Browsing by Author "Tuna, Gamze"

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Citation - WoS: 25
Citation - Scopus: 29
Alterations in Levels of 8-Oxo '-deoxyguanosine and 8-Oxoguanine Dna Glycosylase 1 During a Current Episode and After Remission in Unipolar and Bipolar Depression
(Pergamon-Elsevier Science Ltd, 2020) Ceylan, Deniz; Yilmaz, Selda; Tuna, Gamze; Kant, Melis; Er, Ayse; Ildiz, Aysegul; Verim, Burcu
Introduction: Previous studies showed significant increases in DNA base damage markers and significant alterations in base excision repair enzymes in patients with unipolar and bipolar depression. We aimed to investigate changes in urine 8-Oxo-2'-deoxyguanosine (8-oxo-dG) and gene expression levels of 8-Oxoguanine DNA glycosylase 1 (OGG1) during a current depressive episode and after remission in bipolar and unipolar disorders. Methods: Twenty-four acutely depressed bipolar (BD), 33 unipolar depression (UD) patients and 61 healthy controls were included in the study. Clinical evaluations, blood and urine sampling were completed at baseline and at remission after eight weeks. The urine 8-oxo-dG levels were assessed by liquid chromatography tandem mass spectrometry and adjusted for urine creatinine levels. The gene expression levels of OGG1 were determined from cDNA extracted from blood samples, using real time-polymerase chain reaction. Results: At baseline, patients presented significantly higher levels of 8-oxo-dG (p = 0.008), and lower gene expression of OGG1 (p = 0.024) compared to controls. Levels of either 8-oxo-dG or OGG1 expression did not differ between BD and UD. In patients who remitted by the 8th week (n = 30), 8-oxo-dG decreased significantly (p = 0.001), and gene expression levels of OGG1 increased by 2.95 times compared to baseline levels (p = 0.001). All comparisons were adjusted for age, sex, smoking status and body mass index. Conclusion: Our results suggest that patients with bipolar and unipolar mood disorders present increased 8-oxo-dG and decreased gene expression levels of OGG1 in current depressive episodes, and that these changes might be reversed by the resolution of depressive symptoms. The causal relationship between DNA damage and repair requires further exploration.
Depresyonda Dna Hasarının ve Onarımının Belirtili Dönem ve Düzelme İle İlişkisi
(2018) Tuna, Gamze; İşlekel, Hüray; Özerdem, Ayşegül; Tufan Özalp, Deniz Ceylan
Giriş: Depresyonda tıbbi eştanılılık, bilişsel bozukluklar ve mortalite riskinde artış görülmesi, DNA hasarı/onarımı mekanizmalarının depresyonun etyopatogenezinde merkezi bir role sahip olabileceğini düşündürmektedir (Luca vd., 2013). Bu çalışmada DNA hasarı/onarımı ile depresif belirtiler, depresif belirtilerin şiddeti ve belirtilerin düzelmesi arasındaki ilişkilerin değerlendirilmesi amaçlanmıştır.
Citation - WoS: 1
Citation - Scopus: 1
Development and Validation of an Lc-ms/Ms Method for D- and L-2 Acid Measurement in Cerebrospinal Fluid, Urine and Plasma: Application To Glioma
(Future Sci Ltd, 2022) Dal-Bekar, Nazli Ecem; Tuna, Gamze; Islekel, Sertac; Islekel, Gul Huray
Aim: IDH mutations have been identified as frequent molecular lesions in several tumor types, particularly in gliomas. As a putative marker of IDH mutations, elevated D-2-HG has been reported in glioma, acute myeloid leukemia and intrahepatic cholangiocarcinoma. Excessive production of L-2-HG has also been described in renal cell carcinoma and 2-hydroxyaciduria. Materials & methods: The authors present a fully optimized stable isotope dilution multiple reaction monitoring method for quantification of D-/L-2-HG using LC-MS/MS. This is the first method validation study performed on cerebrospinal fluid, plasma and urine demonstrating clinical applicability with samples from glioma patients. Results & conclusion: This method validation study showed high accuracy and precision with low limit of detection and limit of quantification values. The authors believe that the presented approach is highly applicable for basic and clinical research on related pathologies.
