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      • KCI등재후보

        Combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinoma in vitro

        Ayhan Bilir,Mine Erguven,Ezgi Ermis,Mine Sencan,Nuray Yazihan 대한부인종양학회 2011 Journal of Gynecologic Oncology Vol.22 No.4

        Objective: The aim of the study was to investigate whether lithium chloride and medroxyprogesterone acetate can potentiate the cytotoxicity of imatinib mesylate in human endometrial cancer in vitro and the effect of midkine in these therapies. Methods: Imatinib mesylate (50 μM), lithium chloride (100 μM), medroxyprogesterone acetate (200 μM) and their combination were applied to monolayer and three dimensional cultures of human Ishikawa endometrial cancer for 72 hours. The cell proliferation index, apoptotic index, caspase-3 and midkine levels, cell cycle distributions in monolayer cultures and cell ultrastructure in spheroid cultures were evaluated. Results were statistically analyzed using the Student’s t-test. Results: All drug applications inhibited cell proliferation (p<0.05), however the combination were the effective groups for 72 hours (p<0.05). Interestingly, although the loss of efficiency was seen higly seen every 24 hours at single applications, the inhibition rates of the combination groups were almost same for 72 hours. In concordance with these results, the apoptotic index, caspase-3 levels (p<0.05), cell morphology and ultrastructure damages were much higher in the combination groups. Imatinib mesylate induced S-phase arrest, however other groups induced G0+G1-phase arrest at 24 hours and all groups induced G0+G1 arrest at 72 hours (p<0.05). Imatinib mesylate and imatinib mesylate with medroxyprogesterone acetate induced highest decrease in midkine levels, respectively (p<0.05). Conclusion: The present study showed that the combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinoma in vitro and the inhibition of midkine involved in their mechanism of action against endometrium defense. Objective: The aim of the study was to investigate whether lithium chloride and medroxyprogesterone acetate can potentiate the cytotoxicity of imatinib mesylate in human endometrial cancer in vitro and the effect of midkine in these therapies. Methods: Imatinib mesylate (50 μM), lithium chloride (100 μM), medroxyprogesterone acetate (200 μM) and their combination were applied to monolayer and three dimensional cultures of human Ishikawa endometrial cancer for 72 hours. The cell proliferation index, apoptotic index, caspase-3 and midkine levels, cell cycle distributions in monolayer cultures and cell ultrastructure in spheroid cultures were evaluated. Results were statistically analyzed using the Student’s t-test. Results: All drug applications inhibited cell proliferation (p<0.05), however the combination were the effective groups for 72 hours (p<0.05). Interestingly, although the loss of efficiency was seen higly seen every 24 hours at single applications, the inhibition rates of the combination groups were almost same for 72 hours. In concordance with these results, the apoptotic index, caspase-3 levels (p<0.05), cell morphology and ultrastructure damages were much higher in the combination groups. Imatinib mesylate induced S-phase arrest, however other groups induced G0+G1-phase arrest at 24 hours and all groups induced G0+G1 arrest at 72 hours (p<0.05). Imatinib mesylate and imatinib mesylate with medroxyprogesterone acetate induced highest decrease in midkine levels, respectively (p<0.05). Conclusion: The present study showed that the combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinoma in vitro and the inhibition of midkine involved in their mechanism of action against endometrium defense.

      • Prognostic Significance of Peripheral Blood Flow Cytometry Parameters in Patients with Non-Metastatic Breast Cancer

        Engin, Huseyin,Bilir, Cemil,Tekin, Ishak Ozel Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

        Background: Immune functions and their relation to prognosis in breast cancer patients have become areas of great interest in recent years. Correlations between survival outcomes and peripheral blood flow cytometry parameters are therefore of interest. Here we focused on patients with non-metastatic breast cancer (BC). Materials and Methods: A total of 29 patients with pathological confirmed breast carcinoma and flow cytometry data were assessed for overall survival (OS) and progression free survival (PFS). Results: The median age of the patients was 54 years (range, 29-83). Multivariate analysis revealed that OS was significantly associated with absolute cytotoxic T cell count (95%CI, coef 2.26, p=0.035), tumor size (95%CI, coef -14.5, p 0.004), chemotherapy (95%CI, coef 12.9, p 0.0001), MFI of CD4 (95%CI, coef -5.1, P 0.04), MFI of HLA DR (95%CI, coef -5.9, p 0.008) and tumor grade (95%CI, coef -13, P 0.049) with R-Sq(adj)=67%. Similar findings were obtained for PFS. Conclusions: OS and PFS were significantly associated with tumor grade, tumor size, chemotherapy, MFI of CD4, HLA DR and absolute cytotoxic T cell count. The study revealed that MFI of basic CD markers and absolute cytotoxic T cell number may be a prognostic factors in women with non-metastatic BC.

      • ABO Blood Group and Risk of Pancreatic Cancer in a Turkish Population in Western Blacksea Region

        Engin, Huseyin,Bilir, Cemil,Ustun, Hasan,Gokmen, Ayla Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.1

        Background: We aimed to investigate the relationship between blood groups and pancreatic cancer in a Turkish population in Western Blacksea region. Methods: This is a retrospective study. Zonguldak Karaelmas University outpatient oncology clinic records were screened for the period between 2004 and 2011. Results: The median age of patients were 56 (${\pm}16$) and 132 of 633 study population had pancreatic cancer. Pancreatic cancer patients had significantly higher rates of blood group A compared to controls (OR 1.8, 95%CI, p 0.005). Rates of blood group AB was significantly lower than the control group (OR 0.37, 95% CI, p 0.04). The median survival (IR) time in subjects having the blood groups A, B, AB and O were 7.0 (1-28), 7.0 (2-38), 10 (2-36) and 9.0 (2-48) months respectively; the blood group 0 had significantly higher overall survival (OS) compared to the non-0 groups (p 0.04). Conclusions: Pancreatic cancer patients had more common blood group A in our population. Moreover, blood group AB appeared to be a protective factor against pancreatic cancer in our population. Blood group 0 had a significantly longer survival compared to non-0, regardless of prognostic factors.

