title: A therapeutic model for advanced endometrial cancer: systemic progestin in combination with local adenoviral-mediated progesterone receptor expression.
abstract: Cancer of the uterine endometrium is a frequent gynecologic malignant disease for which few therapeutic options are available for advanced disease. Progesterone is the normal female hormone that limits growth and proliferation of endometrial cancers; however, progesterone receptors are frequently down-regulated, leading to treatment failures. The current studies explored the effectiveness of adenoviral-mediated progesterone receptor gene transduction in combination with progestin therapy in mouse xenograft models. Pretreatment of cells with progesterone receptor-encoding adenovirus and progestin inhibited the development of s.c. tumors in athymic mice. In the i.p. xenograft model, replacement of both isoforms of progesterone receptor, PRA and PRB, in combination with progestin treatment resulted in a significant 2.6-fold increase in overall survival time compared with control animals. These studies indicate that when progesterone receptor levels are maintained, progestin therapy is effective in limiting tumor growth. Future therapeutic regimens targeted at enhancing progesterone receptor expression have the potential to improve outcomes in women with endometrial cancer.
authors.affiliation: Reproductive Molecular Biology Laboratory, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of New Mexico Health Sciences Center, MSC10 5580, 1 University of New Mexico, Albuquerque, NM 87131, USA.
authors.forename: Donghai
authors.initials: D
authors.lastname: Dai
authors.forename: Lina
authors.initials: L
authors.lastname: Albitar
authors.forename: Tan
authors.initials: T
authors.lastname: Nguyen
authors.forename: Laura L
authors.initials: LL
authors.lastname: Laidler
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Singh
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Leslie
mesh_terms: D000256:Adenoviridae; D000818:Animals; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010534:Peritoneal Neoplasms / Q000473:pathology; D011372:Progestins / Q000627:therapeutic use*; D011980:Receptors, Progesterone / Q000235:genetics*; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: D011372:Progestins; D011980:Receptors, Progesterone