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Öğe Comparison of the tissue expressions of glutathione S transferase isoenzymes among patients with morphea and healthy controls: A preliminary study(WILEY-HINDAWI, ADAM HOUSE, 3RD FL, 1 FITZROY SQ, LONDON WIT 5HE, ENGLAND, 2020) Uzunçakmak, Tuğba Kevser; Koska, Mahmut Can; Özkanlı, Şeyma; Kaya Koçdoğan, Arzu; Oğuztüzün, Serpil; Karadağ, Ayşe Serap; Akdeniz, Necmettin; Wollina, UweMorphea is an inflammatory connective tissue disorder, which is characterized by sclerosis in skin and subcutaneous tissues with a chronic progress. The oxidative stress in pathogenesis of sclerosing diseases was proposed in several studies with conflicting results. To explore the tissue expressions of Glutathione S transferase (GST) isoenzymes in patients with morphea and compare these expressions with healthy controls. Twenty-two morphea patients and 20 sex and age matched healthy controls were enrolled in this study. Four millimeter punch biopsies were performed from the active sclerotic plaques of morphea patients. Tissue samples of control group were obtained from nonlesional normal skin biopsy specimens. The protein expressions of GST isoenzymes were analyzed immunohistochemically. Tissue expressions of GSTP1, GSTT1, and GSTA1 isoenzymes in morphea patients were found to be significantly higher than in control tissues. There was no significant difference in GSTM1 isoenzyme expression between the two groups. The increased tissue expressions of GSTA1, GSTP1, and GSTT1 isoenzymes in morphea may represent the activated GST enzymes in response to excessive free radical formation and may also support the hypothesis of increased oxidative stress in morphea etiopathogenesis.Öğe Expression of CYP and GST in human normal and colon tumor tissues(TAYLOR & FRANCIS LTD, 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND, 2019) Buluş, Hakan; Oğuztüzün, Serpil; Güler Şimşek, Gülçin; Kılıç, Murat; Ada, Ahmet Oğuz; Göl, Saliha; Kaya Koçdoğan, Arzu; Kaygın, Pınar; Bozer, Büşra; İşcan, MümtazWe investigated the immunohistochemical staining characteristics of cytochrome P450 1A1 (CYP1A1), CYPB1, CYP2E1, and glutathione S-transferase P1 (GSTP1), GSTT1, GSTO1, GSTK1 in colon tumor and surrounding normal colon tissues. Tissues were obtained from 47 patients with colon adenocarcinoma and the staining intensity of tumor and control tissues was compared. CYP1A1, CYP1B1, CYP2E1, GSTP1, GSTT1, GSTO1 and GSTK1 expressions in colon cancer cells were significantly greater than those in normal colon epithelial cells. No significant relation was found between the isoenzyme expressions and age, gender, smoking status, tumor grade and tumor stage. The higher expressions of CYP1A1, CYP1B1, CYP2E1, GSTP1, GSTO1, GSTT1 and GSTK1 in tumor than in normal colon tissues may be important for colon cancer progression and development.Öğe Expressions of CYP and GST Isoenzymes in Human Gastric Tumor and Non-Tumor Tissues(Uluslararası Hematoloji Onkoloji Dergisi, 2018) Güler Şimşek, Gülçin; Oğuztüzün, Serpil; Bozer, Büşra; Kılıç, Murat; Kaya Koçdoğan, Arzu; Kaygın, Pınar; Gürbüz, Nurdan; Buluş, HakanIn this study we investigated the immunohistochemical staining characteristics of cytochrome P450 1A1 (CYP1A1), CYPB1, CYP2E1 and glutathione S-transferase P1 (GSTP1), GSTT1, GSTO1, GSTK1 isoenzymes in gastric tumor and surrounding tumor free (normal) gastric tissues from 40 patients. For immunohistochemical studies, tissues were obtained from 40 patients with gastric adenocarcinoma. Tumor and non-tumoral control tissues of patients were compared according to their staining intensity. Relationships between CYP and GST isoenzyme expressions in adenocarcinoma tissues were examined by the Mann Whitney-U test, and the clinicopathological data were examined by the Spearman’s