Person: EREN, FATİH
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EREN
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FATİH
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Publication Metadata only Investigation of the Therapeutic Efficacy of Codelivery of psiRNA-Vascular Endothelial Growth Factor and pIL-4 into Chitosan Nanoparticles in the Breast Tumor Model(ELSEVIER SCIENCE INC, 2014) EREN, FATİH; Salva, Emine; Turan, Suna O.; Kabasakal, Levent; Alan, Saadet; Ozkan, Naziye; Eren, Fatih; Akbuga, JulideAngiogenesis has been known to increase tumor growth and for its metastatic potential in human tumors. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and is a promising therapeutic target for breast cancer. VEGF is an essential target for RNAi-based gene therapy of breast cancer. Interleukin-4 (IL-4) may act as an anti-angiogenic molecule that inhibits tumor growth and migration in rats. The purpose of the present study was to improve therapeutic efficacy in breast cancer with the codelivery of siRNA-expressing plasmid targeting VEGF and IL-4-expressing plasmid encapsulating into chitosan nanoparticles (NPs). The codelivery of psiVEGF and pIL-4 plasmids greatly enhanced in vitro and in vivo gene-silencing efficiency. For the in vitro study, when psiVEGF and pIL-4 into chitosan NPs were combined (81%), the gene-silencing effect was higher than psiVEGF and pIL-4 NPs alone. The in vivo study breast tumor model demonstrated that the administration of coencapsulation of psiVEGF and pIL-4 into chitosan NPs caused an additive effect on breast tumor growth inhibition (97%), compared with containing NPs psiVEGF or pIL-4 alone. These results indicate that chitosan NPs can be effectively used for the codelivery of pIL-4 and siVEGF-expressing plasmid in a combination therapy against breast cancer. (c) 2013 Wiley Periodicals, Inc.Publication Open Access Evaluation of the Association between Programmed Cell Death-1 Gene Polymorphisms and Hepatocellular Carcinoma Susceptibility in Turkish Subjects. A Pilot Study(MEDICAL UNIV PRESS, 2020-10-27) EREN, FATİH; Demirci, Abdullah Fatih; Demirtas, Coskun Ozer; Eren, Fatih; Yilmaz, Demet; Keklikkiran, Caglayan; Ozdogan, Osman Cavit; Gunduz, FeyzaBackground & Aims: Programmed cell death-1 (PD-1) has a vital role in regulating T-cell function, and immune escape mechanism of cancer cells. It was shown that there could be a relationship between single nucleotide polymorphisms (SNPs) in the PD-I gene and susceptibility to hepatocellular carcinoma (MCC) based on various studies. We aimed to investigate the role of three SNPs within the PD-1 gene in susceptibility to HCC in the Turkish population. Methods: Single nucleotide polymorphisms of PD-1.1, 1.5, and 1.6 were genotyped by using TaqMan Allelic Discrimination Assays in blood samples of 137 HCC and 136 control subjects, matched for age and gender. The genotype, allele and haplotype frequencies were compared in HCC and control groups using logistic regression analysis. Results: Genotype distributions of PD-1.1, PD-1.5 and PD-1.6 SNPs were in Hardy-Weinberg equilibrium. No significant difference was observed in the genotype distribution of PD-I.1, PD-1.5 and PD-1.6 polymorphisms among gender and age-matched HCC (M/F: 96/41; mean age: 61.4 +/- 11.7 years) and control group (M/F: 94/42; mean age: 61.4 +/- 10.1). In the haplotype analysis of P1)-1.1/PD-1.5/PD-1.6, no significant difference was found among HCC and control group adjusted for sex and age (all p values>0.1). Conclusion: Our findings, firstly reporting the association of PD-1.5 polymorphism with I ICC, and PD-I.1 and PD-1.6 with HCC in the Turkish population, suggest that PD-1 polymorphisms are not predisposing factors for HCC development. Future studies with larger sample sizes and different ethnic populations are required to validate our findings.Publication Metadata only Chitosan/Short Hairpin RNA Complexes for Vascular Endothelial