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Öğe Expression of PARP1 gene in breast cancer patients(2013) Ulaşlı, Mustafa; Gürses, Serdar; Cengiz, Beyhan; Öztuzcu, Serdar; Balakan, Ozan; Süner, Ali; Göğebakan, Bülent; İğci, Mehri; Balık, Ahmet; Arslan, Ahmet; Camcı, CemalettinPoli (ADP riboz) polimeraz (PARP), DNA onarım mekanizmasında yer alan bir enzim ailesidir. Bu enzimlerden PARP1, baz kesip- çıkarma onarım (BER) mekanizmasına öncülük eden tek zincir DNA kırıklarının saptanmasında rol alır. BRCA1 ve BRCA2 genlerinden yoksun meme kanseri tümörleri, DNA çift zincir kırıklarının onarımında yetersizdirler. PARP enzimlerinin bu tümörlerdeki aktivitesi ilgi konusudur çünkü PARP aktivitesinin kaybı, tek zincir DNA kırıklarının birikimine, biriken tek zincir DNA kırıklarının çift zincir DNA kırıklarına dönüşmesine ve takiben tamir edilemeyen DNA hasarı ve hücre ölümüne yol açmaktadır. Bu yüzden PARP inhibisyonunun, kanser hücrelerini öldürmede etkili olabileceği düşünülmekte ve PARP inhibitörlerinin seçici olarak meme kanseri tümörlerini öldürmedeki etkinliği araştırılmaktadır. Bu çalışmada, PARP inhibitörlerinin meme kanserine karşı kullanılma potansiyelinin değerlendirilmesi için bir grup meme kanserli hastada, PARP-1 gen ifade düzeyi ve kanser markırlarından östrojen reseptörü (ER), progesteron reseptörü (PR) ve insan epidermal büyüme faktör reseptörü 2 (HER2)’nin gen ifade düzeyleri belirlenmiştir. Hastalarda PARP-1 gen ifade düzeyinin meme kanseri oluşumu ile ilişkili olmadığı gösterilmiştir.Öğe Investigation of Cytotoxic effects of Oxymetazoline on Lungs in a Rat Mod-el of Rhinitis Medicamentosa(Bentham Science Publ Ltd, 2020) Cengiz, Beyhan; Bostanciklioglu, Mehmet; Demir, Tuncer; Karabulut, Hayriye; Dokuyucu, Recep; Ulasli, MustafaBackground: Rhinitis medicamentosa, also known as 'rebound congestion,' is inflammation of the nasal mucosa caused by the overuse of topical nasal decongestants. Although local decongestants resolve the initial nasal obstruction, the overuse causes rebound obstruction. However, how the overuse of the decongestant causes rhinitis medicamentosa is not known. Objectives: Here, we show the intracellular effects of oxymetazoline, commonly used a local decongestant, on the cell death pathways. We also investigated the antioxidative effects of erdosteine suspension (175 mg/5mL), an antioxidative agent. Methods: Thirty Wistar-albino rats were used to form the rhinitis medicamentosa model. After rhinitis medicamentosa was clinically detected, we removed the whole lungs of animals to perform the molecular analyses of cell death pathways. Results: We found a statistically significant decrease in the expression levels of Atg5 (p=0.021), Atg7 (p=0.013) and Ulk1 (p=0.036) in the oxymetazoline group compared to the control group (p<0.05); however, Caspase 3 expression level was recorded to be significantly increased in the oxymetazoline group, and the expression level of Beclin1 recorded to be substantially increased in the erdosteine group (p=0.001). Conclusion: Based on these grounds, we suggest that vasoconstriction in capillary vessels caused by oxymetazoline could lead to a decrease in the blood supply, which triggers autophagy to ensure cellular homeostasis.Öğe NADPH oxidase P22PHOX gene expression in ulcerative colitis(2014) Bülbül, Neşe; Pala, Elif; İğci, Yusuf Ziya; Göğebakan, Bülent; Öztuzcu, Serdar; Cengiz, Beyhan; Bayraktar, Recep; Dağ, Muhammet Sait; Aydınlı, MusaBackground/Aims: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which catalyzes the formation of reactive oxygen species (ROS) in phagocytic cells, has five subunits: p67phox ("phox"refers to "phagocyte oxidase"), p47phox, p40phox, p22phox, and gp91phox (catalytic subunit). Oxidative stress resulting from the accumulation of ROS and/or defective removal of ROS by antioxidants has detrimental effects on cellular functions and may contribute to chronic inflammation. Disruption of the colonic mucosa due to the dysregulation of antioxidants or transformation enzymes may play a role in the pathogenesis of ulcerative colitis (UC) and influence the clinical features of this disease. In this study, we examined the expression of the gene encoding NADPH oxidase subunit p22phox cytochrome b-245, alphapolypeptidein the colonic mucosa to test its possible contribution in the pathogenesis of UC.Materials and Methods: Expression levels of mRNA in the inflamed and non-inflamed colonic mucosa (determined using colonoscopy)of 22 patients with UC and in the normal mucosa of 22 healthy controls were analyzed using real-time polymerase chain reaction.Results: Expression levels of mRNA were not significantly different between patients with inflamed and non-inflamed colonic mucosa (p>0.05) and betweenpatients with inflamed colonicmucosa and healthy controls (p>0.05). Conclusion: Although our data suggest that expression of the gene encoding p22phox is not associated with chronic inflammation in patients with UC, other mechanisms can affect oxidative stress in these patients.