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    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, Soner
    AIM: 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.
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    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, Yusuf
    Background 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.
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    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, Yusuf
    Objective: 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, Basel