84 results on '"Konac E"'
Search Results
2. Different surgical techniques and L-carnitine supplementation in an experimental varicocele model
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Akdemir, S., Gurocak, S., Konac, E., Ure, I., Onen, H. I., Gonul, I. I., Sozen, S., and Menevse, A.
- Published
- 2014
- Full Text
- View/download PDF
3. Transcriptomic expression levels of the VHL, TIMP-3, and RASSF1A genes in renal tumors
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Ure, I., Konac, E., Alp, E., Onen, H. I., Batur, A. F., Gonul, I. I., Menevse, S., Sozen, S., Selçuk Üniversitesi, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, and Batur, A. F.
- Subjects
qPCR ,endocrine system ,mRNA expression ,urologic and male genital diseases ,Renal cell carcinoma - Abstract
WOS: 000499705600020, PubMed: 31773698, OBJECTIVE: In this study, we aimed to investigate the relation between the mRNA expression levels of VHL, TIMP-3 and RASSF1A genes, and the histopathological and clinical characteristics of patients with renal tumors. PATIENTS AND METHODS: Radical nephrectomy specimens of cases presented without neoadjuvant treatment were confirmed to be cancerous, non-cancerous, benign, and healthy after removal from separate localizations. A total of 69 patients with kidney tumors (138 tissue samples) were included in the study group. RNA isolation, reverse transcriptase PCR (RT-PCR), and quantitative real time PCR (qPCR) were performed, and the GAPDH gene was used to normalize mRNA levels. RESULTS: In the RCC cancerous tissue. TIMP-3 levels increased 1.3 times and RASSF1A levels increased 1.4 times compared to the corresponding levels in non-cancerous tissues, and there was no statistically significant difference in these values. On the other hand, VHL gene expression levels in cancerous tissue were 2.8 times higher than in matched adjacent non-cancerous tissues (p < 0.05). In the case of oncocytomas, TIMP-3 levels were found to be 3.2 times higher, RASSF1A levels 3.8 times higher, and VHL levels 2.2 times lower than the corresponding levels in healthy tissues (p < 0.05). CONCLUSIONS: The roles of VHL, TIMP-3, and RASSF1A mRNA expression in contributing to the development of renal tumors could not be clearly established. Further studies are therefore required to elucidate the mechanisms underlying renal tumors., Gazi University Research FundGazi University [01/2010-25], This study was conducted with financial support from the Gazi University Research Fund with the project code number 01/2010-25.
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- 2019
4. Memantine induces apoptosis and inhibits cell cycle progression in LNCaP prostate cancer cells
- Author
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Albayrak, G, primary, Konac, E, additional, Dikmen, AU, additional, and Bilen, CY, additional
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- 2017
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5. Association between methylenetetrahydrofolate reductase (MTHFR ) gene promoter hypermethylation and the risk of idiopathic male infertility
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Karaca, M. Z., primary, Konac, E., additional, Yurteri, B., additional, Bozdag, G., additional, Sogutdelen, E., additional, and Bilen, C. Y., additional
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- 2016
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6. Memantine induces apoptosis and inhibits cell cycle progression in LNCaP prostate cancer cells.
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Albayrak, G., Konac, E., Dikmen, A. U., and Bilen, C. Y.
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METFORMIN , *MEMANTINE , *GLUTAMIC acid , *PROSTATE cancer , *CELL metabolism - Abstract
Deregulated cancer cell metabolism plays an important role in cancer progression. Cancer cell metabolism has been in the centre of attention in therapeutical cancer cell targeting. Repurposed chemical agents, such as metformin and aspirin, have been studied extensively as preventive and therapeutic agents. Metformin is Food and Drug administration (FDA)-approved antidiabetic drug cheaper than other chemotherapeutic agents that were shown to have anticancer effects. Memantine is an FDA-approved Alzheimer’s drug. Drug repositioning studies offer wide range of benefits, such as reduced time, cost and risk over de novo drug discovery. Therefore, we aimed to target glucose and glutamine metabolism in androgen-dependent LNCaP cells by using metformin and memantine and investigate these agents’ effects on prostate cancer cell proliferation in vitro. We evaluated the effects of metformin and memantine on the protein expression levels of genes that play significant roles in apoptosis and cell cycle progression (Casp3, Casp9, Bcl-2, Survivin, Bax, c-Myc, HIF1A, CCND1, CDK4 and GAPDH) by Western blotting. Alzheimer’s drug memantine exerted cytotoxic effects at 0.25 mM and metformin at 2.5 mM. We identified for the first time that memantine exerts antineoplastic activity (0.25 mM) by triggering Bax-dependent pathway of apoptosis. In addition to that both molecules have shown similar patterns on pro- and anti-apoptotic protein expression levels, such as Bcl-2, Casp3, Survivin and Bax. Our preclinic results indicate that memantine might be used as a new repositioned drug in cancer treatment. Beyond targeting glucose metabolism, glutamine metabolism also holds great promise for a potential treatment option. [ABSTRACT FROM AUTHOR]
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- 2018
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7. EF24 and RAD001 potentiates the anticancer effect of platinum-based agents in human malignant pleural mesothelioma (MSTO-211H) cells and protects nonmalignant mesothelial (MET-5A) cells
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Onen, HI, primary, Yilmaz, A, additional, Alp, E, additional, Celik, A, additional, Demiroz, SM, additional, Konac, E, additional, Kurul, IC, additional, and Menevse, ES, additional
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- 2014
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8. Apoptotic effects of proteasome and histone deacetylase inhibitors in prostate cancer cell lines
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Kiliccioglu, I., primary, Konac, E., additional, Varol, N., additional, Gurocak, S., additional, and Yucel Bilen, C., additional
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- 2014
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9. Different surgical techniques and L-carnitine supplementation in an experimental varicocele model
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Akdemir, S., primary, Gurocak, S., additional, Konac, E., additional, Ure, I., additional, Onen, H. I., additional, Gonul, I. I., additional, Sozen, S., additional, and Menevse, A., additional
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- 2013
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10. The DNA methyl transferase inhibitor, 5′-aza-2-deoxycitidine, enhances the apoptotic effect of Mevastatin in human leukemia HL-60 cells
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Yilmaz, A, primary, Menevse, S, additional, Konac, E, additional, and Alp, E, additional
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- 2013
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11. S64 THE IMPACT OF L-CARNITINE AND SURGICAL TECHNIQUES ON SPERMATOGENESIS IN AN EXPERIMENTAL VARICOCELE MODEL
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Akdemir, S., primary, Gürocak, O.S., additional, Konac, E., additional, Üre, I., additional, Önen, I., additional, Gönül, I.I., additional, Sözen, S., additional, and Menevse, A., additional
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- 2012
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12. EF24 and RAD001 potentiates the anticancer effect of platinum-based agents in human malignant pleural mesothelioma (MSTO-211H) cells and protects nonmalignant mesothelial (MET-5A) cells.
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Onen, HI, Yilmaz, A, Alp, E, Celik, A, Demiroz, SM, Konac, E, Kurul, IC, and Menevse, ES
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MESOTHELIOMA ,ANIMAL models in research ,CANCER cells ,CELL lines ,MESSENGER RNA - Abstract
The most widespread neoplasm of the pleura is malignant pleural mesothelioma (MPM) with low prevalence rate. The mechanistic target of rapamycin signaling pathway, inhibited by RAD001, was shown to be deregulated in MPM development and considered a novel target for the MPM therapy. The EF24, a curcumin analog, also affects several signaling pathways and kills cancer cells as a single agent or in combination with classical drugs. We aimed to evaluate possible effects of RAD001, EF24, cisplatin, and oxaliplatin treatments on both malignant pleural mesothelioma (MSTO-211H) and nonmalignant mesothelial (Met-5A) cell lines. The effects of the agents on MSTO-211H and Met-5A cells were evaluated in terms of cell viability, cytotoxicity, DNA synthesis rate, quantitation of apoptotic DNA fragmentation, and cleaved caspase 3 levels. Moreover, quantitative messenger RNA (mRNA) analysis of apoptotic (CASP9) and antiapoptotic (BCL2L1 and BCL2) genes were also performed. We found that both EF24 and RAD001 alone treatments decreased only MSTO-211H cell viability, but cisplatin and oxaliplatin affected both cell lines. Pretreatment with EF24 or RAD001 followed by cisplatin increased the effects of cisplatin alone application. EF24 and RAD001 pretreatment decreased DNA fragmentation rate when compared with cisplatin alone treatment in Met-5A cells. Sequential treatments resulted in a significant increase of CASP9 mRNA expression in MSTO-211H cells but not in Met-5A cells. Our preliminary results suggest that pretreatment with EF24 or RAD001 may reduce cytotoxic effect of cisplatin on nonmalignant mesothelial cells and increase cell death response of MPM cells. Further analyses using animal models are needed to confirm these findings in vivo. [ABSTRACT FROM AUTHOR]
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- 2015
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13. The DNA methyl transferase inhibitor, 5′-aza-2-deoxycitidine, enhances the apoptotic effect of Mevastatin in human leukemia HL-60 cells.
