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Öğe Chemoresistance in Malignant Intracranial Tumors: Longer Survival with Negative MDR1 Expression(Turkish Neurosurgical Soc, 2021) Ezgu, Mehmet Can; Kural, Cahit; Simsek, Gulcin Guler; Kaygin, Pinar; Oguztuzun, Serpil; Kirik, Alparslan; Yasar, SonerAIM: To analyze the Glutathione S-transferase (GST)-P, GST-M, cytochrome p450 (CYP)1-A1, CYP1-B1, and multidrug resistance (MDR)-1 expressions in malignant intracranial tumor (ICT)s, and to elicit their role on patient survival. MATERIAL and METHODS: GST-P, GST-M, CYP1-A1, CYP1-B1, and MDR-1 expressions were analyzed using immunostaining in 149 samples from 141 patients with preoperative ICT diagnosis. The case characteristics were reviewed, and the enzyme expressions were equated based on the age, gender, and tumor type. Then, 77 of 141 patients with malignant ICT and complete medical records postoperative were also investigated in detail for the relationship between the diagnosis, enzyme expression, and overall survival. RESULTS: The average age was 49.44 years, with 83 (58.45%) male patients. Among the 77 malignant ICTs, 38 (49.3%) and 29 were glial tumors and metastases, respectively, with a 13.35-month overall survival. Patients with metastatic tumor have approximately threefold higher GSTP level than those with glial tumors. MDR-1 expression was approximately twofold higher in > 60-year-old patients. No statistically significant association was found between patients' smoking behaviors, alcohol consumption, and overall survival. Only MDR-1 expression was correlated with overall survival. Better overall survival was observed in patients with a negative MDR-1 expression than those with a positive one. CONCLUSION: MDR-1 is an important indicator of survival in malignant intracranial tumor patients. Longer survival is associated with negative MDR-1 expression.Öğe Effects of Different Doses of Systemic Isotretinoin on Eyes: A Histopathological and Immunohistochemical Study in Rats(Lippincott Williams & Wilkins, 2020) Karadag, Remzi; Karadag, Ayse Serap; Ozlu, Emin; Oguztuzun, Serpil; Simsek, Gulcin Guler; Esmer, Oktay; Bilgili, Serap GunesPurpose: To evaluate ocular side effects associated with systemic isotretinoin histopathologically. Methods: In this multicenter study, a total of 15 male and 15 female rats were randomly divided into 3 equal groups according to the oral dose of isotretinoin they were administered: 0 mg/kg/d (group A), 7.5 mg/kg/d (group B), and 15 mg/kg/d (group C). Biopsy specimens were taken from the globe conjunctiva, cornea, and eyelid conjunctiva. Expression levels of human beta-defensin-1, human beta-defensin-2, toll-like receptor (TLR)-2, and TLR-4 were evaluated by immunohistochemical methods. Results: The number of goblet cells in eyelid conjunctiva was significantly lower in group B than that in group A and group C (P = 0.002). The sizes of meibomian gland acini were significantly smaller in group B and group C than those in group A (P < 0.001). Fibrosis of eyelid conjunctiva was significantly higher in group C and group B than that in group A (P = 0.002). The levels of staining of TLR-4 in the cornea with group B were significantly lower compared with group C (P = 0.035). Conclusions: Our study suggests that isotretinoin in the early period affects eyelid conjunctiva and meibomian glands without affecting the globe conjunctiva and cornea. Occurrence of the initial symptoms of isotretinoin on the eyelids, especially on the meibomian glands, suggests that the symptoms of patients occur because of evaporative dry eye.Öğe The expression of GST and CYP isoenzymes in thyroid nodular hyperplasia and papillary thyroid cancer tissue: Correlation with clinical parameters(Entomology & Applied Science Research Letters-Easletters, 2016) Oguztuzun, Serpil; Ergn, Duygu; Kilic, Murat; Bozer, Busra; Simsek, Gulcin Guler; Bulus, HakanThis study investigated the immunohistochemical staining characteristics of glutathione-S-transferase (GST) pi(P), mu(M), theta(T), omega(O) and kappa(K) cytochrome P450 (CYP) A1, B1 and 2E1 isoenzymes in thyroid nodular hyperplasia (NH) and papillary thyroid cancer (PTC) tissues. For immunohistochemical studies, tissues from 18 patients with thyroid nodular hyperplasia, 28 patients with papillary thyroid cancer at the Kecioren Training and Research Hospital, Ankara, Turkey, were used. Relationships between