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Öğe A potential association between the number of CA repeats in the promoter region of the ADAMTS9 gene with lymphatic metastasis of breast cancer(Tubitak Scientific & Technological Research Council Turkey, 2013) Bozer, Mikdat; Asik, Fatma; Acar, Muradiye; Haltas, Hacer; Yenidunya, Sibel; Canbal, Metin; Topcu, VehapAim: We investigated the effect of the number of cytosine-adenine (CA) repeats in the ADAMTS9 promoter region on breast cancer lymphatic metastasis. Materials and methods: Thirty-one postoperative breast cancer patients were selected and examined retrospectively. The patients were classified into 2 groups: metastatic or nonmetastatic. Thirty healthy women were selected as the control group, and their peripheral blood was obtained. Following DNA isolation from the cancer tissue specimens and peripheral blood, the promoter region of the ADAMTS9 gene was directly sequenced and the number of CA repeats was determined. Results: The number of CA repeats ranged between 19 and 21 in the control and metastatic groups. However, in the nonmetastatic group, the number of CA repeats ranged between 17 and 18. This difference in the median number of CA repeats between the control group and the nonmetastatic group was statistically significant. Conclusion: A potential relationship may exist between lymphatic metastasis in breast cancer and the number of CA repeats in the promoter region of the ADAMTS9 gene. Our study indicates a potential association between the number of CA microsatellite repeats in the promoter region of the ADAMTS9 gene and breast cancer lymphatic metastasis.Öğe Association of 5-HT1A and 5-HT1B Gene Polymorphisms with Obsessive-Compulsive Disorder in a Turkish Population(Kure Iletisim Grubu A S, 2016) Aldemir, Secil; Acar, Muradiye; Ocak, Zeynep; Dalbudak, Ercan; Yigitoglu, Muhammet Ramazan; Gunduz, EsraObjective: Obsessive-compulsive disorder (OCD) is a frequent neuropsychiatric disorder, in which genetic factors play important causative roles. We investigated the roles of the (-1019 C/G) promoter region polymorphism of 5-HTR1A and the G861C coding region polymorphism of 5-HTR1B genes in susceptibility to OCD in a Turkish population. Methods: Two single nucleotide polymorphisms, 5-HTR1A (rs6296) and 5-HTR1B (rs6295) genes were genotyped in 76 OCD patients and 57 healthy controls that were unrelated, using PCR-RFLP method. Results: We did not observe any difference in the genotype distributions of rs6296 and rs6295 between the OCD patient and control groups. Conclusions: As far as we know, our study is the first to establish the association of genetic variants 5-HTR1A (rs6296) and 5-HTR1B (rs6295) with OCD in a Turkish population. Based on our results, the relationship between polymorphisms of 5-HTR1A (rs6296) and 5-HTR1B (rs6295) with OCD do not seem.Öğe Functional analysis of ESM1 by siRNA knockdown in primary and metastatic head and neck cancer cells(Wiley, 2018) Bender, Onur; Gunduz, Mehmet; Cigdem, Sadik; Hatipoglu, Omer Faruk; Acar, Muradiye; Kaya, Mesut; Grenman, ReidarBackgroundGenetic factors play a large role in cancer, and thus, there is a great desire to understand the effects of different genes in cancer and to also develop gene therapy for better treatments. Therefore, the development of alternative diagnosis and therapy modalities is of utmost importance. The aim of our study was to illuminate the role of ESM1 (endothelial cell-specific molecule-1, also known as Endocan) in proliferation and migration of head and neck cancer, thus helping to pave the way for new treatment modalities and predictive biomarkers. MethodsESM1 expression was shown with immunofluorescence assay using confocal laser scanning microscope in primary and metastatic head and neck cancer cells. ESM1 expression was knocked down by RNA interference in head and neck cancer cells. Knockdown efficiency was evaluated by quantitative real-time RT-PCR and Western blot. Cell proliferation and migration assays were performed by xCELLigence real-time cell analysis system. ResultsImmunofluorescence assay showed nuclear localization and high expression of ESM1 in primary and metastatic head and neck cancer cells. ESM1 mRNA and protein levels were significantly decreased in ESM1-knockdown cells compared to control. ESM1-knockdown cells showed reduced proliferation and migration activity when compared to control cells. ConclusionThese findings suggest that ESM1 has roles on proliferation and migration of head and neck cancer cells.