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Yilmaz, A, Menevse, S, Konac, E, and Alp, E
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DNA methyltransferases ,CANCER cells ,LACTATE dehydrogenase ,DNA synthesis ,MESSENGER RNA ,REVERSE transcriptase polymerase chain reaction - Abstract
Statins induce antiproliferative effects and apoptotic response in various cancer cell types. Moreover, they also sensitize tumor cell lines from different origins to many agents. We aimed to investigate possible effects of Mevastatin (Mev) alone and sequential treatment of 5′-aza-2-deoxycitidine (DAC) and Mev on HL-60 cell line using XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay, lactate dehydrogenase release assay, flourescence microscopy, DNA fragmentation analysis, determination of DNA synthesis rate, and active caspase-3 assay. Messenger RNA (mRNA) expression of apoptotic and antiapoptotic genes were also evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) for BAX, BCL2, and XIAP genes and quantitative Real-time PCR for CASP3, CASP8, and CASP9 genes. We showed that treatment with Mev alone and DAC followed by Mev resulted in apoptotic response in a time- and dose-dependent manner. We also found that pretreatment with DAC sensitized HL-60 cells to Mev and caused more apoptotic cell death than Mev-alone treatment via caspase-3 activation and DNA fragmentation. Moreover, sequential addition of Mev after DAC diminished DNA synthesis rate more effectively than Mev-alone treatment. Furthermore, DAC pretreatment significantly increased CASP3 and CASP9 mRNA expression even with lower doses of Mev. BAX, BCL2, and XIAP gene mRNA levels were also found to be changed in the presence of DAC and Mev. Determination of the exact molecular effects of statins and DAC would allow us to identify new molecular targets to develop more effective treatment regimens for cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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14. Is cytogenetic diagnosis of 46,XX karyotype spontaneous abortion specimens erroneous? Fluorescence in situ hybridization as a confirmatory technique.
- Author
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Karaoguz MY, Nas T, Konac E, Ince D, Pala E, and Menevse S
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- 2005
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15. An in vitro study of cytotoxic effects of gossypol on human epidermoid larynx carcinoma cell line (HEp-2)
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Konac, E., Ekmekci, A., Yurtcu, E., and mehmet ali ergun
16. Effects of meloxicam, lornoxicam, alone and in combination with chemotherapeutic agents on the RAF/MEK/ERK pathway in Raji cells
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Onen, H. I., AKIN YILMAZ, Alp, E., Yar, A. S., Konac, E., and Menevse, S.
17. Detection of p53 deletions using fish technique in the HL-60, Daudi, Raji and K-562 cell lines
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Konac, E., Ergun, M. A., Feride Iffet Sahin, and Ekmekci, A.
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hemic and lymphatic diseases - Abstract
The work is aimed on the analysis of chromosome 17 centromere and p53 gene-specific signals within interphase and metaphase, determination of p53 deletion ratios and the detection of the cell-cycle progress. The loss of heterozygosity (LOH) has been investigated using FISH method in 4 cell lines (HL-60, Daudi, Raji and K-562) and peripheral blood samples from 3 Burkitt's lymphoma patients and 2 healthy donors. It is concluded that FISH method may be used in aneuploidy as well as in detection of p53 deletions and mutations.
18. Investigating apoptotic and epigenetic effects of mevastatio and 5-aza-2 '-deoxycytidine in HL-60 cell line
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AKIN YILMAZ, Alp, E., Konac, E., and Menevse, S.
19. Investigating anti-angiogenic and apoptotic effects of Bevacizumab in breast cancer cell line
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Alp, E., AKIN YILMAZ, Konac, E., and Menevse, S.
20. Vinorelbine's effects on the cell cycle progression in HeLa cell line
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Gokce, O., AKIN YILMAZ, Gurbuz, V., Konac, E., and Ekmekci, A.
21. Polymorphisms in the vitamin D receptor gene and risk of lung cancer
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Irem Dogan Turacli, Onen, H. I., Yurdakul, A. S., Konac, E., Ozturk, C., Varol, A., and Ekmekci, A.
- Abstract
Background: Differences between the individual variations in DNA may modulate lung cancer process. Many studies reported that Vitamin D Receptor (VDR) gene polymorphisms may influence the cancer risk due to their antiproliferative, antiangiogenic, antimetastatic and apoptoic effects.
22. Investigation of the upregulation of VEGF in mice retina after retinal laser photocoagulation using argon and pattern scan laser system.
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Konac, E., Sonmez, K., Bahcelioglu, M., Take, Kaplanoglu G., Varol, N., Sarac, G. N., and Ozcan, P. Y.
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VASCULAR endothelial growth factors , *GENE expression , *NEOVASCULARIZATION - Abstract
Panretinal photocoagulation still remains the gold standard for the treatment of ischaemic and neovascular diseases of the retina. Pulse energy is directly proportional to the pulse duration and power. Vascular endothelial growth factor (VEGF) is a well-known potent angiogenic factor and also acts as a proinflammatory cytokine and vascular permeability factor. The aim of this study was to investigate the differences in the expression of VEGF in mice subjects treated with argon (AG) or pattern scan laser (PASCAL) systems. Male C57BL/6 mice were randomly assigned to one of three groups: Group 1 (G1) AG photocoagulator (n=16), Group 2 (G2) PASCAL (n=16) and Group 3 (G3) control group (n=6). Molecular and morphological analyses of VEGF were performed on day 1, 2 and 5 by ELISA, Real-time PCR and immuno-histochemical analysis. G1 group showed VEGF mRNA level increased 2.4 folds on day 2, whereas it decreased on day 5 (p<0.001) compared to the G3. In G2, VEGF mRNA level increased 1.8 folds on day 1 and 2.2 folds on day 5 compared to the G3. In G1, VEGF protein level increased significantly on day 2, whereas it decreased on day 5 (p<0.001) compared to G3. In group G2, the VEGF levels significantly increased as compared to control groups at both 2 and 5 days after laser photocoagulation using PASCAL laser (p<0.001, both time points). The peak expressions of VEGF protein in samples which underwent PASCAL and conventional laser were found on day 5 and day 2 respectively. In PASCAL photocoagulation pattern, VEGF-induced vascularization started late and gradually increased; in AG, VEGFinduced VEGFinduced vascularization started early on day 2, then decreased on day 5. Conclusion: AG laser may imposed a higher risk for early complications due to early increase in VEGF levels, whereas the complications due to increment in VEGF level is not expected to be different between conventional and PASCAL laser treatment in the late phase. [ABSTRACT FROM AUTHOR]
- Published
- 2014
23. Male infertility is associated with differential DNA methylation signatures of the imprinted gene GNAS and the non-imprinted gene CEP41.
- Author
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Ozkocer SE, Guler I, Ugras Dikmen A, Bozkurt N, Varol N, and Konac E
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- Male, Humans, Adult, Spermatozoa pathology, Spermatozoa metabolism, Insulin-Like Growth Factor II genetics, Epigenesis, Genetic genetics, CpG Islands genetics, RNA, Long Noncoding genetics, Sperm Count, DNA Methylation genetics, GTP-Binding Protein alpha Subunits, Gs genetics, Chromogranins genetics, Infertility, Male genetics, Infertility, Male pathology, Genomic Imprinting genetics, Oligospermia genetics, Oligospermia pathology
- Abstract
Purpose: To investigate whether the DNA methylation profiles of GNAS(20q13.32), MEST(7q32.2), MESTIT1(7q32.2), IGF2(11p15.5), H19 (7q32.2), and CEP41(7q32.2) genes are related to the transcriptomic and epigenomic etiology of male infertility., Methods: The DNA methylation levels of spermatozoa were obtained from fertile (n = 30), oligozoospermic (n = 30), and men with normal sperm count (n = 30). The methylation status of each CpG site was categorized as hypermethylated or hypomethylated. Expression levels of target gene transcripts were determined using real-time PCR., Results: The oligozoospermia showed a higher frequency of hypermethylation at GNASAS 1st, 3rd, and 5th CpG dinucleotides (66.7%, 73.3%, 73.3%) compared to the fertile group (33.3%, 33.3%, 40%, respectively). The normal sperm count exhibited a higher frequency of hypermethylation at the 3rd CpG of CEP41 (46.7%) than the fertile group (16.7%). Normal sperm count was predicted by CEP41 hypermethylation (OR = 1.750, 95%CI 1.038-2.950) and hypermethylation of both CEP41 and GNASAS (OR = 2.389, 95%CI 1.137-5.021). Oligozoospermia was predicted solely by GNASAS hypermethylation (OR = 2.460, 95%CI 1.315-4.603). In sperms with decreased IGF2 expression in the fertile group, we observed hypomethylation in the 2nd CpG of IGF2 antisense (IFG2AS), and hypermethylation in the 1st, 2nd, and 4th CpGs of H19. No significant relationship was found between IGF2 expression and methylation status of IGF2AS and H19 in infertile groups., Conclusion: The disappearance of the relationship between IGF2 expression and IGF2AS and H19 methylations in the infertile group provides new information regarding the disruption of epigenetic programming during spermatogenesis. A better understanding of sperm GNASAS and CEP41 hypermethylation could advance innovative diagnostic markers for male infertility., (© 2024. The Author(s).)
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- 2024
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24. Determination of In Vitro and In Vivo Effects of Taxifolin and Epirubicin on Epithelial-Mesenchymal Transition in Mouse Breast Cancer Cells.