Rank Correlation test. CYP1B1, GSTT1, GSTO1 and GSTK1 expressions in gastric cancer cells were significantly higher than those in gastric normal epithelial cells (p< 0.05). However, CYP1A1, CYP2E1 and GSTP1 expressions were not significantly higher in tumor epithelium than those in normal epithelium in human gastric adenocancer (p< 0.05). Among the studied CYPs and GSTs, there was not statistically significant association between the studied isoenzyme expressions and age, gender and tumor grade (p> 0.05). In patients with gastric adenocarcinoma, CYP1B1, GSTO1, GSTT1, and GSTK1 protein expressions are higher in tumor than normal gastric tissues.Öğe GSTM1, GSTP1, p53 as some probable predictors of prognosis in primary and metastatic epithelial ovarian cancer(Prusa Medikal Yayıncılık Limited Şirketi, 2023) Özer, Gizem; Kaygın, Pınar; Dirican, Onur; Oğuztüzün, Serpil; Yılmaz Sarıaltın, Sezen; Şimşek, Gülçin Güler; Erdem, Ayşegül; Kılıç, Murat; Çoban, TülayObjectives: Ovarian carcinomas are responsible for the death of more women than all other gynecologic malignancies in the Western world. Ovarian carcinomas are detected in an advanced stage of the disease in approximately 80% of the patients. Glutathione S-transferases (GSTs) are an important family involved in the detoxification of several xenobiotics. Thus, this mechanism protects tissues from the harmful effects of oxidative stress and chemical-induced damages. The expression of them may contribute to the characteristics of ovarian carcinoma as they can metabolise both exogenous and endogenous compounds, which are implicated in the development of ovarian cancer. Therefore, our aim was to determine the expressions of GST Mu 1 (GSTM1), GST Pi 1 (GSTP1), and also p53, which is a tumor suppressor gene, in benign and malign ovarian tumors and metastasis tissues. Methods: A total of the 99 patients with ovarian tumor enrolled in the study. Thirty-one of the tissues was benign tumor, 17 was malign tumor and 51 was metastasis. The immunohistochemical GSTM1, GSTP1, and p53 staining characteristics of these tissues were investigated. Results: The highest GSTM1, GSTP1, and p53 expression was noted in the malignant group followed by the metastasis group. GSTP1 expression was significantly higher in malignant tissues than benign ones (p = 0.015). No statistically significant difference was observed in the level of GSTM1 expression between groups (p = 0.524). p53 expression was significantly higher in the metastasis and malignant tissues than the benign ones (p < 0.001). Conclusions: The higher expressions of GSTP1 and p53 in malignant and metastasis tissues than benign ones indicate that these expressions could be important biomarkers in ovarian cancer development and progression. Further studies with more cases are required to confirm the results of our present study.Öğe Immunohistochemical approach to obesity disease in terms of expression levels of glutathione s-transferase (sigma, zeta, theta) isozymes(Prusa Medikal Yayıncılık Limited Şirketi, 2023) Davudov, Mahammad; Buluş, Hakan; Dirican, Onur; Kaygın, Pınar; Şimşek, Gülçin Güler; Yılmaz Sarıaltın, Sezen; Gürbüz, Fatıma Nurdan; Oğuztüzün, SerpilObjectives: Obesity is a complex multifactorial disease with recently increasing prevalence and incidence. Several studies have been conducted to explain the ethiology, pathophysiology, epidemiology, molecular and genetic mechanisms, and effective treatments of obesity. Glutathione S-transferase (GST) S1, GSTZ1, and GSTT1 are essential enzymes for oxidative stress and metabolism-related disorders. For this purpose, we aimed to reveal the role of GSTS1, GSTZ1, and GSTT1 in obesity. Methods: The gastric tissue samples were taken from the patients diagnosed with obesity who underwent bariatric surgery in Ankara Keçiören Training and Research Hospital General Surgery Clinic between 2017 and 2019. Immunostaining was performed on paraffin-embedded tissues to evaluate GSTS1, GSTZ1, and GSTT1 expressions. Laboratory data of the patients were recorded. All the results were analyzed statistically. Results: Weak GSTS1 expression was observed in 38.1% of tissues and moderate in 6.3%. 