已经被用来潜在地分离 恶性肿瘤中的重要基因，如转移抑制基因 Nm23。要更快速地确定差异基因的表达，请访问 差异显示技术在基因水平上检测到了新的 基因，或建议已知基因在选定的恶性肿瘤中发挥新的作用， 例如，乳腺癌中的maspin和整合素，前列腺癌中的PTI-1。我们 已经通过差异显示分离出了一系列新的和已知的基因 我们已经决定用几种不同的方式来表达 胃肠道恶性肿瘤。这项提议集中在一个这样的基因上， 从肝细胞癌和肝细胞癌的差异显示中分离到HIRH 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。 具体目标是定义1)遗传结构，以及2) 在肝细胞癌和其他组织中可能的功能作用， 我们已经确定几乎一致地失去了它 肝细胞癌与癌旁非肿瘤性病变的比较 肝脏。无论是直接还是间接，类似的细胞因子都很重要 通过诱导炎症反应，在抑制肿瘤 成长。我们计划评估hIRH对白细胞趋化的活性。 和生长抑制，这两个过程在肿瘤中都是非常重要的过程 生物学。