Growth Factor Suppression Invasive Breast Carcinoma(MARY ANN LIEBERT, INC, 2010) EREN, FATİH; Salva, Emine; Kabasakal, Levent; Eren, Fatih; Cakalagaoglu, Fulya; Ozkan, Naziye; Akburga, JuelideVascular endothelial growth factor (VEGF) plays a critical role in angiogenesis. The aim of this study was to use chitosan/short hairpin VEGF (shVEGF) [short hairpin RNA (shRNA)-expressing pDNA targeting VEGF-A] complexes in the treatment of rat breast cancer model. Therefore, chitosan/shVEGF complexes were prepared in (2/1) ratio and injected to the breast-tumor bearing Sprague-Dawley rats. Intratumoral and intraperitoneal injections were applied and compared. Tumor volumes were measured during the 36 days. To investigate the effect of complexes on the VEGF expression, VEGF were analyzed by immunohistochemistry and western blotting. The mRNA levels of VEGF were determined by real-time polymerase chain reaction. Tumor volume decreased at the end of experiments after shRNA treatment. The highest suppression in the tumor volume was observed after intratumoral complex injection to rats (96%). Compared with intratumoral and intraperitoneal injection, higher tumor inhibition was obtained with intratumoral injection. Free shRNA injection indicated lower tumor suppression. The immunohistochemistry and western blotting results correlated with the real-time polymerase chain reaction and tumor volume measurements. The data suggest that chitosan/shVEGF complexes can be used to inhibit tumor growth in breast carcinoma model of rats.Publication Metadata only Local Delivery of Chitosan/VEGF siRNA Nanoplexes Reduces Angiogenesis and Growth of Breast Cancer In Vivo(MARY ANN LIEBERT, INC, 2012) EREN, FATİH; Salva, Emine; Kabasakal, Levent; Eren, Fatih; Ozkan, Naziye; Cakalagaoglu, Fulya; Akbuga, JulideVascular endothelial growth factor (VEGF) is the important angiogenic factor associated with tumor growth and metastasis in a wide variety of solid tumors. The aim of this study is to investigate the tumor suppressive effect of chitosan/small interfering RNA (siRNA)-VEGF nanoplexes in the rat breast cancer model. Chitosan/siRNA nanoplexes (siVEGF-A, siVEGFR-1, siVEGFR-2) and NRP-1 were prepared in a 15 to1 ratio and injected (intratumorally) into the breast-tumor-bearing Sprague-Dawley rats. Tumor volumes were measured during 21 days. To investigate the effect of chitosan/siRNA nanoplexes on VEGF expression in tumors, VEGF was analyzed with immunohistochemistry and western blotting. The mRNA levels of VEGF in tumor samples were determined with real-time PCR (RT-PCR). After siRNA treatment, a marked reduction in tumor volumes was measured in complex-injected rats (97%). Free siRNA injection showed lower tumor inhibition. Reduction of VEGF protein was also shown with western blotting and immunohistochemistry. Similar results were obtained with RT-PCR also. These results indicate that the chitosan/siRNA targeting to VEGF nanoplexes have a remarkably suppressive effect on VEGF expression and tumor volume in breast cancer model of rats.Publication Metadata only Serum osteopontin levels as a predictor of portal inflammation in patients with nonalcoholic fatty liver disease(ELSEVIER SCIENCE INC, 2013) EREN, FATİH; Yilmaz, Yusuf; Ozturk, Oguzhan; Alandab, Yesim Ozen; Senates, Ebubekir; Colak, Yasar; Doganay, Hamdi Levent; Coskunpinar, Ender; Oltulu, Yasemin Musteri; Eren, Fatih; Atug, Ozlen; Tuncer, Ilyas; Imeryuz, NeseBackground: Osteopontin is a secreted phosphorylated glycoprotein that is expressed by a variety of cell types and that mediates numerous and diverse biological functions. Osteopontin knockout mice are protected from obesity-induced hepatic steatosis. In the present study, we sought to investigate whether serum osteopontin concentrations are associated with liver histology in patients with nonalcoholic fatty liver disease. Methods: Serum levels of osteopontin were measured by enzyme-linked immunosorbent assay