Browsing by Author "Aksu, S."
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Item 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.Item 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.Item Open Access A narrow-band multi-resonant metamaterial in near-ir(MDPI AG, 2020) Ali, Farhan; Aksu, S.We theoretically investigate a multi-resonant plasmonic metamaterial perfect absorber operating between 600 and 950 nm wavelengths. The presented device generates 100% absorption at two resonance wavelengths and delivers an ultra-narrow band (sub-20 nm) and high quality factor resonance. The studied perfect absorber is a metal–insulator–metal configuration where a thin MgF spacer is sandwiched between an optically thick gold layer and uniformly patterned gold circular nanodisc antennas. The localized and propagating nature of the plasmonic resonances are characterized and confirmed theoretically. The origin of the perfect absorption is investigated using the impedance matching and critical coupling phenomenon. We calculate the effective impedance of the perfect absorber and confirm the matching with the free space impedance. We also investigate the scattering properties of the top antenna layer and confirm the minimized reflection at resonance wavelengths by calculating the absorption and scattering cross sections. The excitation of plasmonic resonances boost the near-field intensity by three orders of magnitude which enhances the interaction between the metamaterial surface and the incident energy. The refractive index sensitivity of the perfect absorber could go as high as nm/RIU. The presented optical characteristics make the proposed narrow-band multi-resonant perfect absorber a favorable platform for biosensing and contrast agent based bioimaging.Item Open Access Robustness of massively parallel sequencing platforms(Public Library of Science, 2015) Kavak P.; Yüksel, B.; Aksu, S.; Kulekci, M.O.; Güngör, T.; Hach F.; Şahinalp, S.C.; Alkan, C.; Saʇiroʇlu, M.Ş.The improvements in high throughput sequencing technologies (HTS) made clinical sequencing projects such as ClinSeq and Genomics England feasible. Although there are significant improvements in accuracy and reproducibility of HTS based analyses, the usability of these types of data for diagnostic and prognostic applications necessitates a near perfect data generation. To assess the usability of a widely used HTS platform for accurate and reproducible clinical applications in terms of robustness, we generated whole genome shotgun (WGS) sequence data from the genomes of two human individuals in two different genome sequencing centers. After analyzing the data to characterize SNPs and indels using the same tools (BWA, SAMtools, and GATK), we observed significant number of discrepancies in the call sets. As expected, the most of the disagreements between the call sets were found within genomic regions containing common repeats and segmental duplications, albeit only a small fraction of the discordant variants were within the exons and other functionally relevant regions such as promoters. We conclude that although HTS platforms are sufficiently powerful for providing data for first-pass clinical tests, the variant predictions still need to be confirmed using orthogonal methods before using in clinical applications. © 2015 Kavak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.