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Ocak M, Usta DD, Arik Erol GN, Kaplanoglu GT, Konac E, and Yar Saglam AS
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- Female, Animals, Mice, Epirubicin pharmacology, Caspase 3, RNA, Messenger, Cell Line, Tumor, Cell Movement, Cell Proliferation, Epithelial-Mesenchymal Transition, Neoplasms, Quercetin analogs & derivatives
- Abstract
Background: One of the most significant characteristics of cancer is epithelial-mesenchymal transition and research on the relationship between phenolic compounds and anticancer medications and epithelial-mesenchymal transition is widespread. Methods: In order to investigate the potential effects of Taxifolin on enhancing the effectiveness of Epirubicin in treating breast cancer, specifically in 4T1 cells and an allograft BALB/c model, the effects of Taxifolin and Epirubicin, both individually and in combination, were examined. Cell viability assays and cytotoxicity assays in 4T1 cells were performed. In addition, 4T1 cells were implanted into female BALB/c mice to conduct in vivo studies and evaluate the therapeutic efficacy of Taxifolin and Epirubicin alone or in combination. Tumor volumes and histological analysis were also assessed in mice. To further understand the mechanisms involved, we examined the messenger RNA and protein levels of epithelial-mesenchymal transition-related genes, as well as active Caspase-3/7 levels, using quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assays, respectively. Results: In vitro , coadministration of Taxifolin and Epirubicin suppressed tumor growth in BALB/c mice with 4T1 breast cancer cells. Additionally, this combination treatment significantly increased the levels of active caspase-3/7 and downregulated the messenger RNA and protein levels of N-cadherin, β-catenin, vimentin, snail, and slug, but upregulated the E-cadherin gene. It significantly decreased the messenger RNA levels of the Zeb1 and Zeb2 genes. In vivo , coadministration of Taxifolin and Epirubicin suppressed tumor growth in BALB/c mice with 4T1 breast cancer cells. Additionally, this combination treatment significantly increased the levels of active caspase-3/7 and downregulated the messenger RNA and protein levels of N-cadherin, β-catenin, vimentin, snail, and slug, but upregulated the E-cadherin gene. It significantly decreased the messenger RNA levels of the Zeb1 and Zeb2 genes. Conclusion: The in vitro and in vivo results of our study indicate that the concurrent use of Epirubicin with Taxifolin has supportive effects on breast cancer treatment., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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25. Thyroid hormones and ovarian reserve: a comprehensive study of women seeking infertility care.
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Halici M, Seker ME, Gebedek IY, Gokbak MN, Cetisli AF, Ciftci AB, Konac E, Kopuk SY, Tiras B, and Cakiroglu Y
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- Female, Humans, Young Adult, Adult, Middle Aged, Ovarian Follicle, Retrospective Studies, Follicle Stimulating Hormone, Thyroid Hormones, Anti-Mullerian Hormone, Thyrotropin, Ovarian Reserve, Infertility, Female therapy
- Abstract
Background: Ovarian reserve is the number of oocytes remaining in the ovary and is one of the most important aspects of a woman's reproductive potential. Research on the association between thyroid dysfunction and ovarian reserve has yielded controversial results. In our study, we aimed to investigate the relationship between thyroid-stimulating hormone (TSH) levels and ovarian reserve markers., Methods: From 1443 women seeking infertility care, the data of 1396 women aged between 20-45 years old who had a body mass index between 18-30 kg/m
2 were recruited for this retrospective study. The anti-Müllerian hormone (AMH) and TSH relationship was analyzed with generalized linear and polynomial regression., Results: Median age, follicle-stimulating hormone (FSH), AMH, and TSH levels were 36.79 years, 9.55 IU/L, 3.57 pmol/L, and 1.80 mIU/L, respectively. Differences between TSH groups were statistically significant in terms of AMH level, antral follicle count (AFC), and age (p = 0.007 and p = 0.038, respectively). A generalized linear regression model could not explain age-matched TSH levels concerning AMH levels (p > 0.05). TSH levels were utilized in polynomial regression models of AMH, and the 2nd degree was found to have the best fit. The inflection point of the model was 2.88 mIU/L., Conclusions: Our study shows a correlation between TSH and AMH values in a population of infertile women. Our results are as follows: a TSH value of 2.88 mIU/L yields the highest AMH result. It was also found that AMH and AFC were positively correlated, while AMH and FSH were negatively correlated., (© 2023. The Author(s).)- Published
- 2023
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26. Silencing effects of FOXD1 inhibit metastatic potentials of the PCa via N-cadherin - Wnt/β-catenin crosstalk.
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Donmez C and Konac E
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- Cadherins genetics, Cell Line, Tumor, Cell Movement genetics, Cell Proliferation genetics, Epithelial-Mesenchymal Transition genetics, Forkhead Transcription Factors genetics, Forkhead Transcription Factors metabolism, Humans, Male, Neoplasm Invasiveness, Wnt Signaling Pathway genetics, Prostatic Neoplasms pathology, beta Catenin genetics, beta Catenin metabolism
- Abstract
The elucidation of the mechanisms controlling the metastatic processes is important for the development of new treatment methods to prevent the progression of localized disease to metastasis. Forkhead box D1 (FOXD1) is a member of the FOX transcription factor family and has been reported to play an important role in the development and progression of various cancers. However, its role in prostate cancer (PCa) remains only partially understood. Therefore, we aimed to explore the effects on the associated regulatory signal pathway of FOXD1 in prostate cancer. To clarify the roles of FOXD1 in prostate cancer, we used siRNA to suppress its expression in 22Rv1 cells with relatively higher expression of FOXD1. The effects of FOXD1 silencing on cell proliferation, migration and invasion were determined. WST-1 assays were used to determine cell proliferation. Cell migration and invasion were evaluated through wound healing and transwell assays. The possible underlying mechanism of FOXD1 silencing on 22Rv1 was evaluated by determining the expression of proteins related to EMT and Wnt/β-catenin signaling pathway. Our results showed that FOXD1 was highly expressed in prostate cancer cell lines -PC-3, DU145, LNCaP and 22Rv1- compared to normal prostate epithelial cell line RWPE-1. Additionally, silencing of FOXD1 significantly reduced proliferation, migration and invasion of 22Rv1 cells. Furthermore, silencing of FOXD1 decreased the expression of β-catenin and cyclin D1, which are involved in the Wnt/β-catenin signaling pathway. However, it did not appear to affect the expression of EMT-related proteins other than N-cadherin. Our results suggest that silencing of FOXD1 suppresses metastatic potentials of the PCa via N-cadherin - Wnt/β-catenin crosstalk. Therefore, the expression status of FOXD1 may be a new prognostic factor as well as a potential therapeutic target in prostate cancer treatment., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
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27. miR-148a, miR-152 and miR-200b promote prostate cancer metastasis by targeting DNMT1 and PTEN expression.
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Gurbuz V, Sozen S, Bilen CY, and Konac E
- Abstract
MicroRNAs (miRs) modulate the expression of target genes in the signal pathway on transcriptome level. The present study investigated the 'epigenetic-based miRNA (epi-miRNA)-mRNA' regulatory network of miR-34b, miR-34c, miR-148a, miR-152, miR-200a and miR-200b epi-miRNAs and their target genes, DNA methyltransferase (DNMT1, 3a and 3b), phosphate and tensin homolog (PTEN) and NK3 Homeobox 1 (NKX3.1), in prostate cancer (PCa) using reverse transcription-quantitative PCR. The expression level of NKX3.1 were not significantly different between the PCa, Met-PCa and control groups. However, in the PCa and Met-PCa groups, the expression level of DNMT1 was upregulated, while DNMT3a, DNMT3b and PTEN were downregulated. Overexpression of DNMT1 (~5 and ~6-fold increase in the PCa and Met-PCa groups respectively) was accompanied by a decreased expression in PTEN, indicating a potential negative association. Both groups indicated that a high level of DNMT1 is associated with the aggressiveness of cancer, and there is a a directly proportional relationship between this gene and PSA, GS and TNM staging. A significant ~2 to ~5-fold decrease in the expression levels of DNMT3a and DNMT3b was found in both groups. In the PCa group, significant associations were identified between miR-34b and DNMT1/DNMT3b; between miR-34c/miR-148a and all target genes; between miR-152 and DNMT1/DNMT3b and PTEN; and between miR-200a/b and DNMT1. In the Met-PCa group, miR-148a, miR-152 and miR-200b exhibited a significant association with all target genes. A significant negative association was identified between PTEN and DNMT1 in the Met-PCa group. It was also revealed that that miR-148a, miR-152 and miR-200b increased the expression of DNMT1 and suppressed PTEN. Furthermore, the 'epi-miRNA-mRNA' bidirectional feedback loop was emphasised and the methylation pattern in PCa anti-cancer therapeutics was highlighted., Competing Interests: The authors declare that they have no competing interests, (Copyright: © Gurbuz et al.)
- Published
- 2021
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28. The current perspective on genetic and epigenetic factors in sperm maturation in the epididymis.
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Ozkocer SE and Konac E
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- Epigenesis, Genetic, Female, Humans, Male, Sperm Motility, Spermatozoa, Epididymis, Sperm Maturation
- Abstract
Male infertility affects approximately 30% of infertile couples. As spermatozoa mature in the epididymal lumen, their potential for mobility increases, and their protein, lipid and small RNA (sRNA) content changes, whereas capacitation and fertilisation take place in the female reproductive tract. Both of the latter processes are affected by maturation, because impaired maturation causes premature capacitation and fertilization. The epididymis produces a suitable environment for sperm maturation via ion transport, vesicle secretion and protein matrix formation. The microenvironment for sperm maturation varies in three broad segments: the caput, the corpus and the cauda epididymis. Epididymosomes transfer proteins, lipids and sRNAs from the epididymal epithelium to spermatozoa and genetic alterations of epididymal genes can lead to decreased sperm motility, morphological abnormalities of spermatozoa and subfertility. Genetic factors are involved in all aetiological categories in male infertility. However, studies conducted on the genes involved in epididymal functions are limited. The sRNA content of spermatozoa changes during epididymal migration, and these sRNAs play a role in embryo development and epigenetic inheritance. This review aims to clarify the role of the epididymal epithelium in the maturation of spermatozoa in light of the current molecular genomic knowledge., (© 2021 Wiley-VCH GmbH.)
- Published
- 2021
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29. Upregulation of potential regulatory signaling molecules correlate with androgen receptor splice variants AR-V7 and AR-V567es in prostate cancer metastasis.
