Browsing by Author "Okay, M."

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Open Access
Ankaferd Hemostat affects etoposide resistance of the malignant melanoma cells
(Akademi Doktorlar Yayınevi, 2020) Ghasemi, M.; Okay, M.; Malkan, Ü. Y.; Türk, S.; Jabbar, Javaid; Hocaoğlu, H.; Haznedaroğlu, İ. C.
The development of resistance towards chemotherapeutic drugs has become an obstacle in treatment of cancer. Ankaferd Hemostat [ABS] has shown to suppress the proliferation of melanoma cells, but little is known about its’ mechanism. In this study, we demon¬strate that ABS can make some melanoma cell lines such as A2058 more sensitive towards etoposide by altering the genes involved in oxidative phosphorylation [OXPHOS] pathway. ABS treatment has shown to increase the sensitivity of A2058 towards etoposide and showed no effect for SK-MEL-5. Previously known to be more resistant to etoposide, SK-MEL-30 showed least amount of sen¬sitivity to ABS. We found mitochondrion cluster to be the most relevant to genes altered by ABS. To validate our claim, we compared two sets of melanoma cell lines; A375 with A2058 and A375 with SK-MEL-2. The clusters that we obtained from A375 and A2058 comparison did contain mitochondrial related clusters, their corresponding p value was not significant. Whereas, the clusters from A375 and SK-MEL-2 comparison contain 72 genes in ‘oxidoreductase’ cluster with enrichment score of 2.52. To get insight of the oxidoreductase cluster, we put the genes in that cluster to Enrichr. We found that majority of the genes among oxidoreductase cluster participate in oxidative phosphorylation and electron transport chain. Our study suggests that the use of ABS prior to etoposide treat¬ment can increase the response of melanoma cell lines because of the alteration of OXPHOS genes.
Open Access
The impact of At1r inhibition via losartan on the anti-leukaemic effects of doxorubicin in acute myeloid leukaemia
(Sage Publications, 2019-05) Ghasemi, M.; Okay, M.; Türk, S.; Naeemaee, Ronak; Güver, Ebru; Malkan, Ü. Y.; Aksu, S.; Sayınalp, N.; Haznedaroğlu, I. C.
Introduction: Bone marrow renin–angiotensin system(RAS) modulates acute myeloid leukaemia(AML).The aim of this study is to clarify the relationships between RAS and AML, and to show the effect of losartan and doxorubicin treatment in AML cell lines. Methods: AML cell lines including CESS, HL-60, MO-1, P31/FUJ, GDM-1 and KASUMI-3 were used as models in this study. Results:After treating the six AML cell lines with a combination of losartan and doxorubicin, they were divided into two groups based on their behaviour: one became more sensitive to drug treatment (Group A) and the other had no change observed in behaviour after drug treatment (Group B). In silico analyses showed that Group A is involved in cellular apoptosis, while Group B is involved in tumour angiogenesis further supporting the in vitro results. Conclusion:The combined treatment of the AML cell lines with losartan and doxorubicin resulted in an increase in sensitivity of some of the cell lines. Those leukaemic cells are modulated via the induction of apoptosis, whereas the other cells resistant to the drug treatment are closely related to tumour angiogenesis indicating that RAS-AT1R seems to be differently expressed in different leukaemic blast cells and tumour microenvironments. Pharmaco-biological actions of RAS inhibitors may be different in distinct leukaemic cells based on the pathological behaviour of AML genomic subtypes.
Open Access
The impact of JAK/STAT inhibitor ruxolitinib on the genesis of lymphoproliferative diseases
(TÜBİTAK, 2019-04) Türk, Can; Okay, M.; Türk, S.; Temirci, Elif Sena; Javad, Osama; Aksu, S.; Sayınalp, N.; Haznedaroğlu, İ. C.
Background/aim: Ruxolitinib, a JAK/STAT signaling pathway inhibitor targeted drug, has been approved for the controlling of disease symptoms and splenomegaly in patients with myeloproliferative neoplastic diseases. Recently, it has been proposed that ruxolitinibinduced JAK/STAT pathway inhibition in myelofibrosis is associated with an elevated frequency of aggressive B-cell lymphomas. However, the biological basis and significance of this pharmacobiological adverse event is unknown. The aim of this bioinformatics study is to detect any possible confounding effects of ruxolitinib on the genesis of lymphoproliferative disorders. Materials and methods: The gene expression data were retrieved from the E-MTAB-783 Cancer Genome Project database. Gene expression data for all available genes in 26 cell lines belonging to various types of lymphomas were chosen for use in this in silico analysis. Results: We identified genes that were significant in developing resistance to ruxolitinib in lymphoma cell lines. Conclusion: Based on the results of our present study, ruxolitinib may potentially lead to the pathological expression of the transcription factors important in lymphoma genesis, neoplastic commitment on the progenitor lymphoid cells, inhibition of repressor transcriptions protective for lymphoma development, inhibition of apoptosis, promotion of neoplastic proliferation, transcriptional activation, and proliferation of malignant neoplastic B cells.
Open Access
Renin angiotensin system genes are biomarkers for personalized treatment of acute myeloid leukemia with Doxorubicin as well as etoposide
(Public Library of Science, 2020) Türk, S.; Türk, C.; Akbar, Muhammad Waqas; Küçükkaraduman, Barış; İşbilen, Murat; Demirkol-Canlı, S.; Malkan, Ü. Y.; Okay, M.; Uçar, G.; Sayınalp, N.; Haznedaroğlu, İ. C.; Güre, Ali Osmay
Despite the availability of various treatment protocols, response to therapy in patients with Acute Myeloid Leukemia (AML) remains largely unpredictable. Transcriptomic profiling studies have thus far revealed the presence of molecular subtypes of AML that are not accounted for by standard clinical parameters or by routinely used biomarkers. Such molecular subtypes of AML are predicted to vary in response to chemotherapy or targeted therapy. The Renin-Angiotensin System (RAS) is an important group of proteins that play a critical role in regulating blood pressure, vascular resistance and fluid/electrolyte balance. RAS pathway genes are also known to be present locally in tissues such as the bone marrow, where they play an important role in leukemic hematopoiesis. In this study, we asked if the RAS genes could be utilized to predict drug responses in patients with AML. We show that the combined in silico analysis of up to five RAS genes can reliably predict sensitivity to Doxorubicin as well as Etoposide in AML. The same genes could also predict sensitivity to Doxorubicin when tested in vitro. Additionally, gene set enrichment analysis revealed enrichment of TNF-alpha and type-I IFN response genes among sensitive, and TGF-beta and fibronectin related genes in resistant cancer cells. However, this does not seem to reflect an epithelial to mesenchymal transition per se. We also identified that RAS genes can stratify patients with AML into subtypes with distinct prognosis. Together, our results demonstrate that genes present in RAS are biomarkers for drug sensitivity and the prognostication of AML.