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      • Association of miR-1266 with Recurrence/Metastasis Potential in Estrogen Receptor Positive Breast Cancer Patients

        Sevinc, Elif Demirdogen,Egeli, Unal,Cecener, Gulsah,Tezcan, Gulcin,Tunca, Berrin,Gokgoz, Sehsuvar,Tasdelen, Ismet,Tolunay, Sahsine,Evrensel, Turkkan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.1

        The Homeobox B13 (HOXB13):Interleukin 17 Receptor B (IL17BR) index of estrogen receptor (ER)-positive breast cancer (ER (+) BC) patients may be a potential biomarker of recurrence/ metastasis. However, effects of microRNA (miRNA) binding to the 3' untranslated region (3' UTR) of HOXB13 and IL17BR and its function on recurrence/metastasis in ER (+) BC remains elusive. The aims of this study were to determine the expression of miRNAs that bind to 3' UTR of HOXB13 and IL17BR in ER (+) BC patients and asess the effects of these miRNAs on recurrence/metastasis. The expression profiles of HOXB13 and IL17BR were evaluated using RT-PCR in tumors and normal tissue samples from 40 ER (+) BC patients. The expression level of 4 miRNAs, which were predicted to bind the 3' UTR of HOXB13 and IL17BR using TargetScan, microRNA.org and miRDB online databases, were further evaluated with RT-PCR. Our findings demonstrated that high miR-1266 levels might be significant prognostic factor for recurrence/metastasis occurrence (3.05 fold p=0.004) and tamoxifen response (3.90 fold; p=0.2514) in ER (+) BC cases. Although we suggest that modulation of miR-1266 expression may be an important mechanism underlying the chemoresistance of ER (+) BC, advanced studies and validation are required.

      • KCI등재

        The cytotoxic and antitumoral effects of Remdesivir, an antiviral RdRp inhibitor, on different cancer cells in vitro

        Eryilmaz Isil Ezgi,Bergel Ceyda Colakoglu,Egeli Unal,Cecener Gulsah 대한독성 유전단백체 학회 2024 Molecular & cellular toxicology Vol.20 No.3

        Background Previous studies have shown similarities in the metabolism of cancer cells and parasites, suggesting that antiparasitic drugs may be used as anticancer agents. Remdesivir (Rem), an RdRp inhibitor, has been recently used in SARS-CoV-2 pandemic. Although the apoptotic effect of Rem has been demonstrated on the SKOV3 ovarian cancer cell line, its cytotoxic effect has not been analyzed in different cancer cells. Objective We aimed to evaluate its cell death-inducing effects on PC3 prostate cancer, HepG2 hepatocellular carcinoma, and A2058 malignant melanoma cells for the first time, using WST-1, Annexin V, cell cycle analysis, AO/EB staining, live-cell imaging, TEM, and gene expression analysis. Results Rem treatment at 10, 25, and 50 µM significantly decreased cell viability in all cancer cells (p < 0.01). While Rem triggered apoptosis in PC3, vacuole-dependent cell death was detected in HepG2 cells by visualizing the cells with TEM and time-dependent live-cell imaging. Moreover, both forms of cell death were triggered together in A2058. The formation of AVOs were observed more after 12 h and 24 h in HepG2 and A2058 cells, respectively. Additionally, Rem significantly induced cell cycle arrest in the G2/M (p < 0.01). Finally, the mRNA levels of autophagic markers, Atg12, Atg5, p62, Beclin, and LC3, were significantly increased in A2058 and HepG2 (p < 0.01) compared to control groups. Conclusions Our results suggest that Rem has promising cytotoxic effects on various cancer cells. However, it triggers different types of cell death in different cancer types, indicating that further studies should focus on clarifying the molecular mechanism of the specific action of Rem. Background Previous studies have shown similarities in the metabolism of cancer cells and parasites, suggesting that antiparasitic drugs may be used as anticancer agents. Remdesivir (Rem), an RdRp inhibitor, has been recently used in SARS-CoV-2 pandemic. Although the apoptotic effect of Rem has been demonstrated on the SKOV3 ovarian cancer cell line, its cytotoxic effect has not been analyzed in different cancer cells. Objective We aimed to evaluate its cell death-inducing effects on PC3 prostate cancer, HepG2 hepatocellular carcinoma, and A2058 malignant melanoma cells for the first time, using WST-1, Annexin V, cell cycle analysis, AO/EB staining, live-cell imaging, TEM, and gene expression analysis. Results Rem treatment at 10, 25, and 50 µM significantly decreased cell viability in all cancer cells (p < 0.01). While Rem triggered apoptosis in PC3, vacuole-dependent cell death was detected in HepG2 cells by visualizing the cells with TEM and time-dependent live-cell imaging. Moreover, both forms of cell death were triggered together in A2058. The formation of AVOs were observed more after 12 h and 24 h in HepG2 and A2058 cells, respectively. Additionally, Rem significantly induced cell cycle arrest in the G2/M (p < 0.01). Finally, the mRNA levels of autophagic markers, Atg12, Atg5, p62, Beclin, and LC3, were significantly increased in A2058 and HepG2 (p < 0.01) compared to control groups. Conclusions Our results suggest that Rem has promising cytotoxic effects on various cancer cells. However, it triggers different types of cell death in different cancer types, indicating that further studies should focus on clarifying the molecular mechanism of the specific action of Rem.

