WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7150

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Author: search.filters.author.Baran, YusufScopus Q: search.filters.scopusQuartile.Q3

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Now showing 1 - 10 of 48
  • Article
    Citation - WoS: 2
    Citation - Scopus: 3
    Investigating the Potential Therapeutic Role of Targeting Stat3 for Overcoming Drug Resistance by Regulating Energy Metabolism in Chronic Myeloid Leukemia Cells
    (Mashhad University of Medical Sciences, 2022) Tezcanlı Kaymaz, Burçin; Günel, Nur Selvi; Söğütlü, Fatma; Özateş Ay, Neslihan Pınar; Baran, Yusuf; Gündüz, Cumhur; Biray Avcı, Çığır
    Objective(s): STATs are one of the initial targets of emerging anti-cancer agents due to their regulatory roles in survival, apoptosis, drug response, and cellular metabolism in CML. Aberrant STAT3 activity promotes malignancy, and acts as a metabolic switcher in cancer cell metabolism, contributing to resistance to TKI nilotinib. To investigate the possible therapeutic effects of targeting STAT3 to overcome nilotinib resistance by evaluating various cellular responses in both sensitive and nilotinib resistant CML cells and to test the hypothesis that energy metabolism modulation could be a mechanism for re-sensitization to nilotinib in resistant cells. Materials and Methods: By using RNAi-mediated STAT3 gene silencing, cell viability and proliferation assays, apoptotic analysis, expressional regulations of STAT mRNA transcripts, STAT3 total, pTyr705, pSer727 protein expression levels, and metabolic activity as energy metabolism was determined in CML model K562 cells, in vitro. Results: Targeting STAT3 sensitized both parental and especially nilotinib resistant cells by decreasing leukemic cell survival; inducing leukemic cell apoptosis, and decreasing STAT3 mRNA and protein expression levels. Besides, cell energy phenotype was modulated by switching energy metabolism from aerobic glycolysis to mitochondrial respiration in resistant cells. RNAi-mediated STAT3 silencing accelerated the sensitization of leukemia cells to nilotinib treatment, and STAT3-dependent energy metabolism regulation could be another underlying mechanism for regaining nilotinib response. Conclusion: Targeting STAT3 is an efficient strategy for improving the development of novel CML therapeutics for regaining nilotinib response, and re-sensitization of resistant cells could be mediated by induced apoptosis and regulation in energy metabolism.
  • Article
    Citation - WoS: 37
    Mechanisms of Cellular Resistance To Imatinib in Human Chronic Myeloid Leukemia Cells
    (Taylor and Francis Ltd., 2007) Baran, Yusuf; Ural, Ali Uğur; Gündüz, Ufuk
    A 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
    Expression Levels of Ceramide-Metabolising Genes in Newly Diagnosed and Tyrosine Kinase Inhibitor-Resistant Chronic Myeloid Leukemia (cml) Patients: the Discovery of Novel Targets in Cml
    (Elsevier Ltd., 2014) Yandım, Melis Kartal; Kozanoğlu, İlknur; Özdoğu, Hakan; Pişkin, O.; Özcan, Mehmet Ali; Saydam, Göksel; Baran, Yusuf
    [No abstract available]
  • Conference Object
    Effects of Hesperidin on Non-Small Cell Lung Cancer Cells
    (International Institute of Anticancer Research, 2014) Bireller, Elif Sinem; Cincin, Zeynep Birsu; Ünlü, Miray; Kıran, Bayram; Baran, Yusuf; Çakmakoğlu, Bedia
    Background: Hesperidin, a glycoside flavonoid that is found in citrus fruits, and the mechanisms of hesperidin-induced apoptosis are not well understood. In this study, we aimed to investigate the cytotoxic and apoptotic aspect of hesperidin induction in lung cancer.
  • Conference Object
    Inhibition of Jumonji C Domain Containing Histone Demethylases in Acute Myeloid Leukemia
    (Elsevier Ltd., 2014) Hastar, N.; Koca, D.; Baran, Yusuf
    [No abstract available]
  • Conference Object
    Jak/Stat Signalling Pathway Genes in the Regulation of Tyrosine Kinase Inhibitors Induced and Clinical Process in Chronic Myeloid Leukemia Patients
    (Elsevier, 2014) Kiraz, Yağmur; Kartal Yandım, Melis; Kozanoğlu, İlknur; Özdoğu, Hakan; Pişkin, I.; Özcan, Mehmet Ali; Saydam, Göksel; Şahin, Fahri; Avcu, Ferit; Ural, Ali Uğur; Ünal, Ali; Baran, Yusuf
    [No abstract available]
  • Conference Object
    Cytotoxic and Cytostatic Effects of Ponatinib on Imatinib-Sensitive And-Resistant Chronic Myeloid Leukemia Cells
    (Elsevier Ltd., 2014) Yandım, Melis Kartal; Baran, Yusuf
    [No abstract available]
  • 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; Öğretmen, Besim; Baran, Yusuf
    The 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; Baran, Yusuf
    In 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
    A Novel Biomarker for Drug Resistance in Chronic Myeloid Leukemia: Microrna-17
    (Elsevier Ltd., 2014) Baran, Yusuf; Fıratlıgil, Burcu; Kartal Yandım, Melis; Kiraz, Yağmur; Kozanoğlu, İlknur; Özdoğu, Hakan; Ünal, Ali
    miRNAs are single stranded small RNA molecules (20–22 nt), which do not have ability to code for proteins. These types of RNAs play significant roles on gene regulation through inhibition of their target genes. In animals, most of miRNAs show their translational inhibitor effect on target mRNAs by semi-complementation to 3’UTR sequences of mRNAs and deadenylation that cause degradation of these mRNAs. The importance of miRNAs is increasing in cancer diagnosis and treatment since they are one of the major regulators of genes such as oncogenes, tumor suppressor genes. miR-17 is an oncogenic miRNA that suppress the activation of tumor suppressor genes like CDKN1A, p21 and E2F1. Based on previous information, we aimed to determine the correlation between expression levels of miR-17 microRNA in newly diagnosed, tyrosine kinase inhibitors treated and drug resistant CML patients.