WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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

Browse

Filters

2012 - 201619

Settings

Institution Author: search.filters.institutionAuthor.Adan Gökbulut, Aysun

Search Results

Now showing 1 - 10 of 19
  • 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
    Suppression of STAT5A and STAT5B Chronic Myeloid Leukemia Cells Via SiRNA and Antisense-Oligonucleotide Applications With the Induction of Apoptosis
    (Wiley, 2014) Kaymaz, Burcin Tezcanli; Selvi, Nur; Gokbulut, Aysun Adan; Aktan, Cagdas; Gunduz, Cumhur; Saydam, Guray; Kosova, Buket
    Signal transducers and activators of transcription ( STAT) proteins function in the JAK/STAT signaling pathway and are activated by phosphorylation. As a result of this signaling event, they affect many cellular processes including cell growth, proliferation, differentiation, and survival. Increases in the expressions of STAT5A and STAT5B play a remarkable role in the development of leukemia in which leukemic cells gain uncontrolled proliferation and angiogenesis ability. At the same time, these cells acquire ability to escape from apoptosis and host immune system. In this study, we aimed to suppress STAT-5A and -5B genes in K562 CML cells by siRNA transfection and antisense oligonucleotides (ODN) targeting and then to evaluate apoptosis rate. Finally, we compared the transfection efficiencies of these approaches. Quantitative RT-PCR and Western blot results indicated that STAT expressions were downregulated at both mRNA and protein levels following siRNA transfection. However, electroporation mediated ODN transfection could only provide limited suppression rates at mRNA and protein levels. Moreover, it was displayed that apoptosis were significantly induced in siRNA treated leukemic cells as compared to ODN treated cells. As a conclusion, siRNA applications were found to be more effective in terms of gene silencing when compared to ODN treatment based on the higher apoptosis and mRNA suppression rates. siRNA application could be a new and alternative curative method as a supporting therapy in CML patients.
  • 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; Öğretmen, Besim; Baran, Yusuf
    [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
    [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
    [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
    [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
    [No abstract available]
  • Article
    Citation - WoS: 278
    Citation - Scopus: 295
    Molecular Mechanisms of Drug Resistance and Its Reversal in Cancer
    (Taylor and Francis Ltd., 2016) Kartal Yandım, Melis; Adan Gökbulut, Aysun; Baran, Yusuf
    Chemotherapy 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: 28
    Citation - Scopus: 29
    Revealing 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; Selvi Günel, Nur; Ceyhan, Metin; Bozok Çetintaş, Vildan; Özel, Buket; Kartal Yandım, Melis; Kıpçak, Sezgi; Aktan, Çağdaş; Adan Gökbulut, Aysun; Baran, Yusuf; Kosova Can, Buket
    BCR-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 miRNA