Would Lipophilic Statin Therapy as a Prognostic Factor Improve Survival in Patients With Uterine Cervical Cancer?

OBJECTIVES: In vitro studies showed that lipophilic statins inhibit cell growth, adhesion, and invasion and induce apoptosis in cancer cell lines. In uterine cervical cancer, several important factors including age, stage, anemia, lymphovascular invasion, lymph node metastases, and parametrial spread were known to significantly predict survival. We investigated whether statin therapy as a prognostic factor would significantly predict survival in cervical cancer. METHODS: Patients with stages IB to IV cervical cancer who received radical hysterectomy and/or para-aortic lymph node dissection were included. The statin-use group was identified as patients who were continuously prescribed with lipophilic statins from prediagnostic period of the cancer. RESULTS: The baseline characteristics of both statin-use group and control group were comparable. During a median follow-up of 36.6 months, progression-free survival and overall survival of the statin-use group were significantly higher than the control group (P < 0.001 and P = 0.004, respectively). In multivariate analysis, the statin-use group had an independent prognostic significance compared with other prognostic factors (progression-free survival: hazards ratio = 0.062, 95% confidence interval = 0.008-0.517, P = 0.010; overall survival: hazards ratio = 0.098, 95% confidence interval = 0.041-0.459, P = 0.032). CONCLUSIONS: In the present study, continuous lipophilic statin therapy from the prediagnostic period of uterine cervical cancer could reflect favorable outcome, independently.

IL-10-dependent down-regulation of MHC class II expression level on monocytes by peritoneal fluid from endometriosis patients.

Endometriosis is a gynecologic disorder characterized by the ectopic growth of misplaced endometrial cells. Moreover, immunological abnormalities of cell-mediated and humoral immunity may be associated with the pathogenesis of endometriosis. The effects of peritoneal fluid (PF) from endometriosis patients on the expression levels of MHC class II and costimulatory molecules on the cell surfaces of monocytes were investigated. Compared to the PF of controls, the addition of 10% PF (n=10) from patients with endometriosis to culture medium significantly reduced the percentage of MHC class II-positive cells in cultures of a THP-1, monocytic cell line at 48 h. The effect of endometriosis patient PF (EPF) was dose-dependent, and similar effect was observed in peripheral blood monocytes. An inverse correlation was found between MHC class II expression level and IL-10 concentration in EPF (r=-0.518; p=0.019) and in the supernatant of peripheral blood monocyte cultured in EPF (r=-0.459; p=0.042) (n=20). The expression levels of costimulatory molecules (CD80 and CD86), but not of CD54 and B7-H1, were down-regulated by EPF. The mRNA level of HLA-DR was unaffected by EPF but protein level was reduced by EPF. Neutralizing IL-10 antibody abrogated MHC class II down-regulation on monocytes, which had been induced by EPF. However, in a functional assay, monocytes treated with EPF failed to stimulate T cell in mixed leukocyte reaction, although T cell proliferation was increased with EPF-treated monocytes and Staphylococcus enterotoxin B. These results suggest that MHC class II expression level on monocytes is down-regulated by EPF, but the cell stimulatory ability of monocytes does not coincide with MHC class II expression level.