PURE vs. mixed clear cell ovarian carcinomas: Is there any impact on survival?

OBJECTIVE: Our primary aim in this study is to define the clinical characteristics of patients with clear-cell ovarian carcinoma and evaluate the prognostic factors affecting survival. STUDY DESIGN: Records of 85 patients, operated between 2000 and 2018, for an adnexal mass and whose final pathology reported clear cell ovarian carcinoma were reviewed. The study considered demographic data, clinical characteristics of the patients, as well as pure and mixed-type clear cell histology. The patients' follow-up time, disease-free and overall survival recorded. The primary outcomes were disease-free survival (DFS) and overall survival (OS). RESULTS: The median age of the patients at diagnosis was 52. In 64.7 % of the cases, clear cell histology was pure, while the others (35.3 %) were mixed. Patients with ovarian endometriosis constituted 27.1 % of the whole population. The median OS for the entire population was 92 months (95 %CI:72-124). On univariate and multivariate analyses, advanced age was found to have a significant independent impact on OS and DFS (p < 0.05) and, was associated with a worse prognosis. Also, the multivariate analyses showed that the presence of endometriosis has a significant independent impact on OS (p < 0.05). When examining the relationship between the histological origin (mixed vs. pure) and 5-year survival, the mixed type showed longer OS and DFS rates (76.8 % vs. 69.8 %, 61.5 % vs. 53.8 %), the difference was not statistically significant (p > 0.05). CONCLUSION: This retrospective study showed that although mixed type histological origin was associated with higher OS and DFS rates compared to pure type in patients with CCOC, the difference was not statistically significant. Advanced age and the presence of endometriosis was found to have a significant independent effect on OS and DFS and was associated with a worse prognosis. Overall, this study provides useful insights into the clinical characteristics of patients with CCOC and identifies important prognostic factors affecting survival.

The usefulness of p16 and COX-2 expression on the prediction of progression to endometrial cancer.

OBJECTIVES: Endometrial cancer (EC) is the most commonly diagnosed gynecological cancer. Endometrial hyperplasia (EH) is a more common diagnosis than EC. Endometrial hyperplasia is found in approximately 1.5% of all women presenting with abnormal bleeding. Endometrial hyperplasia progresses to EC, and especially, cancer risk increases in cases with atypical hyperplasia. p16, one of the tumor suppressor proteins involved in the cell cycle, and COX-2, one of the key enzymes of prostaglandin synthesis, are important markers for the diagnosis of both EH and EC. There is lack of consensus in the classification, diagnosis and treatment of EH. The subject of changes in the cell cycle in the progression of endometrial pathologies may help to identify and prevent these affected pathways in the treatment stage. The aim of this study is to investigate the expression of p16 and COX-2 during the development of EC from EH. MATERIAL AND METHODS: We investigated COX-2 and P16 expressions in patients with proliferative endometrium, complex/simple endometrial hyperplasia and endometrioid adenocarcinoma. RESULTS: p16 expression increased in EH and EC (p<0.001). COX-2 expression was increased in endometrial cancer compared to other groups, but this increase was not found to be statistically significant. Although p16 and COX-2 expression were increased in patients with advanced grade/stage, lymphovascular invasion, and >50% of myometrial invasion, this increase was not statistically significant. CONCLUSIONS: More detailed studies are needed to investigate the prognostic significance of the COX-2 molecule. COX-2 might be a potential biomarker for the prognosis of endometrial cancer and a potential therapeutic target for EC treatment. Also, it might be used to prevent the progression of precursor lesions to invasive EC.

Effects of leptin on the viability of human ovarian cancer cells and changes in cytokine expression levels.

