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    Association of XRCC3, XRCC4, BAX, and BCL-2 Polymorphisms with the Risk of Breast Cancer
    (Hindawi Ltd, 2022) Özoran, Emre; Trabulus, Fadime Didem Can; Erhan, Duygu; Batar, Bahadır; Güven, Mehmet
    Background. Breast cancer is the most common malignancy in women. Genetic risk factors associated with breast cancer incidence have been identified. Aims. This study is aimed at determining the association of XRCC3 Thr241Met (rs861539), XRCC4 G(-1394) T (rs6869366) DNA repair and BAX G(-248) A (rs4645878), and BCL2 C(-938) A (rs2279115) apoptotic gene polymorphisms with breast cancer. Materials and Methods. Genetic analysis was performed using peripheral blood samples. Gene polymorphisms were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. 175 patients and 158 healthy controls were enrolled in the study. Results. Breast cancer risk was 5.43 times more in individuals with AA genotype of Bax G(-248) A (rs4645878) (P=0.002). The risk of metastasis was 11 times with this genotype. It was associated with 6 times more risk of having a tumor larger than 2 cm. The risk of breast cancer was 2.77 times more in individuals carrying the Met/Met genotype of XRCC3 Thr241Met (rs861539) (P=0.009). The risk of having advanced clinical stage (stage III+IV) with the Met/Met genotype was 4 times more increased. No relationship with breast cancer was found with XRCC4 G(-1394) T (rs6869366) and BCL2 C(-938) A (rs2279115) gene polymorphisms. Conclusion. Multicenter trials using subjects with genetic variations are needed to establish the relationship between breast cancer and single gene polymorphism.
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    DNA repair and apoptosis: Roles in radiotherapy-related acute reactions in breast cancer patients
    (C M B Assoc, 2018) Batar, Bahadır; Mutlu, Tuba; Bostanci, Merve; Akın, Mustafa; Tuncdemir, Matem; Bese, Nuran; Güven, Mehmet
    Normal tissue reactions are therapy limiting factor for the effectiveness of the radiotherapy in cancer patients. DNA repair and apoptosis are estimated to be critical players of adverse effects in response to radiotherapy. Our aim was to define the association of DNA repair (ERCC1 and XPC) and apoptotic (BCL2, CASP3 and NFKB1) gene expression, DNA damage levels, apoptosis changes and DNA repair gene variations with the risk of acute side effects in breast cancer patients. The study included 100 women with newly diagnosed breast cancer; an experimental case group (n=50) with acute side effects and the control group (n=50) without side effects. Gene expression was analyzed by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Micronucleus (MN) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) assays were performed to compare the DNA damage levels. Apoptosis was examined by TDT-mediated dUTP-biotin nick end-labeling (TUNEL) staining. ERCC1 rs3212986 and XPC rs3731055 polymorphisms were genotyped by real-time PCR technique. No significantly correlation of DNA repair and apoptosis gene expression and DNA damage levels with acute side effects in response to radiotherapy. Also, there was no association between apoptosis levels and acute effects. ERCC1 rs3212986 CC genotype showed a protective effect against radiotherapy-induced acute reactions (p<0.001; OR: 0.21; 95% CI=0.08-0.52). Our results suggest that apoptosis and DNA damage levels are not associated with acute radiosensitivity. DNA repair may affect the risk of acute reactions. Further studies are needed to validate the current findings.
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    Impairment of Voice Quality in Paradoxical Vocal Fold Motion Dysfunction
    (Mosby-Elsevier, 2010) Yelken, Kürşat; Gültekin, Erdoğan; Güven, Mehmet; Eyibilen, Ahmet; Aladağ, İbrahim
    Objectives/Hypothesis. To compare subjective and objective voice-quality parameters between asymptomatic paradoxical vocal fold motion dysfunction (PVFMD) patients and healthy individuals. Study Design. Prospective. Methods. A total number of 12 patients with PVFMD and 12 healthy control subjects had voice evaluations by means of laryngostroboscopy, acoustic analysis (jitter, shimmer, and harmonics-to-noise ratio [HNR]), aerodynamic measurements (maximum phonation time [MPT], s/z ratio), and perceptual analysis (Grade, Roughness, Breathiness, Asthenicity, and Strain Scale [GRBAS] and Voice Handicap Index-10 [VHI-10] scales). Evaluations were conducted when all the patients were asymptomatic. Results. False vocal cord adduction, anteroposterior constriction of the supraglottic larynx, decreased amplitude, and decreased mucosa] wave were observed in the great majority of the PVFMD patients during laryngostroboscopy. Mean jitter and shimmer rates were significantly high in PVFMD patients and there was no significant difference in mean HNR between groups (P < 0.05). Mean MPT was significantly long in control subjects (P < 0.05) and mean s/z ratio was nearly equal between patients and control subjects. There was a statistically significant difference between groups about GRBAS and VHI-10 scales (P < 0.05). Conclusions. Based on the subjective and objective voice parameters, voice quality is significantly impaired in asymptomatic PVFMD patients when compared with the healthy control subjects.