in 179 Well-characterized patients with nonalcoholic fatty liver referred for liver histology and 123 control subjects. Results: Serum osteopontin levels were markedly higher in patients with nonalcoholic fatty liver disease than in controls (p < 0.001). Multivariable analysis showed that osteopontin levels were strongly and independently associated with both portal inflammation (beta = 0.294, p < 0.01) and serum aminotransferase levels (aspartate aminotransferase: beta = 0.295, p < 0.01; alanine aminotransferase; beta = 0.285, p < 0.01). Conclusion: In summary, these data demonstrate that serum levels of osteopontin are elevated in nonalcoholic fatty liver disease and are a significant independent predictor of portal inflammation in this clinical entity. (C) 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.Publication Metadata only Serum levels of omentin, chemerin and adipsin in patients with biopsy-proven nonalcoholic fatty liver disease(TAYLOR & FRANCIS LTD, 2011) EREN, FATİH; Yilmaz, Yusuf; Yonal, Oya; Kurt, Ramazan; Alahdab, Yesim Ozen; Eren, Fatih; Ozdogan, Osman; Celikel, Cigdem Ataizi; Imeryuz, Nese; Kalayci, Cem; Avsar, ErolObjective. The novel adipokines omentin, chemerin, and adipsin are associated with insulin resistance and the components of the metabolic syndrome. We assayed circulating levels of these molecules and examined their association with clinical, biochemical, and histological phenotypes in patients with nonalcoholic fatty liver disease (NAFLD). Material and methods. Serum levels of omentin, chemerin, and adipsin were assayed by enzyme-linked immunosorbent assay in 99 patients with biopsy-proven NAFLD and 75 control subjects. We analyzed associations between adipokines and the characteristics of patients with NAFLD using multivariable linear regression models. Results. Adipsin levels did not differ between patients and controls, whereas both omentin and chemerin levels were significantly higher in patients with biopsy-proven NAFLD than in controls (both p values <0.001). Serum omentin levels were significantly associated with C-reactive protein (r = 0.29, p < 0.01) and the degree of hepatocyte ballooning (r = 0.27, p < 0.01), whereas chemerin showed a modest association with liver fibrosis (r = 0.22, p = 0.04). After stepwise linear regression analysis adjusting for potential confounders, serum omentin levels retained their independent significance as a predictor of hepatocyte ballooning in patients with NAFLD (beta = 1.42; t = 2.79, p < 0.01). Conclusions. Our results suggest that serum omentin levels are raised in patients with NAFLD regardless of potential confounders and represent an independent predictor of hepatocyte ballooning.Publication Open Access The relationship between polyphenols and miRNAs: A novel therapeutic strategy for metabolic associated fatty liver disease(2021-05-01) EREN, FATİH; GÜNEŞ, FATMA ESRA; Bayram H. M., EREN F., Gunes F. E.Metabolic-associated fatty liver disease (MAFLD) is a public health problem that is increasingly recognized, currently affecting up to a quarter of the world\"s adult population. Although a biopsy is the current gold standard to diagnose MAFLD, there are potentially serious complications, making it inadequate. Thus far, noninvasive methods have not been able to determine the stage and the subtype of MAFLD. The development and prognosis of MAFLD are modulated by epigenetic factors, including microRNAs (miRNAs), which may be potential biomarkers for MAFLD. Polyphenols, found in many fruits and vegetables, may be useful, as they alter gene expression with epigenetic factors, such as miRNAs. This review presents an overview of the relationship between polyphenols and miRNAs in MAFLD. The literature suggests that miRNAs could be used as a diagnostic method for MAFLD, especially miRNA-122 and miRNA-34a. However, though it has been demonstrated that polyphenols may contribute to improving MAFLD, to our knowledge, no