- Author
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Kiliccioglu I, Bilen CY, Sozen S, and Konac E
- Subjects
- Aged, Alternative Splicing, Case-Control Studies, Gene Expression Regulation, Neoplastic, Humans, Male, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Prostatic Neoplasms genetics, Prostatic Neoplasms metabolism, Signal Transduction, Heat-Shock Proteins metabolism, Molecular Chaperones metabolism, NF-kappa B metabolism, Prostatic Neoplasms pathology, Receptors, Androgen genetics, Up-Regulation
- Abstract
Aim: Androgen receptor splice variants (AR-Vs) produced by alternative splicing of the AR play an important role in the treatment resistance and progression of prostate cancer (PCa). In this study, two most common AR variants and how they associate with the inflammatory response (NF-Kβ) and regulatory transcriptional activity (HSP-27) genes were investigated in patients with PCa and metastatic PCa (Met-PCa)., Methods: Our study was carried out with the whole blood obtained from 25 healthy control subjects, 25 PCa patients and 39 Met-PCa patients. We examined the expression levels of AR, AR-V7 and AR-V567es genes via Real-time PCR and those of HSP-27 and NF-Kβ via ELISA method., Results: AR, AR-V7 and AR-V567es expressions were observed in 84.61%, 64.1%, 23.07% of Met-PCa patients respectively. The expression levels of full-length AR and variants (AR-V7 and AR-V567es) were associated with the prostate cancer stage. In the Met-PCa, the expression levels of AR, AR-V7 and AR-V567es were associated with the Gleason Scores but not with the PSA levels. AR-V7 expression levels in stage T4 patients significantly increased. NF-Kβ and HSP-27 protein levels were significantly higher in Met-PCa patients., Discussion: Our findings highlight the targeting of the proteostasis and inflammation pathways through inhibiting HSP-27 and NF-Kβ. This might be a valuable strategy to overcome anti-androgen resistance and improve drug therapy in Met-PCa patients whose gene expression levels of AR-V7 and AR-V567es variants are high., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2021
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30. Contrast effects of autophagy in the treatment of bladder cancer.
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Konac E, Kurman Y, and Baltaci S
- Subjects
- Apoptosis physiology, Autophagy drug effects, Cell Survival, Endoplasmic Reticulum Stress physiology, Humans, Oxidative Stress physiology, Signal Transduction drug effects, Antineoplastic Agents metabolism, Antineoplastic Agents therapeutic use, Autophagy physiology, Drug Resistance, Neoplasm physiology, Urinary Bladder Neoplasms drug therapy, Urinary Bladder Neoplasms pathology
- Abstract
Bladder cancer is a disease that negatively affects patients' quality of life, but treatment options have remained unchanged for a long time. Although promising results have been achieved with current bladder cancer treatments, cancer recurrence, progression, and therapy resistance are the most severe problems preventing the efficiency of bladder cancer treatments. Autophagy refers to an evolutionarily conserved catabolic process in which proteins, damaged organelles, and cytoplasmic components are degraded by lysosomal enzymes. Autophagy regulates the therapeutic response to the chemotherapy drugs, thus determining the effect of therapy on cancer cells. Autophagy is a stress-induced cell survival mechanism and its excessive stimulation can cause resistance of tumor cells to therapeutic agents. Depending on the conditions, an increase in autophagy may cause treatment resistance or autophagic cell death, and it is related to important anti-cancer mechanisms, such as apoptosis. Therefore, understanding the roles of autophagy under different conditions is important for designing effective anti-cancer agents. The dual role of autophagy in cancer has attracted considerable attention in respect of bladder cancer treatment. In this review, we summarize the basic characteristics of autophagy, including its mechanisms, regulation, and functions, and we present examples from current studies concerning the dual role of autophagy in bladder cancer progression and therapy.
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- 2021
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31. Targeting Cancer Cell Metabolism with Metformin, Dichloroacetate and Memantine in Glioblastoma (GBM).
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Albayrak G, Konac E, Dere UA, and Emmez H
- Subjects
- Antineoplastic Agents therapeutic use, Apoptosis drug effects, Apoptosis physiology, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Cell Line, Tumor, Cell Survival drug effects, Cell Survival physiology, Dichloroacetic Acid therapeutic use, Dopamine Agents pharmacology, Dopamine Agents therapeutic use, Dose-Response Relationship, Drug, Glioblastoma drug therapy, Glioblastoma pathology, Humans, Hypoglycemic Agents pharmacology, Hypoglycemic Agents therapeutic use, Memantine therapeutic use, Metformin therapeutic use, Proto-Oncogene Proteins c-bcl-2 biosynthesis, Antineoplastic Agents pharmacology, Brain Neoplasms metabolism, Dichloroacetic Acid pharmacology, Glioblastoma metabolism, Memantine pharmacology, Metformin pharmacology
- Abstract
Aim: To investigate the effects of metformin, dichloroacetate (DCA), and memantine on T98G and U87-MG human glioblastoma (GBM) cells to target tumor cell metabolism in a multi-directional manner., Material and Methods: IC50 levels for metformin, DCA, metformin+DCA and memantine were determined by MTT assay in T98G and U87-MG cells in vitro. Casp3, Bcl-2, Bax, c-Myc and GSK-3B protein expressions were investigated post treatments. Fifteen GBM+ tumor tissues were assessed for Casp-3, Bcl-2, Bad, Bax for apoptotic protein expression patterns., Results: Cancer cell metabolism targeting drugs metformin, DCA, metformin+DCA and memantine induced cytotoxicity in a dose-dependent manner in T98G and U87-MG cells. IC50 for memantine is found as 0.5 mM (p < 0.01) which is nearly 10 times lower concentration than that of metformin. Fifteen GBM+ tumor tissues had differential apoptotic protein expressions., Conclusion: Memantine exerted anti-cancer mechanism of action in T98G and U87-MG cells, however, such a mechanism requires deeper investigation for GBM treatment.
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- 2021
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32. Comparative analysis of epi-miRNA expression levels in local/locally advanced and metastatic prostate cancer patients.
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Gurbuz V, Kiliccioglu I, Dikmen AU, Bilen CY, Sozen S, and Konac E
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- Biomarkers, Tumor genetics, Epigenesis, Genetic genetics, Humans, Male, Neoplasm Grading, Prognosis, Promoter Regions, Genetic genetics, Prostate-Specific Antigen blood, Prostatic Neoplasms pathology, DNA Methylation genetics, Gene Expression Regulation, Neoplastic genetics, MicroRNAs genetics, Prostatic Neoplasms diagnosis, Prostatic Neoplasms genetics
- Abstract
Abnormal expression of enzymes involved in epigenetic mechanisms, such as DNA methyl transferases, can trigger large chaos in cellular gene expression networks and eventually lead to cancer progression. In our study, which is a pioneer in the literature that clinicopathologically evaluates the expression of 30 epi-miRNAs in prostate cancer (PCa), we investigated which of the new miRNA class epi-miRNAs could be an effective biomarker in the diagnosis and progression of PCa. In this study, the expression levels of 30 epi-miRNAs in whole blood samples from 25 control, 25 PCa and 40 metastatic PCa patients were investigated by the Quantitative Real-Time PCR method. Then, promoter methylation levels of 11 epi-miRNAs, whose expression levels were found to be significantly higher, were examined by methylation-specific qPCR method. The correlations between miRNA expression levels and clinicopathological parameters (Gleason Score (GS), PSA levels, TNM Staging) in different stages of PCa groups as well as disease-specific expression levels were examined. We found a hypomethylation in the promoter regions of miRNAs that showed a direct proportional increase with PSA levels (miR-34b/c, miR-148a, miR-152), GS's (miR-34a-5p, miR-34b/c, miR-101-2, miR-126, miR-148a, miR- 152, miR-185-5p) and T staging (miR-34a-5p, miR-34b/c, miR-101-2, miR-126, miR-140, miR-148a, miR-152, miR-185-5p) (p < 0.05). When miR-200a/b was evaluated according to clinicopathological parameters, it acted as an onco-miR in local/local advanced PCa and as a tumor-suppressor-miR in metastatic stage. This study is novel in the sense that our findings draw attention to the important role of miRNAs as diagnostic and prognostic biomarkers in PCa., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2020
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33. Cucurbitacin B and cisplatin induce the cell death pathways in MB49 mouse bladder cancer model.
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Kurman Y, Kiliccioglu I, Dikmen AU, Esendagli G, Bilen CY, Sozen S, and Konac E
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- Animals, Apoptosis drug effects, Autophagy drug effects, Cell Proliferation drug effects, Disease Models, Animal, Drug Synergism, Mice, Mice, Inbred C57BL, Random Allocation, Antineoplastic Combined Chemotherapy Protocols pharmacology, Cisplatin pharmacology, Triterpenes pharmacology, Urinary Bladder Neoplasms pathology
- Abstract
Impact Statement: Alternative agents that will increase the effectiveness of cisplatin, which are widely used in the advanced stage and metastatic bladder cancer, are being investigated. In previous studies, Cucurbitacin B (CuB), which is a natural compound from the Cucurbitaceae family has been shown to inhibit the proliferation of tumor cells and create synergistic effects with cisplatin. In this study, we investigated the synergistic effect of CuB with cisplatin for the first time in bladder cancer in vitro and in vivo models. Our findings showed that CuB treatment with cisplatin reduced cell proliferation, and reduced tumor development through activating apoptosis and autophagy via PI3K/AKT/mTOR signaling pathway. Our results showed that CuB may be a new agent that can support conventional treatment in bladder cancer. Our study is important in terms of enlightening new pathways and developing new treatment methods in the treatment of bladder cancer.
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- 2020
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34. Transcriptomic expression levels of the VHL, TIMP-3, and RASSF1A genes in renal tumors.