Citation - WoS: 5
Citation - Scopus: 8
Increased Plasma Levels of 8-Oxoguanine Dna Glycosylase-1 in Bipolar Disorder
(Wiley, 2019) Ceylan, Deniz; Yilmaz, Selda; Bora, Ugur; Tuna, Gamze; Ildiz, Aysegul; Akan, Pinar; Veldic, Marin
[Abstract Not Available]
Citation - WoS: 10
Citation - Scopus: 11
Minimally Invasive Detection of Idh1 Mutation With Cell-Free Circulating Tumor Dna and D-2 D/L-2-hydroxyglutarate Ratio in Gliomas
(Oxford Univ Press Inc, 2022) Tuna, Gamze; Dal-Bekar, Nazli Ecem; Akay, Ali; Ruksen, Mete; Islekel, Sertac; Islekel, Gul Huray
Isocitrate dehydrogenase-1 (IDH1) mutation is accepted as one of the earliest events in tumorigenesis in gliomas. This mutation causes preferential accumulation of D- relative to L-enantiomer of 2-hydroxyglutarate (2-HG). Minimally invasive techniques to detect IDH1 mutation may prove useful for clinical practice. We adopted 2 different diagnostic approaches to detect IDH1 mutation status in glioma patients: Evaluation of D- and L-2-HG levels in cerebrospinal fluid (CSF), urine, and plasma, and identification of IDH1 mutation using cell-free circulating tumor DNA (ctDNA) in CSF and plasma. Forty-nine glioma patients in different stages were included. Levels of D- and L-2-HG were determined using liquid chromatography-tandem mass spectrometry; IDH1 R132H mutation was determined by digital-PCR. D-2-HG levels and D/L-2-HG ratio (rDL) in CSF and rDL in plasma were significantly higher in the mutant group than in the wild-type group (p = 0.029, 0.032, 0.001, respectively). The IDH1 mutation detection rates in CSF- and plasma-ctDNA were 63.2% and 25.0%, respectively. These data indicate that D-2-HG values in CSF and rDL in plasma and CSF can be considered as significant contributors to the identification of IDH1 mutation status. In addition, detection of IDH1 mutation in CSF-ctDNA from glioma patients provides a basis for future use of ctDNA for minimally invasive clinical assessment of gliomas.
Oxidation Induced Dna Damage and Base Excision Repair During a Current Episode and After Remission in Bipolar and Unipolar Depression
(Wiley, 2020) Ceylan, Deniz; Yilmaz, Selda; Tuna, Gamze; Kant, Melis; Er, Ayse; Ildiz, Aysegul; Verim, Burcu
[Abstract Not Available]
Citation - WoS: 26
Citation - Scopus: 31
Oxidatively-Induced Dna Damage and Base Excision Repair in Euthymic Patients With Bipolar Disorder
(Elsevier Science Bv, 2018) Ceylan, Deniz; Tuna, Gamze; Kirkali, Guldal; Tunca, Zeliha; Can, Gunes; Arat, Hidayet Ece; Kant, Melis
Oxidatively-induced DNA damage has previously been associated with bipolar disorder. More recently, impairments in DNA repair mechanisms have also been reported. We aimed to investigate oxidatively-induced DNA lesions and expression of DNA glycosylases involved in base excision repair in euthymic patients with bipolar disorder compared to healthy individuals. DNA base lesions including both base and nucleoside modifications were measured using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry with isotope-dilution in DNA samples isolated from leukocytes of euthymic patients with bipolar disorder (n = 32) and healthy individuals (n = 51). The expression of DNA repair enzymes OGG1 and NEIL1 were measured using quantitative real-time polymerase chain reaction. The levels of malondialdehyde were measured using high performance liquid chromatography. Seven DNA base lesions in DNA of leukocytes of patients and healthy individuals were identified and quantified. Three of them had significantly elevated levels in bipolar patients when compared to healthy individuals. No elevation of lipid peroxidation marker malondialdehyde was observed. The level of OGG1 expression was significantly reduced in bipolar patients compared to healthy individuals, whereas the two groups exhibited similar levels of NEIL1 expression. Our results suggest that oxidatively-induced DNA damage occurs and base excision repair capacity may be decreased in bipolar patients when compared to healthy individuals. Measurement of oxidatively-induced DNA base lesions and the expression of DNA repair enzymes may be of great importance for large scale basic research and clinical studies of bipolar disorder.
