43 research outputs found

    Possible role of GADD45γ methylation in diffuse large B-cell Lymphoma: Does it affect the progression and tissue involvement?

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    Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma among adults and is characterized by heterogeneous clinical, immunophenotypic, and genetic features. Different mechanisms deregulating cell cycle and apoptosis play a role in the pathogenesis of DLBCL. Growth arrest DNA damage-inducible 45 (GADD45γ) is an important gene family involved in these mechanisms. The aims of this study are to determine the frequency of GADD45γ methylation, to evaluate the correlation between GADD45γ methylation and protein expression, and to investigate the relation between methylation status and clinicopathologic parameters in DLBCL tissues and reactive lymphoid node tissues from patients with reactive lymphoid hyperplasia. Materials and Methods: Thirty-six tissue samples of DLBCL and 40 nonmalignant reactive lymphoid node tissues were analyzed in this study. Methylation-sensitive high-resolution melting analysis was used for the determination of GADD45γ methylation status. The GADD45γ protein expression was determined by immunohistochemistry. Results: GADD45γ methylation was frequent (50.0%) in DLBCL. It was also significantly higher in advanced-stage tumors compared with early-stage (p=0.041). In contrast, unmethylated GADD45γ was associated with nodal involvement as the primary anatomical site (p=0.040). Conclusion: The results of this study show that, in contrast to solid tumors, the frequency of GADD45γ methylation is higher and this epigenetic alteration of GADD45γ may be associated with progression in DLBCL. In addition, nodal involvement is more likely to be present in patients with unmethylated GADD45γ. © 2015 Turkish Society of Hematology. All rights reserved

    In vitro testing for genotoxicity of 4-CPA by sister chromatid exchange in human lymphocyte culture

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    Certain phenoxyacetate derivatives used as plant growth regulators act as plant hormones. 2,4-D dichlorophenoxyacetic acid and 4-chlorophenoxyacetic acid are widely used in vegetable growing, especially tomatoes, in our region. These phenoxyacetic acid compounds are a potential hazard for the environment. There are conflicting results and inconsistent data about these herbicides in the literature. This is the first report of genotoxicity of 4-CPA evaluated by sister chromatid exchange in human lymphocyte culture. No significant change was found in sister chromatid exchange frequency at the tested 4-CPA concentration

    Investigation of anticancer mechanism of oleuropein via cell cycle and apoptotic pathways in SH-SY5Y neuroblastoma cells

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    Neuroblastoma is one of the most common types of pediatric tumors that can spread quickly in neuronal tissues. Oleuropein which is active compound of olive leaves, belongs to polyphenols group and has antioxidant, anti-microbial, anti-inflammatory, anti-hypertensive and anti-carcinogenic effects. The aim of the study is to determine the therapeutic effects of oleuropein on cell proliferation, invasion, colony formation, cell cycle and apoptotic mechanisms in SH-SY5Y neuroblastoma cell line under in vitro conditions. The effect of oleuropein on cell viability was determined by XTT method. 84 cell cycle control and 84 apoptosis related genes were evaluated by RT-PCR. Effects of oleuropein on apoptosis were researched by TUNEL assay. Protein expressions were determined by western blot analysis. Effects of oleuropein on cell invasion, colony formation and migration were detected by matrigel-chamber, colony formation assay and wound-healing assay, respectively. IC50 value of oleuropein in SH-SY5Y cells was detected as 350 µM at 48th hours. It is determined that oleuropein causes cell cycle arrest by down-regulating of CylinD1,CylinD2,CyclinD3,CDK4,CDK6 and up-regulating of p53 and CDKN2A, CDKN2B, CDKN1A gene expressions. Oleuropein also induces apoptosis by inhibiting of Bcl-2 and activating of Bax,caspase-9 and caspase-3 gene expressions. Apoptotic cell ratio was found 36.4 ± 3.27% in oleuropein dose group. Oleuropein decreased invasion in SH-SY5Y cells and suppressed colony numbers in ratio of 53.6 ± 4.71%.Our results demonstrated that oleuropein can be a therapeutic agent in the treatment of neuroblastoma. © 2016 Elsevier B.V
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