Öğe Investigation of the effects of 5-fluorouracil and thymoquinone on head and neck cancer stem cells(Canadian Soc Clinical Investigation, 2015) Acar, Muradiye; Gunduz, Mehmet; Ocak, Tarik; Gurses, Hacer Esra; Cetin, Elif Nihan; Ceylan, Furkan Sacit; Sefa, AlperenPurpose: A subpopulation of cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC) play a critical role in invasion, metastasis, and tumour recurrence post-therapy. 5-Fluorouracil (5-FU) is a pyrimidine analogue that is used in the treatment of HNSCC. Thymoquinone (TQ), found in Cumin (Nigella sativa) seed oil, has anti-diabetic, anti-oxidant, anti-inflammatory, and antitumour effects. The purpose of this study was to examine the effects of 5-FU and TQ on CSCs. Methods: ALDH1 (+) cells were isolated from the HNSCC cell line UT-SCC-74A using magnetic activated cell sorting (MACS) and sphere formation was confirmed. Real-time RTPCR revealed was used to measure expression levels of a number of stem cell markers, including OCT4, SOX2, and KLF-4. To investigate the effects of the therapeutic agents, 5-FU and TQ, concentration-dependent assay procedures were used and cell viability after treatment was measured using XTT assay. Results: ALDH1 (+) cells formed spheres while the ALDH1 (-) cells did not. Real-time RT-PCR revealed that a number of stem cell markers, including OCT4, SOX2, and KLF-4, were up-regulated in the CSCs. XTT results showed that, when given alone at a dose of 50 ng/mL, neither agent had a statistically significant cytotoxic effect on CSCs. However, when dosed in combination, TQ and 5-FU had a synergistic effect on CSC cytotoxicity. Conclusion: We report the effects of TQ and 5-FU on CSCs in HNSCC.Öğe Investigation of the expression of RIF1 gene on head and neck, pancreatic and brain cancer and cancer stem cells(Canadian Soc Clinical Investigation, 2016) Cila, Hacer E. Gurses; Acar, Muradiye; Barut, Furkan B.; Gunduz, Mehmet; Grenman, Reidar; Gunduz, EsraPurpose: Recent studies have shown that cancer stem cells are resistant to chemotherapy. The aim of this study was to compare RIF1 gene expression in head and neck, pancreatic cancer and glioma cell lines and the cancer stem cells isolated from these cell lines. Methods: UT-SCC-74 from Turku University and UT-SCC-74B primary tumor metastasis and neck cancer cell lines, YKG-1 glioma cancer cell line from RIKEN, pancreatic cancer cell lines and ASPC-1 cells from ATCC were grown in cell culture. To isolate cancer stem cells, ALDH-1 for UT-SCC-74 and UT-SCC-74B cell line, CD-133 for YKG-1 cell line and CD-24 for ASPC-1 cell line, were used as markers of cancer stem cells. RNA isolation was performed for both cancer lines and cancer stem cells. RNAs were converted to cDNA. RIF1 gene expression was performed by qRT-PCR analysis. RIF1 gene expression was compared with cancer cell lines and cancer stem cells isolated from these cell lines. The possible effect of RIF1 gene was evaluated. Results: In the pancreatic cells, RIF1 gene expression in the stem cell-positive cell line was 256 time that seen in the stem cell-negative cell line. Conclusion: Considering the importance of RIF1 in NHEJ and of NHEJ in pancreatic cancer, RIF1 may be one of the genes that plays an important role in the diagnoses and therapeutic treatment of pancreatic cancer. The results of head and neck and brain cancers are inconclusive and further studies are required to elucidate the connection between RIF1 gene and these other types of cancers.