Masazza G, Lucchini V, Tomasoni A, Peccatori F, Lampasona V, Giudici G, Mangioni C, Biondi A, Giavazzi R
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Cancer Res. 1991 Dec 1;51(23 Pt 1):6358-62.
Three human ovarian carcinoma lines (HOC8) derived from the same patient before (P-HOC8) and after (R-HOC8 and Y-HOC8) cycles of chemotherapy were established i.p. in nude mice. The biological characterization showed that these tumor lines had various features in common. Cytological and histopathological characteristics and the expression of tumor-associated antigens OC125 and MOV18 were maintained in the three variants and were comparable to the patient's primary tumor. The HOC8 variants were aneuploid with a chromosome mode number of 80-81. All three tumor lines grew better i.p. than s.c. in nude mice. After i.p. injection the HOC8 lines produced ascites in all the mice, infiltration of pancreas, liver, diaphragm, and lung metastases. The sensitivity to cisplatin was evaluated for HOC8 lines growing in nude mice and mirrored the clinical development of resistance. Treatment with cisplatin of mice transplanted i.p. with P-HOC8 (obtained before the patient received chemotherapy) resulted in a significant increase in survival time; the R-HOC8 and Y-HOC8 lines (obtained after chemotherapy) were less sensitive. HOC8 xenografts, which represent the course of a single patient's disease, are a useful model for investigating the development of drug resistance in ovarian carcinoma.
从同一患者化疗前(P-HOC8)、化疗后(R-HOC8和Y-HOC8)获取的三株人卵巢癌细胞系经腹腔接种在裸鼠体内建立起来。生物学特性表明这些肿瘤细胞系具有多种共同特征。细胞学和组织病理学特征以及肿瘤相关抗原OC125和MOV18的表达在这三个变体中得以维持,且与患者的原发性肿瘤相当。HOC8变体为非整倍体,染色体众数为80 - 81。在裸鼠体内,所有这三株肿瘤细胞系经腹腔接种后的生长情况均优于皮下接种。经腹腔注射后,HOC8细胞系在所有小鼠体内均产生腹水、胰腺浸润、肝转移、膈肌转移和肺转移。对在裸鼠体内生长的HOC8细胞系进行顺铂敏感性评估,其结果反映了临床耐药性的发展情况。用顺铂治疗经腹腔接种P-HOC8(患者接受化疗前获取)的小鼠,可显著延长其存活时间;而R-HOC8和Y-HOC8细胞系(化疗后获取)则对顺铂不太敏感。HOC8异种移植瘤代表了单一患者的病程,是研究卵巢癌耐药性发展的有用模型。