Tulay 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.

Evaluation of sleep disorders in cancer patients based on Pittsburgh Sleep Quality Index

Insomnia, poor sleep quality and short sleep durations are the most common problems seen in cancer patients. More studies are needed about sleep disorders in cancer patients. In our study, we aimed to investigate the prevalence of sleep disorders and the impact of these problems on the quality of life in cancer patients. Pittsburgh Sleep Quality Index (PSQI) was given to a total of 314 patients. The psychometric evaluation of the Turkish version of PSQI in cancer patients revealed that 127 (40.4%) patients had global PSQI scores >5, indicating poor sleep quality. There was no statistically significant relationship between PSQI scores and sexuality, marital status, cancer stage and chemotherapy type (P > 0.05); while the patients with bone and visceral metastasis had much lower PSQI scores (P = 0.006). Patients with Eastern Cooperative Oncology Group performance scores of 3 or more had also significantly lower PSQI scores (P = 0.02). In conclusion, PSQI questionnaire may be used to evaluate the sleep disorders in cancer patients. Consistent use of multi-item measures such as PSQI with established reliability and validity would improve our understanding of difficulties experienced by cancer patients with chronic insomnia.

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.

Tumor deposits in gastric carcinomas

We performed this study to examine the prevalence of tumor deposits (TD) in gastric adenocarcinomas (GACa), and the relevance of their presence, size and type to clinical outcome. Ninety-six patients, histopathologically diagnosed as GACa following a total/subtotal gastrectomy were included, and clinicopathologic data were recorded. Due to the statistical analysis, the majority of TD(+) cases were of intestinal type and showed vascular invasion. In these cases, the incidence of local recurrence was significantly higher. The majority of GACa of intestinal type with TD were of high grade and showed vascular invasion. Recurrence and death were more commonly encountered among them. The recurrence-free survival (RFS) was significantly shorter in patients with TDs, which was also confirmed by multivariate analysis, and there was a significant difference between both RFS and overall survival of TD(+) and TD(-) cases of intestinal type GACa. In conclusion, in this study, we demonstrate that TDs are not infrequently observed in GACa, they are more commonly associated with the intestinal type and vascular invasive gastric cancers. Our study shows the prognostic impact of TDs, especially regarding the RFS. Therefore, the documentation of TDs might be considered for prospective studies, especially for the intestinal type GACa, a shortcoming of this study.

Erythrocyte Deformability and Oxidative Stress in Inflammatory Bowel Disease

BackgroundOxidative stress and reduced microvascular flow are important factors in the pathogenesis of inflammatory bowel disease (IBD). The increased oxidative stress reduces the eriytrocyte deformability. However, in IBD, there are no studies in the literature which evaluate erythrocyte deformability.AimsIn our study, we investigated the effect of oxidative stress and erythrocyte deformability in IBD.MethodsForty-three patients with active IBD, 48 patients with inactive IBD and 45 healthy controls were included. The erytrocyte deformability, malonyldialdehyde levels, glutation peroxidase and sulfhydryl levels were measured in peripheral venous blood samples.ResultsErytrocyte malonyldialdehyde levels in both active and inactive IBD were significantly increased compared with control groups. Plasma glutation peroxidase levels did not show statistically significant difference between all groups. The decreased plasma sulfhydryl levels in active IBD were statistically significant compared with both the inactive IBD and the control group, but plasma sulfhydryl levels in inactive IBD group did not show statistically significant differences when compared with the control group. Elongation index values in both active and inactive IBD increased significantly compared with the control group. Statistically significant correlations were not found between the elongation index and glutation peroxidase, malonyldialdehyde, sulfhydryl levels in all groups.ConclusionsOur study is the first to evaluate the erythrocyte deformability in IBD. In our study, increased erytrocyte malonyldialdehyde levels and decreased plasma sulfhydryl levels manifested the role of oxidative stress in the pathogenesis of the disease. It is thought that the increased erythrocyte malonyldialdehyde values cause the reduction in erythrocyte deformability.

