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.

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.

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.

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.

Comparison of montelukast and cabergoline for prevention of ovarian hyperstimulation syndrome: in an experimental rat model.

Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic complication that can occur during assisted reproductive techniques. The aim of this study is to investigate the effects of the leukotriene receptor antagonist (montelukast) treatment in prevention of OHSS and compare to cabergoline treatment. Twenty-four immature female Wistar rats were assigned to four groups. Group 1 was the control group. In the remaining three groups, OHSS was induced through ovarian stimulation with gonadotropins. No treatment was given to Group 2. Group 3 was administered a low-dose 100 mg/kg cabergoline treatment and Group 4 was received 20 mg/kg montelukast. Body weight, ovarian weight, vasculary permability (VP), peritoneal fluid vascular endothelial growth factor (VEGF) values and VEGF immune-expression were compared between the groups. Both cabergoline and montelukast prevented progression of OHSS compared to the OHSS group. Body weight, ovarian weight, VP, peritoneal fluid VEGF values and VEGF expression were significantly lower in both cabergoline- and montelukast-treated rats than in those not treated OHSS group. In conclusion, montelukast is an effective option for prevention of OHSS, as well as cabergoline. Montelukast may be a new treatment option to prevent and control the OHSS.

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.

Prognostic predictors and spread patterns in adult ovarian granulosa cell tumors: a multicenter long-term follow-up study of 108 patients.

PURPOSE: To identify prognostic predictors and spread patterns in adult ovarian granulosa cell tumors (OGCTs). METHODS: Available retrospective data of 108 OGCT patients managed at three centers between January 1, 1991 and December 31, 2010 were abstracted and analyzed. RESULTS: Stage distributions at diagnosis for stage I, II and III OGCT were 84.3, 5.4, and 9.3 %, respectively. Optimal cytoreduction with no macroscopically visible disease was achieved in 99/108 (91.6 %) patients. The median disease-free interval to first recurrence was 61 months. The overall 5- and 10-year survival rates were 93.3 and 90.9 %, respectively. Disease recurred in 18 (16.6 %) patients, and 8 (7.4 %) patients died of their disease. The first recurrence sites included the pelvic peritoneum (n = 10), liver/liver-capsule (n = 5), rectosigmoid colon (n = 4), retroperitoneal lymph nodes (n = 3), omentum (n = 3), small bowel mesenterium (n = 2), and vaginal cuff (n = 2). Multiple-site recurrence was observed in 9/18 (50 %) patients. Secondary cytoreduction requiring extensive surgery was performed in 14 patients with an optimality rate of 71.4 %. The remaining four patients received only chemotherapy. Multivisceral approaches, including pelvic peritonectomy (n = 9; 64.2 %), rectosigmoid resection (n = 3; 21.4 %), and segmental liver capsule resection (n = 2; 14.2 %) were performed more frequently during the secondary surgery. Definitive retroperitoneal lymph node metastasis rates at the initial and recurrent settings were 5.1 % (3/58) and 21.4 % (3/14), respectively. Both stage and residual tumor status were significantly associated with recurrence in univariate and multivariate analyses. CONCLUSIONS: Stage and residual tumor status are predictors of recurrence. Pelvic peritoneal, nodal and hepatic involvement, and multiple-site spread patterns requiring extensive cytoreductive surgery are likely associated with recurrence of OGCTs.

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 effects of different hormone treatment on endothelial function in healthy postmenopausal women.

We aimed to compare the effects of different types of hormone treatment (HT) on endothelial function by means of brachial artery ultrasonographic examination in postmenopausal women. Sixty-two healthy postmenopausal women were included in this study. Subjects were assigned to one of the five groups receiving 6 months of treatment [estrogen (conjugated estrogen), estrogen (conjugated estrogen) plus progesterone (medroxyprogesterone acetate; MPA), raloxifene, tibolone or control]. Endothelial function was assessed by measurement of flow-mediated dilatation (FMD) and nitrate-dependent dilatation in the brachial artery. At the end of 6 months, FMD values were found to be significantly increased in women with HT use than the control group (p = 0.001). In subgroups, FMD increased significantly in the estrogen [12 ± 7 versus 25 ± 8, p = 0.001] and raloxifene groups [7 ± 5 versus 11 ± 3, p < 0.01] compared to tibolone and estrogen plus progesterone groups. In conclusion, endothelial function is impaired in postmenopausal women. Both estrogen and raloxifene regimens may improve endothelial functions in healthy postmenopausal women. The direct protective effects of these HT on the healthy endothelium may be more remarkable than the favorable effects on lipid profile.

The role of the serum inflammatory markers for predicting the tubo-ovarian abscess in acute pelvic inflammatory disease: a single-center 5-year experience.