Background: Obesity is associated with increased mortality among ovarian cancer and is a poor prognostic factor. There are significant links between the leptin hormone, a product of the obesity gene, and the development of ovarian cancer. Leptin is a vital hormone-like cytokine secreted from adipose tissue and is mainly involved in the maintenance of energy homeostasis. It regulates several intracellular signaling pathways and also interacts with various hormones and energy regulators. It acts as a growth factor by stimulating cell proliferation and differentiation and in this way contributes to cancer cell development. The aim of the study was to investigate the effects of leptin on human ovarian cancer cells. Methods: In this study, the effects of increasing the concentration of leptin were investigated on the cell viability of OVCAR-3 and MDAH-2774 ovarian cancer lines by MTT assay. Moreover, to elucidate the molecular mechanisms of leptin in ovarian cancer cells, changes in the expression levels of 80 cytokines were evaluated after leptin treatment via a human cytokine antibody array. Results: Leptin increases the proliferation of both ovarian cancer cell lines. IL-1 level was increased in OVCAR-3 cells and TGF-ß level was increased in MDAH-2774 cells after leptin treatment. A decrease in IL-2, MCP-2/CCL8 and MCP-3/CCL7 levels was detected in both ovarian cancer cell lines with leptin administration. An increase in IL-3 and IL-10 expressions, insulin-like growth factor binding proteins (IGFBP) IGFBP-1, IGFBP-2 and IGFBP-3 levels were detected in both ovarian cancer cell lines with leptin administration. In conclusion; leptin has a proliferative effect on human ovarian cancer cell lines and affects different cytokines in different types of ovarian cancer cells.

The regulatory effects of clomiphene and tamoxifen on mTOR and LC3-II expressions in relation to autophagy in experimental polycystic ovary syndrome (PCOS).

BACKGROUND: Polycystic ovary syndrome (PCOS) is a metabolic disease that causes infertility due to anovulation in women in reproductive age. It is known that clomiphene citrate (CC) and tamoxifen citrate (TMX) induce ovulation in women with PCOS. In this study, we aimed to investigate the effects of CC and TMX on the autophagy pathway in PCOS. METHODS AND RESULTS: Experimental PCOS model was induced by letrozole (1 mg/kg) in rats by gavage for 21 days. After the last letrozole administration, rats were treated TMX (1 mg/kg) or CC (1 mg/kg) for 5 days. At the end of the experimental procedures, rats in all groups were sacrificed and ovarian tissues were removed. It was observed that mRNA and protein expressions of LC3-II were significantly higher in TMX and CC groups than control and PCOS groups (p < 0.05), while mRNA and protein expressions of mTOR in TMX and CC groups were found significantly lower than control and PCOS groups (p < 0.05). CONCLUSIONS: In conclusion, present study suggests that TMX and CC induce autophagy in ovaries with PCOS. Autophagy is a promising target for understanding pathophysiology of this disease and for developing more effective and safe new protocols for the treatment of PCOS-related anovulation.

The investigation of T-cell receptor subtypes in ovarian cancer: effects on survival and prognostic factors.

The aim of this study was to investigate T-cell receptor (TCR) changes in ovarian carcinoma (OC). The study included 24 malignant and 23 benign adnexal masses. DNA was isolated from ovarian samples. Multiplex PCR was used to determine T-cell gene clonality. PCR products were loaded onto polyacrylamide gel electrophoresis and imaged. The relationship between prognostic parameters and T-cell rearrangement was evaluated. In the study group (SG), TCRB-B positivity was higher than control group (CG) and TCRD receptor positivity was higher in CG. In SG, TCRG-B levels were higher in patients with stage I-II tumours compared to stage III. TCRG-B receptor was higher in patients with overall survival of 36 months and above. In our study, subgroups of TCRs were analysed in OC. According to our findings, significant differences in TCRB-B and TCRD subgroups may be applied to immune therapies. Understanding of TCR pathways will provide new treatment approaches in OC.IMPACT STATEMENTWhat is already known on this subject? Ovarian cancer is the most challenging kind of gynaecologic cancer. Although the main route of spread is direct invasion and peritoneal spread in the abdominal cavity, lymphatic invasion is also very important. Recent studies put forward that immunological mechanisms play crucial role in ovarian cancer. CD3 and CD8 positive lymphocyte infiltration in ovarian tumour is related with better prognosis where, FoxP3 positive lymphocyte infiltration is a predictor of poor survival. Also, immune checkpoints and inhibitors are important topics in ovarian cancer.What the results of this study add? Despite all the improvements and studies regarding immune system and ovarian cancer, the role T-cell receptor (TCR) subtypes is not clear and there are very few number of studies in this area. This is one of the first studies that describe the rearrangement of TCR subtypes between normal ovarian tissue and ovarian cancer tissue.What the implications are of these findings for clinical practice and/or further research? Understanding the role of TCR subtypes has a key role because studies about lymphocyte infiltration in ovarian cancer varies from region to region in the world and same type of lymphocytes has different effects in different studies. Further studies on TCR subtypes may elucidate us about the behaviour of lymphocytes. Additionally, these receptor may be targeted if their roles are better understood.

