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 Metadata only Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease(WILEY-BLACKWELL, 2010) ÇELİKEL, ÇİĞDEM; Yilmaz, Yusuf; Eren, Fatih; Yonal, Oya; Kurt, Ramazan; Aktas, Bilge; Celikel, Cigdem Ataizi; Ozdogan, Osman; Imeryuz, Nese; Kalayci, Cem; Avsar, ErolP>Background The fibroblast growth factor 21 (FGF21) hormonal pathway is a metabolic signalling cascade and has been recently identified as the master hormonal regulator of glucose, lipids and overall energy balance. In this observational, case-control study, we assayed serum levels of FGF21 in patients with nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, and examined their association with clinical, biochemical and histological phenotypes. Materials and methods Serum levels of FGF21 were assayed by ELISA in 82 patients with biopsy-proven NAFLD and 77 controls. We analysed associations between FGF21 and the characteristics of patients with NAFLD by multiple linear regression analysis. Results Levels of FGF21 were significantly higher in patients with NAFLD (median 200 pg mL-1; interquartile range: 87-410 pg mL-1) than in healthy controls (median 93 pg mL-1; interquartile range: 70-180 pg mL-1, Mann-Whitney U-test, P < 0 center dot 001). There was a stepwise increase in serum FGF21 levels according to the liver steatosis score (median level in subjects with score 1: 170 pg mL-1; score 2: 220 pg mL-1; score 3: 280 pg mL-1, P for trend < 0 center dot 01). After stepwise linear regression analysis, serum FGF21 levels were the only independent predictor of hepatic steatosis scores in patients with NAFLD (beta = 0 center dot 26; t = 2 center dot 659, P < 0 center dot 01). Conclusions Serum FGF21 levels are increased in patients with NAFLD regardless of potential confounders and represent an independent predictor of liver steatosis. These findings support further investigation of this molecule in metabolic liver diseases.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 The prevalence of the mutation in codon 249 of the P53 Gene in Patients with Hepatocellular Carcinoma (HCC) in Turkey(Humana Press Inc., 2010) EREN, FATİH; Özdemir F.T., Tiftikci A., Sancak S., Eren F., Tahan V., Akın H., Gündüz F., Kedrah A.E., Üstündağ Y., Avşar E., Tözün N., Özdoğan O.Hepatocellular carcinoma (HCC) is one of the most common cancers in the worldwide. Aflotoxins, products of Aspergillus Flavus found in the high humidity environments induce HCC in humans by causing mutations in oncogenes such as codon 249 mutation of p53 in hepatocytes. In turkey, aflatoxins are found to be increased in some foods in certain areas, such as Istanbul which have high humidity. In present study we aimed to look for the prevalence of codon 249 mutation of p53 in patients with HCC, cirrhosis and chronic hepatitis B (CHB). Methods DNA was extracted from plasma and mutation was detected by PCR-RFLP method. Results the codon 249 mutation of p53 is found one out of 50 HCC (2%) patients. In conclusion, although codon 249 mutation of p53 gene has been found very rare but it exists showing the effect of aflatoxins in HCC patients in Turkey. © Springer Science+Business Media, LLC 2010.Publication Metadata only A comparison of FibroMeter (TM) NAFLD Score, NAFLD fibrosis score, and transient elastography as noninvasive diagnostic tools for hepatic fibrosis in patients with biopsy-proven non-alcoholic fatty liver disease(INFORMA HEALTHCARE, 2014) ÇELİKEL, ÇİĞDEM; Aykut, Umut Emre; Akyuz, Umit; Yesil, Atakan; Eren, Fatih; Gerin, Fatma; Ergelen, Rabia; Celikel, Cigdem Ataizi; Yilmaz, YusufBackground: Noninvasive markers that purport to distinguish patients with non-alcoholic fatty liver disease (NAFLD) with fibrosis from those without must be evaluated rigorously for their classification accuracy. Herein, we seek to compare the diagnostic performances of three different noninvasive methods (FibroMeter (TM) NAFLD score, NAFLD Fibrosis score (NFSA), and Transient Elastrography [TE]) for the detection of liver fibrosis in NAFLD patients. Methods: A total of 88 patients with biopsy-proven NAFLD were included. The Kleiner system was used for grading fibrosis in liver biopsies. The FibroMeter (TM) NAFLD score was determined using a proprietary algorithm (regression score). The NFSA score was calculated based on age, hyperglycemia, body mass index, platelets, albumin and serum aminotransferase levels. TE was performed using the Fibroscan apparatus. Results: The sensitivities/specificities for the FibroMeter (TM) NAFLD score, NFSA, and TE for the diagnosis of significant fibrosis (F2 + F3 + F4 fibrosis) were 38.6%/86.4%, 52.3%/88.6%, and 75.0%/93.2%, respectively. The areas under the receiver operating characteristic curves of TE were significantly higher than those of both the FibroMeter (TM) NAFLD score and NFSA. No significant differences were found between the