OBJECTIVE: To compare patients with tubo ovarian abscess (TOA) and non-TOA acute pelvic inflammatory disease (PID) and to determinate admitted day laboratory cut-off values for the TOA. MATERIALS AND METHODS: Files of inpatients admitted to our clinic with the diagnoses of PID and/or TOA between the years of 2006 and 2011. Laboratory and culture results were obtained from the database of hospital. A total of 73 patients diagnosed with PID and/or TOA were evaluated. Patients who were diagnosed with TOA and PID by physical and sonographic examination were assigned to group 1 and group 2, respectively. Both groups were compared in terms of laboratory, clinical, and epidemiological parameters. RESULTS: Of 73 patients admitted with the diagnosis of PID, 44 (60.3 %) were found to have TOA, and 29 (39.7 %) were not found. Mean age of patients was determined as 41.4 ± 7.7 in group 1 and as 35.1 ± 6.8 in group 2. Abscess was detected more frequently in patients with low socio-cultural level, and this was found to be statistically significant. The diameter of abscess was found to be ≥5 cm in 39 (88.6 %) patients and <5 cm in 5 (11.4 %) patients. The average length of hospital stay was statistically significantly increased in patients with an abscess of ≥5 cm in size compared to patients with an abscess of <5 cm. When C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), leukocyte counts were statistically evaluated by ROC curves, diagnostic ability of CRP, ESR and leukocyte count was found to be 73, 87, and 58 %. CRP has a specificity of 63 % and a sensitivity of 72 % if cut-off value is considered as 11.5 mg/L whereas ESR has a specificity of 83 % and a sensitivity of 79 % if cut-off value is considered as 19.5 mm/1/2 h. CONCLUSION: ESR >19.5 mm/1/2 h and CRP >11.5 mg/L were the best predictors of TOA. The high level of CRP and ESR was associated with longer duration of hospitalization and disease severity, and these levels were statistically significantly associated with TOA size of ≥5 cm.

A clinico-pathological evaluation of 194 patients with ovarian teratoma: 7-year experience in a single center.

OBJECTIVES: To evaluate patients diagnosed with teratoma over a period of seven years with regard to their general characteristics and treatment methods. MATERIAL AND METHODS: A total of 194 patients histologically diagnosed with ovarian teratoma (mature or immature) in the years 2005-2012 at the Ege University Gynecology and Obstetrics Department were evaluated. RESULTS: Average patient age was 34.3 +/- 2.16 years. Of these, 169 (86.3%) were premenopausal and 27 (13.7%) postmenopausal; average cyst diameter, measured during the surgery was 6.9 +/- 0.63 cm. While the teratoma had been an asymptomatic finding in 148 (75.5%) patients, 48 (24.5%) were symptomatic. In 107 patients (54.5%) a laparotomy and in 89 (45.5%) a laparoscopy were performed. The presence of torsion was observed during surgery in 9 (4.5%) patients. The 49 (55%) patients who underwent laparoscopic cystectomy experienced a rupture during the intervention, with no cases of clinical chemical peritonitis following the surgery CONCLUSION: Caution must be exercised with regard to possible cyst rupture in elderly patients and those with large dermoids; an laparoscopic approach may be reserved for younger patients. In case a rupture occurs during the operation, abundant peritoneal lavage is indicated; in order to limit risks during the controlled excision of the cyst an Endobag should be used if possible.

Reproductive outcome after surgical treatment of endometriosis--retrospective analytical study.

OBJECTIVE: The aim of the study was to investigate the reproductive outcomes of patients after surgical treatment of endometriosis. MATERIAL AND METHODS: The study included 100 infertile women, aged 21 to 41 years, who underwent surgical treatment of endometriosis. From January 2007 to January 2012, excision of endometriosis was performed by operative laparoscopy or laparotomy Demographic, clinical, surgical and reproductive outcomes of 52 patients were retrospectively analyzed. RESULT: Twenty-three pregnancies (44%) were obtained in 52 patients, resulting in 16 term pregnancies, 4 spontaneous abortions under 16 weeks gestation, 2 spontaneous abortions at 20 gestational weeks and 1 ectopic pregnancy Twenty nine patients did not achieve pregnancy and 68.9% (20/29) of them were treated with IVF-ICSI. Spontaneous pregnancies were obtained within 7 months after the surgery whereas IVF-ICSI pregnancies were obtained within the period of 11 months. Seven patients were stage 1, 14 patients stage II, 19 patients stage III, and 12 patients stage IV according to the American Fertility Society (AFS) Classification of Endometriosis. The pregnancy rate was 57% in stages I-II, 47% in stage III, 16% in stage IV endometriosis; and the rate of term pregnancies was 83%, 66%, and 0%, respectively Seven pregnancies (7/14) were obtained in patients with bilateral endometriosis and 5 of them resulted in term pregnancy Sixteen pregnancies (16/38) were obtained in patients with unilateral endometriosis and 11 of them resulted in term pregnancy CONCLUSION: After surgical treatment of endometriosis, the pregnancy and live birth rates seem to be improved. Reproductive outcome is closely associated with the AFS score. Bilaterality of endometriosis does not affect pregnancy outcome.

A novel technique for laparoscopic removal of the fallopian tube after ectopic pregnancy via transabdominal or transumbilical port using homemade bag: A randomized trial.

BACKGROUND: The purpose of this study was to evaluate the feasibility and surgical outcome of a novel technique for laparoscopic removal of the fallopian tube using a homemade retrieval bag through a 10-mm transumbilical or 5-mm transabdominal port. MATERIALS AND METHODS: A total of 40 women with ruptured ectopic tubal pregnancy were randomized into a 10-mm transumbilical group (n = 20) or a 5-mm transabdominal group (n = 20) according to the port used for specimen removal. Fallopian tube removal was performed using a new method based on the use of a homemade surgical glove as a retrieval bag. RESULTS: There were no differences in the demographic characteristics between the two groups. The specimen retrieval time was significantly shorter in the transumbilical group than in the transabdominal group. Post-operative pain scores, assessed using a visual analog scale, were similar between the groups. No cases of rupture of the homemade retrieval bag were observed. CONCLUSION: The laparoscopic removal of the fallopian tube through the 10-mm umbilical port using a homemade retrieval bag is associated with shorter operative time than retrieval through a 5-mm abdominal port. The present results showed the feasibility and safety of our homemade retrieval bag and novel technique.

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.

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.

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.

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.