GST and CYP isoenzyme expressions in NH and PTC tissues were examined by the Mann-Whitney U test, and clinicopathological data were examined by the Pearson Correlation Test and Regression Analysis. When the NH and PTC tissues from these cases were compared with respect to their staining intensity, GSTP1, GSTO1, GSTK1, CYP1A1, CYP2E1 expressions in PTC cells were significantly higher than those in NH epithelial cells (p< 0.05). There were no statistically significant differences in the CYP1B1, GSTT1 and GSTM1 expressions between benign and tumor epithelium (p> 0.05). There were significant association between GSTO1, GSTK1 expressions and sT3 levels in PTC (p< 0.05) and CYP1B1 expression in NH. There was a significant association between GSTO1 expression and smoking status in NH ( p< 0.05). There was no statistical relationship between the GSTM1, GSTT1, GSTP1, GSTO1, GSTK1, CYP1A1, CYP1B1, CYP2E1 isoenzyme expressions and the clinicopathological data (age, TSH, sT4 levels, tumor stage) ( p> 0.05). GSTP1, GSTO1, GSTK1, CYP1A1 and CYP2E1 isoenzymes may have roles in the carcinogenesis of the papillary thyroid cancer.Öğe Expression of Sigma-Class Glutathione-S-Transferase in Fetal and Pediatric Filum Terminale Samples: A Comparative Study(Mdpi, 2019) Kural, Cahit; Ogurtuzun, Serpil; Simsek, Gulcin Guler; Guresci, Servet; Kaygin, Pinar; Yasar, Soner; Izci, YusufBackground and objectives: The pathophysiology of tethered cord syndrome (TCS) in children is not well elucidated. An inelastic filum terminale (FT) is the main factor underlying the stretching of the spinal cord in TCS. Our study aimed to investigate the expression of glutathione-S-transferase (GST) in children and fetal FT samples in order to understand the relationship between this enzyme expression and the development of TCS. Materials and Methods: FT samples were obtained from ten children with TCS (Group 1) and histological and immunohistochemical examinations were performed. For comparison, FT samples from fifteen normal human fetuses (Group 2) were also analyzed using the same techniques. Statistical comparison was made using a Chi-square test. Results: Positive GST-sigma expression was detected in eight (80%) of 10 samples in Group 1. The positive GST-sigma expression was less frequent in nine (60%) of 15 samples from Group 2. No statistically significant difference was detected between the two groups (p = 0.197). Conclusions: Decreased FT elasticity in TCS may be associated with increased GST expression in FT. More prospective studies are needed to clarify the mechanism of the GST-TCS relationship in children.Öğe Expressions of glutathione S-transferase alpha, mu, pi, and theta in the skin samples of patients with acne rosacea(WILEY, 2020) Takci, Zennure; Bilgili, Serap Gunes; Kilic, Murat; Oguztuzun, Serpil; Bozer, Busra; Simsek, Gulcin Guler; Akbayrak, AtiyeBackground Data point to the importance of oxidative stress in rosacea. Glutathione S-transferases (GSTs) have substantial roles in a wide variety of oxidative stress-related conditions. Aim To evaluate the immunohistochemical staining characteristics of GST alpha (GSTA), mu (GSTM), pi (GSTP), and theta (GSTT) in patients with rosacea. Patients/Methods The study included 23 women and 7 men with rosacea (mean +/- SD age 49 +/- 11 year) and 15 healthy control subjects (10 women, 5 men; mean +/- SD age 47.86 +/- 10.88 year). For each patient, the average disease duration, disease subtype, ocular involvement, and severity score were recorded. A 3-mm punch biopsy was taken from the facial skin of each patient and control. Expression of GST isoenzymes was analyzed immunohistochemically. Results Expressions of GSTM1, GSTP1, and GSTT1 were significantly elevated in patients with rosacea compared to those in the control group (P = .0001,P = .0002,P < .0001, respectively). In the rosacea group, GSTT1 expression was significantly stronger than GSTP1 and GSTA1 expressions (P = .019,P < .0001, respectively). There were no significant associations between expressions of GST isoenzymes and gender, age, average duration of illness, disease subtype, ocular involvement, or severity score in the patient group (allP > .05). Conclusions In rosacea, the significant increase of GSTT1, GSTP1, and GSTM1 expressions might result from activation of GST as an outcome of extreme free radical generation from triggered neutrophils or ultraviolet vulnerability. These findings support the relevance of oxidant stress in the pathogenesis of rosacea.