[Evaluation of the clinical value of simultaneous hysterectomy and bilateral salpingectomy in perimenopausal women].

OBJECTIVE: To investigate the effects on pelvic pseudocyst, ovarian function and symptoms of peri-menopausal period in patients with benign uterine disease undergoing simultaneous hysterectomy and bilateral salpingectomy. METHODS: From Jan. 2000 to Dec. 2006, 1193 patients with benign uterine disease underwent total or subtotal hysterectomy, they were followed up for 48 months, 334 patients lost follow-up, the other 859 patients were divided into 2 groups, including 348 patients undergoing simultaneous hysterectomy and bilateral salpingectomy in study group and 511 patients undergoing only hysterectomy in control group. The occurrence of pelvic pseudocyst and symptoms of peri-menopausal period and the changes of serum sexual hormone were observed. RESULTS: (1) The rate of pelvic pseudocyst was 1.7% (6/348) in study group, which was significantly lower than 4.3% (22/511) in control group (P = 0.036). (2) There was an increasing trend of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and a decreasing trend of estradiol (E(2)) at range of 6 - 48 months after surgery. At 3 months after surgery, LH in study group was significantly higher than that in control group [(13.9 ± 2.2) U/L vs. (12.6 ± 2.5) U/L, P = 0.032]; FSH in study group at 6 months and 12 months after surgery were (17.6 ± 2.2) U/L and (26.7 ± 5.0) U/L, which were significantly higher than (16.2 ± 2.8) U/L and (24.3 ± 3.1) U/L in control group (P = 0.035 and P = 0.031). At 12 months after surgery, LH in study group of (24.1 ± 3.0) U/L was significantly higher than (22.5 ± 1.8) U/L in control group (P = 0.017). E(2) in control group of (97 ± 22) pmol/L was significantly lower than (109 ± 17) pmol/L in control group at 24 months after surgery (P = 0.028); FSH in study group was lower than that in control group at 48 months after surgery [(34.9 ± 6.7) U/L vs. (38.0 ± 4.8) U/L, P = 0.043]. There were no significant differences of FSH, LH, and E(2) between two groups at the other time points (P > 0.05). (3) At 6 months after surgery, the rate of perimenopausl systems of 21.8% (76/348) in study group was significantly higher than 15.9% (81/511) in control group (P = 0.026). However, at 24 months after surgery, the rate of perimenopausal symptoms of 54.4% (278/511) in control group was significantly higher than 47.1% (164/348) in study group (P = 0.036). CONCLUSION: Simultaneous hysterectomy and bilateral salpingectomy could decrease the occurrence of pelvic pseudocyst, and had similar effects on ovarian function and peri-menopausal symptoms compared with only hysterectomy in patients with benign uterine diseases.

Expression and significance of transforming growth factor-ß1 in epithelial ovarian cancer and its extracellular matrix.

The aim of the present study was to investigate the expression and significance of transforming growth factor-ß1 (TGF-ß1) in the cytoplasm and extracellular matrix (ECM) of epithelial ovarian cancer cells. The expression of TGF-ß1 protein was detected in paraffin-embedded sections of 25 normal ovarian epithelial tissues, 10 benign epithelial cysts and 72 epithelial ovarian cancer specimens, using the Strept Avidin Biotin Peroxidase Complex immunohistochemistry method. In addition, the expression of TGF-ß1 mRNA in normal fibroblasts (NFs) and ovarian cancer-associated fibroblasts (CAFs) was assessed using semi-quantitative polymerase chain reaction (PCR). TGF-ß1 protein was expressed in the cytoplasm and ECM, and no significant difference was identified between normal and benign ovarian tissues (P>0.05). However, the cytosolic expression of TGF-ß1 declined gradually between the benign ovarian tumor and epithelial ovarian cancer, while its expression in the ECM significantly increased (P<0.05). The expression of TGF-ß1 in the cytoplasm and ECM in epithelial ovarian cancer was found to negatively correlate with tumor differentiation, however, it was positively associated with the clinical stages. The positive rates of TGF-ß1 in the cytoplasm and ECM between ovarian cancers in clinical stages I-II and III-IV were significantly different (P<0.05). Furthermore, the PCR data indicated that the relative expression of TGF-ß1 mRNA in ovarian CAFs (1.0270±0.0539) was significantly higher than that in NFs (0.7131±0.0186). Therefore, the expression of TGF-ß1 was identified to be associated with the development and progression of epithelial ovarian cancer, and the high expression of TGF-ß1 in the ECM may be associated with the invasion and metastasis of ovarian cancer.

Establishment of an orthotopic transplantation tumor model in nude mice using a drug-resistant human ovarian cancer cell line with a high expression of c-Kit.

The resistance of ovarian cancer to platinum-based chemotherapy is a critical issue in the clinical setting. The present study aimed to establish animal models to replicate this clinical condition, as well as to investigate the resistance mechanisms of ovarian cancer. A cisplatin (DDP)-resistant human ovarian cancer cell line, SKOV3/DDP, was screened, validated and injected subcutaneously into the neck of female nude mice. Following tumor establishment, the tumor was collected and cut into small sections, which were subsequently implanted into the ovaries of other nude mice. The growth of the orthotopic tumors was observed and the tumor-bearing mice were sacrificed and dissected. The orthotopic and metastatic tumor tissues were collected, sectioned, stained with hematoxylin and eosin and analyzed. In the present study, 16 nude mice underwent orthotopic transplantation surgery and a tumor model was successfully established in 14/16 of the mice, with an in situ tumor formation rate of 87.5%. Following euthanasia, a laparotomy demonstrated the tumor formation at the site of transplantation, as well as varying degrees of metastasis to additional organs and tissues. Therefore, the present study successfully established an orthotopic tumor transplantation model in nude mice using a c-Kit-positive DDP-resistant human ovarian cancer cell line. This model may represent a useful tool for investigating the resistance mechanism of ovarian cancer, as well as evaluating the efficacy of therapeutic strategies.

Methodologies for the establishment of an orthotopic transplantation model of ovarian cancer in mice.

This study used different methods to establish an animal model of orthotopic transplantation for ovarian cancer to provide an accurate simulation of the mechanism by which tumor occurs and develops in the human body. We implanted 4T1 breast cancer cells stably-transfected with luciferase into BALB/c mice by using three types of orthotopic transplantation methodologies: (1) cultured cells were directly injected into the mouse ovary; (2) cell suspension was initially implanted under the skin of the mouse neck; after tumor mass formed, the tumor was removed and ground into cell suspension, which was then injected into the mouse ovary; and (3) a subcutaneous tumor mass was first generated, removed, and cut into small pieces, which were directly implanted into the mouse ovary. After these models were established, in vivo luminescence imaging was performed. Results and data were compared among groups. Orthotopic transplantation model established with subcutaneous tumor piece implantation showed a better simulation of tumor development and invasion in mice. This model also displayed negligible response to artificial factors. This study successfully established an orthotopic transplantation model of ovarian cancer with high rates of tumor formation and metastasis by using subcutaneous tumor pieces. This study also provided a methodological basis for future establishment of an animal model of ovarian cancer in humans.