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Basic and clinical research of peripheral blood stem cell transplant (PBSCT) in chemotherapy for lung cancer

外周血干细胞移植（PBSCT）在肺癌化疗中的基础与临床研究

基本信息

批准号：
06670615
负责人：
SHIMIZU Eiji
金额：
$ 1.22万
依托单位：
University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670615/
关键词：
High dose chemotherapy Lung cancer Oncogene NK cell hematopoietic stem cell PBSC Peripheral blood stem cell transplant RB Cyclin SCF 自家移植

项目摘要

Treatment of inoperable lung cancer consists of radiotherapy and chemotherapy, which have not improved the survival of the patients significantly because of myelosuppression including leukopenia. Peripheral blood stem cell transplant (PBSCT), an alternative of bone marrow transplant, which has recently developed in hematologic malignancy, may improve the survival of the inoperable lung cancer patients in combination with high dose chemotherapy. In this study, we examined the basic and clinical evaluation of PBSCT in patients with lung cancer. Cancer cell contamination was not found in any peripheral blood mononuclear cell sample from 15 patients. Survival rate and cytokine production of mononuclear cells stimulated by IL-12, ratio of CD34+ cell and CD33-/34+ cell, and number of CFU-GM in PBSC samples did not decrease after freezing and thawing. Under written informed consent, we did clinical application of PBSCT for two patients with small cell lung cancer and experienced rapid recovery from chemotherapy-induced myelosuppression. Megakaryocyte proliferation and differentiation induced by SCF closely related to increased expression of cyclin A and phosphorylation of RB tumor suppressor gene product. Natural killer (NK) activity of peripheral blood lymphocyte decreased after initiation of chemotherapy, reached to nadir 2 weeks later, and then recovered to pretreatment level 4-5 weeks later. Suppression of NK activity by high-dose chemotherapy was abrogated by PBSCT.These results suggest that PBSCT may contribute to not only hematopoietic recovery but also antitumor immunological recovery.

不能手术的肺癌的治疗包括放疗和化疗，但由于包括白细胞减少在内的骨髓抑制，这些治疗并没有显著提高患者的存活率。外周血干细胞移植(PBSCT)是近年来在恶性血液病患者中发展起来的一种骨髓移植的替代方法，与大剂量化疗相结合可提高不能手术的肺癌患者的生存率。在这项研究中，我们研究了肺癌患者PBSCT的基础和临床评估。15例患者的外周血单核细胞样本中均未发现癌细胞污染。冻融后单个核细胞在IL-12刺激下的存活率、细胞因子的产生、CD34+细胞与CD33-/34+细胞的比值及CFU-GM数量均未见下降。在书面知情同意下，我们对两名小细胞肺癌患者进行了PBSCT的临床应用，并经历了化疗引起的骨髓抑制迅速恢复。SCF诱导巨核细胞增殖分化与细胞周期蛋白A表达增加和Rb抑癌基因产物磷酸化密切相关。化疗开始后外周血淋巴细胞自然杀伤(NK)活性下降，2周后降至最低点，4~5周后恢复至化疗前水平。PBSCT可消除大剂量化疗对NK活性的抑制作用，提示PBSCT不仅有助于造血恢复，而且有助于抗肿瘤免疫恢复。