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Responsiveness of gynecologic tumors to chemotherapeutic agents in the 6-day subrenal capsule assay
Authors:Richard E. Hunter M.D.   Steven D. Reich M.D.   Thomas W. Griffin M.D.  Arthur E. Bogden Ph.D.
Affiliation:1. Division of Gynecologic Oncology/Department of Obstetrics and Gynecology, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, Massachusetts 01605 U.S.A.;2. Division of Clinical Pharmacology/Departments of Medicine and Pharmacology, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, Massachusetts 01605 U.S.A.;3. Division of Medical Oncology/Department of Medicine, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, Massachusetts 01605 U.S.A.;4. Laboratory of Immunobiology and Experimental Oncology, EG&G Mason Research Institute, 57 Union Street, Worcester, Massachusetts 01608 U.S.A.
Abstract:Various gynecologic malignancies have been tested in the 6-day subrenal capsule assay, which is an in vivo test of human tumor responsiveness to drug therapy. Fresh surgical explants of ovarian, endometrial, and cervical tumors were implanted as 1-mm3 fragments under the renal capsule of normal mice and tested against a spectrum of clinically active agents. Regardless of the site of origin, human tumors showed variations in growth rate when implanted under the renal capsule that appeared to reflect both the growth potential characteristic of each tumor as well as the heterogeneity of the cell populations comprising each tumor. An average of 60% of tumors showed positive growth and 11% demonstrated no measurable change in size. The response rates of 18 ovarian, 28 endometrial, and 20 cervical carcinomas to clinically active chemotherapeutic agents were determined. A range of responses, in terms of drugs indicated to be active and of the degree of responsiveness to active agents, was obtained with each histologic type. Response rates varied from 6% to tamoxifen in cervical carcinomas to 80% to 5-fluorouracil in ovarian carcinomas. The results of this study support the variability in chemotherapy responsiveness observed clinically with gynecologic tumors and suggest the feasibility of using the subrenal capsule assay as a predictive test.
Keywords:ADR  doxorubicin  cis-Pt  cisplatin  CTX  cyclophosphamide  DES  diethylstilbesterol  5FU  5-fluorouracil  HMM  hexamethylmelamine  L-PAM  melphalan  MTX  methotrexate  TAM  tamoxifen  TP  testosterone proprionate  VCR  vincristine
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