Granulocyte Colony-Stimulating Factor Prevents Ischemia/Reperfusion-Induced Ovarian Injury in Rats: Evaluation of Histological and Biochemical Parameters.

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein commonly used in the field of medicine to treat neutropenia. Granulocyte colony-stimulating factor has also crucial roles in ameliorating the ischemia/reperfusion (I/R) injury in particular tissues. In this study, we aimed to investigate the protective effect of G-CSF on ovarian damage in experimental ovarian I/R injury. Thirty adult female rats were used. Rats were separated randomly into 5 groups; Group 1: sham group (abdominal wall was opened and closed surgically), Group 2: torsion group with 3-hour ischemia using vascular clips. Group 3: torsion + G-CSF group with 3-hour ischemia 30 minutes after the administration intraperitoneal (i.p.) of 100 µg/kg of G-CSF. Group 4: torsion-detorsion group with 3 hour ischemia and 3 hour reperfusion. Group 5: torsion-detorsion + G-CSF group with 3 hour ischemia followed by 100 µg/kg of G-CSF i.p. administration 30 minutes prior to 3 hour of detorsion/reperfusion. Ovarian tissue damage was scored on histopathology. Ovarian tissue malondialdehyde (MDA) was measured biochemically. In comparison with the sham group, both the torsion and torsion-detorsion groups had significantly higher scores for follicular degeneration, vascular congestion, edema, hemorrhage, and leukocyte infiltration (P < .05). When compared group torsion-detorsion + G-CSF to group torsion-detorsion, parameters aforementioned significantly decreased in group torsion-detorsion + G-CSF (P < .05). Granulocyte colony-stimulating factor has also decreased MDA levels notably both in the torsion + G-CSF and torsion-detorsion + G-CSF groups (P < .05, P < .01). Our experimental study suggests that G-CSF can be a novel agent for the treatment of ovarian I/R injury.

Exenatide preserves trabecular bone microarchitecture in experimental ovariectomized rat model.

PURPOSE: The aim of this study is to investigate effects of exenatide (Glucagon-Like Peptide Agonist) replacement on bone mineral density (BMD) and microarchitecture in a surgical menopause-induced osteoporosis model in rats. METHODS: In this study, 24 female Sprague-Dawley albino mature rats were used. Rats were assigned either to the group ovariectomized administered exenatide or to the control group. Bone Mineral Density (BMD), plasma cytokine levels and histomorphometric analysis were measured. RESULTS: Ovariectomized rats showed significant decrease BMD values, trabecular counts, trabecular thickness and trabecular area. Also, significant increase trabecular separation and plasma TNF-α (Tumor Necrosis Factor) and IL-6 (Interleukin) levels. Exenatide treatment reversed these changes and it showed a considerable protective effect on trabecular bone microarchitecture. CONCLUSIONS: Exenatide may be a candidate for use in the treatment of postmenopausal osteoporosis and anti-inflammatory properties can be attributed this effects.

