Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article Citation - Scopus: 1Targeting HDAC Enzymes by SAHA Enhances the Cytotoxic Effects of Cisplatin on Acute Myeloid Leukemia Cells(Ondokuz Mayis Universitesi, 2024) Şansaçar, Merve; Pekin, Özge; Gencer Akçok, Emel BaşakChemotherapy is a widely used therapeutic approach to combat hematopoietic malignancies such as acute myeloid leukemia (AML). Although cisplatin is known as the first-generation platinum-based chemotherapy inhibitor, the wide use of cisplatin eventually leads to drug resistance, which is the biggest impediment to cancer chemotherapy. Histone deacetylase enzyme (HDAC) inhibitors have the ability to induce cell cycle arrest and apoptosis in different types of cancer, which stands as a promising alternative for those cancer patients not appropriate for intensive chemotherapy. This study concluded that there was a significant decrease in the proliferation of MOLM-13 and MV4-11 FLT3-ITD+ AML cell lines with the increasing SAHA and cisplatin concentrations in 48 hours using MTT cell proliferation assay. Moreover, the combination of SAHA and cisplatin led to a reduction in the proliferation of both cell lines correlated with the synergistic effect of the two drugs depending on the combination index (CI). Furthermore, investigating apoptosis for combined administration resulted in increased induction of apoptosis by Annexin-V/PI double staining. In conclusion, although additional studies are needed to fully elucidate the molecular mechanism underlying this combination, we propose a new approach to targeting AML, as AML increases over time with drug resistance and the consequent year-on-year increase in patient mortality. © 2025 Elsevier B.V., All rights reserved.Article Citation - Scopus: 2Prediction of Colorectal Cancer Based on Taxonomic Levels of Microorganisms and Discovery of Taxonomic Biomarkers Using the Grouping-Scoring (G-S-M) Approach(Elsevier Ltd, 2025-03) Bakir-Güngör, Burcu; Temiz, Mustafa; Canakcimaksutoglu, Beyza; Yousef, MalikColorectal cancer (CRC) is one of the most prevalent forms of cancer globally. The human gut microbiome plays an important role in the development of CRC and serves as a biomarker for early detection and treatment. This research effort focuses on the identification of potential taxonomic biomarkers of CRC using a grouping-based feature selection method. Additionally, this study investigates the effect of incorporating biological domain knowledge into the feature selection process while identifying CRC-associated microorganisms. Conventional feature selection techniques often fail to leverage existing biological knowledge during metagenomic data analysis. To address this gap, we propose taxonomy-based Grouping Scoring Modeling (G-S-M) method that integrates biological domain knowledge into feature grouping and selection. In this study, using metagenomic data related to CRC, classification is performed at three taxonomic levels (genus, family and order). The MetaPhlAn tool is employed to determine the relative abundance values of species in each sample. Comparative performance analyses involve six feature selection methods and four classification algorithms. When experimented on two CRC associated metagenomics datasets, the highest performance metric, yielding an AUC of 0.90, is observed at the genus taxonomic level. At this level, 7 out of top 10 groups (Parvimonas, Peptostreptococcus, Fusobacterium, Gemella, Streptococcus, Porphyromonas and Solobacterium) were commonly identified for both datasets. Moreover, the identified microorganisms at genus, family, and order levels are thoroughly discussed via refering to CRC-related metagenomic literature. This study not only contributes to our understanding of CRC development, but also highlights the applicability of taxonomy-based G-S-M method in tackling various diseases. © 2025 Elsevier B.V., All rights reserved.Article Citation - Scopus: 1Possible Drug-Drug Interactions Between Mesalamine and Tricyclic Antidepressants Through CYP2D6 Metabolism - in Silico and in Vitro Analyses(Georg Thieme Verlag, 2025-04-01) Ozen, Melek B.; Gazioğlu, Işil; Ozgun-Acar, Özden; Guner, Hüseyin; Semiz, Gürkan; Sen, Alaattin; Ozgun Acar, OzdenMesalamine (mesalazine, 5-aminosalicylic acid, 5-ASA) is an essential anti-inflammatory agent both used for therapy and as a remission