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Malignant Behavior and Resistance to Cisplatin of Human Ovarian Carcinoma Xenografts Established from the Same Patient at Different Stages of the Disease¹

Mario Negri Institute for Pharmacological Research, Via Gavazzeni 11, 24100 Bergamo [G. M., A. T., R. G.]; Mario Negri Institute for Pharmacological Research, Via Eritrea 62, 20157 Milano [F. P., V. L.]; and Departments of Pathology [V. L.], Pediatrics [G. G., A. B.] and Obstetrics and Gynecology [C. M.], S. Gerardo Hospital, Via Solferino, 20052 Monza, Italy.

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.

¹ This research was supported by grants from the Italian Association for Cancer Research, Milan, Italy, the National Research Council, Rome, Italy, and the Developmental Therapeutics Program DCT, NCI. Drs. A. Biondi and G. Giudici are supported by Fondazione Tettamanti.

² To whom requests for reprints should be addressed, at Istituto di Ricerche Farmacologiche, Mario Negri, Via Gavazzeni 11, 24100 Bergamo, Italy.

Received 6/ 3/91. Accepted 9/24/91.