The Impact of Surgical Staging on the Prognosis of Mucinous Borderline Tumors of the Ovaries: A Multicenter Study.

BACKGROUND/AIM: The purpose of this study was to prove the effect of complete surgical staging of patients with mucinous borderline ovarian tumors (mBOTs) especially appendectomy on progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: The database of 14 gynecological oncology departments from Turkey and Germany were comprehensively searched for women who underwent primary surgery for an ovarian tumor between January 1, 1998, and December 31, 2015, and whose final diagnosis was mBOT. RESULTS: A total of 364 patients with mBOT with a median age of 43.1 years were included in this analysis. The median OS of all patients was 53.1 months. The majority of cases had Stage IA (78.6%). In univariate and multivariate analyses, radical surgery, omentectomy, appendectomy, lymphadenectomy, and adding adjuvant chemotherapy were not independent prognostic factors for PFS and OS. Furthermore, FIGO stage (≥IC vs.

In Vitro Determination of Wound Healing Potential of Axonge

BACKGROUND: Research on treatment alternatives that improve wound healing is an ever-evolving area in medicine, and a wound healing agent that carries minimal pain, discomfort, and scarring for patients with burn wounds, venous and decubitis ulcers, traumatic wounds, and many others is needed. The phases of wound healing include homeostasis, inflammation, migration, proliferation, and maturation. Adeps suillus (axonge) is known as a therapeutic agent for skin diseases and mainly consists of triglycerides. OBJECTIVE: In the current study, the proliferation effect of axonge was determined on human normal epidermal keratinocyte (HaCaT) cells and human normal foreskin fibroblast cell line (BJ) cells. MATERIALS AND METHODS: Experimental steps included preparation of HaCaT and BJ cell lines, axonge's stable tetrazolium salt-based proliferation assay, and evaluation of the wound healing effect of axonge on HaCaT and BJ cells. RESULTS: Axonge concentrations of 3.12 µg/mL, 6.25 µg/mL, 12.5 µg/mL, 25 µg/mL, and 50 µg/mL showed no cytotoxic effect on both HaCaT and BJ cells for 24, 48, and 72 hours. Considering the wound area of HaCaT cells, after 6 hours the wound healing effect of the axonge group reached almost 70% and then stopped. According to the results of the study on BJ cells, after 6 hours axonge wound closure was found to be 50% while the control group was only 10%. CONCLUSION: On the basis of this study, the authors determined that axonge might have potential for use in wound healing.

Do tumor-infiltrating lymphocytes really indicate favorable prognosis in epithelial ovarian cancer?

OBJECTIVE: The aim of this study is to evaluate the impact of lymphocyte infiltration on prognostic parameters, recurrence and survival in ovarian cancer. STUDY DESIGN: Sixty-two patients who were primarily operated for epithelial ovarian carcinoma between 1997 and 2008 were included. CD3, CD4, CD8, CD20 and FoxP3 expressions were evaluated immunohistochemically on sections obtained from paraffin-embedded tissues. RESULTS: Median follow up was 87 months. In whole cohort, CD3+ and CD8+ T lymphocyte infiltrations were significantly higher in patients with high-grade tumors, advanced stage tumors and the patients with omental metastasis (for CD3 p=0.0001, p=0.029, p=0.016; for CD8 p=0.044, p=0.002, p=0.046, respectively). DFS was significantly lower among patients with CD8+ T lymphocytes with regard to patients who did not have CD8+ T lymphocyte infiltration (p=0.028). In univariate analysis, presence of CD8 cytotoxic T lymphocyte infiltration (p=0.03), stage (0.0001), tumor grade (p=0.007), omental metastasis (p=0.0001) and lymph node metastasis (p=0.0001) were significant risk factors for recurrence. But in multivariate analysis, only stage [HR: 116.6 (95% CI: 13.09-1039.45) (p=0.0001)] was found as an independent risk factor for recurrence. CONCLUSION: CD3+ and CD8+ T lymphocyte infiltrations were related with advanced stage, high-grade tumor and the omental metastasis in ovarian cancer. DFS was significantly shorter in patients with CD8+ T lymphocyte infiltration. CD3+ and CD8+ T lymphocyte infiltrations were related with poor prognosis in ovarian cancer.

