Person: ÖZER, SIDIKA AYŞE
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ÖZER
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SIDIKA AYŞE
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Publication Open Access Identification of Differentially Expressed IGFBP5-Related Genes in Breast Cancer Tumor Tissues Using cDNA Microarray Experiments(MDPI AG, 2015-11-10) GÜLLÜ AMURAN, GÖKÇE; Akkiprik, Mustafa; Peker, Irem; Ozmen, Tolga; Amuran, Gokce Gullu; Gulluoglu, Bahadir M.; Kaya, Handan; Ozer, AyseIGFBP5 is an important regulatory protein in breast cancer progression. We tried to identify differentially expressed genes (DEGs) between breast tumor tissues with IGFBP5 overexpression and their adjacent normal tissues. In this study, thirty-eight breast cancer and adjacent normal breast tissue samples were used to determine IGFBP5 expression by qPCR. cDNA microarrays were applied to the highest IGFBP5 overexpressed tumor samples compared to their adjacent normal breast tissue. Microarray analysis revealed that a total of 186 genes were differentially expressed in breast cancer compared with normal breast tissues. Of the 186 genes, 169 genes were downregulated and 17 genes were upregulated in the tumor samples. KEGG pathway analyses showed that protein digestion and absorption, focal adhesion, salivary secretion, drug metabolism-cytochrome P450, and phenylalanine metabolism pathways are involved. Among these DEGs, the prominent top two genes (MMP11 and COL1A1) which potentially correlated with IGFBP5 were selected for validation using real time RT-qPCR. Only COL1A1 expression showed a consistent upregulation with IGFBP5 expression and COL1A1 and MMP11 were significantly positively correlated. We concluded that the discovery of coordinately expressed genes related with IGFBP5 might contribute to understanding of the molecular mechanism of the function of IGFBP5 in breast cancer. Further functional studies on DEGs and association with IGFBP5 may identify novel biomarkers for clinical applications in breast cancer.Publication Metadata only Impact of glucocorticoid receptor gene (NR3C1) polymorphisms in Turkish patients with metabolic syndrome(SPRINGER, 2016) AKKİPRİK, MUSTAFA; Kaya, Z.; Caglayan, S.; Akkiprik, M.; Aral, C.; Ozisik, G.; Ozata, M.; Ozer, A.Background The metabolic syndrome (MetS) is characterized by a cluster of metabolic factors, including insulin resistance and type-2 diabetes, abdominal obesity, dyslipidemia, hypertension and microalbuminuria. Impaired glucocorticoid receptor (GR) activity also plays an important role in the etiology of MetS. The objective of our study is to evaluate the effects of GR gene polymorphisms (BclI, N363S, TthIII1 and ER22/23EK) in Turkish patients with MetS. Materials and methods Seventy subjects with MetS and 185 healthy controls were enrolled in the study. PCR-RFLP analysis was used for genotyping. Results for each polymorphism have been verified by allele-specific oligonucleotide analysis. Results BclI GG genotype was significantly associated with an increased risk of MetS (p = 0.02). Also, only in women, the G allele carriers were significantly associated with higher C-peptide. T allele carriers of TthIII1 polymorphism were significantly associated with higher C-peptide, triglyceride, insulin and C-reactive protein (CRP, p value 0.048, 0.022, 0.005 and 0.022, respectively), and lower fasting blood glucose (FBG, p = 0.02). The combined carriers of BclI polymorphism G allele and TthIII1 polymorphism T allele were significantly associated with higher diastolic blood pressure in all patients, and lower FBG and postprandial blood glucose in only men. All the ER22/23EK polymorphisms coexisted with polymorphic variant of TthIII1 (p = 0.0058). Conclusion The presence of homozygote polymorphic variant of BclI might be good predictive markers for the disease susceptibility. The BclI and the TthIII1 polymorphism are associated with sex-specific clinical parameters. Our findings also suggest that the combination of BclI and TthIII1 polymorphisms may play a protective role in blood glucose.Publication Metadata only Mutation distributions and clinical correlations of PIK3CA gene mutations in breast cancer(SAGE PUBLICATIONS LTD, 2016) AKKİPRİK, MUSTAFA; Dirican, Ebubekir; Akkiprik, Mustafa; Ozer, AyseBreast cancer (BCa) is the most common cancer and the second cause of death among women. Phosphoinositide 3-kinase (PI3K) signaling pathway has a crucial role in the cellular processes such as cell survival, growth, division, and motility. Moreover, oncogenic mutations in the PI3K pathway generally involve the activation phosphatidylinositol-4,5-bisphosphate 3-kinase-catalytic subunit alpha (PIK3CA) mutation