Relationship between Epidermal Growth Factor Receptor Gene Mutations and Clinicopathological Features in Patients with Non-Small Cell Lung Cancer in Western Turkey

BACKGROUND To investigate epidermal growth factor receptor (EGFR) gene mutations in patients with non- small cell lung cancer (NSCLC) and to analyze any relationship with clinicopathological features and prognosis. MATERIALS AND METHODS EGFR gene exons 18-21 in 48 specimens of paraffin-embedded tumor tissue from NSCLC patients were amplified by PCR, followed by direct sequencing and analysis of links to clinicopathological features and prognosis. RESULTS EGFR mutations were detected in 18 of 48 (42.6%) patients with NSCLC. There were 9 cases of mutations in exon 20, 7 in exon 19 and 2 in exon 21. Mutations were more frequently observed in women (5/7 pts, 71.4%) than in men (13/41 pts, 31.7%) (p=0.086) and in non-smokers (5/5 pts, 100%) than smokers (13/43 pts, 30.2%). There was negative correlation of EGFR mutations with smoking status (p=0.005). EGFR mutations were more frequently observed with adenocarcinoma histology (13/32 pts, 40.6%) than in other types (5/16 pts, 31.3%) (p=0.527). The patients with EGFR mutations had better survival than those with wild- type EGFR (p=0.08). There was no association of EGFR mutations with metastatic spread. CONCLUSIONS EGFR mutations in NSCLC were here demonstrated more frequently in females, non-smokers and adenocarcinoma histology in the western region of Turkey. Patients with EGFR mutations have a better prognosis.

Clinical and pathologic features of patients with rare ovarian tumors: multi-center review of 167 patients by the anatolian society of medical oncology.

BACKGROUND Non-epithelial malignant ovarian tumors and clear cell carcinomas, Brenner tumors, transitional cell tumors, and carcinoid tumors of the ovary are rare ovarian tumors (ROTs). In this study, our aim was to determine the clinicopathological features of ROT patients and prognostic factors associated with survival. MATERIALS AND METHODS A total of 167 patients with ROT who underwent initial surgery were retrospectively analyzed. Prognostic factors that may influence the survival of patients were evaluated by univariate and multivariate analyses. RESULTS Of 167 patients, 75 (44.9%) were diagnosed with germ-cell tumors (GCT) and 68 (40.7%) with sex cord-stromal tumors (SCST); the remaining 24 had other rare ovarian histologies. Significant differences were found between ROT groups with respect to age at diagnosis, tumor localization, initial surgery type, tumor size, tumor grade, and FIGO stage. Three-year progression-free survival (PFS) rates and median PFS intervals for patients with other ROT were worse than those of patients with GCT and SCST (41.8% vs 79.6% vs 77.1% and 30.2 vs 72 vs 150 months, respectively; p=0.01). Moreover, the 3-year overall survival (OS) rates and median OS times for patients with both GCT and SCST were better as compared to patients with other ROT, but these differences were not statistically significant (87.7% vs 88.8% vs 73.9% and 170 vs 122 vs 91 months, respectively; p=0.20). In the univariate analysis, tumor localization (p<0.001), FIGO stage (p<0.001), and tumor grade (p=0.04) were significant prognostic factors for PFS. For OS, the univariate analysis indicated that tumor localization (p=0.01), FIGO stage (p=0.001), and recurrence (p<0.001) were important prognostic indicators. Multivariate analysis showed that FIGO stage for PFS (p=0.001, HR: 0.11) and the presence of recurrence (p=0.02, HR: 0.54) for OS were independent prognostic factors. CONCLUSIONS ROTs should be evaluated separately from epithelial ovarian cancers because of their different biological features and natural history. Due to the rarity of these tumors, determination of relevant prognostic factors as a group may help as a guide for more appropriate adjuvant or recurrent therapies for ROTs.

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.

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.

Clinicopathological Features in Bilateral Breast Cancer

INTRODUCTION AND PURPOSE The frequency of bilateral breast cancer is 1.4-11.0% among all breast cancers. It can present as synchronous (SC) or metachronous (MC). Data regarding clinical course of bilateral breast cancer are scarce. In this study, we therefore evaluated demographic, pathological and clinical characteristics, treatments and responses in bilateral breast cancer cases; making distinctions between metachronous-synchronous and comparing with historic one-sided data for the same parameters. MATERIALS AND METHODS One hundred fifty bilateral breast cancer cases from ten different centers between 2000 and 2011 were retrospectively scanned. Age of the cases, family history, menopausal status, pathological features, pathological stages, neoadjuvant, surgery, adjuvant and palliative chemotherapy/radiotherapy were examined in the context of the first and second occurrence and discussed with reference to the literature. RESULTS Metachronous and synchronous groups showed similar age, menopausal status, tumor type, HER2/neu expression; the family history tumor grade, tumor stage, ER-negativity rate, local and distant metastases rates, surgery, adjuvant chemotherapy application rates were identified as significantly different. Palliative chemotherapy response rate was greater in the metachronous group but median PFS rates did not differ between the groups. CONCLUSION Although bilateral breast cancer is not frequent, MC breast cancer is different from SC breast cancer by having more advanced grade, stage, less ER expression, more frequent rates of local relapse and distant metastasis and better response to chemotherapy in case of relapse/metastasis.