study to date has shown the relationship between polyphenols and miRNAs in MAFLD. The exact mechanisms of polyphenols on miRNAs in MAFLD remain unclear. Future studies may provide hope for diet therapy for MAFLD patients as well as the development of polyphenol-related foods or drugs that target miRNAs to treat MAFLD.Publication Open Access Serum levels of soluble receptor for advanced glycation endproducts (sRAGE) are higher in ulcerative colitis and correlate with disease activity(ELSEVIER SCIENCE BV, 2011-10) EREN, FATİH; Yilmaz, Y.; Yonal, O.; Eren, F.; Atug, O.; Hamzaoglu, H. OverInteraction of the receptor for advanced glycation endproducts (RAGE) with its ligands results in expression of inflammatory mediators, activation of NF-kappa B, and induction of oxidative stress, all of which have been implicated in the pathogenesis of inflammatory bowel diseases (IBD). Soluble receptor for advanced glycation endproducts (sRAGE) has recently emerged as a reliable biomarker of inflammation in numerous RAGE-mediated disorders. Objective: To assess sRAGE levels in adult patients with IBD. Method: Serum was collected from adult patients with Crohn's disease (CD, 56 patients), ulcerative colitis (UC, 60 patients), and healthy controls (HC, 113 subjects). Levels of sRAGE were determined by enzyme-linked immunosorbent assay. Results: Serum sRAGE levels were elevated in IBD compared to HC and were higher in UC patients compared to CD and HC. Levels of sRAGE were significantly higher in the serum of UC patients with active disease compared to patients with inactive disease, but no association with the Montreal Classification was evident. Serum sRAGE was lower in CD patients with biological therapies. Conclusions: These findings suggest that serum levels of sRAGE are altered in patients with intestinal inflammation and may reflect distinct immunoinflammatory pathogenesis of UC and (C). 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.Publication Metadata only The enhancement of gene silencing efficiency with chitosan-coated liposome formulations of siRNAs targeting HIF-1 alpha and VEGF(ELSEVIER SCIENCE BV, 2015) EREN, FATİH; Salva, Emine; Turan, Suna Ozbas; Eren, Fatih; Akbuga, JulideRNA interference (RNAi) holds considerable promise as a novel therapeutic strategy in the silencing of disease-causing genes. The development of effective delivery systems is important for the use of small interfering RNA (siRNA) as therapy. In the present study, we investigated the effect on breast cancer cell lines and the co-delivery of liposomes containing siHIF1-alpha and siVEGF. In order to achieve the co-delivery of siHIF1-alpha and siVEGF and to obtain lower cytotoxicity, higher transfection and silencing efficiency, in this study, we used chitosan-coated liposomal formulation as the siRNA delivery system. The obtained particle size and zeta potential values show that the chitosan coating process is an effective parameter for particle size and the zeta potential of liposomes. The liposome formulations loaded with siHIF1-alpha and siVEGF showed good stability and protected siRNA from serum degradation after 24-h of incubation. The expression level of VEGF mRNA was markedly suppressed in MCF-7 and MDA-MB435 cells transfected with chitosan-coated liposomes containing siHIF1-alpha and VEGF siRNA, respectively (95% and 94%). In vitro co-delivery of siVEGF and siHIF1-alpha using chitosan-coated liposome significantly inhibited VEGF (89%) and the HIF1-alpha (62%) protein expression when compared to other liposome formulations in the MDA-MB435 cell. The co-delivery of siVEGF and siHIF1-alpha was greatly enhanced in the vitro gene silencing efficiency. In addition, chitosan-coated liposomes showed 96% cell viability. Considering the role of VEGF and HIF1-alpha in breast cancer, siRNA-based therapies with chitosan coated liposomes may have some promises in cancer therapy. (C) 2014 Elsevier B.V. All rights reserved.