Öğe Investigation Of The Expression Of Rif1 Gene On Head And Neck, Pancreatic And Brain Cancer And Cancer Stem Cells(The Canadian Society for Clinical Investigation, 2016) Cila, Hacer E.Gurses; Acar, Muradiye; Barut, Furkan B.; Gündüz, Mehmet; Grènman, Reidar A.; Gündüz, EsraAbstract Purpose: Recent studies have shown that cancer stem cells are resistant to chemotherapy. The aim of this study was to compare RIF1 gene expression in head and neck, pancreatic cancer and glioma cell lines and the cancer stem cells isolated from these cell lines. Methods: UT-SCC-74 from Turku University and UT-SCC-74B primary tumor metastasis and neck cancer cell lines, YKG-1 glioma cancer cell line from RIKEN, pancreatic cancer cell lines and ASPC-1 cells from ATCC were grown in cell culture. To isolate cancer stem cells, ALDH-1 for UT-SCC-74 and UT-SCC-74B cell line, CD-133 for YKG-1 cell line and CD-24 for ASPC-1 cell line, were used as markers of cancer stem cells. RNA isolation was performed for both cancer lines and cancer stem cells. RNAs were converted to cDNA. RIF1 gene expression was performed by qRT-PCR analysis. RIF1 gene expression was compared with cancer cell lines and cancer stem cells isolated from these cell lines. The possible effect of RIF1 gene was evaluated. Results: In the pancreatic cells, RIF1 gene expression in the stem cell-positive cell line was 256 time that seen in the stem cell-negative cell line. Conclusion: Considering the importance of RIF1 in NHEJ and of NHEJ in pancreatic cancer, RIF1 may be one of the genes that plays an important role in the diagnoses and therapeutic treatment of pancreatic cancer. The results of head and neck and brain cancers are inconclusive and further studies are required to elucidate the connection between RIF1 gene and these other types of cancers © 2022 Elsevier B.V., All rights reserved.Öğe Is There a Relationship Between Pelvic Organ Prolapse and Tissue Fibrillin-1 Levels?(Korean Continence Soc, 2015) Eser, Ayla; Unlubilgin, Eylem; Hizli, Fatih; Acar, Muradiye; Kamalak, Zeynep; Kosus, Aydin; Kosus, NerminPurpose: Pelvic organ prolapse is a multifactorial disorder in which extracellular matrix defects are implicated. Fibrillin-1 level is reduced in stress urinary incontinence. In Marfan syndrome, which is associated with mutations in Fibrillin-1, pelvic floor disorders are commonly observed. We hypothesize that Fibrillin-1 gene expression is altered in pelvic organ prolapse. Methods: Thirty women undergoing colporrhaphy or hysterectomy because of cystocele, rectocele, cystorectocele, or uterine prolapse were assigned to a pelvic prolapse study group, and thirty women undergone hysterectomy for nonpelvic prolapse conditions were assigned to a control group. Real-time polymerase chain reaction was conducted on vaginal tissue samples to measure the expression of Fibrillin-1. Expression levels were compared between study and control groups by Mann-Whitney U test with Bonferroni revision. Results: Fibrillin-1 gene expression was not significantly lower in the study group than in the control group. Similarly, no significant correlation between Fibrillin-1 levels and grade of pelvic prolapse was found. Age over 40 years (P = 0.018) and menopause (P = 0.027) were both associated with reduced Fibrillin-1 levels in the pelvic prolapse group, whereas the delivery of babies weighing over 3,500 g at birth was associated with increased Fibrillin-1 expression (P = 0.006). Conclusions: The results did not indicate a significant reduction in Fibrillin-1 gene expression in pelvic prolapse disorders; however, reduced Fibrillin-1 may contribute to increased pelvic organ prolapse risk with age and menopause. Increased Fibrillin-1 gene expression may be a compensatory mechanism in cases of delivery of babies with high birth weight. Further studies are needed for a better understanding of these observations.Öğe Loss of heterozygosity in ING3 and ING5 genes in breast cancer(Tubitak Scientific & Technological Research Council Turkey, 2014) Gunduz, Esra; Nas, Gokhan; Acar, Muradiye; Uctepe, Eyyup; Bozer, Mikdat; Oznur, Murat; Bayrak, ReyhanThe tumor suppressor genes (TSGs) ING3 and ING5, members of the inhibitor of growth gene family, are effective in inhibition of cell growth and induction of apoptosis. However, in many cancer types, one of the alleles of a TSG is lost through carcinogenesis, while the remaining allele is usually inactivated through a process called loss of heterozygosity (LOH). Previous studies in head and neck cancer revealed that allelic loss and reduced expression is a common pattern of ING gene family members. Fifty paraffin-embedded breast cancer tissues were analyzed by polymerase chain reaction and denatured-polyacrylamide gel electrophoresis for LOH status. The allelic deletion frequency of ING3 and ING5 were detected as 14% and 17% in breast cancer patients, respectively. No significant relationship was detected between ING3 LOH status and clinicopathological variables. Our data also suggest that both ING3 and ING5 LOH statuses have no significant effect in overall survival and disease-free survival of breast cancer patients. These results provide a rational explanation and relative contribution for the complexity of tumor formation, whereby allelic loss of ING3 and ING5 genes is not a major factor for breast cancer but is rather a part of a larger complex mechanism.