Öğe A novel tumor suppressor gene in basal cell carcinoma: inhibition of growth factor-2(Springer, 2015) Temel, Metin; Turkmen, Arif; Dokuyucu, Recep; Cevik, Cengiz; Oztuzcu, Serdar; Cengiz, Beyhan; Mutaf, MehmetIn loss of heterozygosity (LOH) studies at the chromosome 4q22-35 region, it was shown that the amount of deletion was high in basal cell carcinoma (BCC). It has been proposed that genes located in this chromosomal region could be tumor suppressor genes in BCC. It has been thought that deletions in the ING2 gene located in the same region can play a role in the pathophysiology of BCC and that deletions occurring in this region may influence the level of ING2 expression in BCC. Tumoral and non-tumoral tissues from 75 patients with BCC (45 men and 30 women) were included to the study. Lesions were excised by a surgical margin of 0.5 cm. After excision, RNA was isolated from tumoral and non-tumoral tissue samples. ING2 messenger RNA (mRNA) expression level was determined in tumoral and non-tumoral tissues by the real-time polymerase chain reaction (RT-PCR). It was detected that ING2 mRNA expression level decreased in tumoral tissues when compared to non-tumoral tissues from BCC patients (p = 0.0001). It was found that expression levels of this gene were comparable among patients with primary, recurrent, or multiple BCC. It is thought that ING2 gene expression level could contribute to the development of BCC but not be associated with the stage and the prognosis of the tumor.Öğe The role of hepcidin and its related genes (BMP6, GDF-15, and HJV) in rats exposed to ischemia and reperfusion(2014) Dokuyucu, Recep; Demir, Tuncer; Yumrutaş, Önder; Erbağcı, Ayşe Binnur; Örkmez, Mustafa; Bahar, Abdulkadir Yasir; Bayraktar, Recep; Bozgeyik, İbrahim; Kaplan, Davut Sinan; Cengiz, Beyhan; Bağcı, CahitBackground/aim: To determine the roles of hepcidin and its related genes in a renal ischemia/reperfusion model. Materials and methods: A total of 20 Wistar albino rats were equally divided into 2 groups: Group I was the control group and Group II was the ischemia and reperfusion (I/R) group (60 min of ischemia + 48 h of reperfusion). I/R was performed on the left kidneys of these rats and then the I/R-treated kidneys were removed. The levels of serum biochemical markers were evaluated after renal I/R. The expression levels of hepcidin-linked genes [growth differentiation factor 15 (GDF-15), bone morphogenetic protein 6 (BMP6), and hemojuvelin (HJV)] were also measured by RT-PCR technique. In addition, the tissues were evaluated histopathologically. Results: No significant association was found between renal dysfunction and I/R when compared to biochemical parameters (P > 0.05). However, differences in platelet values were statistically significant (P < 0.05). Expression levels of GDF-15, BMP6, and HJV genes increased, but this increase was not statistically significant. In addition, histopathological evaluation was performed using hematoxylin and eosin stain. This showed a significant relationship between the control group and I/R group for ischemic and nonischemic kidney scoring. Conclusion: Hepcidin and BMP6, HJV, and GDF-15 should be taken into account when investigating the process of I/R.Öğe Thr21Met (T21M) but not Ser89Asn (S89N) polymorphisms of the urotensin-II (UTS-II) gene are associated with Behcet's disease (BD)(Elsevier Science Inc, 2013) Oztuzcu, Serdar; Ulasli, Mustafa; Pehlivan, Yavuz; Cevik, Muhammer Ozgur; Cengiz, Beyhan; Gogebakan, Bulent; Igci, Yusuf ZiyaBehcet's disease (BD) is multisytemic vasculitis or chronic inflammation that may lead to various autoimmune and autoinflammatory syndromes. Exact etiopathogenesis of BD has not been clarified yet. Urotensin II (UTS-II) is predominantly a vasoactive peptide and Thr21Met polymorphism in UTS-II gene was proved to increasing in some autoimmune diseases. Considering these, our objective was to evaluate whether two UTS-II gene polymorphisms (Thr21Met and Ser89Asn) were responsible in genetic susceptibility to BD in a Turkish population. A total of 198 patients with BD and 275 healthy controls were enrolled. We analyzed the genotype and allele frequencies of two UTS-II gene polymorphisms, Thr21Met and Ser89Asn, in BD patients and in controls. We found that Thr21Met but not Ser89Asn polymorphisms of the UTS-II gene were markedly associated with the risk of developing BD (p<0.0001), The Met21Met genotype was less common among BD patients (6.1% in patients vs. 17.1% in controls; p<0.0001). There was also an increase in the 21Thr allele (54.8% in BD patients vs. 43.8% in controls) and a decrease in 21Met allele frequencies (45.2% in controls vs. 56.2% in patients) in the BD groups (p<0.0044). To the best of our knowledge, for the first time in the literature, our study claims that there is an association between Thr21Met, and not between Ser89Asn polymorphisms in the UTS-II gene and BD. These results put a new player to the field of undiscovered pathogenesis of BD and hopefully provide new insights to the treatment options. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.
