Kikuchi H, Asamura M, Gamoh M, Ohuchi H, Wakui A
Dept. of Clinical Cancer Chemotherapy, Tohoku University.
Gan To Kagaku Ryoho. 1990 Mar;17(3 Pt 2):532-41.
Six-day subrenal capsule assay (SRCA) using normal immunocompetent mice developed by Bogden et al. is a promising in vivo chemosensitivity test. This method, however, has a problem of influence of the host reaction. We compared the tumor growth kinetics and host reaction between normal immunocompetent and nude mice. The tumor diameter increased until day 6 in normal and day 16 in nude mice, respectively. However the histological finding revealed many host reactive cells and few viable tumor cells on day 6 in normal mice, and well preserved tumour cells on day 16 in nude mice. These results were supported by flow cytometrical analysis. Then, we examined two immunosuppressive drugs; cyclophosphamide (EX) and cyclosporin A (CSA) in SRCA. The tumors increased in the diameter until day 16 in both EX and CSA-treated groups, but the results of the histological examination showed that tumor cells were preserved in tissue on day 14 in CSA-treated and day 6 in EX-treated group. These results were also supported by flow cytometrical analysis. From the investigation of antitumour activities of adriamycin (ADR) and mitomycin C, it was suggested that the 12-day assay was suitable if nude mice were used in SRCA, and six-day assay also, if EX-treated normal mice were used. In CSA-treated group, more toxicity of anticancer drugs was manifested than usual. We studied whether or not CSA had a usefulness in SRCA with normal immunocompetent mice. Sixty mg/kg of CSA was given to BDF1 mice daily SC, and various dosage of ADR was given i.v. on day 2. The body weight of BDF1 mice decreased over 20% within 10 days when ADR was given at more than 5 mg/kg. MX-1, a human breast carcinoma cell line, is known to be sensitive to ADR. This tumor was implanted SC in the back of BALB/c nu/nu mice and chemosensitivity was tested against ADR. ADR resulted to be positive at the dose of 8 mg/kg. On the other hand, the dose of 5 mg/kg proved to be negative, and hence the result of SRCA would be false negative, if the dose of ADR is reduced to avoid the toxicity of CSA. The tumor grew slowly when only 60 mg/kg of CSA was given daily for three weeks, and the inhibition rate was 56.2%. The toxicity of CSA was neglected because the body weight loss was approximately 13%. CSA may have the antitumor effect by itself, and EX did not suppress the host reaction sufficiently.(ABSTRACT TRUNCATED AT 400 WORDS)
由博登等人开发的使用正常免疫活性小鼠的六日肾包膜下测定法(SRCA)是一种很有前景的体内化学敏感性测试方法。然而,该方法存在宿主反应影响的问题。我们比较了正常免疫活性小鼠和裸鼠之间的肿瘤生长动力学及宿主反应。肿瘤直径在正常小鼠中到第6天增大,在裸鼠中到第16天增大。然而,组织学检查显示,正常小鼠在第6天时存在许多宿主反应性细胞且存活肿瘤细胞很少,而裸鼠在第16天时肿瘤细胞保存良好。这些结果得到了流式细胞术分析的支持。然后,我们在SRCA中研究了两种免疫抑制药物;环磷酰胺(EX)和环孢素A(CSA)。在EX和CSA治疗组中,肿瘤直径均增大到第16天,但组织学检查结果显示,CSA治疗组在第14天、EX治疗组在第6天时肿瘤细胞在组织中得以保存。这些结果也得到了流式细胞术分析的支持。通过对阿霉素(ADR)和丝裂霉素C抗肿瘤活性的研究表明,如果在SRCA中使用裸鼠,12日测定法是合适的;如果使用EX处理的正常小鼠,六日测定法也是合适的。在CSA治疗组中,抗癌药物的毒性比平时更明显。我们研究了CSA在正常免疫活性小鼠的SRCA中是否有用。每天给BDF1小鼠皮下注射60mg/kg的CSA,并在第2天静脉注射不同剂量的ADR。当ADR剂量超过5mg/kg时,BDF1小鼠的体重在10天内下降超过20%。人乳腺癌细胞系MX - 1已知对ADR敏感。将该肿瘤皮下植入BALB/c nu/nu小鼠背部,并对ADR进行化学敏感性测试。ADR在8mg/kg剂量时结果为阳性。另一方面,5mg/kg剂量被证明为阴性,因此,如果降低ADR剂量以避免CSA的毒性,SRCA的结果将为假阴性。当仅连续三周每天给予60mg/kg的CSA时,肿瘤生长缓慢,抑制率为56.2%。由于体重减轻约13%,CSA的毒性可忽略不计。CSA本身可能具有抗肿瘤作用,且EX没有充分抑制宿主反应。(摘要截断于400字)