Publications (5)12.91 Total impact
-
Article: Methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms and therapy-related toxicity in children treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma.
[show abstract] [hide abstract]
ABSTRACT: 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 24 h (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 48 h (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.Leukemia & lymphoma 05/2009; 50(6):912-7. · 2.40 Impact Factor -
Article: Protein phosphatase 2A (PP2A) has a potential role in CAPE-induced apoptosis of CCRF-CEM cells via effecting human telomerase reverse transcriptase activity.
[show abstract] [hide abstract]
ABSTRACT: 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 IC(50) of 1 muM. 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 IC(20) of inhibitors and IC(50) 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 activity in CAPE treated cells simultaneously. Treating cells with IC(50) 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.Hematology (Amsterdam, Netherlands) 01/2008; 12(6):519-25. · 1.33 Impact Factor -
Article: Prothrombin G20210A mutation in cases with recurrent miscarriage: a study of the mediterranean population.
[show abstract] [hide abstract]
ABSTRACT: Thrombophilic predisposition may be one of the underlying causes of recurrent miscariage (RM). The purpose of this study was to evaluate the Prothrombin G20210A mutation in cases with history of RM. A total of 104 cases, 55 with diagnosis of RM and 49 control cases, were included in this controlled study. In all cases, in addition to full examination tests, Prothrombin 20210A mutation analysis was carried out by means of Polymerase Chain Reaction (PCR). Mean number of the abortion was 3.51 +/- 0.74 in the RM group and 0.08 +/- 0.27 in the control group (p < 0.05). As a consequence of comprehensive examinations, in 24 (43.6%) of 55 RM cases at least one etiologic factor was put forth. Prothrombin G20210A mutation was observed in six (10.9%) cases of the RM group and one (2.04%) in the control group (p < 0.05). Four of the six cases (66.7%) of Prothrombin G20210A mutation had a subsequent pregnancy. Among these four pregnancies, there was one spontaneous loss at 14 weeks of gestation and one severe pre-eclampsia. Our data together with literature suggest that Prothrombin G20210A mutation may be associated with RM. We recommend this genetic testing as a screening tool for women with history of RM.Archives of Gynecology and Obstetrics 12/2005; 273(3):170-3. · 1.28 Impact Factor -
Article: The role of angiotensin-converting enzyme and apolipoprotein-E gene polymorphisms on lipid compositions in newborn infants with intrauterine growth restriction.
[show abstract] [hide abstract]
ABSTRACT: Recent findings suggest that hypertension, dyslipidemia, diabetes mellitus, coronary heart disease are more common in adults who born with intrauterine growth restriction (IUGR). Several studies have shown that polymorphisms in angiotensin-converting enzyme (ACE) and apolipoprotein-E (Apo-E) are effective in developing the insulin resistance and also in increasing the risk of coronary heart disease. In present study, the frequencies of ACE, Apo-E gene polymorphisms, apolipoprotein-B (Apo-B) mutation and lipid compositions were determined in full-term newborn infants with IUGR. Forty-four newborn infants who had completed 36 weeks of gestational age, 24 healthy infants and 20 with IUGR, were taken into the scope of the study. While total cholesterol (TC) and Apo-B concentrations in infants with IUGR was found to be significantly higher than that of the control group (p<0.05), triglyceride (TG), low-density lipoproteins (LDL), high-density lipoproteins (HDL) and Apo-A1 levels were similar (p>0.05). An insertion/deletion (I/D) polymorphism with a significantly increased frequency was observed in the IUGR group (65%) as compared with the control group (33%) (p<0.05). When the distribution of the Apo-E gene polymorphism (E2, E3 and E4) was studied, no difference was found between the IUGR and control groups with respect to frequency. No Apo-B gene mutation was identified in the study groups. In conclusion, we may suggest that I/D polymorphism is responsible, though in part, for the etiology of intrauterine growth restriction. Levels of total cholesterol and Apo-B are elevated in IUGR infants, suggesting a linkage between low birth weight and atherosclerosis.Early Human Development 08/2004; 78(2):95-103. · 2.05 Impact Factor -
Article: Electrochemical genosensor based on colloidal gold nanoparticles for the detection of Factor V Leiden mutation using disposable pencil graphite electrodes.
[show abstract] [hide abstract]
ABSTRACT: Electrochemical genosensors for the detection of the Factor V Leiden mutation from polymerase chain reaction (PCR) amplicons using the oxidation signal of colloidal gold (Au) is described. A pencil graphite electrode (PGE) modified with target DNA, when hybridized with complementary probes conjugated to Au nanoparticles, responded with the appearance of a Au oxide wave at approximately +1.20 V. Specific probes were immobilized onto the Au nanoparticles in two different modes: (a) Inosine-substituted probes were covalently attached from their amino groups at the 5' end using N-(3-dimethylamino)propyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysulfosuccinimide (NHS) as a coupling agent onto a carboxylate-terminated l-cysteine self-assembled monolayer (SAM) preformed on the Au nanoparticles, and (b) probes with a hexanethiol group at their 5' phosphate end formed a SAM on Au nanoparticles. The genosensor relies on the hybridization of the probes with their complementary targets, which are covalently immobilized at the PGE surface. Au-tagged 23-mer capture probes were challenged with the synthetic 23-mer target, 131-base single-stranded DNA or denatured 256-base polymerase chain reaction (PCR) amplicon. The appearance of the Au oxidation signal shortened the assay time and simplified the detection of the Factor V Leiden mutation from PCR amplified real samples. The discrimination between the homozygous and heterozygous mutations was also established by comparing the peak currents of the Au signals. Numerous factors affecting the hybridization and nonspecific binding events were optimized. The detection limit for the PCR amplicons was found to be as low as 0.78 fmol; thus, it is suitable for point-of-care applications.Analytical Chemistry 06/2003; 75(9):2181-7. · 5.86 Impact Factor
