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Öğe Ameliorative Effects of Resveratrol on Acute Ovarian Toxicity Induced by Total Body Irradiation in Young Adult Rats(Elsevier Science Inc, 2012) Simsek, Yavuz; Gurocak, Simay; Turkoz, Yusuf; Akpolat, Nusret; Celik, Onder; Ozer, Ali; Yilmaz, ErcanObjective: The purpose of this study was to investigate the ovarian protective effects of resveratrol in rats exposed to total body irradiation. Design: Experimental study. Settings: University hospital. Participants and Interventions: Thirty female rats were randomized into four groups: (1) control group (n = 7); (2) low-dose (10 mg/kg) resveratrol group (n = 8); (3) high-dose (100 mg/kg) resveratrol group (n =7); and (4) sham irradiation group (n = 8). The drugs were administered intraperitoneally as single doses, and the rats were exposed to total body radiation 24 h after the treatment. The animals were sacrificed the following day, and their ovaries were excised for histopathological and biochemical analysis. Main Outcome Measures: The ovarian follicle counts were calculated, and irradiation-dependent ovarian damage and tissue levels of antioxidant enzymes were evaluated. Results: Group 2 and Group 3 showed significantly higher numbers of total follicle counts compared with Group 1 (P < 0.01). The low-dose resveratrol treatment was associated with significantly higher numbers of primary follicles than the high-dose group. The tissue activities of glutathione peroxidase (GsH-Px) and catalase (CAT) were significantly elevated in the resveratrol-treated animals. Evaluation of ovarian histology revealed no remarkable changes in fibrosis and leucocyte infiltration among the resveratrol-treated and control rats; however, vascularity was significantly reduced in the high-dose group (P = 0.014). Conclusion: Resveratrol attenuated irradiation-dependent ovarian damage, suggesting that this natural antioxidant is effective in reducing the follicle loss induced by ionizing radiation.Öğe Apricot attenuates oxidative stress and modulates of Bax, Bcl-2, caspases, NF?-B, AP-1, CREB expression of rats bearing DMBA-induced liver damage and treated with a combination of radiotherapy(Pergamon-Elsevier Science Ltd, 2014) Karabulut, Aysun Bay; Karadag, Nese; Gurocak, Simay; Kiran, Tugba; Tuzcu, Mehmet; Sahin, KazimWe evaluated the ability of apricot to attenuate apoptosis and oxidative stress developed during the process of 7,12-dimethylbenz[a]anthracene (DMBA) and radiotherapy in the liver of rats bearing liver damage. Fifty female Wistar rats were divided into 7 groups; (i) normal control rats; (ii) rats fed with standard diet with apricot (20%), (ii) rats fed with standard diet and administrated 6 gray radiotherapy with Co 60 device applied to a single fraction, (iv) rats fed with standard diet and administered intraperitoneally DMBA (20 mg/kg), (v) rats fed with standard diet and administered DMBA and 6 gray radiotherapy, (vi) rats fed with standard rat diet and administered DMBA and supplemented apricot, (vii) rats fed with standard diet supplemented apricot administered DMBA and radiotherapy (RT) for 6 weeks. Expression of Bax, caspase 3, and glutathione activity decreased in the liver but liver expression of NF-kappa B, AP-1, CREB, Bcl-2 and ALT, AST, 5'NT, MDA, NO levels increased in DMBA-induced liver damage rats. In conclusion, the results suggest that apricot supplementation and irradiation given in combination, offer maximum protection against DMBA-induced hepatic carcinogenesis. (C) 2014 Elsevier Ltd. All rights reserved.Öğe Combinatorial effect of zoledronic acid and irradiation on the prevention of DMBA-induced precancerogenic changes in the mammary tissues of rats(Wolters Kluwer Medknow Publications, 2016) Gurocak, Simay; Karabulut, Aysun Bay; Tuzcu, Mehmet; Sahin, Nurhah; Temelli, Oztun; Ince, Volkan; Sahin, KazimBackground: At present, the rates of breast cancer are continuously increasing, with over a million new cases being diagnosed worldwide each year. Hence, the development of new breast cancer chemopreventive drugs with acceptable efficacy and toxicity that are suitable for use for a protracted period of time is urgently needed. The present study investigated the potential preventive effects of zoledronic acid [ZOL] and radiotherapy [RT], both alone and in combination, on precancerogenic changes on the breast tissues of females. Materials and Methods: Wistar rats were treated with 7,12-dimethylbenz [a] anthracene [DMBA] at the acute phase. Fifty female rats were divided into seven groups: Control group [I]; ZOL, group [II]; RT, group [III]; DMBA, group [IV]; DMBA + RT, group [V]; DMBA + ZOL, group [VI]; and DMBA + ZOL + RT, group [VII]. Results: The treatment of DMBA-exposed rats with ZOL and RT, both alone and in combination, successfully upregulates the transcriptional levels of Bax, caspase-3, caspase-9, p21, and BRCA 1 in mammary tissues, which may account for the elevated apoptotic activities observed and the eventual inhibition of tumor growth. The administration of RT and ZOL both alone and in combination was found to be effective for inhibiting the DMBA-induced precancerogenic changes on breast tissues and modulating the expression of apoptosis-associated proteins in the acute phase. Conclusions: The combination of RT and ZOL was more effective than either agent alone. Our results suggest that the administration of ZOL and irradiation in combination can offer maximal protection against DMBA-induced mammary precancerogenic changes.