Person: YILMAZ, BETÜL
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YILMAZ
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BETÜL
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Publication Metadata only Molecular signatures in acute myeloid leukemia: from diagnosis to targeted therapy and drug repositioning(Springer, 2022-01-01) YILMAZ, BETÜL; ARĞA, KAZIM YALÇIN; KELEŞOĞLU N., YILMAZ B., ARĞA K. Y.Publication Metadata only Design and fabrication of electrospun polycaprolactone/chitosan scaffolds for ligament regeneration(PERGAMON-ELSEVIER SCIENCE LTD, 2021) İNAN, AHMET TALAT; Saatcioglu, Elif; Ulag, Songul; Sahin, Ali; Yilmaz, Betul Karademir; Ekren, Nazmi; Inan, Ahmet Talat; Palaci, Yuksel; Ustundag, Cem Bulent; Gunduz, OguzhanTendon and ligament impairments are among the most familiar injuries of the knee with acute or chronic pain conditions. The defects of anterior cruciate ligament (ACL) stay a known clinical problem. In the present study, the electrospinning method was used to fabricate 10wt.%PCL/(1, 3, 5)wt.%Chitosan (CS) appropriate and biocompatible scaffolds with a similar connective ligament geometry and structure. 10wt.%PCL/3wt.%CS demonstrated higher tensile strength value (0.58854 MPa) than other scaffolds in the tensile test. Moreover, 10wt.%PCL/3wt.%CS scaffolds had high mesenchymal stem cells (MSCs) viability value for all incubation periods. Swelling and degradation behaviours of the ligament-like scaffolds were examined in vitro for 15 days. Results reported that the highest swelling ratio was observed with CS addition for 10wt.%PCL/5wt.%CS scaffolds which value nearly reached to the 270% ratio. Scanning electron microscope proved the geometry of the scaffolds, which were suitable for ligament-like tissue. Attachment of MSCs on the scaffolds proved the network-like structure of the cells on the scaffolds.Publication Metadata only The potential use of natural products to negate hepatic, renal and neuronal toxicity induced by cancer therapeutics(PERGAMON-ELSEVIER SCIENCE LTD, 2020) YALÇIN, AHMET SUHA; Prsa, Patrik; Karademir, Betul; Bicim, Gokhan; Mahmoud, Hatem; Dahan, Inbal; Yalcin, A. Suha; Mahajna, Jamal; Milisav, IrinaDifferent types of chemotherapeutics are used for cancer treatment. These drugs act on several signal pathways, lead to programmed cell death, and damage cancer cells. Although many specific mechanisms of action have been suggested for chemotherapeutics, there are still gaps in understanding their effects. They may affect different components of the cell, particularly proteins with specific functions, such as enzymes. Recently, targeted and immuno therapies were introduced for treatment of different cancers. However, many cancer patients still depend on traditional and well-known drugs. Doxorubicin and platinum-based drugs are among the most frequently used chemotherapeutics. They are highly cytotoxic for cancer cells, but they also act on healthy cells. Hence, it is crucial to understand the mechanisms involved in order to decrease their side effects. Natural products, many of which are also available over-the-counter, may be considered to decrease various cancer drug-induced side effects. This review focuses on the use of these compounds to overcome side effects of chemotherapeutics, primarily doxorubicin and cisplatin, in the liver, kidney, and neuronal systems.Publication Metadata only Glioblastoma cell adhesion properties through bacterial cellulose nanocrystals in polycaprolactone/gelatin electrospun nanofibers(ELSEVIER SCI LTD, 2020) YILMAZ, BETÜL; Unal, Semra; Arslan, Sema; Yilmaz, Betul Karademir; Kazan, Dilek; Oktar, Faik Nuzhet; Gunduz, OguzhanGlioblastoma (GBM), the most common and extremely lethal type of brain tumor, is resistant to treatment and shows high recurrence rates. In the last decades, it is indicated that standard two-dimensional (2D) cell culture is inadequate to improve new therapeutic strategies and drug development. Hence, well-mimicked three-dimensional (3D) tumor platforms are needed to bridge the gap between in vitro and in vivo cancer models. In this study, bacterial cellulose nano-crystal (BCNC) containing polycaprolactone (PCL) /gelatin (Gel) nanofibrous composite scaffolds were successfully fabricated by electrospinning for mimicking the extracellular matrix of GBM tumor. The fiber diameters in the nanofibrous matrix were increased with an increased concentration of BCNC. Moreover, fiber morphology changed from the smooth formation to the beaded formation by increasing the concentration of the BCNC suspension. In-vitro biocompatibilities of nanofibrous scaffolds were tested with U251 MG glioblastoma cells and improved cell adhesion and proliferation was compared with PCL/Gel. PCL/Gel/BCNC were found suitable for enhancing axon growth and elongation supporting communication between tumor cells and the microenvironment, triggering the process of tumor recurrence. Based on these results, PCL/Gel/BCNC composite scaffolds are a good candidate for biomimetic GBM tumor platform.Publication Metadata only In vitro evaluation of biomaterials