|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1999 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1998 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1997 : ¥800,000 (Direct Cost : ¥800,000)
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
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