FibroMeter (TM) NAFLD score and NFSA for the detection of significant and severe fibrosis, although the diagnostic performance of the FibroMeter (TM) NAFLD score was higher than that of the NFSA score for cirrhosis. Conclusions: In summary, TE showed the best diagnostic performance for the noninvasive assessment of liver fibrosis in NAFLD patients. The diagnostic performances of the FibroMeter (TM) NAFLD score and NFSA did not differ significantly for the detection of both significant and severe fibrosis.Publication Metadata only Preliminary evidence of an association between the functional c-kit rs6554199 polymorphism and achalasia in a Turkish population(WILEY, 2012) EREN, FATİH; Alahdab, Y. O.; Eren, F.; Giral, A.; Gunduz, F.; Kedrah, A. E.; Atug, O.; Yilmaz, Y.; Kalayci, O.; Kalayci, C.Background C-kit-positive interstitial cells of Cajal (ICC) of the lower esophageal sphincter are reduced in achalasia. Two functional gene polymorphisms (rs2237025 and rs6554199) within the c-kit gene may affect its transcriptional activity. In this pilot study, we hypothesized that these polymorphisms would be associated with achalasia. Methods Genomic DNA was extracted and real-time PCR reactions were used to determine the rs2237025 and rs6554199 c-kit polymorphisms in 88 Turkish patients with achalasia and 101 healthy controls. Key Results The frequency of the T allele of rs6554199 was significantly higher in patients with achalasia [odds ratio (OR): 1.55; 95% confidence interval (CI), 1.03-2.34; P = 0.038] compared with the G allele. Under a dominant model of inheritance, the carriage of at least one T allele was significantly more frequent in patients with achalasia (80.7%) than in controls (65.3%; OR: 2.21; 95% CI, 1.13-4.33; P = 0.022). No association of the c-kit rs2237025 polymorphism with achalasia was detected. Conclusions & Inferences Despite the small sample size and the possibility of a false positive finding, our preliminary data support the hypothesis that the T allele of the c-kit rs6554199 polymorphism may be associated with achalasia in the Turkish population. These findings need to be replicated in other racial-ethnically diverse populations.Publication Metadata only Nonalcoholic steatohepatitis and gut microbiota: Future perspectives on probiotics in metabolic liver diseases(AVES, 2017) EREN, FATİH; Yilmaz, Yusuf; Eren, FatihPublication Metadata only A Systems Genetics Approach to Dyslipidemia in Children and Adolescents(MARY ANN LIEBERT, INC, 2015) EREN, FATİH; White, Marquitta J.; Eren, Fatih; Agirbasli, Deniz; Chen, Jane; Hu, Ting; Moore, Jason H.; Williams, Scott M.; Agirbasli, MehmetElevated triglycerides (TG) or low high density lipoprotein cholesterol (HDL-C) levels are common cardiometabolic risk factors in children. From a systems genetics standpoint, Visualization of Statistical Epistasis Networks (ViSEN) is a nonparametric entropy-based method that can characterize the global structure of interacting genetic factors. We identified a novel set of connected genetic and cardiometabolic risk factors with strong and significant interaction effects on two important dyslipidemia phenotypes (low HDL-C and high TG) in children and adolescents. Study participants were recruited from five schools in Istanbul, Turkey (n=360; 170 boys, 190 girls). Participants with TG levels >= 75th and HDL-C levels <= 25th percentile were defined as 'high TG' and 'low HDL-C', respectively. We genotyped participants for six single nucleotide polymorphisms (SNPs) in five genes with known associations to lipid levels (rs328 in LPL, rs708272 in CETP, rs1800588 in LIPC, rs1800977 in ABCA1, rs1799941 and rs6257 in SHBG gene). ViSEN was used to identify associations with dyslipidemia phenotypes. There were 71 (50 males, 21 females) and 93 (60 males and 33 females) subjects with low HDL-C and high TG, respectively. Biological variables including age, gender, and BMI were significantly associated with both phenotypes (p<0.001). Importantly, a single SNP, rs708272, was associated with low HDL-C (IG=2.24%, p=0.026). Pairwise and higher order interaction analyses in the full dataset for low HDL-C and high TG revealed the largest effects in the models containing rs1800977, rs708272, age (IG=6.20%, p=0.046) and rs1800588, age, BMI (IG, 3.06%, p=0.022), respectively. In conclusion, the present study brings us a step closer to a systems genetic approach in understanding lipid phenotypes in children. Further efforts can integrate population and laboratory-based studies, hence accelerate the preventive medicine efforts.Publication Metadata only Development of multiplex single base primer extension assay for the detection of potential association between MTNR1B gene polymorphisms and NASH(ELSEVIER SCIENCE BV, 2018) EREN, FATİH; Yilmaz, Demet; Eren, Fatih; Gocmen, Tuba; Yilmaz, YusufPublication 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.