PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Citation - WoS: 6Citation - Scopus: 6Therapeutic Potentials of Inhibition of Jumonji C Domain-Containing Demethylases in Acute Myeloid Leukemia(Aves, 2020) Koca, Duygu; Hastar, Nurcan; Engür, Selin; Kiraz, Yağmur; Ulu, Gizem Tuğçe; Çekdemir, Demet; Baran, YusufAcute myeloid leukemia (AML) is a complex disease affected by both genetic and epigenetic factors. Histone methylation and demethylation are types of epigenetic modification in chromatin remodeling and gene expression. Abnormal expression of histone demethylases is indicated in many types of cancer including AML. Although many commercial drugs are available to treat AML, an absolute cure has not been discovered yet. However, inhibition of demethylases could be a potential cure for AML. Methylstat is a chemical agent that inhibits the Jumonji C domain-containing demethylases.Article Citation - WoS: 3Citation - Scopus: 3A Minimally Invasive Transfer Method of Mesenchymal Stem Cells To the Intact Periodontal Ligament of Rat Teeth: a Preliminary Study(TÜBİTAK, 2018) Gül Amuk, Nisa; Kurt, Gökmen; Kartal Yandım, Melis; Adan, Aysun; Baran, YusufThe aim of this study was to introduce a minimally invasive procedure for mesenchymal stem cell (MSC) transfer into the intact periodontal ligament (PDL) of the molar teeth in rats. Ten 12-week-old Wistar albino rats were used for this preliminary study. MSCs were obtained from bones of two animals and were labeled with green fluorescent protein (GFP). Four animals were randomly selected for MSC injection, while 4 animals served as a control group. Samples were prepared for histological analysis, Cox-2 mRNA expression polymerase chain reaction analysis, and fluorescent microscopy evaluation. The number of total cells, number of osteoclastic cells, and Cox-2 mRNA expression levels of the periodontal tissue of teeth were calculated. The number of total cells was increased with MSC injections in PDL significantly (P < 0.001). The number of osteoclastic cells and Cox-2 mRNA expression were found to be similar for the two groups. GFP-labeled MSCs were observed with an expected luminescence on the smear samples of the PDL with transferred MSCs. The results of this preliminary study demonstrate successful evidence of transferring MSCs to intact FIX in a nonsurgical way and offer a minimally invasive procedure for transfer of MSCs to periodontal tissues.Article Citation - WoS: 9Citation - Scopus: 10Effects of Notch Signalling on the Expression of Sema3c, Hmga2, Cxcl14, Cxcr7, and Ccl20 in Breast Cancer(TÜBİTAK, 2019) Küçükköse, Cansu; Yalçın Özuysal, ÖzdenMetastasis is the main reason for death in breast cancer. Understanding the molecular players in metastasis is crucial for diagnostic and therapeutic purposes. Notch signalling plays an oncogenic role in breast tumorigenesis and is involved in metastasis. Downstream mediators of Notch signalling in prometastatic processes are not yet fully discovered. Here we aimed to investigate whether Notch signalling regulates the expression of SEMA3C, HMGA2, CXCL14, CXCR7, and CCL20, which are involved in prometastatic processes, in breast cell lines. To this end, expression of the selected genes was analysed following Notch activation by overexpression of the Notch1 intracellular domain in the normal breast epithelial cell line MCF10A, and inhibition by silencing of the Notch transcriptional mediator RBPj kappa in the breast cancer cell line MDA MB 231. SEMA3C and HMGA2 mRNA were decreased, while CXCL14 and CXCR7 mRNA were increased significantly in response to Notch activation in MCF10A cells. Notch inhibition in MDA MB 231 cells significantly decreased HMGA2 and CCL20 mRNA. Protein levels were not significantly altered by Notch modulation. In conclusion, we showed that Notch signalling regulates expression of SEMA3C, CXCL14, CCL20, CXCR7, and HMGA2, which are prominent candidate genes that might function downstream of Notch to induce prometastatic processes.Article Citation - WoS: 6Citation - Scopus: 8Deep Sequencing Reveals Two Jurkat Subpopulations With Distinct Mirna Profiles During Camptothecin-Induced Apoptosis(TUBITAK, 2018) Erdoğan, İpek; Coşacak, Mehmet İlyas; Nalbant, Ayten; Akgül, BünyaminMicroRNAs (miRNAs) are small noncoding RNAs of about 19-25 nt that regulate gene expression posttranscriptionally under various cellular conditions, including apoptosis. The miRNAs involved in modulation of apoptotic events in T cells are partially known. However, heterogeneity associated with cell lines makes it difficult to interpret gene expression signatures, especially in cancer-related cell lines. Treatment of the Jurkat T-cell leukemia cell line with the universal apoptotic drug, camptothecin, resulted in identification of two Jurkat subpopulations: one that is sensitive to camptothecin and another that is rather