Levent Akman

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.

Can preoperative neutrophil:lymphocyte and platelet:lymphocyte ratios be used as predictive markers for lymph node metastasis in squamous cell carcinoma of the vulva?

OBJECTIVE To determine whether the neutrophil:lymphocyte ratio (NLR) and platelet:lymphocyte ratio (PLR) before complete surgical staging provide information on lymph node metastasis in vulvar squamous cell carcinoma (SCC). STUDY DESIGN All patients with vulvar SCC who underwent complete surgical staging at two institutions between 1 January 2005 and 31 December 2011 were identified retrospectively from patient databases. Receiver operating characteristic (ROC) curve analysis was used to evaluate cut-off, sensitivity, and specificity values for preoperative NLR and PLR to predict lymph node metastasis. RESULTS Data from 64 women with adequate information were analyzed. Lymph node involvement was detected in 19 (29.7%) patients. NLR and PLR were higher in the lymph node--positive group than in the--negative group (p < 0.001). The best cut-off values for predicting lymph node metastasis were 2.81 for the NLR, with 84.5% sensitivity and 89.5% specificity, and 139.5 for the PLR, with 68.9% sensitivity and 89.5% specificity. Forty of the 64 (62.5%) patients had NLRs ≤ 2.81 and 24 (37.5%) had NLRs >2.81. Lymph node involvement was more common in the NLR >2.81 group [60.7% vs. 5.6%; relative risk RR = 10.9, 95% confidence interval CI = 2.7-43.4; p < 0.001]. Mean tumor sizes were 4.2 ± 2.3 cm in the NLR >2.81 group and 2.1 ± 1.2 cm in the NLR ≤ 2.81 group (p = 0.001). The rate of lymph node involvement was higher in the PLR >139.5 group than in the PLR ≤ 139.5 group (54.8% vs. 6.1%; RR = 9.0, 95% CI = 2.2-35.9; p<0.001). CONCLUSION Preoperative NLR and PLR are directly associated with nodal involvement status of vulvar SCC. These markers are simple, readily obtained and calculated, and easy to integrate into the surgical work-up of patients with vulvar SCC, at no extra cost.

The effects of sunitinib on endometriosis

Abstract The aim of the present study was to evaluate the effect of sunitinib on endometriotic implants and adhesions in a rat endometriosis model. An experimental endometriosis model was created in 21 rats. These rats were randomly divided into three groups: Group 1 (control group, 7 rats) was given no medication; Group 2 (sunitinib group, 7 rats) was given 3 mg/kg per day of oral sunitinib; and Group 3 (danazol group, 7 rats) was given 7.2 mg/kg per day of oral danazol. The volume of endometriotic implants was calculated. The extent and severity of adhesions were evaluated. The groups were compared by the Students t-test, analysis of variance (ANOVA) and the Mann–Whitney U test. There was no statistically significant difference in the mean volume of endometriotic implants before medication between three groups. The volume of implants and extent, severity, total score of adhesions were significantly decreased after medication in Group 2 and Group 3. We noted that the volume of the endometriotic implants and adhesion formation were decreased both after sunitinib and danazol treatment. As a result, sunitinib seems to be effective for endometriotic peritoneal lesions. The effects of sunitinib in rat models give hope for improving the treatment of human endometriosis and prevention of pain symptoms.

Oxytocin ımproves follicular reserve in a cisplatin-ınduced gonadotoxicity model in rats

Cisplatin (CP), an antitumor agent, has been shown to cause ovarian injury and dysfunction in both animal and human studies. The present study was conducted to investigate the protective effect of oxytocin (OT) on CP-induced ovarian toxicity in rats. Twenty-one adult female rats were included in the study. Fourteen rats were administered intraperitoneally CP (2 mg/kg/day) twice a week for 5 weeks. Control group (n = 7) did not receive any treatment. Following treatment, CP-received rats were randomly divided into two groups and treated with either saline (1 mL/kg/day, n = 7) or OT (160 μg/kg/day, n = 7) for 5 weeks. Then, ovarian toxicity and effects of OT were evaluated by histomorphological and biochemical analysis. Our findings revealed a significant reduction in the number of follicles at each grade in saline-treated group. AMH level was significantly lower in saline group compared to control (P < 0.0005). OT treatment significantly attenuated CP toxicity in ovaries and increased AMH levels compared to saline group (P < 0.005). Also, administration of OT lessened lipid peroxidation and prevented glutathione depletion in CP-treated rats (P < 0.05). These results indicated that OT could lessen the CP-induced ovarian damage and improve follicular reserve by preventing oxidative damage.

Topotecan in platinum-resistant epithelial ovarian cancer.