control in patients with inflammatory bowel diseases (IBD) such as ulcerative colitis (UC). Tricyclic antidepressants (TCAs) are used to alleviate remaining symptoms in patients already receiving IBD therapy or with quiescent inflammation. The cytochrome P4502D6 enzyme is involved in the metabolism of TCAs. Hence, it is crucial to investigate the role of CYP2D6 in 5-ASA metabolism. Initially, in silico analysis involving the docking of 5-ASA to CYP2D6 and molecular dynamics simulations was conducted. Next, the rate of O-demethylation of a nonfluorescent probe 3-[2-(N,N-diethyl-N-methylammonium)-ethyl]-7-methoxy-4-methylcoumarin (AMMC) into a fluorescent metabolite AMHC (3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-hydroxy-4-methylcoumarin) was optimized with baculosomes co-expressing human CYP2D6 and human P450 oxidoreductase (hCPR) to monitor CYP2D6 activity in a microtiter plate assay. The apparent Km and Vmax were found to be 1.30 μM and 32.68 pmol/min/mg of protein for the O-demethylation of AMMC to AMHC, and the reaction was linear for 40 min. Then, nonselective inhibition of CYP2D6 activity with various concentrations of 5-ASA was detected. Finally, the conversion of AMMC to metabolites was analyzed by HPLC-ESI-MS/MS spectrometry, and none were identified. Thus, this study suggests that concurrent use of mesalamine with TCA may lead to adverse effects, and CYP2D6 genotyping should be routinely performed on these patients to eliminate possible threats. © 2025 Elsevier B.V., All rights reserved.Book Part Citation - Scopus: 1Measurement of Autophagic Activity in Cancer Cells With Flow Cytometric Analysis Using Cyto-Id Staining(Humana Press Inc., 2024) Şansaçar, Merve; Gencer Akçok, Emel BaşakAutophagy is an evolutionarily conserved process providing the energy that cells need to survive, especially in stress situations, through catabolic processes. Considering the dual role of autophagy in cancer cells depending on the cellular context, it is crucial to comprehend the effect of drug candidates put forward to prevent cancer through the autophagy pathway. The CYTO-ID® Autophagy Detection Kit allows a rapid, specific and quantitative measurement of autophagic activity at the cellular level using a 488 nm-excitable green fluorescent detection reagent via flow cytometer. In this chapter, we present the CYTO-ID® Autophagy Detection method with a stepwise protocol to monitor the autophagy flux after the application of any compound to suspension cancer cell lines with flow cytometric analysis. © 2025 Elsevier B.V., All rights reserved.Article Citation - Scopus: 5Hyperplastic and Tubular Polyp Classification Using Machine Learning and Feature Selection(Elsevier B.V., 2024) Doǧan, Refika Sultan; Akay, Ebru; Doǧan, Serkan; Yilmaz, BulentPurpose: The aim of this study is to develop an effective approach for differentiating between hyperplastic and tubular adenoma colon polyps, which is one of the most difficult tasks in colonoscopy procedures. The main research challenge is how to improve the classification of these polyp subtypes applying various focusing levels on the polyp images, data preprocessing approaches, and classification algorithms. Methods: This study employed 202 colonoscopy videos from a total of 201 patients, focusing on 59 videos containing hyperplastic and tubular adenoma polyps. Manually extract key frames and several feature extraction and classification techniques were applied. The influence of different datasets with various focuses as well as data preprocessing steps on the performance of classification was examined, and AUC values were calculated using ten classifiers. Results: The study discovered that the optimal dataset, data preprocessing method, and classification algorithm all had significant effects on classification results. The Random Forest model with the Recursive Feature Elimination (RFE) feature selection approach, for example, consistently outperformed other models and achieved the highest AUC value of 0.9067. In terms of accuracy, F1 score, recall, and AUC, the suggested model outperformed a gastroenterologist, nevertheless precision remained slightly lower. Conclusion: This study emphasizes the importance of dataset selection, data preprocessing, and feature selection in enhancing the classification of difficult colon polyp subtypes. The suggested model