The discovery of more active therapeutic compounds is essential if the outcome for patients with advanced-stage epithelial ovarian cancer is to be improved. Gedunin, an extract of the neem tree, has been used as a natural remedy for centuries in Asia. Recently, gedunin has been shown to have potential in vitro antineoplastic properties; however, its effect on ovarian cancer cells is unknown. We evaluated the in vitro effect of gedunin on SKOV3, OVCAR4, and OVCAR8 ovarian cancer cell lines proliferation, alone and in the presence of cisplatin. Furthermore, we analyzed in vitro gedunin sensitivity data, integrated with genome-wide expression data from 54 cancer cell lines in an effort to identify genes and molecular pathways that underlie the mechanism of gedunin action. In vitro treatment of ovarian cancer cell lines with gedunin alone produced up to an 80% decrease in cell proliferation (P < 0.01) and, combining gedunin with cisplatin, demonstrated up to a 47% (P < 0.01) decrease in cell proliferation compared with cisplatin treatment alone. Bioinformatic analysis of integrated gedunin sensitivity and gene expression data identified 52 genes to be associated with gedunin sensitivity. These genes are involved in molecular functions related to cell cycle control, carcinogenesis, lipid metabolism, and molecular transportation. We conclude that gedunin has in vitro activity against ovarian cancer cells and, further, may enhance the antiproliferative effect of cisplatin. The molecular determinants of in vitro gedunin response are complex and may include modulation of cell survival and apoptosis pathways.
Laparoscopy is a safe and effective approach for surgical staging of selected patients with endometrial cancer. Further studies and cost-benefit analyses are required to determine if the use of robotics improves outcomes over standard laparoscopy and can extend the benefits of minimally invasive surgery to a larger proportion of patients with this common gynecologic malignancy.
The development of appropriate animal model systems has been proposed as a means of facilitating the study of human colorectal cancer. This report describes the development and use of a blind-colorectal pouch in a carcinoma mouse model. The blind-pouch was prepared in C57BL/6J mice by surgically exteriorizing the descending colon and producing two stomata in the abdominal wall. The proximal stoma served as an end colostomy and the distal stoma created as a mucous fistula. Surgical closure of the anus thus provided a colorectal pouch. In pilot studies it was found that N-methyl-N-nitrosourea (MNU) and radiation together but neither separately produced tumors in the pouch of surviving mice. Further, inoculation of C38 syngeneic tumor cell suspension into the pouch and immediate closure resulted in tumor takes within three to four weeks. The use of this model in carcinogenesis and the immunology of colon cancer simulate the human colorectal cancer problem more closely than previous animal models.
During robotically-assisted pelvic lymphadenectomy, four venous injuries occurred that did not resolve with pressure. After the application of tightly woven, oxidized regenerated cellulose and a fibrin sealant, all four venotomies were hemostatic. There were no sequelae.
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