      • SCOPUSKCI등재

        Evaluation of Occupational Health Teaching Sessions for Final Year Medical Students

        Yildiz, Ali Naci,Bilir, Nazmi,Camur, Derya,Caman, Ozge Karadag Occupational Safety and Health Research Institute 2012 Safety and health at work Vol.3 No.2

        Objectives: The study was conducted with the aim of evaluating applied occupational health teaching for final-year medical students at Hacettepe University, Faculty of Medicine. Methods: The study included all sixth grade medical students (n=293) during one academic year. Pre- and post-training tests were used to assess the magnitude of change in knowledge and attitude of students on occupational health, whereas the opinion of students on several aspects of the quality of teaching sessions were assessed by using post-training questionnaires. Results: Post-training tests revealed that the level of knowledge on all aspects of occupational health increased among medical students. An evaluation of the teaching sessions showed favorable results for the overall quality of the sessions: 81.3% of the students stated that the sessions were well organized, 81.7% remarked the workplace/factory visit was a valuable experience, and 91.0% stated feeling more competent on occupational health issues. Conclusion: There was a greater increase in students' knowledge on technical precautions than their knowledge on issues related to medical practice in the workplace. Visiting a workplace was found to contribute to the overall aim of knowledge and attitude change on occupational health issues. The scope of undergraduate medical education should be extended by improving occupational health education with respect to educational content, duration, and methods.

      • Effect of curing treatments on the material properties of hardened self-compacting concrete

        Salhi, M.,Ghrici, M.,Li, A.,Bilir, T. Techno-Press 2017 Advances in concrete construction Vol.5 No.4

        This paper presents a study of the properties and behavior of self-compacting concretes (SCC) in the hot climate. The effect of curing environment and the initial water curing period on the properties and behavior of SCC such as compressive strength, ultrasonic pulse velocity (UPV) and sorptivity of the SCC specimens were investigated. Three Water/Binder (W/B) ratios (0.32, 0.38 and 0.44) have been used to obtain three ranges of compressive strength. Five curing methods have been applied on the SCC by varying the duration and the conservation condition of SCC. The results obtained on the compressive strength show that the period of initial water curing of seven days followed by maturation in the hot climate is better in comparison with the four other curing methods. The coefficient of sorptivity is influenced by W/B ratio and the curing methods. It is also shown that the sorptivity coefficient of SCC specimens is very sensitive to the curing condition. The SCC specimens cured in water present a low coefficient of sorptivity regardless of the ratio W/B. Furthermore, the results show that there is a good correlation between ultrasonic pulse velocity and the compressive strength.

      • KCI등재

        Lycopene Protects Against Spontaneous Ovarian Cancer Formation in Laying Hens

        Kazim Sahin,Engin Yenice,Mehmet Tuzcu,Cemal Orhan,Cengizhan Mizrak,Ibrahim H. Ozercan,Nurhan Sahin,Bahiddin Yilmaz,Birdal Bilir,Bulent Ozpolat,Omer Kucuk 대한암예방학회 2018 Journal of cancer prevention Vol.23 No.1

        Background: Dietary intake of lycopene has been associated with a reduced risk of ovarian cancer, suggesting its chemopreventive potential against ovarian carcinogenesis. Lycopene’s molecular mechanisms of action in ovarian cancer have not been fully understood. Therefore, in the present study, we investigated the effects of lycopene on the ovarian cancer formation using the laying hen model, a biologically relevant animal model of spontaneous ovarian carcinogenesis due to high incidence rates similar to humans. Methods: In this study, a total of 150 laying hens at age of 102 weeks were randomized into groups of 50: a control group (0 mg of lycopene per kg of diet) and two treatment groups (200 mg or 400 mg of lycopene per kg of diet, or ~26 and 52 mg/d/hen, respectively). At the end of 12 months, blood, ovarian tissues and tumors were collected. Results: We observed that lycopene supplementation significantly reduced the overall ovarian tumor incidence (P < 0.01) as well as the number and the size of the tumors (P < 0.004 and P < 0.005, respectively). Lycopene also significantly decreased the rate of adenocarcinoma, including serous and mucinous subtypes (P < 0.006). Moreover, we also found that the serum level of oxidative stress marker malondialdehyde was significantly lower in lycopene-fed hens compared to control birds (P < 0.001). Molecular analysis of the ovarian tumors revealed that lycopene reduced the expression of NF-B while increasing the expression of nuclear factor erythroid 2 and its major target protein, heme oxygenase 1. In addition, lycopene supplementation decreased the expression of STAT3 by inducing the protein inhibitor of activated STAT3 expression in the ovarian tissues. Conclusions: Taken together, our findings strongly support the potential of lycopene in the chemoprevention of ovarian cancer through antioxidant and anti-inflammatory mechanisms. (J Cancer Prev 2018;23:25-36)

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