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    Assocıatıon Of The Seh Gene Promoter Polymorphısms And Haplotypes Wıth Preeclampsıa
    (SCIndeks, 2020) Ökten, Hatice; Aktan, Çağdaş; Sarı, İsmail; Cihad, Esra
    Background: The epoxyeicosatrienoic acids (EETs) have antihypertensive, anti-inflammatory, and organ protective properties and their circulation levels are related to hypertension, diabetes mellitus, cardiovascular diseases, and preeclampsia. Soluble epoxide hydrolase (sEH) catalyses the degradation of EETs to less biologically active dihydroxyeicosatrienoic acids. Here, we sequenced the promoter region of EPHX2 to investigate the association between promoter sequence alterations that we thought to affect the expression levels of the enzyme and preeclampsia (PE). Methods: Nucleotide sequencing of the promoter region of the EPHX2, spanning from position -671 to +30, was performed on 100 pregnant women with PE and, 20 or more weeks pregnant normotensive, healthy women (n=100). Results: Pregnant women who carry rs4149235, rs4149232, rs73227309, and rs62504268 polymorphisms have 4.4, 2.4, 2.3, and 2.8 times significantly increased risk of PE, respectively. CCGG (OR: 3.11; 95% CI: 1.12-8.62) and CCCA (OR: 0.45; 95% CI: 0.36-0.55) haplotypes were associated with an increased and decreased risk of PE, respectively. Conclusions: Four SNPs (rs4149232, rs4149235, rs73227309, and rs62504268) in the promoter region of the EPHX2, and CCGG and CCCA haplotypes of these 4 SNPs were significantly associated with PE. These SNPs in the promoter region may affect sEH expression and enzyme activity and may play a role in PE pathogenesis by causing individual differences in EET levels. However, future studies are needed to confirm our findings and examine the effect of these SNPs on the sEH expression and/or enzyme activity.
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    Clinical Prognosis Evaluation of Covid-19 Patients: an Interpretable Hybrid Machine Learning Approach
    (Elsevier, 2021) Aktan, Çağdaş; .;, ve diğer
    This retrospective cohort study deals with evaluating severity of COVID-19 cases on the first symptoms and blood-test results of infected patients admitted to Emergency Department of Koc University Hospital (Istanbul, Turkey). To figure out remarkable hematological characteristics and risk factors in the prognosis evaluation of COVID-19 cases, the hybrid machine learning (ML) approaches integrated with feature selection procedure based Genetic Algorithms and information complexity were used in addition to the multivariate statistical analysis. Specifically, COVID-19 dataset includes demographic features, symptoms, blood test results and disease histories of total 166 inpatients with different age and gender groups. Analysis results point out that the hybrid ML methods has brought out potential risk factors on the severity of COVID-19 cases and their impacts on the prognosis evaluation, accurately.
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    Determining Expression of miRNAs That Potentially Regulate STAT5A And 5B in Dasatinib-sensitive K562 Cells
    (TUBITAK SCIENTIFIC & TECHNICAL RESEARCH COUNCIL TURKEY, 2017) Aktan, Çağdaş
    In the era of tyrosine kinase inhibitors, resistance still constitutes a problem in chronic myeloid leukemia (CML) patients; thus, new pathway-specific inhibitors like miRNAs have become important in the treatment of refractory patients. There are no satisfying data regarding the miRNAs and anti-miRNA treatment targeting STAT5A and 5B. In this study, we first researched the effect of dasatinib on apoptosis in the CML cell line K562. The expressions of miRNAs possibly targeting both STAT5A and 5B were then determined. The down- and upregulation of the miRNAs were compared using the ??CT method. At the last stage of the study, we used a new primer probe in order to validate the results. The level of hsa-miR-940 was decreased 4.4 times and the levels of hsa-miR-527 and hsa-miR-518a-5p were increased 12.1 and 8 times, respectively, in the dasatinib-treated group when compared to the control group. We detected similar results in the validation step. As a conclusion, we determined the expression profiles of miRNAs targeting STAT5A and 5B that had an important role in the pathogenesis of CML. The data obtained could lead to determining new therapeutic targets for CML patients.
