Malignant behavior and resistance to cisplatin of human ovarian carcinoma xenografts established from the same patient at different stages of the disease.
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.
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
G
G
Masazza
V
V
Lucchini
A
A
Tomasoni
F
F
Peccatori
V
V
Lampasona
G
G
Giudici
C
C
Mangioni
A
A
Biondi
R
R
Giavazzi
D000818:Animals; D001201:Ascites / Q000209:etiology; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D002945:Cisplatin / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007621:Karyotyping; D051379:Mice; D008819:Mice, Nude; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D002945:Cisplatin