Study on Biochemical Modulation Therapy for Drug Resistant SCLS

耐药SCLS的生化调节治疗研究

基本信息

批准号：
09671358
负责人：
KOBAYASHI Shunsuke
金额：
$ 1.47万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

1) The modulating activity of indomethacin to vincristine was investigated in thirty human pulmonary carcinoma cell lines and five other cell lines. The survival of these cell lines treated with VCR with or without indomethacin (2μg/ml) for 72 hours were examined using MTT assay. Mean modulating activity (MI) was 2.91 in adenocarcinomas, 1.92 in squamous cell carcinomas, 3.06 in large cell carcinomas and 1.67 in small cell carcinomas. Other tumors cell lines showed the potent combined effect of VCR and indomethacin.2) NSE and CEA levels in the culture supernatant of 65 pulmonary carcinoma cell lines were measured by a radioimmunoassay (RIA). The mean value of NSE was 30 【minus-plus】 22 ng/ml and 9.1 【minus-plus】 8.7 ng/ml in SCLC and non-SCLC, respectively (p<0.001). The mean value of CEA was 14.4 【minus-plus】 20.6 ng/ml and 32.3 【minus-plus】 80.3 ng/ml in SCLC and non-SCLC, respectively. There was a significant inverse proportional correlation between NSE and CEA production in each SC … More LS cell lines (r=-0.42, p<0.05). In the SCLC lines, cell proliferation ability and growth characteristic in vitro had correlation with NSE and CEA levels. There was significant correlation between NSE levels and their prognosis (p<0.05).3) We examined the modulating effect of indomethacin for VCR and MTX in 4 large cell like variant SCLC cell lines originated from tumors which recurred after chemotherapy and 6 pure SCLC cell lines with floating colony type or neurocyte type sing MTT assay. The survival of these cell lines treated with VCR and MTX with or without indomethacin (2μg/ml) for 72 hours were examined. The MI for VCR in variant SCLC cells were significantly high as compared those of classical pure SCLC cells (p<0.05).4) Recently, the modulation therapy combined with VCR, MTX and indomethacin was treated for 2 patients with stage IV SCLC recurred after ordinary chemotherapy, and both of the patients achieved almost CR in only one cycle of the modulation therapy without obvious adverse effects at outpatient clinic.5) We demonstrate that combined use of indomethacin and cyclosporin A reveal a potent synergistic modulation effect to VCR cytotoxicity in human lung carcinoma cells in vitro.(Conclusion) It is considered that modulating activity of indomethacin for VCR is a general effect for various human cancer cells, and that modulation therapy combined with VCR, MTX and indomethacin may be an effective treatment for the stage IV SCLC recurred after ordinary chemotherapy. Less

1）在三十种人类肺癌细胞系和其他五个细胞系中研究了吲哚美辛对散霉素的调节活性。使用MTT测定法检查了用有或没有吲哚美辛（2μg/ml）的VCR处理72小时的这些细胞系的存活。在腺癌中，平均调节活性（MI）为2.91，鳞状细胞癌为1.92，大细胞癌为3.06，在小细胞癌中为1.67。其他肿瘤细胞系显示了VCR和吲哚美辛的潜在综合作用。2）NSE和CEA水平在65个肺癌细胞系的培养上清液中的NSE和CEA水平通过放射免疫分子（RIA）测量。 NSE的平均值分别为22 ng/ml和9.1 [Minus-Plus] 8.7 ng/ml，分别为SCLC和非SCLC（p <0.001）。 CEA的平均值分别为14.4 [减去] 20.6 ng/ml和32.3 [MINUS-PLUS] 80.3 ng/ml，分别为SCLC和非SCLC。在每个SC中，NSE和CEA产生之间存在显着的反比例相关性……更多的LS细胞系（r = -0.42，p <0.05）。在SCLC系中，体外细胞增殖能力和生长特征与NSE和CEA水平具有相关性。 NSE水平与其预后之间存在显着相关性（p <0.05）。3）我们检查了在4个大细胞中VCR和MTX在4个大细胞（如变体SCLC细胞系）中的调节作用，该肿瘤起源于化学疗法后复发的肿瘤和6个纯净的SCLC细胞系带有浮体CLONY类型类型或Neurocyte type sing Mitty M.ty M.Tys sassay。检查了这些细胞系用VCR和MTX处理有或没有吲哚美辛（2μg/mL）72小时的生存期。由于比较经典的纯SCLC细胞的MI（p <0.05）。4）最近，与VCR，MTX和Indomethacin结合的调节治疗对2阶段IV SCLC在普通化学疗法后的临床效果几乎不适合于一次临床效果，并且在不证实的情况下，调节疗法与VCR，MTX和Indomethacin结合了治疗。证明在人类肺癌细胞中对VCR细胞毒性的潜在协同调节作用的结合使用揭示了潜在的协同调节作用。普通化学疗法后重复。较少的