which has been identified in numerous BCa subtypes. In this review, correlations between PIK3CA mutations and their clinicopathological parameters on BCa will be described. It is reported that PIK3CA mutations which have been localized mostly on exon 9 and 20 hot spots are detected 25-40 % in BCa. This relatively high frequency can offer an advantage for choosing the best treatment options for BCa. PIK3CA mutations may be used as biomarkers and have been major focus of drug development in cancer with the first clinical trials of PI3K pathway inhibitors currently in progress. Screening of PIK3CA gene mutations might be useful genetic tests for targeted therapeutics or diagnosis. Increasing data about PIK3CA mutations and its clinical correlations with BCa will help to introduce new clinical applications in the near future.Publication Open Access Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women(WILEY, 2017-09) GÜLLÜ AMURAN, GÖKÇE; Kaya, Zehra; Akkiprik, Mustafa; Karabulut, Sevgi; Peker, Irem; Amuran, Gokce Gullu; Ozmen, Tolga; Gulluoglu, Bahadir M.; Kaya, Handan; Ozer, AyseBackgroundBoth insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. MethodsTelomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. ResultsTelomeres were shorter in tumor tissues compared to controls (P<.0001). The mean TL was higher in breast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. ConclusionThese results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association.Publication Open Access Molecular screening and the clinical impacts of BCR-ABL KD mutations in patients with imatinib-resistant chronic myeloid leukemia(SPANDIDOS PUBL LTD, 2017-12-13) TUĞLULAR, AYŞE TÜLİN; Kockan, Betul; Toptas, Tayfur; Atagunduz, Isik; Tuglular, Ayse Tulin; Ozer, Ayse; Akkiprik, MustafaThe present study aimed to detect the frequency of kinase domain (KD) mutations in order to evaluate their clinical significance and functional importance in 45 patients with chronic myeloid leukemia (CML) who were resistant to imatinib therapy. Sanger sequencing was used (45 patients), along with allele-specific oligonucleotide polymerase chain reaction (ASO-PCR; 3 patients), for the screening of mutations. BCR/ABL KD was amplified by nested PCR and sequencing was performed. Secondly, ASO-PCR was performed to confirm the results of the sequence analysis for E255K mutations. Mutations were detected in 11/45 patients (24.44%) via Sanger sequencing. D241G (4.4%), C369C (4.4%), K285N (2.2%), A380T (2.2%) and A366V (2.2%) mutations were detected. E255K (8.8%) was detected by ASO-PCR and Sanger sequencing. Mutations are a primary reason for suboptimal responses, loss of response and resistance to imatinib. In particular, the E255K mutation, which is characterized by resistance to imatinib and nilotinib, was detected in four patients. Analyzing the mutations and monitoring patients with CML may improve their prognosis and survival rate. ASO-PCR assays will be beneficial for the routine monitoring of mutations.Publication Metadata only Association of ACP1 genotypes and clinical parameters in patients with metabolic syndrome(TUBITAK SCIENTIFIC & TECHNICAL RESEARCH COUNCIL TURKEY, 2011) AKKİPRİK, MUSTAFA; Akkiprik, Mustafa; Sertoglu, Filiz Ozdemir; Caglayan, Sinan; Aral, Cenk; Ozisik, Gokhan; Atabey, Zebra; Ozata, Metin; Ozer, Sidika AyseAim: Acid phosphatase locus 1 (ACP1) encodes a polymorphic enzyme and has potential implications for the development of metabolic syndrome (MS) by altering insulin sensitivity. The aim of this study was to determine whether a relationship exists between ACP1 genotypes and various metabolic syndrome risk factors. Materials and methods: We employed a PCR-RFLP based genotyping of ACP1 in a cohort of 70 patients with MS and 168 healthy individuals. Results: When compared to controls, genotypes associated with low enzyme activity were observed at significantly lower frequencies in both sexes. Of note, high enzyme activity genotypes were more common in patients with MS when compared with medium and low enzyme activity genotypes. *A allele frequency was not different between patients and controls even considering sex; however, there was a good correlation of the presence of the allele with body composition, serum cortisol levels and suppressibility of cortisol, particularly in women with MS. Conclusion: Our findings suggest that low enzyme activity genotypes seem to be associated with a protective effect for the development of MS. Additionally, *A allele carriage affects body composition in women but not in men, and the presence of this allele might modulate serum cortisol levels as well as its suppressibility in both sexes, in an inverse manner.Publication