for neural tissue engineering(Elsevier Science, Oxford/Amsterdam , 2023-04-01) ŞAHİN, ALİ; YILMAZ, BETÜL; Şahin A., Çıkı B., Yılmaz B.Publication Metadata only Past, present, and future of therapies for pituitary neuroendocrine tumors: need for omics and drug repositioning guidance(2022-03-01) ERDOĞAN, ONUR; ARĞA, KAZIM YALÇIN; BOZKURT, SÜHEYLA; BAYRAKLI, FATİH; YILMAZ, BETÜL; TURANLI, BESTE; Aydin B., Yildirim E., ERDOĞAN O., ARĞA K. Y., Yilmaz B., BOZKURT S., BAYRAKLI F., TURANLI B.Innovation roadmaps are important, because they encourage the actors in an innovation ecosystem to creatively imagine multiple possible science future(s), while anticipating the prospects and challenges on the innovation trajectory. In this overarching context, this expert review highlights the present unmet need for therapeutic innovations for pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas. Although there are many drugs used in practice to treat PitNETs, many of these drugs can have negative side effects and show highly variable outcomes in terms of overall recovery. Building innovation roadmaps for PitNETs\" treatments can allow incorporation of systems biology approaches to bring about insights at multiple levels of cell biology, from genes to proteins to metabolites. Using the systems biology techniques, it will then be possible to offer potential therapeutic strategies for the convergence of preventive approaches and patient-centered disease treatment. Here, we first provide a comprehensive overview of the molecular subtypes of PitNETs and therapeutics for these tumors from the past to the present. We then discuss examples of clinical trials and drug repositioning studies and how multi-omics studies can help in discovery and rational development of new therapeutics for PitNETs. Finally, this expert review offers new public health and personalized medicine approaches on cases that are refractory to conventional treatment or recur despite currently used surgical and/or drug therapy.Publication Metadata only Fabrication of tissue-engineered tympanic membrane patches using 3D-Printing technology(ELSEVIER, 2021) ŞAHİN, ALİ; Ilhan, Elif; Ulag, Songul; Sahin, Ali; Yilmaz, Betul Karademir; Ekren, Nazmi; Kilic, Osman; Sengor, Mustafa; Kalaskar, Deepak M.; Oktar, Faik Nuzhet; Gunduz, OguzhanIn recent years, scaffolds produced in 3D printing technology have become more widespread tool due to providing more advantages than traditional methods in tissue engineering applications. In this research, it was aimed to produce patches for the treatment of tympanic membrane perforations which caused significant hearing loss by using 3D printing method. Polylactic acid(PLA) scaffolds with Chitosan(CS) and Sodium Alginate(SA) added in various ratios were prepared for artificial eardrum patches. Different amounts of chitosan and sodium alginate added to PLA increased the biocompatibility of the produced scaffolds. The created patches were designed by mimicking the thickness of the natural tympanic membrane thanks to the precision provided by the 3D printed method. The produced scaffolds were analyzed separately for chemical, morphological, mechanical and biocompatibility properties. Scanning electron microscope (SEM), Fourier-transform infrared (FT-IR) spectroscopy was performed to observe the surface morphology and chemical structure of the scaffolds. Mechanical, thermal and physical properties, swelling and degradation behaviors were examined to fully analyze whole characteristic features of the samples. Cell culture study was also performed to demonstrate the biocompatibility properties of the fabricated scaffolds with human adipose tissue-derived mesenchymal stem cells (hAD-MSCs). 15 wt % PLA was selected as the control group and among all concentrations of CS and SA, groups containing 3 wt% CS and 3 wt% SA showed significantly superior and favorable features in printing quality. The research continued with these two scaffolds (3 wt% CS, and 3 wt% SA), which showed improved print quality when added to PLA. Overall, these results show that PLA/CS and PLA/SA 3D printed artificial patches have the potential to tissue engineering solutions to repair tympanic membrane perforation for people with hearing loss.Publication Metadata only Transcriptomics-based drug repurposing unravels novel therapeutic strategies in AML(2022-11-16) TURANLI, BESTE; ARĞA, KAZIM YALÇIN; YILMAZ, BETÜL; KELEŞOĞLU N., Korkmaz N. S., TURANLI B., ARĞA K. Y., YILMAZ B., ATEŞ DURU Ö.Acute myeloid leukemia (AML) is a disease of the hematopoietic system in which abnormal cells multiply rapidly, accumulate in the blood and bone marrow, and prevent the production of healthy blood cells. To date, first-line treatment of AML has been based primarily on conventional chemotherapy. Despite progress, the rate of complete remission in AML remains low, especially in older patients, and the relapse rate after complete remission remains high. The combination of clinical and laboratory data has been shown to play an important role in the development of new therapeutic strategies in AML, in addition to features of tumor histopathogenesis and transcriptional regulation. 