Öğe The Effect of Prognostic Factors and Adjuvant Radiotherapy on Survival in Patients with High-Grade Early-Stage Endometrial Cancer: A Retrospective Clinical Study(Int Scientific Information, Inc, 2019) Yilmaz, Ercan; Gurocak, Simay; Melekoglu, Rauf; Koleli, Isil; Faydali, Simge; Temelli, Oztun; Yar, TubaBackground: This retrospective clinical study aimed to investigate the effect of prognostic factors and adjuvant radiotherapy in patients with high-grade early-stage endometrial cancer on overall survival (OS) and disease-free survival (DES). Material/Methods: The medical records of patients diagnosed with high-grade, early stage (I or II) endometrial adenocarcinoma who had received adjuvant radiotherapy after surgery were reviewed. Results: Seventy-nine patients included 39 patients (49.4%) with stage II endometrial cancer, 25 patients (31.6%) with histologic grade 3 tumors, and 47 patients (59.5%) with endometrial cancer showing lymphovascular space invasion (LVSI). There were 45 patients (57.0%) who received external pelvic radiotherapy with an average dose of 46.0 Gy (range, 11.2-50.4 Gy), and 34 patients (43.0%) received vaginal brachytherapy (VBT) with an average dose of 21.5 Gy (range, 10-36 Gy). Multivariate analysis showed that tumor stage (HR, 4.066; 95% CI, 1.227-13.467; p=0.022) and histologic grade (HR, 16.652; 95% CI, 4.430-62.589; p<0.001) were independent predictors for OS. Increased serum CA-125 levels (HR, 1.136; 95% CI, 0.995-1.653; p=0.047) and histologic grade (HR, 3.236; 95% CI, 1.107-15.156; p=0.015) were independent predictors for DES. Adjuvant radiotherapy was not found to be significantly associated with improved OS (HR, 1.259; 95% CI, 0.518-3.058; p=0.612) or DES (HR, 1.056; 95% CI, 0.994-1.123; p=0.078). Conclusions: This retrospective study showed that in high-grade early-stage endometrial cancer treated with postoperative adjuvant radiotherapy, independent predictors for OS were tumor stage and grade. Adjuvant radiotherapy was not associated with improved OS or DES.Öğe Factors Affecting Treatment and Prognosis in Thymomas: A Multi-Center Experience(Kare Publ, 2020) Karabulut Gul, Sule; Tepetam, Huseyin; Karaman, Sule; Gurocak, Simay; Korkmaz Kirakli, Esra; Babalioglu, Ibrahim; Erdis, EdaOBJECTIVE Thymomas, a rare malignancy, are located in 95% anterior mediastinum. They are associated with paraneoplastic syndromes, especially myasthenia graves. Although many classifications are used considering the depth of invasion, presence of metastasis, predominant cell type, or immunohistochemical properties in staging, Masoaka classification is commonly used. Surgery is the most effective method in the treatment of thymoma, and neoadjuvant chemotherapy is recommended in advanced stages (III-IV). Adjuvant radiotherapy has proven efficacy in advanced and inoperable patients. In this study, we aimed to evaluate treatment outcomes and factors affecting prognosis in thymoma patients. METHODS Patients with thymoma who were included in this study voluntarily from seven centers between January 2002 and August 2018 were evaluated retrospectively. RESULTS Of the 158 patients with thymoma, 125 patients with complete data were included in this study. The mean age of the patients was 51.84 (18-84), and 72 were male. Myasthenia graves were present in 64 patients. One hundred thirteen patients were operated and 12 were inoperable. One hundred patients were stage 2, 9 were stage 3, and 16 were stage 4. In our study, 3-year survival was 84.4%, and 5-year survival was 74.9%; inoperable patients, surgical margin positivity, advanced disease and radiotherapy dose less than 50.4'Gy were found to be negative factors affecting survival. In patients with myasthenia graves (MG), survival was higher in patients with stage 2B and less. Survival was lower in epithelial type B3 and type C histologic types. Age, sex, and capsule involvement did not seem to affect survival. CONCLUSION Thymoma is a locally controlled disease with long survival and the results of our study are consistent with the literature. The number of patients should be increased to better define prognostic factors.