Öğe Matrix Metalloproteinases 2 and 9 Polymorphism in Patients With Myeloproliferative Diseases A STROBE-Compliant Observational Study(Lippincott Williams & Wilkins, 2015) Maral, Senem; Acar, Muradiye; Balcik, Ozlem Sahin; Uctepe, Eyyup; Hatipoglu, Omer Faruk; Akdeniz, Derya; Altun, Hatice UludagChronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling. The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases. Patients were selected from outpatient clinks of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people. DNA was isolated from peripheral blood. Using polymerase chain reaction restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gin279Arg polymoiphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates. In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-librosis provides a better understanding of the pathophysiology of PV and ET diseases mid will allow new approaches to diagnosis and treatment.Öğe Oncogenes and tumor suppressor genes as a biomarker in breast cancer(Springer India, 2014) Üçtepe, Eyyüp; Acar, Muradiye; Gündüz, Esra; Gündüz, MehmetBreast cancer is the most common cause of cancer in women in the United States and the Western world. The important question is what can be done to limit the human suffering associated with cancer and to reduce the burden on society? One solution is early detection. Early diagnosis of breast cancer before symptoms emerge is the most effective prevention of breast cancer. Currently, mammography is the gold standard for breast cancer screening. The procedure is suggested and often reimbursed for women between the ages of 50 and 75. Yet it is presumed that between 15 and 25 % of women with early-stage breast cancers are presently missed by commonly used diagnostic procedures such as mammography. Since breast cancer is also diagnosed in an increasing number of younger women, the screening strategy should be modified. Hence, oncogenes and tumor suppressor genes could be used as biomarkers for early detection of breast cancer. Eventually, researchers aim to use the molecular data collected from an individual tumor for prognostication and personalized therapy for each patient. Genetic profiles of tumors are now providing information about clinical outcome, and some prognostic and predictive indicators have appeared based on this research. In the near future, prospective tissue collection for molecular analysis may become routine in order to classify patients for alternative treatment options and to optimize treatment strategies based on molecular structure of the cancer. © 2015 Elsevier B.V., All rights reserved.Öğe Pharmaco-epigenomics(Springer India, 2013) Gündüz, Mehmet; Acar, Muradiye; Erdogan, Kubra; Cetin, Elif Nihan; Gündüz, EsraEpigenetic modifications are defined as the study of heritable changes in phenotype that do not involve alterations in the DNA sequence. DNA methylation, posttranslational modifi cations of the histone proteins, and miRNAs are regulating the expression of genes as well as drug- metabolizing genes. Epigenetic regulation is essential for normal developmental and cellular processes. Conversely, abnormal epigenetic regulation is a character of complex diseases, including cancer, hematological malignancies, psychiatric disorders, and other diseases. Pharmaco-epigenomics is a novel discipline and involves the study of epigenetic factors in the interpersonal variation to drugs. Epigenetic biomarkers can be used to diagnose disease, estimate disease progression, or predict interpersonal variations in response to therapy. Unlike genetic alterations, changes in epigenetic machinery are reversible, and this reversible characteristic makes them an attractive therapeutic targets. © 2018 Elsevier B.V., All rights reserved.