Prognostic value of miliary versus non-miliary sub-staging in advanced ovarian cancer.

OBJECTIVE: The presence of miliary disease during initial ovarian cancer debulking may reflect a distinct mode of peritoneal spread independent from size-based tumor staging and may explain variation in response to treatment and survival outcomes. To infer the prevalence, presentation and clinical implications of miliary disease we reviewed existing surgical records. METHODS: Reports were available for 1008 primary debulking surgeries for ovarian, primary peritoneal or fallopian tube cancer between 2001 and 2015 (685 reports from 2005 to 2015). Clinical outcome data was available for 938 patients. We analyzed a high-stage sub-cohort for survival (N=436). RESULTS: Most records were evaluable for miliary disease (761/938); for these, the miliary phenotype was highly prevalent (249/761, 32.7%) and often accompanied by ascites (185/249, 74%). While optimal debulking rates were unaffected by miliary disease, total resection (R0) rates were poorer. Liver, stomach, spleen or bladder appeared to be sporadically involved while the omentum, mesentery, bowel, peritoneum and diaphragm were affected simultaneously (Spearman rho>0.5). Overall, miliary disease was associated with worse progression free survival, overall survival, and time from relapse to death independent of stage. Survival effects were particularly strong for Stage IV disease where median overall survival varied by over 30months (log-rank p=0.002). CONCLUSIONS: Miliary disease is an identifiable surgical phenotype reflecting a distinct clinical trajectory that adds prognostic information to standard disease burden-based staging. These findings should permit further retrospective investigation in a wider cohort and prompt the consideration of prospective structured operative reporting standards and treatment strategies.

Comparison Of Early-Stage High-Grade Serous Primary Fallopian Tube Cancers and Epithelial Ovarian Cancers: A Multicenter Study.

INTRODUCTION: We compared the disease free-survival (DFS) and overall survival (OS) rates of patients with high-grade serous primary fallopian tube cancer (HG-sPFTC) and high-grade serous epithelial ovarian cancer (HG-sEOC). METHODS: 22 early-stage cancer patients (International Federation of Gynecology and Obstetrics (FIGO) stages I-II) with HG-sPFTC were retrospectively evaluated. In addition, 44 control patients diagnosed with HG-sEOC were matched to these patients with respect to tumor stage at diagnosis. All patients underwent complete surgical staging, followed by adjuvant chemotherapy. Kaplan-Meier curves were used to generate survival data. RESULTS: The mean age of HG-sPFTC patients was 59.4 ± 6.2 years, and that of HG-sEOC patients 55.2 ± 11.0 years (p = 0.002). All patients underwent 6 cycles of platinum-based adjuvant chemotherapy. All operations were optimal. The 5-year DFSs were 77.3% for HG-sPFTC patients and 75% for HG-sEOC patients (p = 1.00).The 5-year OS rates were 81.8% in women with HG-sPFTC and 77.3% in those with HG-sEOC (p = 0.75). CONCLUSION: The DFS and OS rates of patients with early-stage (FIGO stages I and II) HG-sPFTC and HG-sEOC were similar. The surgical and adjuvant therapy management of these malignancies should be similar.

The prediction of myometrial infiltration by three-dimensional ultrasonography in patients with endometrial carcinoma: a validation study from Ege University Hospital.