Öğe Melatonin Protects Inner Ear Against Radiation Damage in Rats(Wiley, 2015) Karaer, Isil; Simsek, Gokce; Gul, Mehmet; Bahar, Leyla; Gurocak, Simay; Parlakpinar, Hakan; Nuransoy, AyseObjectives/Hypothesis: To examine the effects of N-acetyl-5-methoxytryptamine (melatonin) on radiation-induced inner ear damage. Study Design: An experimental animal model. Methods: Forty rats were randomized into five groups, as follows: 1) melatonin and then radiotherapy group (n = 8), which received intraperitoneal (i.p.) melatonin (5 mg/kg) followed by irradiation 30 minutes later; 2) radiotherapy and then melatonin group (n = 8), which received irradiation with i.p. melatonin (5 mg/kg) 30 minutes later; 3) melatonin group (n = 8), which received i.p. melatonin (5 mg/kg); 4) radiotherapy group (n = 8), which underwent only irradiation; 5) and the control group (n = 8), which received i.p. 0.9% NaCl. The medications and irradiation were administered for 5 days. All rats underwent the distortion product otoacoustic emission (DPOAE) test before and 10 days after the experiment. The middle ears of the rats were excised, and assessment of tissue alterations in the organs of Corti, spiral ganglions, and stria vascularis were compared among the groups. Results: In the radiotherapy group, the DPOAE amplitudes at frequencies of 4000 to 6000 Hz were significantly decreased when compared with the controls. The DPOAE amplitudes both in the melatonin and then radiotherapy group and the radiotherapy and then melatonin group exhibited better values than they did in the radiotherapy group. Histopathological evidence of damage to the organs of Corti, spiral ganglions, and stria vascularis damage was markedly reduced in both these two groups when compared to the radiotherapy group. Conclusion: These results indicate that melatonin may have significant ameliorative effects on cochlear damage secondary to ionizing radiation.Öğe Melatonin's protective effect on the salivary gland against ionized radiation damage in rats(Wiley, 2016) Karaer, Isil Cakmak; Simsek, Gokce; Yildiz, Azibe; Vardi, Nigar; Polat, Alaadin; Tanbek, Kevser; Gurocak, SimayObjectivesThe aim of this study was to examine the effects of melatonin on ionized radiation-induced salivary gland damage using an experimental model. Materials and MethodsThirty-two rats were randomized into four groups: (i) the control group (C, n = 8) that received intraperitoneal (i.p.) 0.9% NaCl; (ii) the melatonin group (M, n = 8) that received i.p. 5 mg/kg melatonin; (iii) the radiotherapy group (RT, n = 8) that underwent irradiation; (iv) the melatonin plus radiotherapy group (M+RT, n = 8) that received i.p. 5 mg/kg of melatonin, followed by irradiation 30 min later; and (v) the radiotherapy plus melatonin group (RT+M, n = 8) that received irradiation followed by i.p. 5 mg/kg of melatonin 30 min later. The medications and irradiation were administered for 5 days and the salivary glands of the rats were excised 10 days later; the histopathological changes in the salivary glands were assessed and biochemical analyses were conducted (tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI)). ResultsRegardless of whether melatonin was administered before or after radiotherapy, melatonin decreased the radiation-induced parotid and submandibular histological damage. In addition, regardless of whether administration occurred before or after radiotherapy, melatonin decreased oxidative stress markers, such as MDA, TOS, and OSI. On the contrary, levels of antioxidative markers, such as CAT and GPx, were increased by melatonin. ConclusionsMelatonin may have a significant protective effect on salivary gland damage secondary to ionizing radiation.Öğe Outcomes of radiotherapy in early stage glottic laryngeal carcinoma: a single center experience(Medicine Science, 2016) Ekici, Kemal; Temelli, Oztun; Eraslan, Ayse Fatma; Gurocak, Simay; Kaplan Bozdag, Nihal; Elkiran, Emin Tamer; Kekilli, Ersoy; Kizilay, Ahmet[Abstract Not Acailable]Öğe Preventive Effects of Resveratrol against Azoxymethane Induced Damage in Rat Liver(Asian Pacific Organization Cancer Prevention, 2013) Gurocak, Simay; Karabulut, Ercan; Karadag, Nese; Ozgor, Dincer; Ozkeles, Neslihan; Karabulut, Aysun BayBackground: In recent years, due to modern lifestyles and exposure to chemical carcinogens, cancer cases are steadily increasing. From this standpoint, azoxymethane (AOM), a chemical carcinogen which causes de novo liver damage, and resveratrol, which is an antioxidant found in foods and protects against oxidative stress damage, are of interest. We here aimed to evaluate whether resveratrol could protect the liver tissues from the effects of AOM. Materials and Methods: The study was conducted in 4 groups, each consisting of seven rats, the first receiving only AOM (2 times per week, 5 mg/kg), group 2 AOM and resveratrol (2 times a week, 20 mg/kg), group 