offers a promising model for the clinical differentiation of hyperplastic and tubular adenoma polyps, potentially improving diagnostic accuracy in gastroenterology. © 2024 Elsevier B.V., All rights reserved.Article Citation - WoS: 5Citation - Scopus: 6Genetic Variants in Genes Correlated to the PI3K/AKT Pathway: The Role of ARAP3, CDH5, KIF and RELN Primary Lymphedema(International Society of Lymphology, 2024-08-28) Dundar, Mehmet Sait; Belanová, I.; Bonetti, Gabriele; Gelanová, V.; Kozáčiková, R.; Vešelényiová, Dominika; Donato, Kevin; Michelini, S.Genetic anomalies affecting lymphatic development and function can lead to lymphatic dysfunction, which could manifest as lymphedema- Understanding the signaling pathways governing lymphatics function is crucial for developing targeted diagnostic and therapeutic interventions. This study aims to characterize genetic variants in genes involved in the PUKIAKT signaling pathway, which plays a critical role in lymphangiogenesis. 408 patients diagnosed with primary lymphedema were sequenced usinga next-generation sequencing (NGS) gene panel composed of 28 diagnostic genes and 71 candidate genes. The analysis revealed six variants in genes RFLN, ARAP3,CDHS and K1F11. Five of these variants have never been reported in the literature. All these genes have been correlated to lymphatic activity and are involved in the P13K/AKT pathway. As the P13K/AKT signaling pathway plays an essential role in lymphangiogenesis and lymphatic function, genetic variants in genes correlated to this pathway could lead to lymphedema. Our findings underscore the potential of the P13K/AKT pathway in lymphedema pathogenesis, supporting the role of RELN,ARAP3,CDH5,and KIF11 as diagnostic and therapeutic targets. © 2024 Elsevier B.V., All rights reserved.Article Evaluation of HOTAIR, HOXD8, HOXD9, HOXD11 Gene Expression Levels in Turkish Patients With Acute and Chronic Myeloid Leukemia: A Single Center Experience(Cellular and Molecular Biology Association, 2024-11-27) Saraymen, Esma; Erdem, Yakut; Akalin, Hilal Ünlü; Taşçıoğlu, Nazife; Saraymen, Berkay; Celik, Serhat; Özkul, Yusuf T.Homeobox (HOX) transcript antisense RNA (HOTAIR) and HOX genes are reported to be more expressed in various cancers in humans in recent studies. The role of HOTAIR and HOXD genes in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) is not well known. In this study, expression levels of HOXD8, HOXD9 and HOXD11 from HOXD gene family and HOTAIR were determined from peripheral blood samples of 30 AML and 30 CML patients and 20 healthy volunteers by quantitative Real Time PCR. We determined that the expression levels of HOXD9 and HOXD11 in the AML patients were significantly lower than the control group (p<0.001 and p=0.002, respectively). There was no significant difference in the expression levels of HOTAIR and HOXD8 when compared to the control group. In the CML patients there was a significant increase in the expression level of HOTAIR when compared to the control group (p=0.002). The expression levels of HOXD9 and HOXD11 were found to be significantly lower than the control group (p<0.001). Our study showed that HOTAIR may not be a biomarker in the diagnosis and is not significantly correlated with the clinicopathological prognostic characteristics of AML. Additionally; it can be said that HOTAIR is oncogenic by suppressing the expression of HOXD9 and HOXD11 but not HOXD8 in CML patients. The expression profiles of HOTAIR may be a potential biomarker in the diagnosis of CML patients in predicting and monitoring drug resistance. © 2025 Elsevier B.V., All rights reserved.Article Anticancer Effect of Ethanolic Yellow Hawthorn Extract on Chronic Myeloid Leukemia Cells and Acute Myeloid Leukemia Cells(Ondokuz Mayis Universitesi, 2025) Arslan, Ayşe Nur; Akçok, IsmailCancer is a disease characterized by abnormal cell growth and invasion and metastasis of these cells to other tissues or organs of the body. Natural products have been used for centuries as drugs or in drug development, especially for the treatment of cancer. Besides, extracting natural products with several bioactive compounds has a promising effect on cancer treatment. In this study, we aimed to investigate the anticancer effect of the ethanolic extract of yellow hawthorn fruits on K562 (Chronic Myeloid Leukemia) and MOLM-13 (Acute Myeloid