The objectives of this study were to determine the effects of adenovirus-mediated p16 and p53 on growth and apoptosis in ovarian cancer cells and on survival in nude mice implanted with human ovarian cancer cells.SKOV-3 ip1 (p53 and p16 null), 2774 (p53 and p16 mutant), and OVCA 420 (p53 and p16 wild-type) cells were used for in vitro studies. SKOV-3 ip1, 2774, and Hey A8 (p53 and p16 wild-type) cells were used in the nude mouse studies. The E1-deleted adenoviruses containing p53, p16, or beta-galactosidase cDNA were transfected into the different cell types or inoculated into the nude mice after injection with ovarian cancer cells.Cell counting, microtetrazolium, and anchorage-independent growth assays on transfected cells demonstrated that p16 and the p16/p53 combination suppressed growth, whereas p53 did not (except in the anchorage-independent growth assay). Although cells infected with the p16/p53 combination had decreased growth compared with cells infected with either tumor suppressor alone, the difference was only statistically significant compared with p53. p16, p53, and the p16/p53 combination all increased apoptosis in the cells. In the nude mice, p16 treatment resulted in the longest survival for all three models, although it only reached statistical significance for the 2774 and SKOV-3 ip1 groups.Overall, p16 demonstrated greater growth inhibition than p53 both in vivo and in vitro. The p16/p53 combination demonstrated a consistent trend toward increased growth suppression and apoptosis over p16 or p53 alone. Adenovirus-mediated p16 may be a viable future treatment for ovarian cancer.
Hintergrund/Einleitung: Effekte psychologischer und physiologischer Stressoren auf Immunfunktionen sind bekannt, aber ob Übelkeit (Nausea) infolge vestibulärer Stimulation (Bewegungskrankheit) die Glucocorticoid-Sensitivität (GS) des zellulären Immunsystems beeinflusst, wurde bislang noch nicht untersucht.
The objective of the current study was to update the authors' experience with patients with ovarian serous borderline tumors with invasive peritoneal implants to gain additional insight into the biologic behavior of these tumors and a better understanding of the effect of postoperative treatment.Thirty-nine patients with ovarian serous borderline tumors with invasive peritoneal implants were identified through a retrospective review. Major endpoints selected for analysis were surgicopathologic response, time to recurrence, type of recurrence, progression free survival, and overall survival. Univariate and multivariate regression analyses also were performed.Median follow-up time was 111 months. Four of 7 evaluable patients who had second-look surgery (57%) had a response to chemotherapy. Twelve of 39 patients (31%) either developed progressive disease or had a recurrence. The median time from date of diagnosis to recurrence was 24 months. In 10 of these 12 patients with a recurrence, tissue was available; 9 had invasive low grade serous carcinoma and 1 had a recurrent borderline tumor. Macroscopic residual disease was the only factor studied that had a significant effect on survival; patients with no macroscopic residual tumor had a significantly better survival than those with any macroscopic residual tumor (P < 0.01). In univariate regression analysis, macroscopic residual disease and the presence of frankly invasive implants were significant predictors of progression free survival. Platinum-based chemotherapy was associated with a significantly shorter progression-free survival. Only macroscopic residual tumor was a significant predictor of survival.Greater than 30% of patients with ovarian serous borderline tumors with invasive peritoneal implants will develop progressive or recurrent tumor, most commonly serous carcinoma. The presence of macroscopic residual disease appears to be the major predictor of recurrence and survival. However, in this study, the authors were unable to elucidate the role of postoperative therapy or the criteria for selection of patients for such therapy.