Öğe Potential genetic biomarkers in the early diagnosis of Alzheimer disease: APOE and BIN1(Tubitak Scientific & Technological Research Council Turkey, 2015) Kaya, Gulhan; Gunduz, Esra; Acar, Muradiye; Hatipoglu, Omer Faruk; Acar, Burcu; Ilhan, Atilla; Gunduz, MehmetBackground/aim: Alzheimer disease (AD) is triggered by interactions of multiple genetic and environmental factors. The APOE gene E4 allele is the best-known risk factor for AD, yet it represents a small ratio of genetic factors. According to genome-wide association studies, the BIN1 gene is the second important risk factor for AD, following the APOE gene. We aimed to identify a novel biomarker indicating susceptibility to AD by investigating APOE alleles and BIN1 gene polymorphisms in a Turkish population. Materials and methods: Fifty-three AD patients and 56 controls were included to examine polymorphism and allele frequency of the APOE and BIN1 genes. Genomic DNAs were isolated from whole blood by SDS/proteinase K treatment, phenol-chloroform extraction, and ethanol precipitation. RFLP was done for identification of polymorphisms in the APOE gene and allele-specific PCR was used for the BIN1 gene. Results: Frequency of the APOE E4 allele was higher in the AD patient group, while the frequency of the E2 allele was higher in controls. The E4/E4 genotype was detected in the AD patient group, while this genotype was not observed in the controls. The frequencies of BIN1 alleles were similar in both groups. Conclusion: There was a strong association between AD and the APOE E4 allele, while no such relation was observed with BIN1 gene polymorphism.Öğe Relationship between cytosine-adenine repeat polymorphism of ADAMTS9 gene and clinical and radiologic severity of knee osteoarthritis(Wiley, 2018) Gok, Kevser; Cemeroglu, Ozlem; Cakirbay, Hasim; Gunduz, Esra; Acar, Muradiye; Cetin, Elif Nihan; Gunduz, MehmetObjectiveThe aim of this study is to determine the role of cytosine-adenine (CA) micro-satellite repeat sequence of ADAMTS9 gene on the development and progression of osteoarthritis (OA). MethodsA total of 110 participants, including those with primary knee OA and healthy controls were enrolled in the study. Patients were stratified into two groups using the Kellgren-Lawrence staging (K-L staging) as group 1 for controls and mild OA and group 2 for moderate and severe OA. Genetic analyses were performed to determine the CA repeat length in ADAMTS9 gene. ResultsTwenty CA repeats were found to be statistically significant for differentiating groups 1 and 2 (P = 0.020). Age was the most significant risk factor involved, followed by 20 CA repeats and body mass index (P < 0.05). CA repeat length of 20 showed a 6.1-fold increase in probability for having OA at stage 3 or 4 compared to those of CA repeat length of < 20 (P = 0.004). In conclusion, the CA repeat length of 20 has a six-fold increase in probability for having severe OA. ConclusionADAMTS9 gene CA repeat polymorphism may be used to determine the prognosis for OA radiologic progression. Being the first in the literature reporting the CA repeat in the promotor region of ADAMTS9 gene in patients with OA, our study could be highlighted further in future research with larger sample size.Öğe Serum and aqueous xanthine oxidase levels, and mRNA expression in anterior lens epithelial cells in pseudoexfoliation(Springer, 2015) Simavli, Huseyin; Tosun, Mehmet; Bucak, Yasin Y.; Erdurmus, Mesut; Ocak, Zeynep; Onder, Halil I.; Acar, MuradiyeThe aim of this study was to determine serum and aqueous xanthine oxidase (XO) levels, and mRNA expression in anterior lens epithelial cells in pseudoexfoliation (PEX). In this prospective study, serum, aqueous and anterior lens capsules were taken from 21 patients with PEX and 23 normal subjects who had undergone routine cataract surgery. Serum and aqueous XO levels were analyzed using the colorimetric method. mRNA expression of XO in anterior lens epithelial cells was evaluated using reverse transcription polymerase chain reaction analysis. Serum XO levels (means +/- standard deviations) were 207.0 +/- 86.1 IU/mL and 240.6 +/- 114.1 IU/mL in the normal and PEX groups, respectively (p = 0.310). Aqueous XO levels (means +/- standard deviations) were 65.5 +/- 54.3 IU/mL in the normal group and 130.5 +/- 117.4 IU/mL in the PEX group (p = 0.028). There was a 2.9 fold decrease in mRNA expression in anterior lens epithelial cells of PEX, which is significantly lower than the normal group (p = 0.01). Higher aqueous XO levels lacking associated different serum XO suggests higher oxidative stress in the aqueous. Higher aqueous XO levels in PEX with decreased mRNA expression in anterior lens epithelial cells indicate possible overexpression of XO in other structures related to the aqueous.