Progesterone reduces neurofilament (NF)--positive nerve fibers in eutopic endometrium of patients with endometriosis and myomata.

OBJECTIVE: To evaluate whether there are neurofilament (NF)-positive nerve fibers in the eutopic endometrium of patients with myoma and endometriosis by using stromal cell culture and to verify whether progesterone has an effect on the NF-positive nerve fiber by using stromal cell culture. STUDY DESIGN: Patients with uterine myoma (N = 11), ovarian and pelvic endometriosis (N = 10), and without myoma and endometriosis (N = 10) were included in the study. Human endometrial tissues were obtained from hysterectomy and curettage. The stromal cells were cultured and immunostaining was performed before and after treatment with progesterone by using NF. RESULTS: Before progesterone treatment the percentage of NF-positive nerve fibers between the uterine myoma group (4.91 +/- 2.05) and the endometriosis group (2.22 +/- 0.92) was statistically significant, and there was a significantly different percentage of NF-positive nerve fibers between the uterine myoma group (4.91 +/- 2.05) and the levonorgestrel intrauterine device-inserted group (1.50 +/- 0.25). After progesterone treatment the percentage of NF-positive nerve fibers was significantly decreased in the uterine myoma (2.09 +/- 1.73) and the endometriosis (1.48 +/- 0.80) groups. CONCLUSION: We showed that the NF-positive nerve fibers were reduced after progesterone treatment by using stromal cell culture and suggest that progesterone could have a role in the decrease of endometriosis/myoma-associated pain.

CA-125 level as a prognostic indicator in type I and type II epithelial ovarian cancer.

OBJECTIVE: Most patients with epithelial ovarian cancer achieve a complete clinical remission (CCR) with normal CA-125 but will still relapse and die from their disease. The present study was designed to determine whether CA-125 levels before, during, and after primary treatment provide prognostic information for both type I and type II ovarian cancer. METHODS: In this retrospective study, we identified 410 patients with epithelial ovarian cancer who had achieved a CCR between 1984 and 2011. A Cox proportional hazards model and log-rank test were used to assess associations between the nadir CA-125, histotype, and prognosis. RESULTS: The baseline serum CA-125 concentration was higher in patients with type II ovarian cancer than in those with type I ovarian cancer (P < 0.001). The nadir CA-125 was an independent predictor of progression-free survival (PFS; P < 0.001) and overall survival (OS; P = 0.035) duration. The PFS and OS durations were 21.7 and 79.4 months in patients with CA-125 of 10 U/mL or less and 13.6 and 64.6 months in those with CA-125 of 11 to 35 U/mL, respectively (P = 0.01 and P = 0.002, respectively). Histotype was an independent predictor of PFS (P = 0.041): the PFS and OS durations of the patients with type I ovarian cancer were longer than those of the patients with type II ovarian cancer (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: The nadir CA-125 and histotype are predictive of PFS and OS durations in patients with ovarian cancers who experienced a CCR. Progression-free survival and OS durations were shorter in the patients with CA-125 levels of 11 to 35 U/mL and type II disease than in those with CA-125 levels of 10 U/mL or less and type I ovarian cancer.

Sex-determining region Y-box 2 expression predicts poor prognosis in human ovarian carcinoma.

Sex-determining region Y-box 2 is proposed to be a key transcription factor in embryonic stem cells. The known roles of sex-determining region Y-box 2 in development and cell differentiation suggest that it is relevant to the aberrant growth of tumor cells. Thus, sex-determining region Y-box 2 may play an important role in tumor progression. However, its clinical significance in human ovarian carcinoma has been uncertain until recently. The aim of the present study was to clarify the clinical role of sex-determining region Y-box 2 expression in ovarian carcinoma. Immunohistochemical staining of 540 human ovarian carcinoma samples for sex-determining region Y-box 2 was performed using tissue microarray. The associations among sex-determining region Y-box 2 expression and clinical factors (diagnosis, tumor grade, International Federation of Gynecology and Obstetrics stage, and response to chemotherapy), overall survival, and disease-free survival were analyzed. We observed sex-determining region Y-box 2 expression in 15% of the ovarian carcinoma samples. Use of the Fisher exact test suggested that sex-determining region Y-box 2 expression was associated with high-grade carcinoma (P = .009), especially high-grade serous carcinoma (P = .048); International Federation of Gynecology and Obstetrics stage (II-IV; P = .005); and malignant mixed müllerian tumors (P = .048). Sex-determining region Y-box 2 expression was also associated with decreased disease-free survival durations (P = .035; log-rank test). Our results showed that sex-determining region Y-box 2 expression may be a potential marker related to tumor recurrence, as implicated by its role in cancer stem cells.

