TR-Dizin İndeksli Yayınlar Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/396

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    Article
    Citation - WoS: 3
    Combined Effect of Midostaurin and Sphingosine Kinase-1 Inhibitor on FMS-Like Tyrosine Kinase 3 (FLT3) Wild Type Acute Myeloid Leukemia Cells
    (Walter de Gruyter Gmbh, 2022) Sahin, Hande Nur; Adan, Aysun; 01. Abdullah Gül University; 04. Yaşam ve Doğa Bilimleri Fakültesi; 04.02. Moleküler Biyoloji ve Genetik
    Objectives Therapeutic potential of clinically approved FLT3 inhibitor midostaurin has been neglected in wild-type FLT3 positive acute myeloid leukemia (AML). Sphingosine kinase-1 (SK-1) having anti-proliferative functions is studied in various cancers, but not in FLT3 wild-type AML. We aimed to develop new therapeutic strategies to combat FLT3 wild-type AML by combining midostaurin with SK-1 inhibitor (SKI II) in THP1 cells. Methods The anti-proliferative effects of midostaurin, SKI II and in combination on THP1 cells were determined by MTT assay. The combination indexes were calculated using calcusyn software. SK-1 expression and PARP cleavage were checked by western blot. Cell cycle distributions (PI staining) and apoptosis (annexin-V/PI dual staining) were assessed by flow cytometry for each agent alone and in combinations. Results Midostaurin decreased SK-1 protein level. Midostaurin, SKI II and certain combinations decreased cell viability in a dose dependent manner. The combined anti-leukemic effects of the aforementioned drug combination afforded additive effect. Co-administration induced both necrosis and apoptosis via phosphatidylserine externalization, PARP cleavage and cell cycle arrest at G0/G1 and S phases. Conclusions Targeting sphingosine kinase-1 together with FLT3 inhibition could be a novel mechanism to increase limited clinic response to midostaurin in wild-type FLT3 overexpressing AML after further pre-clinical studies.
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    Citation - WoS: 1
    Citation - Scopus: 1
    The Comparison of Fragility Curves of Moment-Resisting and Braced Frames Used in Steel Structures Under Varying Wind Load
    (Turkish Chamber Civil Engineers, 2025) Ozalp, Abdulkadir; Gokdemir, Hande; Ciftci, Cihan; 01. Abdullah Gül University; 02.03. İnşaat Mühendisliği; 02. Mühendislik Fakültesi
    In this study, the performance of two different steel structure types (moment-resisting frame and braced frame) under wind loading was compared by addressing the fragility curves of these structure types. To perform this comparison, the dimensions of the members of these structural systems were first determined. Then, nonlinear static pushover analyses were conducted to assess the performance levels of each frame type. After applying these analyses, time-history analyses were performed with 100 different wind loads for each varying equivalent mean wind speed. Afterwards, the probability of exceeding the predetermined structural performance limits of the structure types was determined using Monte Carlo simulation method. Finally, the results of the simulation method were used to adapt the maximum likelihood estimation method to obtain the fragility curves of the structures. To conclude, it has been revealed that the material cost of the structure doubles when diagonal elements are used, but the wind speed required for a 100% collapse probability to occur in the braced frame is twice as high compared to the moment-resisting frame.