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HIRH IN GASTROINTESTINAL MALIGNANCIES

胃肠道恶性肿瘤中的 HIRH

基本信息

批准号：
6328950
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
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-12-16 至 2002-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6328950
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

项目摘要

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、生长因子等参与细胞间信号传导的分子。他们发挥着重要作用在广泛的正常和病理中具有刺激或抑制作用生长调节、炎症、修复、病毒和恶性疾病。本研究提案的长期目标是定义角色在肿瘤形成、扩散或新人类细胞因子的治疗中，我们将选定的胃肠道组织和恶性肿瘤称为 hIRH。比较基因差异的消减杂交技术 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，例如转移抑制基因 nm23。为了更快速地测定差异基因表达差异显示技术在cDNA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。我们通过差异展示分离出一系列新的和已知的基因我们已经确定在几个方面有差异表达胃肠道恶性肿瘤。该提案重点关注这样一个基因， hIRH，从肝细胞癌的差异表现中分离出来邻近的非肿瘤性肝脏，并继续研究以确定其在某些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发挥的功能作用，我们已经确定几乎一致地丢失了 hIRH 肝细胞癌与邻近的非肿瘤性癌相比肝脏。类似的细胞因子直接或间接都很重要通过诱导炎症反应，抑制肿瘤生长。我们计划评估 hIRH 对白细胞趋化性的活性和生长抑制，这两个过程在肿瘤中都非常重要生物学。