Metadata only R72P Polymorphism of TP53 in Ulcerative Colitis Patients is Associated with the Incidence of Colectomy, Use of Steroids and the Presence of a Positive Family History(SPRINGER, 2010) ÇELİKEL, ÇİĞDEM; Eren, Fatih; Akkiprik, Mustafa; Atug, Ozlen; Sonmez, Ozgur; Tahan, Gulgun; Ozdemir, Filiz; Hamzaoglu, Hulya Over; Celikel, Cigdem Ataizi; Imeryuz, Nese; Avsar, Erol; Ozer, AyseP53 tumor suppressor protein is one of the pivotal regulators for genome integrity, cell cycle and apoptosis. The most commonly and extensively studied single nucleotide polymorphism (SNP) of p53 is Arg>Pro substitution on codon 72 (R72P). Although we know that the SNP has unique functional effects on the protein, its clinical significance is not clearly identified yet. Aim of the study was to access the relationship between R72P genotype distribution and clinical variables in patients with ulcerative colitis (UC) and colorectal cancer (CRC). Genomic DNA samples were extracted from 95 UC, 50 CRC, and 219 healthy controls. R72P genotype analysis was carried out with polymerase chain reaction following by restriction enzyme digestion. We observed that Pro allele carriage is a strong risk factor for CRC (OR=3.03; 95%CI=1.91-2.40; p=0.003), but only modest association with UC (OR=1.61; 95%CI=0.98-2.65; p =0.059) (Pro/Pro and Pro/Arg genotypes vs. Arg/Arg genotype). We did not find any correlation between genotype distribution of the polymorphism and clinical parameters of CRC, but in UC, Pro/Pro genotype was significantly related to an inflammatory bowel disease family history (OR=8.0; 95%CI=1.68-38.08, p=0.015), and Arg/Pro genotype was significantly associated with the history of disease-related colectomy (OR=17.77; 95%CI=0.98-323.34, p=0.012) and steroid use (OR=10.14; 95%CI=2.63-39.12, p=0.0002). Our data suggest that R72P variant seems to be associated with high risk for development of CRC but carries low risk for development of UC. R72P genotypes might be a useful predictive marker for surgical and medical treatment of UC.Publication Metadata only Treatment with either obestatin or ghrelin attenuates mesenteric ischemia-reperfusion-induced oxidative injury of the ileum and the remote organ lung(ELSEVIER SCIENCE INC, 2015) YEGEN, BERRAK; Sen, Leyla Semiha; Karakoyun, Berna; Yegen, Cumhur; Akkiprik, Mustafa; Yuksel, Meral; Ercan, Feriha; Ozer, Ayse; Yegen, Berrak C.To evaluate the effects of exogenous ghrelin or obestatin on intestinal injury and accompanying pulmonary injury, intestinal ischemia-reperfusion (I/R) was induced in rats by obstructing the superior mesenteric artery for 60 min, whereas laparotomy was performed in the sham group. At the beginning of the 90-min reperfusion period, the rats were injected with obestatin (100 mu g/kg), ghrelin (10 ng/kg), or saline intravenously (iv). At the end of reperfusion, the blood, ileum, and lung samples were taken for the histological and biochemical assays. In the saline-treated I/R group, the increased serum interleukin (IL)-1 beta level, high damage scores, and elevated tissue malondialdehyde level and collagen content in both tissues were significantly reduced by obestatin or ghrelin. Increased ileal myeloperoxidase activity of the saline-treated I/R group was reduced by treatment with obestatin or ghrelin, whereas increased pulmonary myeloperoxidase activity was reduced with administration of obestatin. Increased DNA fragmentation in the ileum of the saline-treated I/R group was reduced by both peptides. Elevated luminol-lucigenin chemiluminescence levels and nuclear factor kappa B (NF-kappa B) messenger RNA ( mRNA) expression in the ileum of the saline-treated-I/R group were significantly decreased by obestatin or ghrelin treatment. I/R-induced depletion of the antioxidant glutathione in both ileal and pulmonary tissues was prevented with either obestatin or ghrelin treatment. Administration of either obestatin or ghrelin exerts similar protective effects against I/R-induced ileal and pulmonary injury, thus warranting further investigation for their possible use against ischemic intestinal injury. (C) 2015 Elsevier Inc. All rights reserved.Publication Metadata only Targeted custom gene panel sequencing for cardiac ion channelopathies: Efficiently detects candidate pathogenic mutations in Long QT syndrome(ELSEVIER SCIENCE BV, 2017) ÖZER, SIDIKA AYŞE; Temel, S. G.; Turkgenc, B.; Karadag, O.; Aykan, H. H.; Uysal, F.; Bastuhan, I. Y.; Sulu, A.; Atik, S. U.; Cinar, B.; Dedeoglu, R.; Gunay, E.; Ramoglu, M.; Cilsal, E.; Sahin, M.; Mese, T.; Ciftci, O.; Oztunc, F.; Karagoz, T.; Baspinar, O.; Bostan, O. M.; Akalin, F.; Kervanoglu, M.; Ayabakan, C.; Cil, E.; Alanay, Y.; Celiker, A.; Ozer, S. A.; Yakicier, M. C.