      • Validation of Three Breast Cancer Nomograms and a New Formula for Predicting Non-sentinel Lymph Node Status

        Derici, Serhan,Sevinc, Ali,Harmancioglu, Omer,Saydam, Serdar,Kocdor, Mehmet,Aksoy, Suleyman,Egeli, Tufan,Canda, Tulay,Ellidokuz, Hulya,Derici, Solen Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

        Background: The aim of the study was to evaluate the available breast nomograms (MSKCC, Stanford, Tenon) to predict non-sentinel lymph node metastasis (NSLNM) and to determine variables for NSLNM in SLN positive breast cancer patients in our population. Materials and Methods: We retrospectively reviewed 170 patients who underwent completion axillary lymph node dissection between Jul 2008 and Aug 2010 in our hospital. We validated three nomograms (MSKCC, Stanford, Tenon). The likelihood of having positive NSLNM based on various factors was evaluated by use of univariate analysis. Stepwise multivariate analysis was applied to estimate a predictive model for NSLNM. Four factors were found to contribute significantly to the logistic regression model, allowing design of a new formula to predict non-sentinel lymph node metastasis. The AUCs of the ROCs were used to describe the performance of the diagnostic value of MSKCC, Stanford, Tenon nomograms and our new nomogram. Results: After stepwise multiple logistic regression analysis, multifocality, proportion of positive SLN to total SLN, LVI, SLN extracapsular extention were found to be statistically significant. AUC results were MSKCC: 0.713/Tenon: 0.671/Stanford: 0.534/DEU: 0.814. Conclusions: The MSKCC nomogram proved to be a good discriminator of NSLN metastasis in SLN positive BC patients for our population. Stanford and Tenon nomograms were not as predictive of NSLN metastasis. Our newly created formula was the best prediction tool for discriminate of NSLN metastasis in SLN positive BC patients for our population. We recommend that nomograms be validated before use in specific populations, and more than one validated nomogram may be used together while consulting patients.

      • Evaluation of Genetic Variations in miRNA-Binding Sites of BRCA1 and BRCA2 Genes as Risk Factors for the Development of Early-Onset and/or Familial Breast Cancer

        Erturk, Elif,Cecener, Gulsah,Polatkan, Volkan,Gokgoz, Sehsuvar,Egeli, Unal,Tunca, Berrin,Tezcan, Gulcin,Demirdogen, Elif,Ak, Secil,Tasdelen, Ismet Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