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Ure I, Konac E, Alp E, Onen HI, Batur AF, Gonul II, Menevse S, and Sozen S
- Subjects
- Adolescent, Adult, Aged, Carcinoma, Renal Cell genetics, Case-Control Studies, Female, Humans, Kidney Neoplasms genetics, Male, Middle Aged, Transcriptome genetics, Young Adult, Carcinoma, Renal Cell metabolism, Gene Expression Regulation, Neoplastic genetics, Kidney Neoplasms metabolism, Tissue Inhibitor of Metalloproteinase-3 biosynthesis, Tumor Suppressor Proteins biosynthesis, Von Hippel-Lindau Tumor Suppressor Protein biosynthesis
- Abstract
Objective: In this study, we aimed to investigate the relation between the mRNA expression levels of VHL, TIMP-3 and RASSF1A genes, and the histopathological and clinical characteristics of patients with renal tumors., Patients and Methods: Radical nephrectomy specimens of cases presented without neoadjuvant treatment were confirmed to be cancerous, non-cancerous, benign, and healthy after removal from separate localizations. A total of 69 patients with kidney tumors (138 tissue samples) were included in the study group. RNA isolation, reverse transcriptase PCR (RT-PCR), and quantitative real time PCR (qPCR) were performed, and the GAPDH gene was used to normalize mRNA levels., Results: In the RCC cancerous tissue, TIMP-3 levels increased 1.3 times and RASSF1A levels increased 1.4 times compared to the corresponding levels in non-cancerous tissues, and there was no statistically significant difference in these values. On the other hand, VHL gene expression levels in cancerous tissue were 2.8 times higher than in matched adjacent non-cancerous tissues (p < 0.05). In the case of oncocytomas, TIMP-3 levels were found to be 3.2 times higher, RASSF1A levels 3.8 times higher, and VHL levels 2.2 times lower than the corresponding levels in healthy tissues (p < 0.05)., Conclusions: The roles of VHL, TIMP-3, and RASSF1A mRNA expression in contributing to the development of renal tumors could not be clearly established. Further studies are therefore required to elucidate the mechanisms underlying renal tumors.
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- 2019
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35. Hsp-27 and NF-κB pathway is associated with AR/AR-V7 expression in prostate cancer cells.
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Kiliccioglu I, Konac E, Dikmen AU, Sozen S, and Bilen CY
- Subjects
- Anisoles pharmacology, Apoptosis physiology, Cell Line, Tumor, HSP27 Heat-Shock Proteins antagonists & inhibitors, HSP27 Heat-Shock Proteins genetics, Heat-Shock Proteins, Humans, I-kappa B Kinase genetics, I-kappa B Kinase metabolism, Isoxazoles pharmacology, Male, Molecular Chaperones, NF-kappa B genetics, Nitriles, Prostatic Neoplasms genetics, Receptors, Androgen genetics, Receptors, Androgen metabolism, Signal Transduction, Sulfones, HSP27 Heat-Shock Proteins metabolism, NF-kappa B metabolism, Prostatic Neoplasms metabolism, Receptors, Androgen biosynthesis
- Abstract
In the present study, NF-κB inhibitor BAY 11-7082 and/or Hsp-27 inhibitor KRIBB-3 agents were used to investigate the molecular mechanisms mediating androgen receptor expression on prostate cancer cell lines. The decrease observed in androgen receptor and p65 expressions, particularly at 48 h, in parallel with the decrease in the phosphorylation of the p-IKK α/β and p-Hsp-27 proteins in the LNCaP cells, indicated that androgen receptor inactivation occurred after the inhibition of the NF-κB and Hsp-27. In 22Rv1 cells, androgen receptor variant-7 was also observed to be decreased in the combined dose of 48 h. The association of this decrease with the decrease in androgen receptor and p65 expressions is a supportive result for the role of NF-κB signaling in the formation of androgen receptor variant. In androgen receptor variant-7 siRNA treatment in 22Rv1 cell lines, decrease of expression of androgen receptor variant-7 as well as decrease of expression of androgen receptor and p65 were observed. The decrease statistically significant in androgen receptor and p65 expressions was even greater when siRNA treatment was followed with low dose and time (6 h) combined treatment after transfection. We also showed that increased Noxa and decreased Bcl-2 protein level, indicated that apoptotic induction after this combination. In conclusion, inhibition of NF-κB and Hsp-27 is also important, along with therapies for androgen receptor variant-7 inhibition., (Copyright © 2019 Elsevier B.V. All rights reserved.)
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- 2019
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36. FOXA1 knock-out via CRISPR/Cas9 altered Casp-9, Bax, CCND1, CDK4, and fibronectin expressions in LNCaP cells.
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Albayrak G, Konac E, Ugras Dikmen A, and Bilen CY
- Subjects
- Apoptosis, CRISPR-Cas Systems, Caspase 9 metabolism, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Cyclin D1 metabolism, Cyclin-Dependent Kinase 4 metabolism, Epithelial-Mesenchymal Transition, Fibronectins metabolism, Gene Knockout Techniques, Humans, Male, Mutation, Prostatic Neoplasms pathology, Protein Binding, Protein Interaction Mapping, Signal Transduction, bcl-2-Associated X Protein metabolism, Gene Expression Regulation, Neoplastic, Hepatocyte Nuclear Factor 3-alpha genetics, Prostatic Neoplasms metabolism
- Abstract
Prostate cancer is one of the most common types of cancer in men and the leading cause of death in developed countries. With the aid of molecular and genetic profiling of cancers, cancer molecular subtypes are paving the way for tailored cancer therapy. FOXA1 has been identified as one of the seven molecular subtypes of prostate cancer. FOXA1 is involved in a variety of metabolic process such as glucose homeostasis and deregulation of its expression is crucial in prostate cancer progression. In this study, we investigated the effects of FOXA1 gene knock-out on the expression levels of various cancer cell metabolism and cell cycle-related protein expressions. FOXA1 gene was knocked-out by using CRISPR/Cas9 technique. While FOXA1 gene knock-out significantly altered Casp-9, Bax, CCND1, CDK4, and fibronectin protein expressions (P < 0.05, fold change: ∼40, 4.5, 2.5, 4.5, and 4, respectively), it did not affect the protein expression levels of Casp-3, Bcl-2, survivin, β-catenin, c-Myc, and GSK-3B. Knocking-out FOXA1 gene in androgen-dependent LNCaP prostate cancer cells inhibited CCND1 protein expression. Our pre-clinical results demonstrate the importance of FOXA1 as a drug target in the treatment of prostate cancer. Impact statement Knock-out studies offer a unique way of studying the function of genes especially for developmentally lethal genes. FOXA1 has prominent roles both in breast and prostate cancer pathogenesis due to its role in ER receptor signaling pathway. FOXA1 has also been identified as one of the seven molecular subtypes of primary prostate cancer. In the present study, we used an efficient gene knock-out method, CRISPR/Cas9, in order to investigate FOXA1 function on LNCaP prostate cancer cells in vitro. FOXA1 knock-out altered cell-cycle regulator CCND1 protein expression levels. Therefore, our results suggest that FOXA1 might be a plausible drug target for prostate cancer treatment.
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- 2018
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37. The effects of thymoquinone and genistein treatment on telomerase activity, apoptosis, angiogenesis, and survival in thyroid cancer cell lines.
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Ozturk SA, Alp E, Yar Saglam AS, Konac E, and Menevse ES
- Subjects
- Caspase 3 metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Enzyme Activation drug effects, Gene Expression, Humans, NF-kappa B genetics, NF-kappa B metabolism, Neovascularization, Pathologic drug therapy, PTEN Phosphohydrolase genetics, PTEN Phosphohydrolase metabolism, Telomerase genetics, Antineoplastic Agents pharmacology, Apoptosis drug effects, Benzoquinones pharmacology, Genistein pharmacology, Telomerase metabolism
- Abstract
Context: Thyroid cancers (TCs) are the most common endocrine malignancies. There were two problems with the current cancer chemotherapy: the ineffectiveness of treatment due to resistance to cancer cell, and the toxic effect on normal cells., Aims: This study was aimed to determine the effects of thymoquinone (TQ) and genistein (Gen) phytotherapeutics on telomerase activity, angiogenesis, and apoptosis in follicular and anaplastic thyroid cancer cells (TCCs)., Materials and Methods: Cell viability, caspase-3 (CASP-3) activity, and messenger RNA (mRNA) expression levels of human telomerase reverse transcriptase (hTERT), phosphatase and tensin homolog (PTEN), nuclear factor-kappa B (NF-kB), cyclin-dependent kinase inhibitor 1 (p21), and vascular endothelial growth factor-A (VEGF-A) genes were analyzed., Results: It was found that TQ and Gen treatment on TCCs caused a statistically significant decrease of cell viability, and mRNA expression levels of hTERT, VEGF-A, and NF-kB genes, but a statistically significant increase of PTEN and p21 mRNA expression levels. In addition, TQ and Gen treatment also caused a statistically significant increase active CASP-3 protein level in TCCs. Moreover, our results demonstrated that, when compared with follicular TCCs, anaplastic TCCs were more sensitive to the treatment of TQ and Gen., Conclusions: Based on these results, two agents can be good options as potential phytochemotherapeutics against TCCs., Competing Interests: There are no conflicts of interest.