Leukemia) cell lines. The antiproliferative effect of the ethanolic extract of yellow hawthorn fruits was investigated in time-and dose-dependent manners. The Annexin-V/Propidium Iodide (PI) double staining was used to examine the apoptosis. Furthermore, cell cycle analysis is conducted by PI staining. The cell viability of K562 and MOLM-13 cell lines was significantly reduced by the ethanolic extract of yellow hawthorn fruits with IC50 values of 9144 µg/mL and 3515 µg/mL in 48-hour incubation time, respectively. Moreover, the results showed that the ethanolic extract of yellow hawthorn fruits caused an increased apoptosis by 12.7-and 8.87-fold changes in K562 and MOLM-13 cell lines compared to control groups, respectively. Ethanolic extract of yellow hawthorn fruit has reduced cell proliferation, induced apoptosis and arrested the cell cycle at G0/G1 phase by 71% in MOLM-13 and at G2/M phase by 80.3% and G0/G1 phase by 38.2 % in K562 cells. Further studies should be conducted to elucidate the mechanism of the effect of yellow hawthorn fruit on these cancer cells. © 2025 Elsevier B.V., All rights reserved.Article Citation - Scopus: 24Analyzing the Nexus Between Environmental Sustainability and Clean Energy for the USA(Springer, 2024-03-22) Dogan, Eyup; Si Mohammed, Kamel; Khan, Zeeshan Anis; BinSaeed, Rima Hassan; Mohammed, Kamel SiEnvironmental sustainability is a key target to achieve sustainable development goals (SDGs). However, achieving these targets needs tools to pave the way for achieving SDGs and COP28 targets. Therefore, the primary objective of the present study is to examine the significance of clean energy, research and development spending, technological innovation, income, and human capital in achieving environmental sustainability in the USA from 1990 to 2022. The study employed time series econometric methods to estimate the empirical results. The study confirmed the long-run cointegrating relationship among CO<inf>2</inf> emissions, human capital, income, R&D, technological innovation, and clean energy. The results are statistically significant in the short run except for R&D expenditures. In the long run, the study found that income and human capital contribute to further aggravating the environment via increasing CO<inf>2</inf> emissions. However, R&D expenditures, technological innovation, and clean energy help to promote environmental sustainability by limiting carbon emissions. The study recommends investment in technological innovation, clean energy, and increasing R&D expenditures to achieve environmental sustainability in the USA. © 2024 Elsevier B.V., All rights reserved.Article Citation - Scopus: 3Combined Effect of Midostaurin and Sphingosine Kinase-1 İnhibitor on FMS-Like Tyrosine Kinase 3 (FLT3) Wild Type Acute Myeloid Leukemia Cells(De Gruyter Open Ltd, 2022) Şahin, Hande Nur; Adan, AysunObjectives: Therapeutic potential of clinically approved FLT3 inhibitor midostaurin has been neglected in wild-type FLT3 positive acute myeloid leukemia (AML). Sphingosine kinase-1 (SK-1) having anti-proliferative functions is studied in various cancers, but not in FLT3 wild-type AML. We aimed to develop new therapeutic strategies to combat FLT3 wild-type AML by combining midostaurin with SK-1 inhibitor (SKI II) in THP1 cells. Methods: The anti-proliferative effects of midostaurin, SKI II and in combination on THP1 cells were determined by MTT assay. The combination indexes were calculated using calcusyn software. SK-1 expression and PARP cleavage were checked by western blot. Cell cycle distributions (PI staining) and apoptosis (annexin-V/PI dual staining) were assessed by flow cytometry for each agent alone and in combinations. Results: Midostaurin decreased SK-1 protein level. Midostaurin, SKI II and certain combinations decreased cell viability in a dose dependent manner. The combined anti-leukemic effects of the aforementioned drug combination afforded additive effect. Co-administration induced both necrosis and apoptosis via phosphatidylserine externalization, PARP cleavage and cell cycle arrest at G0/G1 and S phases. Conclusions: Targeting sphingosine kinase-1 together with FLT3 inhibition could be a novel mechanism to increase limited clinic response to midostaurin in wild-type FLT3 overexpressing AML after further pre-clinical studies. © 2022 Elsevier B.V., All rights reserved.