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    Absence of apolipoprotein B-3500 mutation in Turkish patients with coronary and cerebrovascular atherosclerosis
    (Aves Yayincilik, 2008) Eroglu, Zuhal; Selvi, Nur; Kosova, Buket; Biray, Cigir; Kumral, Emire; Topcuoglu, Nejat; Kayikcioglu, Meral
    Objective: The arginine-to-glutamine change at codon 3500 of the apolipoprotein B-100 (apo B) is a well-known genetic cause of hypercholesterolemia. Since increased cholesterol levels lead to atherosclerosis, identification of the carries of the apo B-3500 mutation is an important step in the risk stratification of individuals and families with hypercholesterolemia. The prevalence of this mutation in Turkish population is not well known. We aimed to investigate the frequency of apo B-100 mutations (codon 3500) C9774T (Arg 3500 -> Trp) and G9775A (Arg 3500 -> Gln) in patients with atherosclerosis in comparison with healthy subjects. Methods: This cross-sectional study included 442 unrelated subjects living on the West coast of Turkey. Subgroups consisted of 165 patients with coronary artery disease, 163 patients with ischemic stroke, and 114 healthy control subjects. Results: We did not find any apo B-100 mutation both in the patient and control groups. Conclusion: As it is hypothesized that this mutation arose within the Central European region from a common ancestor approximately 7000 years ago and spread across Europe, our result of the absence of the R3500Q mutation in Turkish patients give an important information about the geographical distribution of the apo B-R3500Q, that the mutation has not reached to Anatolia.
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    INFLUENCES OF GENE POLYMORPHISMS OF FOLATE METABOLISM ENZYMES ON METHOTREXATE TOXICITY
    (John Wiley & Sons Inc, 2009) Tetik, Ash; Bozok-Cetintas, Vildan; Kucukaslan, Ali Sahin; Keser, Gokhan; Inal, Vedat; Topcuoglu, Nejat; Eroglu, Zuhal
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    Leukemogenesis as a new approach to investigate the correlation between up regulated gene 4/upregulator of cell proliferation (URG4/URGCP) and signal transduction genes in leukemia
    (Springer, 2013) Dodurga, Yavuz; Oymak, Yesim; Gunduz, Cumhur; Satiroglu-Tufan, N. Lale; Vergin, Canan; Cetingul, Nazan; Avci, Cigir Biray; Topcuoglu, Nejat
    The aim of the study is to the determine the profiles of cell cycle genes and a new candidate oncogene of URG4/URGCP which play role in leukemia, establishing the association between the early prognosis of cancer and the quantitation of genetic changes, and bringing a molecular approach to definite diagnosis. In this study, 36 newly diagnosed patients' with ALL-AML in the range of 0-18 years and six control group patients' bone marrow samples were included. Total RNA was isolated from samples and then complementary DNA synthesis was performed. The obtained cDNAs have been installed 96 well plates after prepared appropriate mixtures and assessed with LightCycler(A (R)) 480 Real-Time PCR quantitatively. CHEK1, URG4/URGCP, CCNG1, CCNC, CDC16, KRAS, CDKN2D genes in the T-ALL group; CCND2, ATM, CDK8, CHEK1, TP53, CHEK2, CCNG2, CDK4, CDKN2A, E2F4, CCNC, KRAS genes in the precursor B-ALL group and CCND2, CDK6 genes in the AML group have shown significant increase in mRNA expression level. In the featured role of acute leukemia the regulating signaling pathways of leukemogenesis partially defined, although identification of new genetic markers in acute leukemia subgroups, will allow the development of early diagnostic and new treatment protocols.
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    Methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms and therapy-related toxicity in children treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma
    (Taylor & Francis Ltd, 2009) Kantar, Mehmet; Kosova, Buket; Cetingul, Nazan; Gumus, Sevinc; Toroslu, Ertug; Zafer, Nur; Topcuoglu, Nejat; Aksoylar, Serap; Cinar, Mehtap; Tetik, Asli; Eroglu, Zuhal
    This study aimed to investigate the association of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms with serum drug levels and toxicities after high-dose methotrexate (MTX) infusion. The study included 37 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma. Serum MTX levels and toxicities of bone marrow, liver and kidney were analysed. Genotype analysis of the C677T and A1298C gene polymorphisms from genomic DNA of the subjects was performed by real-time PCR. Subjects with MTHFR polymorphism for C677T (CT, TT) had significantly higher MTX levels at 24h (p=0.009), and these genotypes did not seem to cause toxicity. Subjects with MTHFR polymorphism for A1298C (AC, CC) had significantly higher MTX levels at 48h (p=0.02), and had more grade III/IV anemia (p=0.02), thrombocytopenia (p=0.0001), elevated AST levels (p=0.04) and frequent febrile neutropenic episodes (p=0.004). The present study suggests that A1298C gene, but not C677T polymorphism is associated with MTX-related toxicity.