Öğe Glutathione S-Transferases and Cytochrome P450 Enzyme Expression in Patients with Intracranial Tumors: Preliminary Report of 55 Patients(Karger, 2019) Kural, Cahit; Kocdogan, Arzu Kaya; Simsek, Gulcin Guler; Oguztuzun, Serpil; Kaygin, Pinar; Yilmaz, Irmak; Izci, YusufObjective: Intracranial tumors are one of the most frightening and difficult-to-treat tumor types. In addition to surgery, protocols such as chemotherapy and radiotherapy also take place in the treatment. Glutathione S-transferase (GST) and cytochrome P450 (CYP) enzymes are prominent drug-metabolizing enzymes in the human body. The aim of this study is to show the expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 in different types of brain tumors and compare our results with those in the literature. Subjects and Methods: The expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 was analyzed using immunostaining in 55 patients with intracranial tumors in 2016-2017. For GST and CYP expression in normal brain tissue, samples of a portion of surrounding normal brain tissue as well as a matched far neighbor of tumor tissue were used. The demographic features of the patients were documented and the expression results compared. Results: The mean age of the patients was 46.72 years; 29 patients were female and 26 were male. Fifty-seven specimens were obtained from 55 patients. Among them, meningioma was diagnosed in 12, metastases in 12, glioblastoma in 9, and pituitary adenoma in 5. The highest GSTP1, GSTM1, and CYP1A1 expressions were observed in pituitary adenomas. The lowest GSTP1 expression was detected in glioblastomas and the lowest CYP1B1 expression in pituitary adenomas. Conclusion: GSTP1 and CYP expression is increased in intracranial tumors. These results should be confirmed with a larger series and different enzyme subtypes. (c) 2018 The Author(s) Published by S. Karger AG, BaselÖğe Glutathione-S-Transferase And P53 Expressions In Human Malignant, Benign And Metastasis Ovarian Tumor Tissues(Wiley, 2019) Dirican, Onur; Kaygin, Pinar; Oguztuzun, Serpil; Erdem, Aysegul; Simsek, Gulcin Guler; Sarialtin, Sezen Yilmaz; Coban, Tulay…Öğe Immunocytochemical Evaluation of Glutathione-S-Transferase P1 Enzyme in Patients with Rheumatoid Arthritis(Wiley, 2019) Dirican, Onur; Kaygin, Pinar; Oguztuzun, Serpil; Simsek, Gulcin Guler; Hayat, Buket; Sarialtin, Sezen Yilmaz; Coban, Tulay…Öğe Investigation of Glutathione S-Transferase Isoenzyme Protein Expression in Patients With Pterygium(Lippincott Williams & Wilkins, 2016) Karadag, Remzi; Bayram, Nurettin; Oguztuzun, Serpil; Bozer, Busra; Bayramlar, Huseyin; Simsek, Gulcin Guler; Rapuano, Christopher J.Purpose: We investigated glutathione S-transferase (GST) enzymes in terms of their potential effects on the pathogenesis of pterygium. Methods: Twenty-six pterygium specimens and 15 normal conjunctival specimens of 15 control subjects were investigated. Expressions of GST (alpha, mu, pi, and theta) enzymes were assessed by immunohistochemical staining. A brown color in the cytoplasm and/or nuclei of epithelial cells was evaluated as positive staining for GST enzymes. For each antibody, the intensity of the reaction [negative (-), weak (1+), moderate (2+), or strong (3+)] was determined to describe the immunoreactions. Results: The median age was 52 years in the both groups. There was no significant difference between the groups in terms of age, sex, and intraocular pressure measurements (P > 0.05 for all). Of the 26 pterygium specimens, 15 (57.7%) (8 weak, 4 moderate, and 3 strong staining) were identified with GST pi-1 (GSTP1) expression and 20 (76.9%) (12 weak, 7 moderate, and 1 strong staining) with GST theta-1 (GSTT1) expression. Of the 15 control specimens, 4 (26.7%) (4 weak staining) were identified with the GSTP1 expression, and 1 (6.7%) with GSTT1 expression. GSTP1 and GSTT1 expressions were significantly higher in the pterygium specimens than in the controls (P = 0.043, P < 0.001; respectively). None of tissue specimens had positive staining for GST mu-1 or GST alpha-1 in both groups (both; P = 1.00). Conclusions: The significant increase of GSTP1 and GSTT1 expressions in pterygium may be because of the increased activation of GST in response to excessive free radical formation from ultraviolet exposure to maintain antioxidant capacity in pterygium.