Öğe The effect of survivin gene promoter polymorphism on breast cancer(Tubitak Scientific & Technological Research Council Turkey, 2014) Altiparmak, Mehmet Deniz; Bilgic, Celal Ismail; Dener, Nuzhet Cenap; Gunduz, Esra; Yenidunya, Sibel; Acar, Muradiye; Sen, MeralBreast cancer is the most common malignant tumor in women and accounts for about 25% of all cancer diagnoses. Survivin is a member of the apoptosis inhibitor protein family of antiapoptotic proteins. In our study, we investigated one of those, the survivin gene promoter 31G/C polymorphism. Included in this study were 111 breast cancer patients who were operated on in our hospital and 101 healthy female subjects. Blood samples from the healthy subjects and paraffin-embedded tissue samples from the patients were used for DNA extraction and subsequent genetic analysis. PCR-RFLP was used for genotype analysis. We established the clinicopathologic characteristics of patients. No significant difference was found between survivin 31G/C promoter polymorphism of tumor characteristics and breast cancer. Between the control and breast cancer groups, survivin promoter polymorphism 31G/C differences were not significantly different (P = 0.058). The risk of developing cancer, having the relevant GC or CC genotype, is 1.413 times higher than those having genotype GG (95% confidence interval: 1.040 to 1.918). Carrying the C allele was statistically significant in terms of susceptibility to breast cancer. In conclusion, the use of survivin gene polymorphism as a risk factor in breast cancer is recommended based on the results of this study.Öğe The effects and interactions of APOE and APH-1A polymorphisms in Alzheimer disease(Tubitak Scientific & Technological Research Council Turkey, 2015) Acar Cinleti, Burcu; Yardimci, Nilgul; Ayturk, Zubeyde; Ilhan, Atilla; Kaya, Gulhan; Acar, Muradiye; Koc, Emine RabiaBackground/aim: Alzheimer disease (AD) is characterized by the accumulation of senile plaques composed of amyloid beta-peptide, which is derived from beta-amyloid precursor protein through degradation by beta-secretase and.-secretase complexes. One of the major components of gamma-secretase complex, anterior pharynx-defective-1 (APH-1), is responsible for the activity of the.-secretase complex. In this study, we searched for not only the most known common genetic risk factor, APOE, but also the APH-1a gene polymorphism in AD patients in a Turkish population. Materials and methods: In this study, 49 AD patients and 45 healthy controls were included. The genetic polymorphisms and allele frequencies of APOE and APH-1a were investigated. Patients were evaluated for behavioral, cognitive, and functional domains by detailed neurocognitive tests, and comparison between the above-mentioned polymorphisms and disease severity was made. Results: Although there was an increased tendency of the APO epsilon 4 allele in the AD group, no statistically significant difference was detected either in APOE or APH-1a polymorphisms, not suggesting a strong susceptibility to the development of AD. Conclusion: While searching for the pathogenesis of AD in order to develop novel diagnostic as well as therapeutic approaches, analysis of other genes with a possible role in AD is warranted.