        Although genetic markers identifying women at an increased risk of developing breast cancer exist, the majority of inherited risk factors remain elusive. Mutations in the BRCA1/BRCA2 gene confer a substantial increase in breast cancer risk, yet routine clinical genetic screening is limited to the coding regions and intronexon boundaries, precluding the identification of mutations in noncoding and untranslated regions. Because 3' untranslated region (3'UTR) polymorphisms disrupting microRNA (miRNA) binding can be functional and can act as genetic markers of cancer risk, we aimed to determine genetic variation in the 3'UTR of BRCA1/BRCA2 in familial and early-onset breast cancer patients with and without mutations in the coding regions of BRCA1/BRCA2 and to identify specific 3'UTR variants that may be risk factors for cancer development. The 3'UTRs of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis and DNA sequencing in 100 patients from 46 BRCA1/2 families, 54 non-BRCA1/2 families, and 47 geographically matched controls. Two polymorphisms were identified. SNPs $c.^*1287C$ >T (rs12516) (BRCA1) and $c.^*105A$ >C (rs15869) (BRCA2) were identified in 27% and 24% of patients, respectively. These 2 variants were also identified in controls with no family history of cancer (23.4% and 23.4%, respectively). In comparison to variations in the 3'UTR region of the BRCA1/2 genes and the BRCA1/2 mutational status in patients, there was a statistically significant relationship between the BRCA1 gene polymorphism $c.^*1287C$ >T (rs12516) and BRCA1 mutations (p=0.035) by Fisher's Exact Test. SNP $c.^*1287C$ >T (rs12516) of the BRCA1 gene may have potential use as a genetic marker of an increased risk of developing breast cancer and likely represents a non-coding sequence variation in BRCA1 that impacts BRCA1 function and leads to increased early-onset and/or familial breast cancer risk in the Turkish population.

      • Molecular Markers for Patients with Thymic Malignancies: not Feasible at Present?

        Avci, Nilufer,Cecener, Gulsah,Deligonul, Adem,Erturk, Elif,Tunca, Berrin,Egeli, Unal,Tezcan, Gulcin,Akyildiz, Elif Ulker,Bayram, Ahmet Sami,Gebitekin, Cengiz,Kurt, Ender,Evrensel, Turkkan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

        Background: Thymomas and thymic carcinomas are rare malignancies and devising clinically effective molecular targeted therapies is a major clinical challenge. The aim of the study was to analyze BLC2 and vascular endothelial growth factor receptor (VEGFR) expression and KRAS and EGFR mutational status and to correlate them with the clinical characteristics of patients with thymomas and thymic carcinomas. Materials and Methods: A total of 62 patients (mean age: $50.4{\pm}13.2$ years) with thymomas and thymic carcinomas were enrolled. The expression of BLC2 and VEGFR in tumor cells and normal tissues was evaluated by RT-PCR. The mutational status of the KRAS and EGFR genes was investigated by PCR with sequence specific primers. Results: The BLC2 and VEGFR expression levels did not differ significantly between tumor and normal tissues. Moreover, there were no clearly pathogenic mutations in KRAS or EGFR genes in any tumor. None of the molecular markers were significantly related to clinical outcomes. Conclusions: Changes in levels of expression of BLC2 and VEGFR do not appear to be involved in thymic tumorigenesis. Moreover, our data suggest that KRAS and EGFR mutations do not play a major role in the pathogenesis of thymomas and thymic carcinomas.

      • Effects of EGFR, CK19, CK20 and Survinin Gene Expression on Radiotherapy Results in Patients with Locally Advanced Head and Neck Cancer

        Kekilli, Kezban Esra,Abakay, Candan Demioz,Tezcan, Gulcin,Tunca, Berrin,Egeli, Unal,Saraydaroglu, Ozlem,Esbah, Onur,Ekinci, Ahmet Siyar,Arslan, Sonay,Uslu, Nuri,Ozkan, Lutfi Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