AIM: To predict the myometrial invasion with three-dimensional (3D) ultrasonography in a cohort of patients with endometrial carcinoma by a previously described technique. MATERIAL AND METHODS: The moyometrial infiltration was evaluated by 3D ultrasonography before surgery in 54 patients with endometrial carcinoma. After scanning the whole uterus by ultrasonography, three perpendicular planes were identified to find the shortest myometrial tumor-free distance to serosa (TDS) by examining the lateral, anterior, posterior, and fundal parts of the myometrium. Myometrial infiltration was also estimated by the subjective impression of the examiner. The reference standards consist of myometrial infiltration and TDS which are measured by an experienced pathologist. RESULTS: Forty-five patients (age range 45-86 years) were included for the final analysis. Myometrial invasion was ˂50% in 36 and ≥50% in 9 cases at histologic sections. The TDS which is measured with 3D ultrasonography was positively correlated with histologically measured TDS (r=0.474, p=0.001). The best cut-off value for ultrasonographically measured TDS was 9 mm with a sensitivity of 89%, specificity of 61%, positive predictive value of 36%, and negative predictive value of 96%. Subjective impression has a sensitivity of 100%, specificity of 88%, positive predictive value of 69%, and negative predictive value of 100%. Cervical involvement was correctly identified in all 6 cases by subjective impression. CONCLUSION: This validation study confirms the 3D ultrasonography as a valuable tool for the evaluation of myometrial infiltration in patients with endometrial carcinoma.

Ovarian sertoli-leydig cell tumors: A multicenter long-term clinicopathological analysis of 27 patients.

AIM: Information on the clinical behavior of ovarian Sertoli-Leydig cell tumors (SLCTs) as well as its prognostic factors and optimal management is limited due to a substantially low incidence of the disease. Also, limited data is available regarding the role of chemotherapy in the management of SLCTs. The aim of the study is to evaluate clinicopathological features and outcome of patients with ovarian SLCTs. MATERIALS AND METHODS: Twenty-seven patients with SLCT treated at two centers were reviewed retrospectively during 21 years. RESULTS: The median age was 45 years (range, 16-81) and the mean follow-up time was 86 months (range, 16-181). Twenty-three patients had stage IA, three patients had IC, and one patient had stage II disease. Eleven tumors (41%) were well-differentiated and 16 (59%) tumors were intermediately differentiated. Nine patients underwent unilateral salpino-oophorectomy and one patient, with a history of infertility, underwent cystectomy for fertility preservation. Eight patients with intermediately differentiated types of SLCT received adjuvant systemic chemotherapy including the combination bleomycin, etoposide, and cisplatin (BEP). Recurrence occurred in one patient with intermediated differentiated type SLCT with heterologous elements. She received four cycles of BEP chemotherapy. Twelve months later, she underwent cytoreductive surgery and received six cycles of cisplatin plus carboplatin. She died 24 months after the initial diagnosis. CONCLUSION: SLCTs of the ovary are usually in early stage, unilateral, and benign. Fertility-sparing surgery is the preferred option in young women. In the adjuvant treatment setting, although information about chemotherapy is limited, BEP is a commonly used regimen. The degree of differentiation and the presence of heterologous elements relate to a poor prognosis.

The retrospective analysis of patients with uterine sarcomas: A single-center experience.

BACKGROUND: Uterine sarcomas are rare, malignant, gynecological tumors and show diverse histopathological features. Therefore, there is no consensus on risk factors for poor outcome and optimal treatment. The aim of this retrospective analysis is to report the clinical outcome of patients with uterine sarcoma treated at a single center. MATERIALS AND METHODS: The data was obtained regarding the patient's demographic characteristics, pathological results, treatments given, survival, and complications of all uterine sarcoma patients treated in a single center between the years 2000 and 2012. The 80.month overall survival. (OS) was determined with respect to prognostic factors including age, stage of disease, histopathological type, and adjuvant treatment. RESULTS: A total of 57 case records are retrieved for this retrospective analysis. The mean age of the patients is 62.5 ± 11.2 years. International Federation of Gynecology and Obstetrics (FIGO) stage distribution is stage I: 29; stage II: 13; stage III: 9; stage IV: 6. Fifty-seven patients underwent surgery, 33 received postoperative radiotherapy (PORT), and 32 received chemotherapy. Median follow-up period was 25 months (range 2-85 months). The 80-month OS for the entire group of patients was 36.7%. The significant prognostic factors for survival are age under 50 years, stage of disease, and adjuvant chemotherapy. CONCLUSION: Although limited by small sample size and retrospective nature, age under 50 years, stage of disease, and adjuvant chemotherapy are significant prognostic factors for survival for uterine sarcomas.