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- 2018
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38. Expression profiles of CD11b, galectin-1, beclin-1, and caspase-3 in nasal polyposis
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Dilci A, Varol N, Kılıçcıoğlu İ, Konac E, Aydil U, Kızıl Y, and Uslu S
- Subjects
- Adult, Apoptosis, Blotting, Western, Female, Humans, Male, Middle Aged, Nasal Polyps pathology, RNA, Messenger, Real-Time Polymerase Chain Reaction, Beclin-1 metabolism, CD11b Antigen metabolism, Caspase 3 metabolism, Galectin 1 metabolism, Nasal Mucosa pathology, Nasal Polyps metabolism
- Abstract
Background/aim: Nasal polyposis is a chronic inflammatory disease affecting the paranasal sinuses and nasal mucosae. It is thought that genetic and molecular mechanisms in inflammatory and apoptotic pathways are the main factors in the etiopathogenesis of nasal polyposis. The aim of this study was to investigate the expression patterns of CD11b, galectin-1, beclin-1, and caspase-3 in nasal polyps.Materials and methods: The mRNA expression levels of CD11b, galectin-1, beclin-1, and caspase-3 protein and western blot analysis of caspase-3 protein were evaluated in inferior turbinate mucosae and nasal polyp tissues.Results: CD11b expression was markedly higher in nasal polyp tissues when compared to turbinate mucosae (5.5 times higher, P < 0.05). Expression of galectin-1 was not statistically higher in nasal polyp tissues when compared to the controls. Beclin-1 expression in nasal polyp tissues was lower than in controls (17 times lower, P < 0.05). Caspase-3 expression was significantly lower in nasal polyp tissues than in controls (5.5 times lower, P < 0.05).Conclusion: Inflammation, apoptosis, and hyperproliferation are the major cellular processes in nasal polyposis and these proteins may take part and play some important roles in formation of this disease and the targeting of new treatment protocols.
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- 2017
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39. Do the expressions of epithelial-mesenchymal transition proteins, periostin, integrin-α4 and fibronectin correlate with clinico-pathological features and prognosis of metastatic castration-resistant prostate cancer?
- Author
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Konac E, Kiliccioglu I, Sogutdelen E, Dikmen AU, Albayrak G, and Bilen CY
- Subjects
- Adult, Aged, Aged, 80 and over, Bone Neoplasms genetics, Bone Neoplasms metabolism, Cell Line, Tumor, Humans, Male, Middle Aged, Prostatic Neoplasms, Castration-Resistant genetics, Prostatic Neoplasms, Castration-Resistant therapy, Epithelial-Mesenchymal Transition physiology, Fibronectins metabolism, Gene Expression Regulation, Neoplastic, Integrin alpha4 metabolism, Prostatic Neoplasms, Castration-Resistant metabolism
- Abstract
Development of metastatic castration-resistant prostate cancer is a result of the lack of an apoptotic response by the tumor cells and loss of the ability to stick to adjacent cells through epithelial-mesenchymal transition. Although there are several strongly recommended biomarkers for determining prognosis of metastatic castration-resistant prostate cancer, only few of them may help decide the selection of the optimal treatment option. The mode of treatment sequencing in metastatic castration-resistant prostate cancer will be based on the individual characteristics of the patient. In this study, we aimed to explain the correlation between the expression characteristics of periostin, integrin-α4, and fibronectin in metastatic castration-resistant prostate cancer patients and their clinico-pathological data comprising Gleason score, PSA levels, and metastatic sites in the process of epithelial-mesenchymal transition. We evaluated by using Western blotting, periostin, integrin-α4, and fibronectin expressions in peripheral blood samples of metastatic castration-resistant prostate cancer patients ( n = 40), benign prostatic hyperplasia patients ( n = 20), and the healthy control group ( n = 20). Associations between changes in the protein expressions and clinico-pathological parameters were also analyzed in the metastatic castration-resistant prostate cancer group. When comparing BPH and healthy groups with the metastatic castration-resistant prostate cancer group, a reduced expression of integrin-α4 was found in metastatic patients, albeit being statistically insignificant ( P > 0.05). Protein expressions of periostin and fibronectin in the metastatic castration-resistant prostate cancer group were higher than those in the BPH and heathy groups ( P < 0.001). Increased periostin expression in metastatic patients was significantly associated with bone metastasis ( P < 0.05). Elevated periostin and fibronectin levels in metastatic castration-resistant prostate cancer patients may be appropriate targets of therapeutic intervention in the future. Impact statement Prostate cancer is the third most common cancer in the world and the most common cancer among men. Development of metastatic castration-resistant prostate cancer (mCRPC) is a result of the lack of an apoptotic response by the tumor cells and loss of the ability to stick to adjacent cells through epithelial-mesenchymal transition (EMT). The present study analyzes for the first time the expressions of EMT marker proteins - periostin, integrin α4, fibronectin - in mCRPC and in benign prostatic hyperplasia (BPH) with the aim to determine the clinical relevance of changes in these three proteins vis-a-vis the PCa aggressive phenotype. In doing so, it sheds light on the molecular mechanism underlying the disease. We concluded that elevated periostin and fibronectin levels in mCRPC patients may be appropriate targets of therapeutic intervention in the future; hence, adopting methods that target these proteins may help treat prostate cancer effectively.
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- 2017
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40. Might E-cadherin promoter polymorphisms of rs16260 and rs5030625 associate with the risk of nephrolithiasis?
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Donmez C, Konac E, Aydogan BT, and Bilen CY
- Abstract
Purpose: To study whether -160 C > A (rs16260) and -347 G > GA (rs5030625) single nucleotide polymorphisms of the regulatory region (rSNPs) of CDH1 gene modulate the risk of nephrolithiasis., Methods: Genomic DNA of 101 patients with calcium oxalate nephrolithiasis and 114 healthy controls were screened for both polymorphisms, using polymerase chain reaction-restriction fragments length polymorphism method (PCR-RLFP). Haplotype frequencies were also analyzed. To determine the association of rSNPs of CDH1 gene with the clinicopathological features of nephrolithiasis, nearly all possible etiological factors were documented. These factors were family history, gender, age, body mass index, liquid consumption, eating habits, tea-coffee and meat (oxalate rich) consumption, adequate physical activity, and all serum and urine levels-the serum levels of Na, K, Cl, phosphate, Ca, Mg, uric acid, albumin, blood urea nitrogen (BUN), creatinine and serum parathyroid hormone (PTH) as well as 24 h urine excretions of creatinine, Na, K, Cl, phosphate, Ca, Mg, citrate, oxalate, uric acid, albumin and BUN., Results: Significant differences were found between rs16260 and the risk of nephrolithiasis. Patients having CA genotype of rs16260 CDH1 polymorphism were associated with an almost trifold increased risk for developing kidney stone than those with the AA genotype (95 % CI 1.08-7.28, OR 2.8, P = 0.033). We also found that non-A allele carriers (CC) had significantly higher nephrolithiasis risk associated with the clinicopathological characteristics including serum calcium ( P = 0.027) and 24 h urinary magnesium level ( P = 0.042). Moreover, we did find a directly proportional relationship between the CA genotype and serum calcium levels ( P = 0.041). There was no significant difference between patients and controls in terms of the distribution of rs5030625 genotypes and alleles ( P > 0.05). Likewise, no associations between the rs16260 and rs5030625 haplotypes and susceptibility to kidney stone were observed ( P > 0.05)., Conclusion: Regulatory variants of rs16260 of the CDH1 gene may confer susceptibility to nephrolithiasis. This may have important implications for understanding the pathophysiological mechanisms of the disease and suggesting novel targets for drug treatment.
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- 2016
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41. Synergistic effects of cisplatin and proteasome inhibitor bortezomib on human bladder cancer cells.
- Author
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Konac E, Varol N, Kiliccioglu I, and Bilen CY
- Abstract
The proteasome inhibitor bortezomib is a promising novel agent in bladder cancer therapy; however, inducible cytoprotective mechanisms may limit its potential efficacy. To date, the cellular and molecular effects of proteasome inhibitors on bladder cancer cells have been poorly characterized. Despite the consistent rate of initial responses, cisplatin treatment typically results in the development of chemoresistance, leading to therapeutic failure. Therefore, the present study aimed to characterize the molecular mechanisms underlying the anti-proliferative effects of cisplatin and bortezomib combination therapy on the human T24 bladder cancer cell line, by analyzing the protein expression levels of apoptotic genes. Cytotoxic effects were measured using a water-soluble tetrazolium salt-1 assay, and the apoptosis-associated molecules were examined using western blot analysis and ELISA. It was observed that combined administration of cisplatin and bortezomib induced upregulation of caspase-3, -8 and -9, B-cell lymphoma-2 (Bcl-2)-like 11 and Bcl-2-interacting killer, but downregulated Bcl-2 and Bcl-extra large protein expression levels in T24 cells in a dose-dependent manner. Furthermore, enhanced protein expression of caspase-8 and -9, in line with the significantly increased caspase-3 activation, was detected when the cells were treated with a combination of cisplatin and bortezomib, compared with that of either agent alone. Bortezomib appeared to synergize with cisplatin to promote apoptosis via the extrinsic and intrinsic apoptotic pathways. Taken together, the results of the current study provide the preclinical framework for additional evaluation of the effects of combining bortezomib with other agents to induce apoptosis in bladder cancer cells.
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- 2015
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42. Does Wnt/β-catenin pathway contribute to the stability of DNMT1 expression in urological cancer cell lines?
