WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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Article Citation - WoS: 37Mechanisms of Cellular Resistance To Imatinib in Human Chronic Myeloid Leukemia Cells(Taylor and Francis Ltd., 2007) Baran, Yusuf; Baran, Yusuf; Ural, Ali Uğur; Gündüz, Ufuk; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyA major advancement in the treatment of chronic myeloid leukemia (CML) has been the development of imatinib, which has shown striking activity in the chronic phase and the accelerated phase, but less so in the blast phase of the disease. Despite high rates of hematologic and cytogenetic responses to therapy, the emergence of resistance to imatinib has been recognized as a major problem in the treatment of patients with CML. Various cellular mechanisms may be involved in the nature of cellular resistance. Increased amount of target, alteration in structure of target proteins, decreased drug uptake and increased detoxification are well-known mechanisms of resistance. On the other hand, in some cases, even if anticancer drugs reach their sites of action, bypassing drug efflux system of the cells, some cells still may survive via the dysregulation of apoptotic signalling. In this study, mechanisms of resistance to imatinib-induced apoptosis in human Meg-01 CML cells were examined. Continuous exposure of cells to step-wise increasing concentrations of imatinib resulted in the selection of 200- and 1000 nM imatinib-resistant sub-lines referred to as Meg-01/IMA-0,2 and Meg-01/1MA-1, respectively. MTT cell proliferation, cell cycle analyses and trypan blue dye exclusion analyses showed that Meg-0l/IMA-1 cells were resistant to imatinib-induced apoptosis as compared to parental sensitive cells. There was an increased expression of BCR/ABL, Bcl-2 and an increase in mitochondrial membrane potential (MMP) detected in resistant cells comparing to parental sensitive cells. There was no mutation detected in imatinib binding site of ABL kinase region. Various diverse mechanisms have been reported for their involvement in the multidrug resistance. In this study, it has been shown that the degree of BCR/ABL expression appears to be directly proportional to the levels of imatinib resistance. In addition, there have been BCR/ABL-independent mechanisms reported for deriving resistance against imatinib. Our results revealed that besides BCR/ABL overexpression, imatinib resistance also depends on the inhibition of apoptosis as a result of up-regulation of anti-apoptotic stimuli and down-regulation of pro-apoptotic stimuli through MMP but does not depend on any mutation on imatinib binding site of ABL kinase.Conference Object The Cytoprotective Effects of Zinc on Cyclophosphamide Induced Hematoxicity(Elsevier Ltd., 2007) Ayhancı, Adnan; Doğan, Sevgi Zeynep; Appak, Sıla; Doğan, Sevgi; 02.02. Department of Architecture; 02. Faculty of Architecture; 01. Izmir Institute of Technology[No abstract available]Conference Object Citation - WoS: 1A Study of Multiple Drug Resistance Mechanisms Improved Against Bortezomib on Multiple Myeloma Cell Lines in Vitro(American Society of Hematology, 2007) Uyuklu, Tolga; Baran, Yusuf; Ural, A. Uğur; Sarper, Metal; Avcu, Ferit; Baran, Yusuf; Elçi, Pınar; Akar, Nejat; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyThe most important problem in the treatment of Multiple Myeloma (MM) is the multi drug resistance (MDR) observed before and after the treatment. For this reason in MM cases an early resistance to treatment can be developed or the disease can relapsed in early period. Yet, there has been no improved drug resistance against proteazom inhibitor Bortezomib (Bor), which is used alone or with other chemotherapeutic agents in resistant or relapsed MM casesConference Object Dietary Garlic Prevents Development of Diabesity in Mice(FASEB, 2009) Tu, Chen-Pei David; Akgül, Bünyamin; Akgül, Bünyamin; Lin, Kai-Wei; Pan, Huei-Ju; Chen, Yen-Hui; Lu, Tzu-Huan; Chen, Yuan-Tsong; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology[No abstract available]Conference Object Accumulation of Apoptotic Ceramides Increased Apoptotic Effects of Nilotinib in Philadelphia Positive Meg-01 Cells Synergistically(Ferrata Storti Foundation, 2009) Baran, Yusuf; Baran, Yusuf; Gençer, Emel Başak; Ural, Ali Uğur; Avcu, Ferit; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology[No abstract available]Conference Object Increasing De Novo Synthesis of Ceramides Increased Nilotinib Induced Apoptosis in Human Meg-01 Chronic Megacaryoblastic Cells(Ferrata Storti Foundation, 2009) Baran, Yusuf; Baran, Yusuf; Gençer, Emel Başak; Ural, Ali Uğur; Avcu, Ferit; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology[No abstract available]Conference Object Targeting Ceramide Metabolism Increased Sensitivity of Philadelphia Positif Chronic Megacaryoblastic Leukemia Cells To Dasatinib(Ferrata Storti Foundation, 2009) Gençer, Emel Başak; Baran, Yusuf; Ural, Ali Uğur; Avcu, Ferit; Baran, Yusuf; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology[No abstract available]Conference Object The Effects of Ceramide, Glucosylceramide and Sphingosine 1 Phosphate in Resveratrol Induced Cell Death in Hl60 Acute Promyelocytic Leukemia Cells(Ferrata Storti Foundation, 2009) Çakır, Zeynep; Baran, Yusuf; Saydam, Güray; Şahin, Fahri; Baran, Yusuf; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology[No abstract available]Conference Object Citation - WoS: 1Increasing Intracellular Generation or Accumulation of Ceramides Increased Cytotoxic Effects of Resveratrol in Human K562 Chronic Myeloid Leukemia Cells(Ferrata Storti Foundation, 2009) Kartal Yandım, Melis; Baran, Yusuf; Saydam, Güray; Şahin, Fahri; Baran, Yusuf; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology[No abstract available]Conference Object Nilotinib Significantly Induces Apoptosis in Imatinib Resistant K562 Cells, as Effectively as in Parental Sensitive Counterparts(Ferrata Storti Foundation, 2009) Baran, Yusuf; Ekiz, Hüseyin Atakan; Can, Geylani; Baran, Yusuf; Ekiz, Hüseyin Atakan; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology[No abstract available]