37.3% of the tissues presented weak GSTZ1 expression, and 11 (8.7%) displayed moderate. There were weak GSTT1 expressions in 7.1% of the tissues and moderate 0.8% of them. A positive and statistically significant correlation was observed between GSTS1 and GSTT1 expression levels ((r) = 0.028, p = 0.010; p < 0.05). There were no significant differences between expression levels and gender, age, comorbidities, and medication usage (p > 0.05). Conclusions: GSTs, in particular GSTS1, GSTT1, and GSTZ1, might contribute to molecular mechanisms and the progression of obesity. In our study, GSTS1, GSTT1, and GSTZ1 were found to be moderately expressed in gastric tissues taken from obese patients. However, new studies using more samples and advanced techniques are needed to elucidate the relationship.Öğe Immunohistochemical Evaluation of Apoptosis and Multidrug Resistance- Related Markers in Gallbladder Dysplasia and Carcinoma(Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, 2022) Başak, Kayhan; Demir, Derya; Kaya Koçdoğan, Arzu; Oğuztüzün, SerpilObjective: The search for treatment success in gallbladder carcinomas, which is one of the tumors with the most aggressive course, poor prognosis, and tendency to show resistance to treatment, continues today. Treatments targeting pathways related to genetic changes de- tected in most solid tumors offer new hope in the treatment of these tumors. Some of these treatment modalities target apoptosis-related pathways, and mammalian target of rapamycin (mTOR), p38, Bcl-2, and caspase-3 are important components of this pathway. Methods: In the study, mTOR, caspase-3, p38, Bcl-2, LL-37, MDR1, multidrug resistance protein (MRP)1, MRP6, and MRP7 immunohistochemical staining were applied to paraffin blocks of 27 gallbladder cancer and 62 cases with gallbladder dysplasia. The immunohisto- chemically stained sections were evaluated and scored. Results: mTOR, p38, and caspase-3 expressions were found to be significantly increased in dysplasia and tumor groups, and in dysplastic and malignant cells. While there was no signifi- cant difference in the expression of MRP1 and MRP7, MRP6 was significantly overexpressed. Conclusion: In this study, increased expression of mTOR, p38, and caspase-3 in the dys- plastic and malignant cells of the gallbladder may show that it has a role in the carcinogenesis process in the gallbladder. The study also shows that MRP6 may also play a role in the devel- opment of drug resistance in gallbladder carcinoma.Öğe MCF-7 İnsan Meme Kanseri Hücre Soyunda Doksorubisin Öncesi ve Sonrası GST İzozimlerinin, İlaç Dirençlilik Proteinlerinin ve Apoptotik Etkisinin Araştırılması(İstanbul Gelişim Üniversitesi Yayınları / Istanbul Gelisim University Press, 2020) Kaya Koçdoğan, Arzu; Oğuztüzün, Serpil; Güler Şimşek, Gülçin; Türk, MustafaAmaç: Kanser hastalığının tedavisinde karşılaşılan klinik sorunlardan biri hastalara uygulanan kemoterapiye karşı tümör hücrelerinin geliştirdiği dirençtir. Tümör hücrelerinin ilaçlara karşı gösterdiği direncin asıl kaynaklarından biri, ilaçların hücre dışına atılmasını sağlayan membran proteinlerinin en önemli üyelerinden ABC (ATP-binding cassette) taşıyıcı proteinleridir. İlaç dirençlilik proteinlerinin yanında diğer hücre içi proteinlerinde etkin olabileceği bilinmektedir. Bu bağlamda, alkilleyici özellikteki kanser ilaçlarına gelişen dirençte, hücre içi glutatyon ve glutatyon S- konjugatlarının seviyelerinin artmasının rolünün