- Author
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Varol N, Konac E, and Bilen CY
- Subjects
- Adaptor Proteins, Signal Transducing genetics, CCAAT-Enhancer-Binding Proteins metabolism, Cell Line, Tumor, Cell Proliferation drug effects, DNA (Cytosine-5-)-Methyltransferase 1, DNA Methylation, Humans, Indoles pharmacology, Maleimides pharmacology, Promoter Regions, Genetic, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Repressor Proteins genetics, Ubiquitin Thiolesterase metabolism, Ubiquitin-Protein Ligases, Ubiquitin-Specific Peptidase 7, Urinary Bladder Neoplasms enzymology, Urinary Bladder Neoplasms pathology, DNA (Cytosine-5-)-Methyltransferases metabolism, Urinary Bladder Neoplasms metabolism, Wnt Proteins metabolism, beta Catenin metabolism
- Abstract
DNA methylation is considered as one of the most important epigenetic mechanisms and it is catalyzed by DNA methyltransferases (DNMTs). DNMT1 abundance has been frequently seen in urogenital system tumors but the reasons for this abundance are not well understood. We aimed to look into the effects of Wnt/β-catenin signaling pathway on overexpression of DNMT1 and aberrant expression of UHRF1 and HAUSP which are responsible for stability of DNMT1 at transcriptional and protein levels in urogenital cancers. In this context, firstly, Wnt/β-catenin signaling pathway was activated by using SB216763 which is a glycogen synthase kinase-3 (GSK3) β inhibitor. Cell proliferation levels in bladder cancer cells, renal cell carcinoma, and prostate cancer cells treated with GSK3β inhibitor (SB216763) were detected by WST-1 reagent. WIF-1 gene methylation profile was determined by methylation-specific PCR (MSP); expression levels of target genes β-catenin and WIF-1 by real-time PCR; and protein levels of β-catenin, DNMT1, pGSK3β(Ser9), HAUSP, and UHRF1 by Western Blot. Our results indicated that treatment with SB216763 caused an increased cell proliferation at low dose. mRNA levels of β-catenin increased after treatment with SB216273 and protein levels of pGSK3β(Ser9), β-catenin, and DNMT1 increased in comparison to control. HAUSP and UHRF1 were either up-regulated or down-regulated at the same doses depending on the type of cancer. Also, we showed that protein levels of DNMT1, β-catenin, HAUSP, and UHRF1 decreased after re-expression of WIF-1 following treatment with DAC. In Caki-2 cells, β-catenin pathway might have accounted for the stability of DNMT1 expression, whereas such relation is not valid for T24 and PC3 cells. Our findings may offer a new approach for determination of molecular effects of Wnt/β-catenin signal pathway on DNMT1. This may allow us to identify new molecular targets for the treatment of urogenital cancers., (© 2014 by the Society for Experimental Biology and Medicine.)
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- 2015
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43. The Inhibitory Effect of Platelet-Rich Plasma on Botulinum Toxin Type-A: An Experimental Study in Rabbits.
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Bulam H, Ayhan S, Sezgin B, Zinnuroglu M, Konac E, Varol N, Findikcioglu K, Tuncer S, and Cenetoglu S
- Subjects
- Animals, Male, Rabbits, Botulinum Toxins, Type A antagonists & inhibitors, Neuromuscular Agents antagonists & inhibitors, Platelet-Rich Plasma
- Abstract
Background: Combination treatments of botulinum toxin type-A and other rejuvenation agents or instruments are gradually becoming more popular. After observing a high incidence of therapy failure following simultaneous applications of botulinum toxin type-A and platelet-rich plasma mesotherapy, we aimed to investigate whether PRP has an inhibitory effect on botulinum toxin type-A., Methods: Twenty-four New Zealand white rabbits were divided into 4 groups, and the anterior auricular muscle and overlying skin were used for injections. Groups I and II both received onabotulinumtoxinA intramuscular injections. In addition, autologous platelet-rich plasma mesotherapy was performed in Group I while Group II received saline mesotherapy. Group III was designed as the in vitro mixture group in which onabotulinumtoxinA and platelet-rich plasma were mixed and then administered intramuscularly. Group IV received saline within the mixture instead of platelet-rich plasma. The contralateral ears of all the rabbits served as control and were only treated with onabotulinumtoxinA. Visual evaluation of ear positions and electroneuromyographic studies were done prior to all procedures and at day 14. Anterior auricular muscles were harvested at day 14 and were evaluated with quantitative real-time PCR., Results: Visual and electroneuromyographic studies revealed less onabotulinumtoxinA activity in Groups I and III. When platelet-rich plasma was administered through skin mesotherapy, onabotulinumtoxinA activity failure was more severe in comparison with direct contact. No significant difference in SNAP-25 mRNA expression through quantitative real-time PCR was observed between groups., Conclusion: Although we could not explain the exact mechanism underlying this interaction, platelet-rich plasma applications result in less onabotulinumtoxinA muscle paralysis activity.
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- 2015
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44. The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder.
- Author
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Gurocak S, Konac E, Ure I, Senol C, Onen IH, Sozen S, and Menevse A
- Subjects
- Adolescent, Child, Child, Preschool, Cytochrome P-450 CYP3A genetics, Female, Humans, Male, Receptors, Adrenergic, beta-3 genetics, Rho Guanine Nucleotide Exchange Factors genetics, Treatment Outcome, Urinary Bladder, Overactive genetics, rho-Associated Kinases genetics, Cholinergic Antagonists therapeutic use, Mandelic Acids therapeutic use, Polymorphism, Restriction Fragment Length, Urinary Bladder, Overactive drug therapy
- Abstract
Aim: To determine the impact of gene polymorphisms on detrusor contraction-relaxation harmony in children with lower urinary tract symptoms (LUTS)., Materials and Methods: Toilet trained children older than 5 years of age with LUTS and normal neurological examination underwent videourodynamic study. The control group was composed of age matched children with no voiding complaints. The study group who filled out the voiding dysfunction symptom score before and after the treatment received standard oxybutynin treatment and was reevaluated 1 year after treatment. Genomic DNA was isolated from all patients and subjected to PCR for amplification. Genotyping of ARGHEF10, ROCK2, ADRB3, and CYP3A4 was carried out with Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method., Results: 34 (45%) and 42 (55%) patients were enrolled in the study and control group, respectively. ARGEF10 GG, ADRB3 TC, and CYP3A4 AG genotype patients displayed insignificant difference between pre- and posttreatment voiding dysfunction symptom score and bladder volumes., Conclusions: The polymorphism of genes in the cholinergic pathway did not significantly differ clinical parameters. On the other hand, polymorphic patients in the adrenergic pathway seemed to suffer from clinical disappointment. For this reason, we think that the neglected adrenergic pathway could be a new therapeutic target for the treatment of anticholinergic resistant LUTS in children.
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- 2015
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45. Does Pattern Scan Laser (PASCAL) photocoagulation really induce less VEGF expression in murine retina than conventional laser treatment?
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Konac E, Sonmez K, Bahcelioglu M, Kaplanoglu GT, Varol N, Sarac GN, and Ozcan PY
- Subjects
- Animals, Argon, Gene Expression Regulation, Male, Mice, Mice, Inbred C57BL, RNA, Messenger genetics, Retina metabolism, Time Factors, Laser Coagulation adverse effects, Laser Coagulation instrumentation, Retina surgery, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A metabolism
- Abstract
To investigate the differences in the mRNA and protein expression levels of vascular endothelial growth factor (VEGF) in murine retina between mice subjected to conventional laser (AG) and those subjected to Pattern Scan Laser (PASCAL) system. Male C57BL/6 mice were randomly assigned to one of three groups: Group 1 (G1) receiving retinal scatter laser photocoagulation using with AG photocoagulator (n=16), Group 2 (G2) receiving retinal scatter laser photocoagulation using with PASCAL (n=16) and Group 3 (G3) served as an untreated control group (n=6). Molecular and morphological analyses of VEGF were performed on days 1, 2 and 5 by ELISA, real-time PCR and immuno-histochemical analysis. In samples which underwent AG (G1), when compared with the control group (G3), VEGF mRNA level increased 2.4 folds on day 2, whereas it decreased on day 5 (p□0.001). In samples which underwent PASCAL (G2), on the other hand, VEGF mRNA level increased 1.8 folds on day 1 and 2.2 folds on day 5 when compared with the control group (G3). In samples which underwent AG (G1), when compared with the control group (G3), VEGF protein level increased significantly on day 2, whereas it decreased on day 5 (p□0.001). In group G2, the VEGF levels in the sensory retina significantly increased as compared to control groups at both 2 and 5 days after laser photocoagulation using PASCAL laser (p=0.012, both time points). The peak expressions of VEGF protein in samples which underwent PASCAL and conventional laser were found on day 5 and day 2 respectively. In retinas of PASCAL-treated mice, VEGF immunoreactivity gradually increased during the 5-day follow-up. However, in argon laser group, the strongest VEGF immunoreactivity was detected on day 2, then started to decrease on day 5. In summary, the expression of VEGF protein and mRNA gradually increase during a 5-day follow-up period in PASCAL-treated mouse eyes, whereas in AG group they reach their peak levels on the second day of follow-up and started decreasing after then. These results may also explain why the PASCAL system is less effective in regressing neovascularization in the clinic., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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46. The epigenetically regulated effects of Wnt antagonists on the expression of genes in the apoptosis pathway in human bladder cancer cell line (T24).
- Author
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Varol N, Konac E, Onen IH, Gurocak S, Alp E, Yilmaz A, Menevse S, and Sozen S
- Subjects
- Antineoplastic Agents pharmacology, Azacitidine pharmacology, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Cyclin D genetics, Cytidine Triphosphate pharmacology, Dose-Response Relationship, Drug, Genes, myc genetics, Humans, Urinary Bladder Neoplasms drug therapy, beta Catenin genetics, Apoptosis drug effects, Azacitidine analogs & derivatives, Cytidine Triphosphate analogs & derivatives, Epigenomics, Gene Expression Regulation, Neoplastic drug effects, Hydroxamic Acids pharmacology, Wnt Proteins antagonists & inhibitors
- Abstract
The epigenetic suppression of Wnt antagonists (sFRPs, DKKs, and WIF-1) causes the activation of both β-catenin and target genes, which play an important role in cell proliferation, metastasis, and angiogenesis. This study is aimed to investigate, on transcriptional and protein levels, the synergic effects of unaccompanied and/or combined use of 5-aza-2'-deoxycytidine (DAC, 5-aza-dC), trichostatin A (TSA), and gemcitabine+cisplatin chemotherapeutic agents on the apoptotic pathway of human bladder cancer cell line T24. The anti-tumor effects of gemcitabine (0-500 nM), cisplatin (0-10 μM), DAC (10 μM), and TSA (300 nM) alone and/or together on T24 cells were determined by WST-1. ELISA method was used to analyze the effects of unaccompanied and combined use of gemcitabine+cisplatin, DAC, and TSA on cell proliferation and determine the cytotoxic and apoptotic dosages at the level of H3 histone acetylation. Methylation-specific PCR was used to evaluate methylation profiles of Wnt antagonist gene (WIF-1). In the case of unaccompanied and/or combined use of specified drugs, the variations in the expression levels of CTNNB1, GSK3β, c-MYC, CCND1, CASP-3, CASP-8, CASP-9, BCL2L1, and WIF-1 genes were determined by quantitative real-time PCR. Our results indicate that through inhibition of DNA methylation, expression of β-catenin and Wnt antagonist re-activation and expressions of canonical Wnt/β-catenin pathway target genes, c-myc and cyclin D1 (CCND1), have decreased. In addition, DAC, TSA, and gemcitabine+cisplatin combination caused an increase in GSK3β mRNA levels, which in turn significantly decreased CCND1 mRNA levels. Moreover, BCL2L1, an anti-apoptotic gene, was downregulated significantly. Meanwhile, both CASP-3 mRNA and active caspase-3 protein levels increased with respect to control (p<0.01). The results revealed that use of quadruplicate gemcitabine+cisplatin+DAC+TSA combination led to a reduced inhibition of canonical Wnt/β-catenin pathway and reduced cell proliferation. Our findings may offer a new approach to consider in the treatment of bladder cancer.