Öğe The effects of hypericin on ADAMTS and p53 gene expression in MCF-7 breast cancer cells(Imprimatur Publications, 2014) Acar, Muradiye; Ocak, Zeynep; Erdogan, Kubra; Cetin, Elif Nihan; Hatipoglu, Omer Faruk; Uyeturk, Ummugul; Gunduz, EsraPurpose: The purpose of this study was to determine the effects of hypericin on MCF-7 (Michigan Cancer Foundation-7) breast cancer cells, as it is known to exert an antitumor effect on the expression and regulation of ADAMTS1, 3, 10 and the p53 gene in breast cancer cells. Methods: MFC-7 cells were cultured and subjected separately to various doses (1, 5 and 7.5 mu g/mL) hypericin. After 24 hrs, RNA was isolated and transcribed into cDNA. Expression analysis was performed by real time (RT)-PCR and cell survival was determined by the XTT assay. Results: While the expression of ADAMTS1 in MFC-7 cells decreased to 0.04-fold after exposure to 1 mu g/mL hypericin, the expression increased by 5.6- and 36-fold with 5 and 7.5 mu g/mL, respectively. Furthermore, ADAMTS3 expression in MCF7 cells increased 3.9-fold with the use of 5 mu g/mL of hypericin. These concentrations of hypericin did not lead to significant changes in the expression of ADAMTS10 and the p53 gene. Viability of cancer cells as evaluated by the XTT assay showed that hypericin concentration of 7.5 mu g/mL led to increased apoptosis of cancer cells. Conclusion: The increase in ADAMTS1 expression may prevent metastasis or facilitate the development of an adjuvant factor with tumor-suppressive effects. Hypericin may therefore exert its antitumor and apoptotic effects in MFC-7 cells via ADAMTS1 and ADAMTS3.Öğe The Role of ADAMTS9 Gene Promoter (Ca) Repeat in Developmental Hip Dysplasia(Canadian Soc Clinical Investigation, 2015) Yilmaz, Ayse E.; Atalar, Hakan; Acar, Muradiye; Dogan, Mikail; Aytekin, Mahmut N.; Gunduz, Mehmet; Gunduz, EsraPurpose: The relationship between the number of cytosine-adenine base pair repetition [(CA)n] in the promoter zone of ADAMTS9 gene, which may affect the collagen structure, and the developmental hip dysplasia was investigated. Methods: Using DNA isolating from 26 patients diagnosed with developmental hip dysplasia (DDH) and 29 patients without DDH, the (CA) n in the promoter zone of ADAMTS9 was calculated. The distributions of groups were measured by Shapiro-Wilk test, and the average results of the groups in the state of their normal distributions were compared using parametric Student t test. Results: While the (CA) n values varied between 15 and 30, the group average was found to be 17.9. While the (CA) n values of the patient group varied between 11 and 20, its average was computed to be 17.3. The averages of groups were not statistically different (p = 0.960). Conclusion: According to the results of our study, AD-AMTS9 gene promoter (CA)n in the individuals with developmental hip dysplasia was not found to be different from that of healthy individuals. Nevertheless, when strong impact of ADAMTS9 gene on the ligament tissue is considered, it is necessary to evaluate ADAMTS9 gene role with different aspects.Öğe The role of human Dectin-1 Y238X gene polymorphism in recurrent vulvovaginal candidiasis infections(Springer, 2014) Usluogullari, Betul; Gumus, Ilknur; Gunduz, Esra; Kaygusuz, Ikbal; Simavli, Serap; Acar, Muradiye; Oznur, MuratRecurrent vulvovaginal candidiasis (RVVC) is defined as having four or more symptomatic vulvovaginal candidiasis (VVC) attacks within a year. This study aimed to investigate whether Human Dectin-1 Y238X Gene Polymorphism plays a role in RVVC pathogenesis. In order to examine and explore this aim, an experimental study was undergone. The clinical study design was conducted with 50 women diagnosed with RVVC and had four or more symptomatic VVC attacks who were included in the experimental group; while 50 women who did not have previous RVVC history and diagnosis and did not have vaginal discharge and itching in the past year were included in the control group. Blood samples were collected from these patients and transferred to EDTA tubes, to investigate the Dectin-1 Y238X gene polymorphism, and stored at -80A degrees. When Dectin-1 genotypes were compared, there was no significant difference between the two groups (p = 0.452, p = 0.615, p = 0.275). History of familial RVVC was significantly higher in the experimental group (p = 0.001). When the multivariate analysis was used to evaluate factors that could determine RVVC frequency, history of familial RVVC was found to increase the frequency of RVVC attacks by 3.3 units. This study is the first-of-its-kind to investigate the correlation between Dectin-1 Y238X polymorphism, which has not been previously studied in the Turkish population, and RVVC. The result of this study suggests that there is no correlation between this polymorphism and RVVC.
