WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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Conference Object Targeting Sphingosine Kinase-1/Spingosine-1-phosphate Receptor 2 Signalling Pathway To Overcome T315i Mutation in 32dcl3 Cells(Elsevier Ltd., 2014) Adan Gökbulut, Aysun; Baran, Yusuf; Öğretmen, Besim; Adan Gökbulut, Aysun; Baran, Yusuf; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyThe main problem in chronic myeloid leukemia patients is the development of resistance against tyrosine kinase inhibitors. The expression of BCR-ABL1 having T315 mutation is responsible for the development of nilotinib resistance. The alterations in sphingolipid signalling pathway is a significant BCR-ABL1-dependent resistance mechanism. Recently, we showed that sphingosine kinase-1 (SK-1)/sphingosine-1 phosphate (S1P)-mediated drug resistance is transduced via sphingosine-1 phosphate receptor 2 (S1P2) that inhibits protein phosphatase 2A (PP2A), causing increased stability of BCR-ABL1. However, specific signaling cascade involved in this process remain unkown. In this study, BCR-ABL1 expressing 32Dcl3 cells, 32D-p210Bcr-Abl(wt) and 32D-p210Bcr-Abl (T315I) were used. The antiproliferative effects of nilotinib, SK-1 inhibitor (PF-543), S1P2 inhibitor (JTE-013), phospholipase C inhibitor (U-73122) and nilotinib/PF-543 and nilotinib/JTE-013 combinations on wt and resistant cells were determined by MTT assay. Isobologram analysis was performed using CompuSyn program.Conference Object Therapeutic Potential of Fisetin, Vitexin and Hesperetin on Chronic Myeloid Leukemia Cells(Elsevier Ltd., 2014) Adan Gökbulut, Aysun; Adan Gökbulut, Aysun; Baran, Yusuf; Baran, Yusuf; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyIn Chronic Myeloid Leukemia (CML) treatment, despite therapeutic efficacy of tyrosine kinase inhibitors, resistance development and side effects cause problems. Fisetin, vitexin and hesperetin are plant-derived flavonoids. In this study, therapeutic potentials of fisetin, vitexin and hesperetin were determined in CML cells. Cytotoxic effects of flavonoids were determined by MTT assay while apoptotic effects were determined by changes in caspase- 3 activity, loss of mitochondrial membrane potential (MMP) and Annexin V/PI double staining. Cytostatic effects of the flavonoids were evaluated by propidium iodide staining using flow cytometry.Conference Object Sphingosine-1 Receptor 2/Gq C Axis Is a Novel Mechanism To Overcome Nilotinib Resistance in T315i Mutation Expressing 32dcl3 Murine Cells(Ferrata Storti Foundation, 2015) Adan Gökbulut, Aysun; Adan Gökbulut, Aysun; Öğretmen, Besim; Baran, Yusuf; Baran, Yusuf; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology[No abstract available]Conference Object A Genome-Wide Analyses of Differentially Expressed Genes and Related Networks Affected by Fisetin and Hesperetin in Chronic Myeloid Leukemia Cells(Ferrata Storti Foundation, 2015) Adan Gökbulut, Aysun; Baran, Yusuf; Baran, Yusuf; Adan Gökbulut, Aysun; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology[No abstract available]Conference Object The Microarray Gene Profiling Analysis of Acute Promyelocytic Leukemia Cells in Response To Fisetin and Hesperetin(Ferrata Storti Foundation, 2015) Adan Gökbulut, Aysun; Baran, Yusuf; Baran, Yusuf; Adan Gökbulut, Aysun; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology[No abstract available]Conference Object Investigation of Effects of Fisetin, Vitexin and Hesperetin on Chronic Myeloid Leukemia Cells(Ferrata Storti Foundation, 2014) Adan Gökbulut, Aysun; Baran, Yusuf; Baran, Yusuf; Adan Gökbulut, Aysun; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology[No abstract available]Conference Object Therapeutic Potential of Fisetin and Identification of Its Mechanisms in Action in Chronic Myeloid Leukemia and Acute Promyelocytic Leukemia Cells(John Wiley and Sons Inc., 2015) Adan Gökbulut, Aysun; Baran, Yusuf; Baran, Yusuf; Adan Gökbulut, Aysun; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology[No abstract available]Article Citation - WoS: 278Citation - Scopus: 295Molecular Mechanisms of Drug Resistance and Its Reversal in Cancer(Taylor and Francis Ltd., 2016) Kartal Yandım, Melis; Adan Gökbulut, Aysun; Adan Gökbulut, Aysun; Baran, Yusuf; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyChemotherapy is the main strategy for the treatment of cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance. The resistance can be intrinsic or acquired. The resistance phenotype is associated with the tumor cells that gain a cross-resistance to a large range of drugs that are structurally and functionally different. Multidrug resistance arises via many unrelated mechanisms, such as overexpression of energy-dependent efflux proteins, decrease in uptake of the agents, increase or alteration in drug targets, modification of cell cycle checkpoints, inactivation of the agents, compartmentalization of the agents, inhibition of apoptosis and aberrant bioactive sphingolipid metabolism. Exact elucidation of resistance mechanisms and molecular and biochemical approaches to overcome multidrug resistance have been a major goal in cancer research. This review comprises the mechanisms guiding multidrug resistance in cancer chemotherapy and also touches on approaches for reversing the resistance.Article Citation - WoS: 28Citation - Scopus: 29Revealing Genome-Wide Mrna and Microrna Expression Patterns in Leukemic Cells Highlighted “hsa-Mir as a Tumor Suppressor for Regain of Chemotherapeutic Imatinib Response Due To Targeting Stat5a(SAGE Publications Inc., 2015) Tezcanlı Kaymaz, Burçin; Baran, Yusuf; Ceyhan, Metin; Bozok Çetintaş, Vildan; Adan Gökbulut, Aysun; Kartal Yandım, Melis; Kıpçak, Sezgi; Aktan, Çağdaş; Adan Gökbulut, Aysun; Baran, Yusuf; Kosova Can, Buket; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyBCR-ABL oncoprotein stimulates cell proliferation and inhibits apoptosis in chronic myeloid leukemia (CML). For cure, imatinib is a widely used tyrosine kinase inhibitor, but developing chemotherapeutic resistance has to be overcome. In this study, we aimed to determine differing genome-wide microRNA (miRNA) and messenger RNA (mRNA) expression profiles in imatinib resistant (K562/IMA-3 μM) and parental cells by targeting STAT5A via small interfering RNA (siRNA) applications. After determining possible therapeutic miRNAs, we aimed to check their effects upon cell viability and proliferation, apoptosis, and find a possible miRNAArticle Citation - WoS: 6Citation - Scopus: 7Nilotinib Does Not Alter the Secretory Functions of Carotid Artery Endothelial Cells in a Prothrombotic or Antithrombotic Fashion(SAGE Publications Inc., 2015) Katgı, Abdullah; Sevindik, Ömer Gökmen; Baran, Yusuf; Adan Gökbulut, Aysun; Yüksel, Faize; Solmaz, Şerife Medeni; Alacacıoğlu, İnci; Özcan, Mehmet Ali; Demirkan, Fatih; Baran, Yusuf; Pişkin, Özden; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyBackground: There have been concerns about the possible prothrombotic effects of nilotinib, especially in patients having cardiovascular risk factors. The potential mechanism behind the increased risk of thromboembolic events is still not clear. Objectives: In this study, we aimed to evaluate possible harmful effects of nilotinib on endothelial cells. To this aim, we examined proliferative capacity and secretory functions of healthy human carotid artery endothelial cells (HCtAECs) in response to nilotinib. Methods: 3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation method was used to determine antiproliferative effects of nilotinib on HCtAECs. The HCtAECs were incubated with 5, 10, and 100 nmol/L doses of nilotinib for 72 hours. Then, in order to assess the endothelial function, levels of nitric oxide (NO), von Willebrand factor (vWF), tissue plasminogen activator, plasminogen activator inhibitor 1 (PAI-1), and endothelin 1 (ET-1) were evaluated using enzyme-linked immunosorbent assay from tissue culture supernatants. Results: There were slight but statistically significant decreases in cell proliferation in response to nilotinib. Nilotinib increased the secretion of t-PA, PAI-1, and vWF in a dose-dependent manner when compared with the untreated control group. The ET-1 secretion was lower in 5 nmol/L and higher in 10 and 100 nmol/L nilotinib-treated cells as compared to untreated cells. Regarding NO secretion, lower levels were observed in 5 and 10 nmol/L, and higher levels were detected in 100 nmol/L nilotinib-treated cells as compared to untreated control group cells. Conclusion: Considering the results obtained in our study, nilotinib does not affect the functions of endothelial cells either in a prothrombotic or an antithrombotic fashion, despite a dose-dependent decline in cell viability.