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    Molecular evaluation and clinical correlation of T(14;18)(bcl-2/IgH) in 26 cases of follicular lymphoma: The impact of different molecular approaches
    (Springer, 2007) Selvi, Nur; Kosova, Buket; Hekimgil, Mine; Gunduz, Cumhur; Tezcanli, Burcin; Karaca, Emin; Saydam, Güray; Ertan, Yesim; Topcuoglu, Nejat
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    N-acetyltransferase 2 gene polymorphisms and susceptibility to prostate cancer: a pilot study in the Turkish population
    (Tubitak Scientific & Technical Research Council Turkey, 2010) Kosova, Buket; Cetintas, Vildan Bozok; Cal, Ahmet Cag; Tetik, Asli; Ozel, Rukiye; Aktan, Cagdas; Gunduz, Cumhur; Topcuoglu, Nejat; Cureklibatir, Ibrahim Kadri; Eroglu, Fatma Zuhal
    Aim: To Investigate the association between the 3 most frequently observed single nucleotide polymorphisms of the NAT2 gene and the risk of developing prostate cancel in the Turkish population. Materials and methods: A total of 110 unrelated patients with prostate cancer were Included in this case-control association study and constituted the study group The control group also consisted of 150 unrelated but healthy men Genomic DNA was Isolated from peripheral blood leukocytes of all patients and analyzed with a sensitive real-time PCR method After melting curve analysis genotypes were Identified for the NAT2*5A, NAT2*6A, and NAT2*7A/B polymorpisms Results: Prostate cancer patients had a higher frequency of the mutant NAT2*6A (13.6% versus 4.0%, P = 0 009) and heterozygote NAT2*7A/B (20 9% versus 9 3%, P = 0 008) genotypes when compared with the controls Conclusion: The NAT2*6A and NAT2*7A/B gene polymorphisms were significantly associated with prostate cancer in the Turkish population Real-time PCR analysis of the NAT2 acetylator phenotype can therefore be used to recognize individuals with a high risk of developing prostate cancer
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    Protein phosphatase 2A (PP2A) has a potential role in CAPE-induced apoptosis of CCRF-CEM cells via effecting human telomerase reverse transcriptase activity
    (Maney Publishing, 2007) Avci, Cigir Biray; Sahin, Fahri; Gunduz, Cumhur; Selvi, Nur; Aydin, Hikmet Hakan; Oktem, Gulperi; Topcuoglu, Nejat; Saydam, Güray
    Caffeic acid phenethyl ester (CAPE) is one of the most effective components of propolis which is collected by honey bees. The aim of this study was to investigate the cytotoxic and apoptotic effects of CAPE in the CCRF-CEM cell line and to clarify the role of serine/threonine protein phosphatase 2A (PP2A) and human telomerase reverse transcriptase (hTERT) activity as an underlining mechanism of CAPE-induced apoptosis. Trypan blue dye exclusion test and XTT methods were used to evaluate the cytotoxicity and ELISA based oligonucleotide detection, which can be seen during apoptosis, was used to determine apoptosis. Acridine orange/ethidium bromide dye technique was also used to evaluate apoptosis. The cytotoxic effect of CAPE was detected in a dose and time dependent manner with the IC50 of 1 mu M. ELISA and acridine orange/ethidium bromide methods have shown remarkable apoptosis at 48th hour in CAPE treated cells. To investigate the role of PP2A in CAPE-induced apoptosis of CCRF-CEM cells, we performed combination studies with CAPE and, Calyculin A and Okadaic acid, which are very well known inhibitors of PP2A, in IC20 of inhibitors and IC50 of CAPE. Combination studies revealed synergistic effect of both drugs by concomitant use. Western blot analyses of PP2A catalytic and regulatory subunits showed down-regulation of expression of PP2A catalytic subunit in CAPE treated cells at 48th hour. Since, PP2A is important in hTERT (telomerase catalytic subunit) activation and deactivation, we also performed hTERT activiry in CAPE treated cells simultaneously. Treating cells with IC50 of CAPE for 96 h with the intervals of 24 h showed marked reduction of hTERT activity. The reduction of hTERT activity in CAPE treated CCRF-CEM cells was more prominent in the initial 48 h. The variation of hTERT activity in CAPE treated CCRF-CEM cells may be the reason for the protein phosphatase interaction that occurred after treatment with CAPE.