1 Therefore, we integrated transcriptomics data from relapsed, refractory, and previously untreated AML patients based on their response to therapy using disease-specific signatures with biological and pharmacological data to enable rational identification of the potential of signaling pathways and drugs in AML. Based on the integration of transcriptomics data, we identified eight drug candidates by repurposing and evaluated their potential by in vitro testing in the HL60 and KG -1 cell lines. Six repurposed drugs, including nortriptyline, desipramine, doxepin, estramustine, risedronate, and hydrochlorothiazide, were proposed as potential drug candidates for the treatment of AML. We confirmed possible mechanisms of action of the drugs on cell viability HL -60 and KG -1 by apoptosis assays and Western blotting. Given the beneficial effects of the drugs on the apoptosis pathway, our results are intriguing and suggest that these therapies may prove useful and be potential candidates for the future treatment of AML.Publication Metadata only Acute myeloid leukemia: New multiomics molecular signatures and implications for systems medicine diagnostics and therapeutics innovation(2022-07-01) ARĞA, KAZIM YALÇIN; TURANLI, BESTE; YILMAZ, BETÜL; Kelesoglu N., Kori M., TURANLI B., ARĞA K. Y., Yilmaz B., Duru O. A.Acute myeloid leukemia (AML) is a common, complex, and multifactorial malignancy of the hematopoietic system. AML diagnosis and treatment outcomes display marked heterogeneity and patient-to-patient variations. To date, AML-related biomarker discovery research has employed single omics inquiries. Multiomics analyses that reconcile and integrate the data streams from multiple levels of the cellular hierarchy, from genes to proteins to metabolites, offer much promise for innovation in AML diagnostics and therapeutics. We report, in this study, a systems medicine and multiomics approach to integrate the AML transcriptome data and reporter biomolecules at the RNA, protein, and metabolite levels using genome-scale biological networks. We utilized two independent transcriptome datasets (GSE5122, GSE8970) in the Gene Expression Omnibus database. We identified new multiomics molecular signatures of relevance to AML: miRNAs (e.g., mir-484 and miR-519d-3p), receptors (ACVR1 and PTPRG), transcription factors (PRDM14 and GATA3), and metabolites (in particular, amino acid derivatives). The differential expression profiles of all reporter biomolecules were crossvalidated in independent RNA-Seq and miRNA-Seq datasets. Notably, we found that PTPRG holds important prognostication potential as evaluated by Kaplan-Meier survival analyses. The multiomics relationships unraveled in this analysis point toward the genomic pathogenesis of AML. These multiomics molecular leads warrant further research and development as potential diagnostic and therapeutic targets.Publication Metadata only Combination of second-generation proteasome inhibitor carfilzomib with bortezomib in four different breast cancer cell lin(2022-01-01) YILMAZ GÖLER, AYŞE MİNE; ŞAHİN, ALİ; YILMAZ, BETÜL; Altundag E. M., Yilmaz A. M., Sahin A., Yilmaz B.Background: Proteasome inhibitors target different pathways in cells and therefore are promising drugs in cancer therapy. The use of these inhibitors is approved mainly in hematological cancers, and recently many clinical trials and preclinical studies have been conducted on efficacy in solid tumors. Carfilzomib is a second-generation inhibitor and was developed to decrease the side effects of bortezomib. Although there are many valid therapies for breast cancer, resistance and recurrence are inevitable in many cases and the proteasomal system plays an important role in related pathways. Objective: This study is a preliminary work to evaluate the combined effects of bortezomib and carfilzomib in four different breast cancer cells. Methods: MDA-MB-231, MCF-7, UACC-2087, and SKBR-3 cell lines were used. Cell viability was determined using bortezomib and carfilzomib alone and in combination. Combination effect values were determined using the Chou-Talalay method. Apoptosis, proteasome activity, cleaved PARP, and HSP70 expressions were analyzed in the determined doses. Results: The response to the combination of the two inhibitors was different in four cell lines. Apoptosis was significantly higher in combination groups compared to carfilzomib in three cell lines except for SKBR-3, and higher in the combination group compared to bortezomib only in UACC-2087. Combination decreased cleaved PARP levels in MDA-MB-231 and MCF-7 and increased SKBR-3 compared to bortezomib. HSP70 levels decreased in combination with UACC-2087 and SKBR-3 compared to carfilzomib. Conclusion: Taken together, the combination of the two inhibitors was more apoptotic compared to carfilzomib and apoptosis was higher only in UACC-2087 compared to bortezomib. This apoptosis data can not be directly correlated to the degree of proteasome inhibition, PARP cleavage, and HSP70 response.