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    Identification of Ferroptosis-Related Genes in Laryngeal Carcinoma Using an Integrated Bioinformatics Approach
    (İstanbul Gelişim Üniversitesi, 2022) Aktan, Çağdaş
    Aim: Ferroptosis, which is characterized by intracellular iron accumulation and lipid peroxidation, is a newly described form of regulated cell death that may play a key role in tumour suppression. There is still a lack of knowledge regarding the association between laryngeal squamous cell carcinoma (LSCC) and ferroptosis. The aim of this study is finding ferroptosis-related markers in LSCC to explore new directions for LSCC diagnosis and treatment using in silico methods.Method: The ferroptosis-related genes were obtained from FerrDb database. mRNA expression data from LSCC patients from The Cancer Genome Atlas (TCGA) datasets were used to screen for some genes related to ferroptosis. GSE143224 and GSE84957 microarray datasets about LSCC were obtained from the GEO database. Overlapping data was used to obtain genes associated with ferroptosis and LSHK using all datasets. The differentially expressed genes (DEGs) and ferroptosis-related DEGs between the LSCC group and normal controls were analyzed using bioinformatics methods. Then the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and the protein-protein interaction (PPI) network analyses were performed using STRING and Cytoscape softwares.Results: 259 ferroptosis-related genes were fetched from FerrDb database and intersected them with TCGA-HNSC (523 samples), GSE143224 (25 samples) and GSE84957 (18 samples) to identify ferroptosis DEGs. Finally, it was found that 13 upregulated (NOX4, BID, ABCC1, TNFAIP3, PANX1, SLC1A4, SLC3A2, FTL, TFRC, AURKA, HSF1, PML, CA9; p<0.05) and 3 downregulated genes (CHAC1, LPIN1, MUC1; p<0.05). The result of the enrichment gene dataset analysis (cellular stress, inflammation, oxidative stress and carcinogenesis; p<0.05) indicated that the genes significantly enriched were involved in progression of LSCC.Conclusions: In conclusion, 16 potential genes that are closely associated with ferroptosis in LSCC and may differentiate LSCC patients from controls. Our study may provide a broader idea for exploring the molecular mechanism and therapeutic targets of LSCC.
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    In Vitro Effects Of Methylsulphonylmethane İn Mcf7 Cells
    (Marmara University Press, 2020) Aktan, Çağdaş; Yıldırım, Işıl
    Methylsulphonylmethane (MSM) is the best source of organic sulfur with the best bio-utilization in the body. MSM provides Sulphur support to fragile tissues such as hair. It provides elasticity to connective tissue. It is required for collagen production. Despite its many advantages, there are only few published papers about the anticancer research regard to MSM, no known studies on Bioinformatics Analysis and the possible mechanisms such an effect remain unknown. Therefore, we aimed to investigate the anticancer effects of MSM associated with a bioinformatics analysis on the breast cancer cell MCF7 and to give the information about possible molecular mechanisms. A cytotoxicity assay was performed using the MTT method. The cell migration analysis was performed using wound healing analysis. An apoptotic effect was performed by DNA fragmentation analysis. A Bioinformatics analysis was performed using a protein data bank. Study results indicated that this component exhibited an anti-proliferative effect as based on dosage increases and it showed apoptotic effects at high concentrations on MCF7 cells and results were supported by previous studies. Consequently, a detailed study of the molecular mechanisms of this matter would allow for the identification of possible new targets for breast cancer treatments.
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    Thiopurine-S-Methyltransferase Gene Polymorphism and Drug-related Toxicity in Children Treated for Acute Leukemia and Non-Hodgkin’s Lymphoma
    (Galenos Publishing House, 2022) Aktan, Çağdaş; Ataseven, Eda; Kosova, Buket; Kurugöl, Zafer; Kantar, Mehmet
    Aim: Thiopurine S-methyltransferase (TPMT) is an essential enzyme in the metabolism of thiopurine drugs, and its activity may change due to different polymorphisms in the TPMT gene. The TPMT gene has different genetic polymorphisms in different ethnic groups. This study aimed to determine the frequency of TPMT polymorphisms in children with acute leukemia/non-Hodgkin lymphoma (AL/NHL) and healthy children and to evaluate their association with severe toxicities in the study population. Materials and Methods: Sixty-seven pediatric AL/NHL patients and 84 healthy children were evaluated. Genotyping for the TPMT*2, TPMT*3A, TPMT*3B, TPMT*3C, TPMT*4, TPMT*5, TPMT*6, and TPMT*7 alleles were performed by the real-time polymerase chain reaction technique. The number of grade 3 or higher hematologic and hepatic toxicities were recorded from the patient charts. Results: In the AL/NHL patients, we found that the patients had generally wild-type TPMT*1 allele in 80.6%, whereas TPMT*2 (238G>C) was seen in 1.5%, TPMT*3A (c.460G>A and c.719A>G) in 0%, and TPMT*3B polymorphisms (460G>A) in 17.9%. We found wild-type TPMT*1 allele in 98.8% and TPMT*3B polymorphisms (460G>A) in 1.2% of the healthy volunteers. Grade ?3 myelosuppression developed in 22/54 patients with the wild type allele, and it developed in 5/12 patients with TPMT*3B allele. Six (8.9%) patients had grade ?3 aspartate aminotransferase elevations, 17 (25%) patients had grade ?3 alanine transaminase elevations (1-5 times), and 42 patients had (62.6%) grade ?3 total bilirubin elevations. Conclusion: TPMT*3B polymorphism was the most common allele detected in our study group. This allele frequency is very high in comparison to other studies from our country and it was over-represented in comparison to the healthy volunteers. We did not find any relationship between severe hematologic/hepatic toxicities and TPMT gene polymorphisms.