olduğu bildirilmiştir. Bu çalışmada, Michigan Cancer Foundation-7 (MCF-7) meme kanseri hücre hattında Glutatyon S-transferaz (GST) izozimlerinin çoklu ilaç direnç mekanizmasındaki bazı önemli proteinlerin doksorubisin uygulamasıyla ilişkilerinin incelenmesi amaçlanmıştır. Yöntem: Bu çalışmada ilaç uygulanmış ve uygulanmamış meme kanserli MCF-7 hücre hattında GST enzim ailesi ve ABC taşıyıcı proteinlerin ekspresyon ifadeleri immünositokimya yöntemiyle incelenmiştir. Bulgular: Bu çalışmada, ilaç uygulanmış hücre hatlarında GSTP1, GSTT1, GSTM1, GSTA1, GSTO1, GSTZ1 ve GSTK1 protein ifadelerinin ilaç uygulanmamış hücrelere oranla daha yüksek olduğu görülmüştür; GSTS1 proteini kontrol ve deney gruplarının ikisinde de tespit edilememiştir. İlaç uygulanmış MCF-7 hücre hattında MRP (Multidrug resistance-associated) 2,3,6,7 protein ifadelerinin ilaç uygulanmamış hücrelere oranla daha fazla olduğu görülmüştür. MDR1 (multidrug resistance protein) ve MRP1 proteinleri izlenememiştir. İlaç uygulanmış meme kanserli MCF-7 hücre hattında Bcl-2, p53, p38, caspase-3 protein ifadelerinin ilaç uygulanmamış hücrelere oranla daha fazla olduğu görülmüştür. Sonuç: ABC süper ailesi üyelerinden MRP 2,3,6 ve 7 ile Faz II enzimleri arasında bulunan GSTP1, GSTT1, GSTM1, GSTA1, GSTO1, GSTZ1 ve GSTK1 izozimlerinin, MCF-7 kanser hücre hattında doksorubisine karşı oluşan ilaç dirençliliğinde rolleri olduğu belirlenmiştir.Öğe Unveiling the etiological impact of GST-M1, GST-T1, and P53 genotypic variations on brain carcinogenesis(SPRINGERVAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS, 2024) Dirican, Onur; Kaygın, Pınar; Oğuztüzün, Serpil; Husseini, Abbas Ali; Yılmaz Sarıaltın, Sezen; Yılmaz, Can; Ünlü, Nihan; İzci, YusufBackground Functional variants of glutathione-S-transferase (GST)-M1, GST-T1, p53 might modulate brain cancer risk by altering the rate of metabolism and clearance of carcinogens from the brain tissue. In this study, the role of GST-M1, GSTT1, p53 polymorphisms on brain tumor was investigated. Methods and results Brain tumor tissues of 143 patients were obtained from the Gulhane Training and Research Hospital, Department of Neurosurgery between 2019 and 2020. In the xenobiotic mechanism, the null allele frequency in the GST-T1, GST-M1 gene regions of Phase II enzymes by qPCR method were investigated. Single nucleotide polymorphism encoding Arg/Pro conversion in the p53 gene region was analyzed in 120 cases by sequence analysis method. The data were analyzed statistically with patient’s demographic and clinical data. GST-M1, GST-T1, p53 genotypes of the patient group were determined. The most frequent genotype was null genotype (0/0) for GST-M1 (?2=39.756, p<0.001). GST-M1 genotype frequencies were 30.8%, 23.1%, 44.3% for 1/1, 1/0, 0/0, respectively. The most frequent genotype was GST-T1 1/1 following by GST-T1 1/0 (?2=0.335, p=0.846). GST-T1 genotype frequencies were 64.3%, 30.8%, 4.9% for 1/1, 1/0, 0/0, respectively. GST-M1 null genotype might be associated with the development of brain tumors. Genotype distribution obtained in p53 exon 4 codon 72; Arg/Arg was determined as 31 (25.8%), Arg/Pro 70 (58.3%), and Pro/Pro 19 (15.8%) in the case group, while there were 18 (38.3%), 23 (48.9%), and 6 (12.8%) respectively in the control group. However, the genotype distribution of p53 exon 4 codon 72 among tumorous tissue did not significantly vary from healthy control tissues (?²=2.536, p=0.281). Conclusion The null allele frequency encountered in the GST-M1, GST-T1 gene regions is consistent with the rates in the gene pool called Caucasian in the literature. GST-M1 gene polymorphism may play a crucial role in brain carcinogenesis in Turkish patients. This study based on clinical data is thought to help to understand the important epidemiological features of brain tumors.