Citation - WoS: 5
Citation - Scopus: 3
Urinary 8-Hydroxy Levels Are Elevated in Patients With Idh1-Wildtype Glioblastoma and Are Associated With Tumor Recurrence in Gliomas
(Elsevier, 2023) Tuna, Gamze; Bekar, Nazli Ecem Dal; Islekel, Sertac; Islekel, Gul Huray
2021 World Health Organization (WHO) Central Nervous System (CNS) Tumor Classification includes molecular diagnostic parameters such as isocitrate dehydrogenase (IDH) mutation or 1p19q codeletion status, in addition to the classical histological classification. Several studies have revealed that patients with IDH1 mutation have a longer survival rate compared to wildtype individuals. In glioma cells, increased oxidative stress has been identified. However, till now, the relation between oxidative stress levels and IDH1 mutation status in those patients was not examined. Therefore, the aim of this study was to investigate the urinary levels of oxidatively induced DNA damage products, 8-hydroxy-2 '- deoxyguanosine (8-OH-dG), (5 ' R) and (5 ' S)-8,5 '-cyclo-2 '-deoxy-adenosines (R-cdA and S-cdA) as reliable oxidative stress markers in patients with IDH1-wildtype (n = 20) and IDH1-mutant (n = 22) glioma. Absolute quantification of 8-OH-dG, R-cdA and S-cdA was achieved by liquid chromatography-tandem mass spectrometry with isotope dilution. The levels of 8-OH-dG were significantly greater in IDH1-wildtype glioma patients than those in IDH1-mutant ones (p = 0.017). No statistically significant difference was observed for R-cdA and S-cdA levels. 8-OH-dG levels were positively correlated with patients' tumor recurrence in all patients (r = 0.382, p = 0.014). The mutation status of glioma is well correlated with oxidative stress. Examination of noninvasively measured oxidative DNA damage products along with IDH1 mutation status in glioma patients, might be particularly important in terms of evaluating and monitoring the effectiveness of treatment.
Citation - WoS: 4
Citation - Scopus: 4
Vitamin D Attenuates Elevated Oxidative Dna Damage in Scleroderma Patients With Organ Involvement: a Prospective Study
(Pergamon-Elsevier Science Ltd, 2023) Dal-Bekar, Nazlı Ecem; İşlekel, Gül Huray; Köken-Avşar, Aydan; Yarkan-Tuğsal, Handan; Tuna, Gamze; Zengin, Berrin; Birlik, Ahmet Merih
Scleroderma is a rare autoimmune disease characterized by progressive fibrosis of the skin and internal organs. Oxidative damage to macromolecules has been reported to occur in scleroderma. Among the macromolecular damages, oxidative DNA damage is a sensitive and cumulative marker of oxidative stress and is of particular interest because of its cytotoxic and mutagenic effects. Vitamin D supplementation is an important part of treatment, as vitamin D deficiency is a common problem in scleroderma. Furthermore, the antioxidant role of vitamin D has been demonstrated in recent studies. In light of this information, the present study aimed to comprehensively investigate oxidative DNA damage in scleroderma at baseline and to evaluate the contribution of vitamin D supplementation to the attenuation of DNA damage in a prospectively designed study. In accordance with these objectives, oxidative DNA damage in scleroderma was evaluated by measurement of stable damage products (8-oxo-dG, S-cdA, and R-cdA) in urine by liquid chromatography-tandem mass spectrometry (LC-MS/ MS); serum vitamin D levels were determined by high-resolution mass spectrometry (HR-MS); VDR gene expression and four polymorphisms in the VDR gene (rs2228570, rs1544410, rs7975232, and rs731236) were analyzed by RT-PCR and compared with healthy subjects. In the prospective part, the DNA damage and the VDR expression of the patients who received vitamin D were re-evaluated after the replacement. As a result of this study, we demonstrated that all DNA damage products were increased in scleroderma patients compared to healthy controls, whereas vitamin D levels and VDR expression were significantly lower (p < 0.05). After sup-plementation, statistical significance (p < 0.05) was reached for the decrease in 8-oxo-dG and the increase in VDR expression. Attenuated 8-oxo-dG after replacement in patients with lung, joint, and gastrointestinal system involvement demonstrated the efficacy of vitamin D in scleroderma patients with organ involvement. To the best of our knowledge, this is the first study to examine oxidative DNA damage in scleroderma comprehensively and to evaluate the effects of vitamin D on DNA damage using a prospective design.