Treatment results and prognostic factors of patients with vulvar cancer treated with postoperative or definitive radiotherapy.

PURPOSE: Vulvar cancer is a relatively uncommon type of gynecologic cancer. The aim of this study is to analyze the treatment results and prognostic factors of vulvar cancer. METHODS: Forty-four vulvar cancer patients treated between 2000 and 2011 at the Department of Radiation Oncology, Ege University Faculty of Medicine, were retrospectively reviewed. External radiotherapy (RT) was applied with 6-18 MV linear accelerators with 1.8 Gy daily fractions with a median total dose of 50.4 Gy (45-59.4 Gy) for postoperative cases and 64.8 Gy (range 54-66 Gy) for definitive cases. Statistical analyses were performed with SPSS 13.0. RESULTS: Among 44 patients with a median age of 68 years (range 28-86), 14 (31.8%) were treated with curative and 30 (68.2%) were treated with postoperative RT or radiochemotherapy (RCT). According to International Federation of Gynecology and Obstetrics staging, 11 (25%) had stage IB, 10 (22.7%) had stage II, 6 (13.6%) had stage IIIA, 5 (11.4%) had stage IIIB, and 12 (27.3%) had stage IVA disease. Within a median of 24 months (range 6-135) of follow-up, 11 (27.3%) patients had local recurrence, 8 had regional recurrence, 2 had both local and regional recurrence, and 6 had distant metastases. Five-year locoregional, disease-free, and overall survival rates were 45%, 40%, and 54%, respectively. Older age, poor tumor differentiation, positive surgical margin, and lymphovascular space invasion were found to be important prognostic factors for disease-related outcomes. CONCLUSIONS: Prognosis of vulvar cancer remains poor even with a multidisciplinary approach. Molecular prognostic factors need to be defined for individualized treatment options to achieve better treatment results.

Do preoperative serum vascular endothelial growth factor and migration-inhibitory factor predict the nature of the adnexal masses? A prospective-controlled trial.

The aim of this study was to identify the role of preoperative serum vascular endothelial growth factor (VEGF) and migration inhibitor factor (MIF) in differentiation of benign and malignant adnexal masses, as well as the relationship between prognostic factors and VEGF and MIF in ovarian cancer patients. This prospective study included 41 patients who were admitted between November 2010 and March 2012. In the malignant group, there were 21 patients, and remaining 20 had benign adnexal masses. Age, CA125 levels, grade, stage, presence of ascites and the degree of cytoreduction performed were noted. There was no significant difference between two groups in preoperative serum VEGF and MIF levels (p = 0.118 and p = 0.297, respectively). CA125 levels were significantly higher in the malignant group (p < 0.0001). There was no significant difference for VEGF and MIF between the groups evaluated for tumour grade, stage, presence of ascites and degree of cytoreduction performed in the malignant group. Preoperative serum, VEGF and MIF levels are not suitable for the differentiation of malignant and benign adnexal masses, and they do not correlate with the prognostic factors of ovarian cancer in this cohort of patients.

Levetiracetam ameliorates ovarian function in streptozotocin-induced diabetic rats.

