期刊
CLINICAL CANCER RESEARCH
卷 12, 期 5, 页码 1593-1598出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-05-2108
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- NCI NIH HHS [CA 17393] Funding Source: Medline
- NICHD NIH HHS [HD 32212] Funding Source: Medline
Purpose: Mullerian inhibiting substance (MIS) is a glycoprotein hormone that causes Mullerian duct regression in male embryos. In short-term experiments, recombinant human MIS (rhMIS) inhibits xenotransplanted human ovarian cancer cell lines that are thought to be of Mullerian origin. Because this highly lethal cancer has a high recurrence rate after conventional chemotherapy, new treatments are warranted. We examined whether rh MIS as a novel, nontoxic, naturally occurring growth inhibitor can be an effective anticancer drug in long-term studies in vivo against allograft tumors that recapitulate human ovarian carcinoma. Experimental Design: Mouse ovarian carcinoma (MOVCAR) cell lines expressing the early region of the SV40 virus, including the large and small T-antigen genes under transcriptional control of a portion of the murine MIS receptor type II (MISRII) gene promoter, were derived from TgMISIIR-TAg transgenic mice. rh MIS was tested against MOVCAR cells in growth inhibition assays in vitro, and in vivo in 6-week-old female nude mice. Tumor growth in animals was measured at weekly intervals for up to 20 weeks. Results: MOVCAR cells and tumors express MISRII by Western blot, immunohistochemical, and Northern blot analyses. rh MIS significantly inhibited MOVCAR cell growth in vitro and in vivo in three separate long-term allotransplantation experiments. Conclusions: Because rh MIS is an effective anticancer agent in in vitro and in long-term in vivo preclinical experiments against MISRII-positive tumors, we predict that rh MIS can be used safely and effectively to treat human ovarian malignancies.
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