        Purpose: To investigate the effects of epidermal growth factor receptor (EGFR), cytokeratin 19 (CK19), cytokeratin 20 (CK20) and survinin gene expression on local control (LC) and overall survival (OS) in patients with locally advanced head and neck cancer (LAHNC) who were administered radiotherapy (RT). Materials and Methods: Twenty-six patients who were admitted to Uludag University Medical Faculty Department of Radiation Oncology with a diagnosis of LAHNC (GIII-GIV) were included in this study. Gene expression was evaluated in tumor tissues and peripheral blood. RNA isolation was performed on paraffinized tumor tissues and peripheral blood samples obtained before RT (BR). The densities of the obtained RNAs were analyzed at 260/280 nm. cDNA samples obtained from total RNA,EGFR, CK19, CK20 and survinin gene expression levels were assessed via the Sybr Green method and data were analyzed with the ${\Delta}{\Delta}Ct$ method. The same process was repeated for peripheral blood samples taken after RT (AR). Results: The female/male ratio was 3:23 and the mean age was 56.5 years (38-75years). After radiotherapy, CK19 and CK20 levels in the peripheral blood were found to be correlated according to Pearson correlation analysis(p=0.049). This result indicates a possibility of remaining positive for CK19 and CK20 in the peripheral blood even after RT in patients with CK19, CK20, and EGFR positive tumors before RT. There was a statistically significant correlation between survinin levels measured BR and AR (p=0.028). Conclusions: In this study, we found that patients with any EGFR, CK19, CK20 or survinin positivity in their peripheral blood obtain less benefit from radiotherapy. A wider patient population and advanced protein analyses are necessary in order to increase the reliability of our findings.

      • Circulating miR-195 as a Therapeutic Biomarker in Turkish Breast Cancer Patients

        Cecener, Gulsah,Ak, Secil,Eskiler, Gamze Guney,Demirdogen, Elif,Erturk, Elif,Gokgoz, Sehsuvar,Polatkan, Volkan,Egeli, Unal,Tunca, Berrin,Tezcan, Gulcin,Topal, Ugur,Tolunay, Sahsine,Tasdelen, Ismet Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.9

        Background: Dysregulation of miRNA expression may be used as a biomarker for specific tumours because it may contribute to development of cancer. Circulating miRNA profiles have been highlighted for their potential as predictive markers in heterogeneous diseases such as breast cancer. In the literature, there is evidence that miR-195 levels are differentially expressed pre- and post-operative periods in breast cancer patients. At the same time, miRNA expression levels may vary because of ethnic origins. This study aimed to determine expression levels and potential roles of miR-195 in Turkish breast cancer patients. Materials and Methods: The expression patterns of miR-195 were initially examined in breast cancer tissues (luminal A and B type) (n=96). Subsequently, blood samples were prospectively collected from preoperative and postoperative Turkish breast cancer patients and disease free controls. Total RNA was isolated, and the expression level of miR-195 was quantified by real-time PCR. Results: We found that miR-195 level was altered in Turkish breast cancer patients, with down-regulation evident in breast cancer tissues compared to normal adjacent specimens. Furthermore, circulating levels of miR-195 was significantly decreased in post-operative blood samples compared with pre-operative levels (p=0.01 and <0.05). However, miR-195 was significantly increased in pre-operative blood samples of the luminal B type (p=0.04 and <0.05). Conclusions: This study represents the first report of a miR-195 expression profile in Turkish breast cancer patients. Our data suggests that miR-195 levels might be a clinically useful biomarker in the earliest stage of Turkish breast cancer patients.

      • KCI등재

        COMPLEX VALUED DISLOCATED METRIC SPACES

        Ege, Ozgur,Karaca, Ismet The Kangwon-Kyungki Mathematical Society 2018 한국수학논문집 Vol.26 No.4

        In this paper, we introduce complex valued dislocated metric spaces. We prove Banach contraction principle, Kannan and Chatterjea type fixed point theorems in this new space. Moreover, we give some applications of the results to differential equations and iterated functions.

      • KCI등재

        Primary leiomyosarcoma of the thyroid

        Bahadır Ege,Sezai Levento?lu 대한외과학회 2013 Annals of Surgical Treatment and Research(ASRT) Vol.85 No.1

        A 56-year-old male with primary leiomyosarcoma of the thyroid is presented. The paucity of diagnostic maneuvers, including tumor markers, fine needle aspiration, and frozen section biopsy, are stressed, in addition to the fulminate course of the disease.

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