Background: Topotecan has been emerged as a new promising anticancer drug for patients with ovarian cancer. Methods: In this study, patients who were treated with topotecan were reviewed retrospectively. A total of 26 patients was included the study. All patients had received platinum-based regimens previously. Topotecan was administered a dose of 1.5 mg/m2 intravenously 30 min daily for 5 days and repeated every 21 days. Results: The response rates were 30% by CA-125 level and 29% in clinic evaluation. Median duration of response was 8 (3–15) months, median progression-free interval was 12 (4–30) months and median overall survival was 15 (4–36) months. Grade 3–4 neutropenia occurred in 58% of the patients (38% of the courses) and trombocytopenia in 29% of the patients (12% of the courses). Nonhematological toxicities were mild. There was no drug-related death. Conclusion: Topotecan is considered as a reasonable option for treatment of patients with platinum refractory recurrent ovarian cancer.

Granulocyte-colony stimulating factor decreases the extent of ovarian damage caused by cisplatin in an experimental rat model

Objective To investigate whether granulocyte-colony stimulating factor (G-CSF) can decrease the extent of ovarian follicle loss caused by cisplatin treatment. Methods Twenty-one adult female Sprague-Dawley rats were used. Fourteen rats were administered 2 mg/kg/day cisplatin by intraperitoneal injection twice per week for five weeks (total of 20 mg/kg). Half of the rats (n=7) were treated with 1 mL/kg/day physiological saline, and the other half (n=7) were treated with 100 µg/kg/day G-CSF. The remaining rats (n=7, control group) received no therapy. The animals were then euthanized, and both ovaries were obtained from all animals, fixed in 10% formalin, and stored at 4℃ for paraffin sectioning. Blood samples were collected by cardiac puncture and stored at -30℃ for hormone assays. Results All follicle counts (primordial, primary, secondary, and tertiary) and serum anti-Müllerian hormone levels were significantly increased in the cisplatin+G-CSF group compared to the cisplatin+physiological saline group. Conclusion G-CSF was beneficial in decreasing the severity of follicle loss in an experimental rat model of cisplatin chemotherapy.

Synthesis of a theranostic agent: radioiodinated PEGylated PLGA-indocyanine capsules and in vitro determination of their bioaffinity on ovarian, cervical and breast cancer cells

The aim of current study is to synthesize a theranostic (multi-functional) agent, which is targeted on ovary, cervical and breast cancer types with diagnosis and treatment potential and to determine its bioaffinity by using in vitro methods. In conclusion; the designed compound (IPPP), which has fluorescence capability (from Indocyanine), encapsulated structure (with PEGylated PLGA), included an anticancer drug (Paclitaxel) for targeting and radionuclidic tracer (131I) content for tracing, has bioaffinity and promise for diagnosis and therapy on ovarian, cervical and breast cancer cell lines.

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

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

Abstract 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.

Prognostic Significance of Retroperitoneal Lymphadenectomy, Preoperative Neutrophil Lymphocyte Ratio and Platelet Lymphocyte Ratio in Primary Fallopian Tube Carcinoma: A Multicenter Study

Purpose The purpose of this study is to evaluate the prognostic role of preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) and the need for para-aortic lymphadectomy in patients with primary fallopian tube carcinoma (PFTC). Materials and Methods Ninety-one patients with a diagnosis of PFTC were identified through the gynecologic oncology service database of six academic centers. Clinicopathological, surgical, and complete blood count data were collected. Results In univariate analysis, advanced stage, suboptimal surgery, and NLR > 2.7 were significant prognostic factors for progression-free survival, whereas in multivariate analysis, only advanced stage and suboptimal surgery were significant. In addition, in univariate analysis, cancer antigen 125 ≥ 35 U/mL, ascites, advanced stage, suboptimal surgery, NLR > 2.7, PLR > 233.3, platelet count ≥ 400,000 cells/mm3, staging type, and histological subtype were significant prognostic factors for overall survival (OS); however, in multivariate analysis, only advanced stage, suboptimal surgery, NLR > 2.7, and staging type were significant. Inclusion of pelvic and para-aortic lymphadenectomy in surgery showed significant association with longer OS, with a mean and median OS of 42.0 months and 35.5 months (range, 22 to 78 months), respectively, vs. 33.5 months and 27.5 months (range, 14 to 76 months), respectively, for patients who underwent surgery without para-aortic lymphadenectomy (hazard ratio, 3.1; 95% confidence interval, 1.4 to 5.7; p=0.002). Conclusion NLR (in both univariate and multivariate analysis) and PLR (only in univariate analysis) were prognostic factors in PFTC. NLR and PLR are inexpensive and easy tests to perform. In addition, patients with PFTC who underwent bilateral pelvic and para-aortic lymphadenectomy had longer OS.