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    Molecular Approaches in COVID-19 Treatment
    (Nova Science Publishers, Inc., 2024) Güven, Mehmet; Batar, Bahadır
    Coronaviruses are a family of enveloped RNA viruses that cause diseases in various mammals and birds. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus identified as the cause of a global infectious disease called coronavirus disease 2019 (COVID-19). To date, there are currently no specific antiviral drugs that have been shown to effectively treat COVID-19. Moreover, vaccines based on viral-encoded peptides may not be effective against COVID-19, as virus mutations could make them futile. Many therapeutic strategies can be predicted in controlling and preventing the SARS-CoV-2 infections, such as oligonucleotide-based therapy, neutralizing monoclonal antibody therapy, autophagy pathway as therapeutic targets, chimeric antigen receptor Tcell (CAR-T) therapy, and mesenchymal-derived exosome therapy. Synthetic oligonucleotide-based therapeutic options containing small interfering RNA (siRNA) and antisense oligonucleotide (ASO) target the virus itself and mediate the silencing of its genome. Neutralizing monoclonal antibodies that target the receptor-binding motif (RBM) can prevent the virus from binding to angiotensin-converting enzyme 2 (ACE2), and are therefore promising antiviral drugs. On the other hand, vaccines and drugs can be developed to target the spike (S) glycoprotein of the coronavirus. Autophagy plays an important role in viral infection. Autophagosomes can induce apoptotic cell death of virally infected cells and disrupt the virus replication cycle. CAR-T treatment is a successful therapeutic option for patients with relapsed and/or refractory hematologic malignancies. Increased interleukin-6 (IL-6) is related to cytokine storm syndrome (CSS) in COVID-19 patients. CAR-T therapy is used successfully in the blocking of IL-6. Therefore, IL-6 can be a specific target for CAR-T therapy in SARS-CoV-2 infected patients. Mesenchymal-derived exosomes demonstrate anti-inflammatory and immunomodulatory effects. MSC-derived exosomes can modulate the activity of T cells. MSC-derived exosomes may inhibit proinflammatory cytokines and increase the levels of anti-inflammatory cytokines such as IL-10 in SARS-CoV-2 infection. MSCderived exosomes have been considered a specific therapeutic option for COVID-19 patients. Future preclinical and clinical investigations are needed to understand the critical roles of these therapy approaches in COVID-19. © 2024 by Nova Science Publishers, Inc.
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    The role of TMPRSS6 gene variants in iron-related hematological parameters in Turkish patients with iron deficiency anemia
    (Elsevier Science Bv, 2018) Batar, Bahadır; Bavunoglu, Isil; Hacioglu, Yalçın; Cengiz, Mahir; Mutlu, Tuba; Yavuzer, Serap; Güven, Mehmet
    TMPRSS6 gene mutations can result in iron deficiency anemia (IDA) and cause an increased iron-regulatory hormone, hepcidin, levels. TMPRSS6 encodes a serine protease, matriptase-2, which functions as negative regulatory protein of hepcidin transcription. Thus, TMPRSS6 variations might be risk factors for IDA. The aim of the study was to investigate the association of rs855791, rs4820268, rs5756506, rs2235324, rs2413450, rs2111833, rs228919, and rs733655 SNPs in TMPRSS6 gene with IDA susceptibility and iron-related clinical parameters. The study consisted of 150 IDA patients and 100 healthy controls. We analyzed the genotype distributions by using Real-Time polymerase chain reaction (Real-Time PCR) technique. We did not find any statistically differences for all SNPs between patients and controls (P > 0.05). In IDA patients, variations rs855791 and rs2413450 were associated with increased RBC (P = 0.03) and TIBC (P = 0.04), respectively. Also, increased of TIBC for rs4820268 (P < 0.05). On the other hand, in control group, rs5756506 was associated with two parameters, Hb (P = 0.02) and Hct (P = 0.03). We did not find markedly hepcidin levels in IDA patients compared to controls (P = 0.32). Our findings suggest that TMPRSS6 variations may not be risk factors for IDA. However, TMPRSS6 polymorphisms are associated with increased many iron-related hematological parameters.