Diabetes mellitus can adversely affect gonadal function. In the present study, we aimed to investigate the protective effects and mechanism of action of levetiracetam (LEV) on the ovaries in a streptozotocin (STZ)-induced diabetes model in rats. Twenty-one adult female rats were assigned to three groups as control, diabetes group treated with 1 mL/kg/d saline (STZ + SP) and diabetes group treated with 600 mg/kg/d LEV (STZ + LEV). Following 4 weeks treatment, blood samples were collected for biochemical analysis and ovariectomy was performed for histopathological examination. Plasma anti-Mullerian hormone (AMH), glutathione and total anti-oxidant capacity values were significantly lower whereas lipid peroxides and transforming growth factor-ß (TGF-ß) values were significantly higher in STZ + SP group compared to control. LEV treatment successfully decreased lipid peroxidation and TGF-ß levels, and also increased anti-oxidant parameters and AMH levels in diabetic rats. Saline-treated rats significantly displayed ovarian degeneration and decreased counts of follicles. However, treatment of diabetic rats with LEV effectively prevented the degenerative changes and follicle loss. Also, LEV suppressed ovarian nuclear factor-kappa B (NF-kB) immunoexpression in diabetic rats. Taken together, we propose that LEV can ameliorate the adverse effects of diabetes on ovarian function via decreasing NF-kB expression and oxidative stress and increasing anti-oxidant status in rats.

Therapeutic effect of sunitinib on diabetes mellitus related ovarian injury: an experimental rat model study.

The aim of our study is to investigate the effect of sunitinib on diabetes mellitus related-ovarian injury and fibrosis in rat models. An experimental diabetes mellitus model was created in 16 rats, and eight rats with normal blood glucose levels were included in control group (Group-1). The diabetic rats were divided into two groups:diabetic control group (water given) - Group-2 and sunitinib treatment group - Group-3. After four weeks, bilateral oophorectomy was performed and ovaries were examined histologically. The groups were compared by Student's t-test, analysis of variance (ANOVA) and Mann-Whitney's U-test. There was a significant increase in no-medication (water given) diabetic rat's ovary (Group-2) in terms of follicular degeneration, stromal degeneration, stromal fibrosis and NF-kappaB immune-expression compared with control group normal rats' ovary (Group-1) (p < 0.0001). Stromal degeneration (p = 0.04), stromal fibrosis (p = 0.01), follicular degeneration (p = 0.02), NF-kappaB immune-expression (p = 0.001) significantly decreased in sunitinib-treated diabetic rat's ovary (Group-3) when compared with no-medication (water given) diabetic rat's ovary (Group-2) (p < 0.05). When we used sunitinib in the treatment of diabetic rats, ovarian injury, fibrosis and NF-kappaB immunoexpression decreased significantly. The effects of sunitinib in rat models give hope to the improved treatment of premature ovarian failure due to diabetes mellitus in humans.

The preventive effect of oxytocin to Cisplatin-induced neurotoxicity: an experimental rat model.

Peripheral neurotoxicity is a frequent dose-limiting side effect of the chemotherapeutic agent cisplatin. This study was conducted to investigate the preventive effect of oxytocin (OT) on cisplatin-induced neurotoxicity in rats. Forty-four adult female rats were included in the study. Thirty-six rats were administered intraperitoneally (i.p.) single dose cisplatin 10 mg/kg and divided in to 3 groups. The first group (n=12) received saline i.p., whereas the second group (n=12) and the third group (n=12) were injected with 80 µg/kg and 160 µg/kg OT, respectively, for 10 days. The remaining 8 rats served as the control group. Electromyography (EMG) studies were recorded and blood samples were collected for the measurement of plasma lipid peroxidation (malondialdehyde; MDA), tumor necrosis factor (TNF)-α, and glutathione (GSH) levels. EMG findings revealed that compound muscle action potential amplitude was significantly decreased and distal latency was prolonged in the nontreated cisplatin-injected rats compared with the control group (P<0.005). Also, nontreated cisplatin-injected rats showed significantly higher TNF-α and MDA levels and lower GSH level than control group. The administration of OT significantly ameliorated the EMG alterations, suppressed oxidative stress and inflammatory parameters, and increased antioxidative capacity. We suggest that oxytocin may have beneficial effects against cisplatin-induced neurotoxicity.