- Published
- 2014
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47. Effects of AG490 and S3I-201 on regulation of the JAK/STAT3 signaling pathway in relation to angiogenesis in TRAIL-resistant prostate cancer cells in vitro.
- Author
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Gurbuz V, Konac E, Varol N, Yilmaz A, Gurocak S, Menevse S, and Sozen S
- Abstract
The aim of the present study was to analyze the molecular mechanisms involved in blocking the signaling pathway and the effects of this on the progression of prostate cancer (CaP) cells in vitro . LNCaP human CaP cell line was stimulated with interleukin-6 (IL-6) in the presence/absence of Janus kinase (JAK) 2 (AG490), signal transducer and activator of transcription 3 [(STAT3) S3I-201] inhibitors and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Cytotoxic activity, the activation of phosphorylated (p)-STAT3 protein, caspase (CASP) 3 activity at protein level, vascular endothelial growth factor (VEGF) A, VEGFC, vascular endothelial growth factor receptor 2, STAT3, matrix metalloproteinase-2, myeloid cell leukemia sequence 1 (MCL-1), CASP8 and CASP9 messenger RNA (mRNA) levels were determined. Morphology and apoptosis were confirmed by DAPI staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. IL-6 rapidly induced the phosphorylation of STAT3 in a dose- and time-dependent manner with a peak expression at 3 h at a concentration of 25 ng/ml. In addition, AG490 (50 μM) and S3I-201 (300 μM) inhibited STAT3 activation. Western blotting results revealed that p-STAT3 protein expression decreased significantly with AG490 and S3I-201 treatment in LNCaP cells. AG490 and S3I-201 induced the downregulation of VEGFA, MCL-1 and STAT3 and the upregulation of CASP8 and CASP9 mRNA transcription levels. In addition, the inhibitors increased the level of CASP3 protein. Combinations of AG490- and S3I-201-TRAIL did not result in an increase in this effect. Parallel results were found by DAPI staining and TUNEL assay. To the best of our knowledge, this is the first study to investigate the possible clinical use of AG490 or S3I-201, together with the reduced use of chemotherapeutic agents with high cytotoxicity, for their ability to exert an apoptotic effect, targeting the JAK/STAT3 pathway.
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- 2014
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48. DNA methyltransferase inhibitor-mediated apoptosis in the Wnt/β-catenin signal pathway in a renal cell carcinoma cell line.
- Author
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Konac E, Varol N, Yilmaz A, Menevse S, and Sozen S
- Subjects
- Azacitidine analogs & derivatives, Azacitidine pharmacology, Carcinoma, Renal Cell metabolism, Cell Line, Tumor, Cell Proliferation, DNA Fragmentation, DNA Modification Methylases antagonists & inhibitors, Decitabine, Epigenesis, Genetic, Glycogen Synthase Kinase 3 genetics, Glycogen Synthase Kinase 3 metabolism, Glycogen Synthase Kinase 3 beta, Glycoproteins metabolism, Humans, Intracellular Signaling Peptides and Proteins, Apoptosis drug effects, Carcinoma, Renal Cell genetics, DNA Methylation, Glycoproteins genetics, Wnt Signaling Pathway drug effects
- Abstract
The Wnt signaling pathway is activated in most cancer types when Wnt antagonist genes are inactivated. Glycogen synthase kinase 3 (GSK3β) is an important regulator of the Wnt/β-catenin signaling pathway. The mechanisms underlying GSK3β regulation of neoplastic transformation and tumor development are unclear. Studies have raised the possibility that the Wnt signaling pathway may be implicated in renal cell carcinoma (RCC). Therefore, in the present study, we hypothesize that the expression and methylation status of the secreted frizzled-related protein 2 (sFRP2) gene, one of the secreted antagonists that bind Wnt protein, and re-expression of this gene with the demethylation agent (5-aza-2'-deoxycytidine; DAC) may induce apoptosis in RCC cells. To test this hypothesis, we investigated the relationship among epigenetic inactivation of sFRP2 and p-GSK3β (Ser9) and other Wnt antagonists (sFRP1, DKK3, WIF-1) and apoptotic factors (Bax and Caspase3) as well as the anti-apoptotic factor BCL2. Our results indicate that DAC-mediated inhibition of DNA methylation led to a re-activation of sFRP2 expression and increased expression levels of the Wnt antagonists and apoptotic factors. In contrast, the level of β-catenin (CTNNB1) expression decreased. The p-GSK3β (Ser9) protein level in Caki-2 cells was significantly down-regulated, while the DNA fragmentation rate increased after treatment with 5 μM DAC at 96 h. Our data show that sFRP2 functions as a tumor suppressor gene in RCC and that its restoration may offer a new therapeutic approach for the treatment of RCC. Moreover, our study draws attention to the regulatory features of epigenetic molecules and analyses their underlying molecular mechanisms of action and their potential use in clinical practice.
- Published
- 2013
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49. Effects of the adverse life events and Disrupted in Schizophrenia-1 (DISC1) gene polymorphisms on acute symptoms of schizophrenia.
- Author
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Sayın A, Yüksel N, Konac E, Yılmaz A, Doğan B, Tönge S, Sahiner S, and Menevşe A
- Subjects
- Acute Disease, Adult, Case-Control Studies, Child, Child Abuse psychology, Child Abuse statistics & numerical data, DNA Mutational Analysis, Depression complications, Depression epidemiology, Depression genetics, Disease Susceptibility complications, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Schizophrenia epidemiology, Schizophrenia genetics, Stress, Psychological epidemiology, Stress, Psychological genetics, Young Adult, Life Change Events, Nerve Tissue Proteins genetics, Polymorphism, Single Nucleotide physiology, Schizophrenia etiology, Stress, Psychological complications
- Abstract
The aim of this study was to evaluate the effects of traumatic childhood events and recent adverse life events, as well as the Disrupted in Schizophrenia-1 (DISC1) gene polymorphisms on types of last acute symptoms of patients with schizophrenia. Hundred patients with schizophrenia were given the Childhood Trauma Questionnaire, the Social Readjustment Rating Scale, Scale for Assessment of Positive Symptoms (SAPS), Scale for Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), and Calgary Depression Scale for Schizophrenia (CDSS). The patients' and healthy controls' DISC1 gene was evaluated for the -274G>C, c.791G>A, and c.2110A>T polymorphisms. There was no statistically significant difference with regard to the DISC1 gene polymorphisms between patient and healthy control groups. No significant relationship was found between the -274G>C, c.791G>A, and c.2110A>T haplotypes and development of different acute symptoms of schizophrenia. Having a recent stressful life event significantly affected SAPS (95% confidence interval [CI]=-67.547, -21.473; p=0.00) and BPRS-1 scores (95% CI=-51.405, -6.885; p=0.01), whereas emotional abuse at childhood significantly affected SANS scores (95% CI=-37.300, -10.401; p=0.00). This study shows that features of acute symptoms in schizophrenia are not influenced by the polymorphisms on the DISC1 gene, but are influenced by recent adverse life events and emotional abuse at childhood.
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- 2013
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50. NLF2 gene expression in the endometrium of patients with implantation failure after IVF treatment.
- Author
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Turkyilmaz E, Guner H, Erdem M, Erdem A, Biri AA, Konac E, Alp E, Onen HI, and Menevse S
- Subjects
- Adult, Contractile Proteins genetics, Extracellular Matrix Proteins genetics, Female, Humans, Male, Nuclear Proteins, RNA Splicing Factors, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Embryo Implantation genetics, Endometrium metabolism, Fertility genetics, Fertilization in Vitro, Infertility, Female genetics, Infertility, Female therapy, Transcription Factors genetics
- Abstract
The aim of this study was to analyze the expression of microfibril-associated protein 2 (MFAP2), microfibril-associated protein 5 (MFAP5) and nuclear localized factor 2 (NLF2) genes in patients with repeated IVF failure and compare with fertile population. Total RNA was isolated from 38 patients (repeated implantation failure, group 1, n=22; fertile patients, group 2, n=16). mRNA expression levels were measured quantitatively using real-time polymerase chain reaction. Our results showed that mRNA expression of NLF2 significantly decreased in the infertility group as compared to control group (P=0.023). In addition a marked decrease was observed in the expression of MFAP2 in women with repeated implantation failure. In conclusion, NLF2 gene expression levels and differences in MFAP2 and MFAP5 gene expressions (albeit being insignificant) between infertile group and control group draw attention to a genetic basis under implantation failure., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2012
- Full Text
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