3 assessed only as a control and group 4 administered only resveratrol. At the end of the seventh week, the rats were sacrificed. Rat liver MDA, NO, GSH levels were analyzed biochemically, as well as the tissues being evaluated histopathologically. Results: MDA and NO increased in AOM group as signs of increased oxidative stress. The group concomitantly administered resveratrol was been found to be significantly decreased in MDA and NO levels and increased in GSH activity. However, there were no significant findings on histopathological evaluation. Conclusions: In the light of these results, resveratrol appears to exert protective effect on oxidative stress in the liver tissue due to deleterious effects of chemical carcinogens.Öğe Prophylactic cranial irradiation in small cell lung cancer: A single-center experience.(Allied Acad, 2017) Temelli, Oztun; Bozdag, Nihal Kaplan; Eraslan, Fatma Aysun; Gulbas, Hulya; Gurocak, Simay; Dikilitas, MustafaObjective: Small-Cell Lung Cancer (SCLC) constitutes about 15% of all lung cancers. It tends to frequently metastasize to the brain. Prophylactic Cranial Irradiation (PCI) is performed, when the penetration of chemotherapeutic agents to brain is insufficient. The aim of this study was to report our single-center experience with PCI in SCLC cases. Methods: We retrospectively reviewed 28 patients with SCLC diagnosed between March 2007 and November 2016. Cranial Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) was performed from all patients to exclude metastasis before PCI. Radiation Therapy (RT) was conducted using two different instruments: a three-dimensional conformal RT-based Linear Accelerator (LINAC) instrument was used until 2013 and an Intensity-Modulated Radiation Therapy (IMRT) thereafter. All patients were treated with a total of 25-36 Gy with fraction doses of 2-2.5 Gy. Overall survival was estimated in all patients. Results: The mean age was 56 (range: 36 to 72) y. Only one of the patients was female, while the remaining patients were all males. Twenty two patients (78.5%) were in limited stage SCLC, while six patients (21.5%) were in the extensive stage. Seventeen patients died, while 11 of them survived. The mean survival was 35 months, while it was 40 months for limited stage and 17 months for extensive stage (p=0.027). One, two, and five-year OS rates were 81.4%, 58%, and 17%, respectively. Four (14%) patients developed brain metastasis during follow-up. Of these patients, two were treated with Whole Brain RT (WBRT), one with Stereotactic RT (SBRT), and the other with best supportive care. Conclusion: Our study results suggest that PCI is a safe, low-toxicity treatment modality used to prevent brain metastases in SCLC cases.Öğe Protective effects of resveratrol on salivary gland damage induced by total body irradiation in rats(Wiley-Blackwell, 2012) Simsek, Gokce; Gurocak, Simay; Karadag, Nese; Karabulut, Aysun Bay; Demirtas, Erol; Karatas, Erkan; Pepele, EdaObjectives/Hypothesis: One of the most common acute side effects of irradiation is xerostomia, which results from damage to the salivary gland cells by direct ionization. Resveratrol is a natural compound with profound anti-inflammatory and antioxidant properties. The purpose of the present study was to investigate the potential protective effects of resveratrol on injury to the salivary glands of rats that were exposed to total body irradiation. Study Design: An experimental study at the Inonu University School of Medicine. Methods: Twenty-nine female rats were randomized into four groups: group 1, high-dose (100 mg/kg) resveratrol group (n = 7); group 2, low-dose (10 mg/kg) resveratrol group (n = 7); group 3, control (vehicle) rats (n = 7); and group 4, sham-irradiation group (n = 8). The medications were administered as single doses, and the rats were exposed to total body irradiation 24 hours after the treatment. The animals were sacrificed the following day, and the parotid and submandibular glands were excised. Salivary gland histology and the tissue levels of glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) were investigated. Results: The rats in group 1 showed significantly decreased acinar loss and less ductal damage and cell necrosis than those of the control group (P < .05). Antioxidant GSH levels were significantly increased by high doses of resveratrol treatment. The tissue activities of MDA in both the parotid and submandibular glands were significantly reduced in group 1. Low-dose resveratrol treatment did not significantly alter the tissue levels of MDA. Conclusions: Resveratrol at relatively high doses can reduce the irradiation-dependent salivary gland damage, suggesting that this natural antioxidant may be effectively used to lessen the side effects related to salivary gland dysfunction that is induced by irradiation. Laryngoscope, 2012