intrinsically resistant. We sorted apoptotic Jurkat cells from nonapoptotic ones prior to profiling miRNAs through deep sequencing. Our data showed that a total of 184 miRNAs were dysregulated. Interestingly, the apoptotic and nonapoptotic subpopulations exhibited distinct miRNA expression profiles. In particular, 6 miRNAs were inversely expressed in these two subpopulations. The pyrosequencing results were validated by real-time qPCR. Altogether, these results suggest that miRNAs modulate apoptotic events in T cells and that cellular heterogeneity requires careful interpretation of miRNA expression profiles obtained from drug-treated cell lines.Article Citation - WoS: 3Citation - Scopus: 3Cloning, Expression, and Activity Analysis of Human Cathepsin C in the Yeast Pichia Pastoris(TUBITAK, 2017) Dağlıoğlu, CenkThe yeast Pichia pastoris expression system was investigated for the production of human cathepsin C (CatC) recombinant protein. The full-length CatC cDNA, corresponding to amino acids 12-475, was synthesized from interleukin-2 (IL-2) stimulated human peripheral blood mononuclear cells and subcloned in the pGEM-T cloning vector. After confirming the DNA sequence of the insert, the gene was cloned into the pPICZαA expression vector under the control of the methanol-inducible alcohol oxidase (AOX1) promoter and transformed to P. pastoris X-33 cells. The expressed protein was secreted into the culture medium through the α-factor mating signal sequence of the expression vector. Analysis of the culture supernatant revealed that the recombinant human CatC was secreted as a 58-kDa molecule, indicating that human CatC was accumulated in the culture supernatant as proform composed of the residual propart, the activation peptide, and the heavy and light chains. Extracellular recombinant proCatC was further activated by cysteine endoprotease papain in vitro and its activity was confirmed by assays using a synthetic substrate.Article Citation - WoS: 2Citation - Scopus: 3A Novel Natural Product, Kl-21, Inhibits Proliferation and Induces Apoptosis in Chronic Lymphocytic Leukemia Cells(Turkish Society of Hematology, 2015) Adan Gökbulut, Aysun; Yaşar, Mustafa; Baran, YusufObjective: The aims of this study were to examine the cytotoxic and apoptotic effects of KL-21, a novel plant product (produced by naturin natural Products, İzmir, Turkey), on 232B4 chronic lymphocytic leukemia (CLL) cells and to determine the cytotoxic effects on healthy BEAS-2B human bronchial epithelial cells. Materials and Methods: The cytotoxic effect of KL-21 was determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using the caspase-3 colorimetric assay. Changes in mitochondrial membrane potential were determined using the JC-1 dye-based method. Annexin V-FITC/PI double staining was performed to measure the apoptotic cell population. Effects of KL-21 on cell cycle profiles of CLL cells were investigated by flow cytometry. Results: We detected time- and concentration-dependent increases in the cytotoxic effect of KL-21 on 232B4 CLL cells. However, we also showed that, especially at higher concentrations, KL-21 was less cytotoxic towards BEAS-2B healthy cells than towards CLL cells. Annexin-V/PI double staining results showed that the apoptotic cell population increased in 232B4 cells. Increasing concentrations of KL-21 increased caspase-3 enzyme activity and induced loss of mitochondrial membrane potential. KL-21 administration resulted in small increases in the percentage of the cells in the G0/G1 phase while it decreased the S phase cell population up to 1 mg/mL. At the highest concentration, most of the cells accumulated in the G0/G1 phase. Conclusion: KL-21 has a growth-inhibitory effect on 232B4 CLL cells. KL-21 causes apoptosis and cell cycle arrest at G0/G1.Article Citation - WoS: 4Citation - Scopus: 7The Importance of Protein Profiling in the Diagnosis and Treatment of Hematologic Malignancies(Galenos Yayıncılık, 2011) Şanlı Mohamed, Gülşah; Turan, Taylan; Ekiz, Hüseyin Atakan; Baran, YusufProteins are important targets in cancer research because malignancy is associated with defects in cell protein machinery. Protein profiling is an emerging independent subspecialty of proteomics that is rapidly expanding and providing unprecedented insight into biological events. Quantitative assessment of protein levels in hematologic malignancies seeks a comprehensive understanding of leukemiaassociated protein patterns for use in aiding diagnosis, follow-up treatment, and the prediction of clinical outcomes. Many recently developed high-throughput proteomic methods can be applied to protein profiling. Herein the importance of protein profiling, its exploitation in leukemia research, and its clinical usefulness in the treatment and diagnosis of various cancer types, and techniques for determining changes in protein profiling are reviewed.