CD133 expression associated with poor prognosis in ovarian cancer.

As a putative marker for cancer stem cells in human malignant tumors, including ovarian cancer, CD133 expression may define a tumor-initiating subpopulation of cells and is associated with the clinical outcome of patients. However, at this time its clinical significance in ovarian cancer remains uncertain. The aim of this study was to clarify the clinical role of CD133 expression in human ovarian cancer. Immunohistochemical staining of CD133 expression was performed in 400 ovarian carcinoma samples using tissue microarray. The associations among CD133 expression and clinical factors (diagnosis, tumor grade, cancer stage, and clinical response to chemotherapy), overall survival and disease-free survival time were analyzed. CD133 expression was found in 31% of ovarian carcinoma samples. Fisher's exact test and one-way analysis of variance suggested that CD133 expression was associated with high-grade serous carcinoma (P=0.035), late-stage disease (P<0.001), ascites level (P=0.010), and non-response to chemotherapy (P=0.023). CD133 expression was also associated with shorter overall survival time (P=0.007) and shorter disease-free survival time (P<0.001) by log-rank test. Moreover, CD133 expression was an independent predictor of shorter disease-free survival time in an unconditional logistic regression analysis with multiple covariates (P=0.024). Our results thus show that CD133 expression is a predictor of poor clinical outcome for patients with ovarian cancer, supporting the proposed link between CD133 and cancer stem cells.

Tumor necrosis factor-alpha-induced cyclooxygenase-2 overexpression in eutopic endometrium of women with endometriosis by stromal cell culture through nuclear factor-kappaB activation.

OBJECTIVE: To investigate the role of NF-kappaB during the induction of COX-2 by TNF-alpha in the eutopic endometrium of women with and without endometriosis using stromal cell culture. STUDY DESIGN: Experimental study in cultured stromal cells of the eutopic endometrium of women with and without endometriosis in the presence of TNF-alpha. RESULTS: Within 5-20 minutes of stimulation with TNF-alpha, p-IkappaB was clearly observed in the eutopic endometrium of women with endometriosis and in that of women without endometriosis. COX-2 protein was significantly induced by treatment with TNF-alpha in both eutopic endometrial stromal cells of women with and without endometriosis (p < 0.05), but the degree of induction was significantly increased in eutopic endometrial stromal cells of women with endometriosis than those of women without endometriosis (p < 0.05). CONCLUSION: Overexpression of COX-2 by TNF-alpha in the eutopic endometrium of women with endometriosis may play a critical role in such pathophysiologic processes as endometriosis formation.

Vero cell co-culture counteracts the detrimental effects of hydrosalpinx fluid on the development of mouse embryos in vitro.

Recent studies have suggested that the hydrosalpinx has a negative effect on pregnancy outcome, with markedly diminished implantation and increased early pregnancy loss. Fluid from the hydrosalpinx may leak into and accumulate in the uterine cavity. It is not clear, however if this creates a hostile local environment in the uterus for embryo implantation or exerts a direct embryotoxic effect. This study was conducted to investigate the detrimental effects of hydrosalpinx fluid (HSF) on the development of mouse embryos in vitro and to demonstrate whether Vero cells overcome these adverse effects. HSF was collected from three women with bilateral hydrosalpinx at the time of laparoscopic surgery. Collected fluid was centrifuged and the supernatant was frozen at -20 degrees C. For co-culture, Vero cells were commercially obtained in a frozen state and cultured using Ham's F10 medium. Single-cell mouse embryos (B6CBAF1) were cultured for 5 days in 0, 0.4, 0.8, and 1.2% of HSF in media with and without Vero cells and examined daily to record the number of embryos reaching expanded blastocyst and hatching stage. Co-culture of mouse embryos with Vero cells at 0.8% HSF concentration significantly enhanced embryo development, but not at 1.2% hydrosalpinx fluid concentration. These results suggest that HSF is highly embryotoxic and Vero cells are likely to overcome these detrimental effects to some degree.