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CELLULAR INTERACTIONS IN HEMOPOIESIS

造血过程中的细胞相互作用

基本信息

批准号：
3446457
负责人：
HOWARD N STEINBERG
金额：
$ 5.78万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-08-01 至 1986-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3446457
关键词：
bone marrow carcinoma cell differentiation cellular oncology cimetidine erythropoiesis hematopoiesis hematopoietic stem cells leukemia lung neoplasms microcytic /hypochromic anemia neoplasm /cancer immunotherapy stromal cells suppressor T lymphocyte tissue /cell culture

项目摘要

Studies on the origin of anemia in chronic disease will focus on the anemia associated with cancer as an aberration in the control of erythropoiesis by T-lymphocytes during the development of neoplasia. Using a Lewis lung carcinoma, the relationship of tumor-induced T-suppressor cell activity and erythroid cell development will be evaluated. Using the drug cimetidine, the role of immunotherapy to block suppressor cell activity and allow the normal development of erythroid cells in tumor-bearing mice will be examined. The ability of normal physiological regulators of hemopoiesis to induce differentiation in human leukemia cell lines will be examined. In vivo, K562 and HL-60 cells will be seeded into diffusion chambers and implanted into the peritoneal cavities of normal and hematologically perturbated mice. In vitro studies will focus on the abiIity of normal human donors' bone marrow stroma, which appears to play an important role in normal blood cell development, inducing leukemic cell differentiation. Morphological and functional maturation will be assessed in both studies. Finally, the ability of human leukemic cell lines to suppress normal hemopoiesis prior to and after inducing differentiation by chemical agents will be examined in vitro. The objective will be to determine whether the property of leukemic cell inhibition of normal hemopoiesis is lost when leukemic cells undergo differentiation. The efficacy of "induction chemotherapy" as a means of reversing leukemic cell suppression of normal stem cell development may thus provide an alternative to cytotoxic reduction therapy to establish remission and cure. (IS)

对慢性病贫血病因的研究将主要集中在贫血与癌症相关，作为控制红细胞生成的异常，肿瘤形成过程中的T淋巴细胞。用的是刘易斯肺肿瘤诱导的T抑制细胞活性与将评价红系细胞发育。使用西咪替丁，免疫疗法阻断抑制细胞活性并允许在荷瘤小鼠中红系细胞的正常发育将是考察造血的正常生理调节剂诱导将检查人白血病细胞系中的分化。在体内，将K562和HL-60细胞接种到扩散室中并植入进入正常和血液紊乱的腹膜腔小鼠体外研究将集中在正常人类捐赠者的能力上。骨髓基质，它似乎在正常血液中起着重要作用，细胞发育，诱导白血病细胞分化。形态在两项研究中评估功能成熟。最后，人类白血病细胞系抑制正常化学试剂诱导分化前后造血将在体外进行检查。目标是确定白血病细胞抑制正常造血的特性丧失，白血病细胞经历分化。 “诱导”的功效化疗”作为逆转白血病细胞抑制正常因此，干细胞发育可以提供细胞毒性的替代方案，减少治疗，以建立缓解和治愈。（IS）