8 research outputs found
Identification of microRNA profile specific to cancer stem-like cells directly isolated from human larynx cancer specimens
Decreased DNA repair gene XRCC1 expression is associated with radiotherapy-induced acute side effects in breast cancer patients
DNA repair plays a critical role in response to ionizing radiation (IR) and developing of radiotherapy induced normal tissue reactions. In our study, we investigated the association of radiotherapy related acute side effects, with X-ray repair cross complementing group 1 (XRCC1) and Poly (ADP-ribose) polymerase 1 (PARP1) DNA repair gene expression levels, their changes in protein expression and DNA damage levels in breast cancer patients. The study included 40 women with newly diagnosed breast cancer; an experimental case group (n = 20) with acute side effects and the control group (n = 20) without side effects. For gene and protein expression analysis, lymphocytes were cultured for 72 h and followed by in vitro 2 Gray (Gy) gamma-irradiation. For detection of DNA damage levels, lymphocytes were irradiated with in vitro 2 Gy gamma-rays and followed by incubation for 72 h. XRCC1 mRNA and protein expression levels were significantly higher in controls than in experimental cases (P = 0.020). In terms of DNA damage levels, an increased frequency of micronucleus (MN) was observed in experimental cases versus controls, but this association was not significant (P = 0.206). We also observed a significant negative correlation between MN frequency and XRCC1 protein levels in experimental (r=-0.469, P = 0.037) vs control (r = -0.734, P<0.001). Our results suggested that decreased XRCC1 expression levels might be associated with the increased risk of therapeutic IR-related acute side effects in patients with breast cancer. (C) 2016 Elsevier B.V. All rights reserved
Metformin does not prevent DNA damage in lymphocytes despite its antioxidant properties against cumene hydroperoxide-induced oxidative stress
Metformin (1-(diaminomethylidene)-3.3-dimethyl-guanidine), which is the most commonly prescribed oral antihyperglycaemic drug in the world, was reported to have several antioxidant properties such as the inhibition of advanced glycation end-products. In addition to its use in the treatment of diabetes, it has been suggested that metformin may be a promising anti-aging agent. The present work was aimed at assessing the possible protective effects of metformin against DNA-damage induction by oxidative stress in vitro. The effects of metformin were compared with those of N-acetylcysteine (NAC). For this purpose, peripheral blood lymphocytes from aged (n = 10) and young (n = 10) individuals were pre-incubated with various concentrations of metformin (10-50 mu M), followed by incubation with 15 mu M cumene hydroperoxide (CumOOH) for 48 h, under conditions of low oxidant level, which do not induce cell death. Protection against oxidative DNA damage was evaluated by use of the Comet assay and the cytokinesis-block micronucleus technique. Changes in the levels of malondialdehyde + 4-hydroxy-alkenals, an index of oxidative stress, were also measured in lymphocytes. At concentrations ranging from 10 mu M to 50 mu M. metformin did not protect the lymphocytes from DNA damage, while 50 VLM NAC possessed an effective protective effect against CumOOH-induced DNA damage. Furthermore, NAC, but not metformin. inhibited DNA fragmentation induced by CumOOH. In contrast to the lack of protection against oxidative damage in lymphocyte cultures. metformin significantly protected the cells from lipid peroxidation in both age groups, although not as effective as NAC in preventing the peroxidative damage at the highest doses. Within the limitations of this study, the results indicate that pharmacological concentrations of metformin are unable to protect against DNA damage induced by a pro-oxidant stimulus in cultured human lymphocytes, despite its antioxidant properties. (c) 2006 Elsevier B.V. All rights reserved
Polymorphisms of the DNA Repair Genes XPD and XRCC1 and the Risk of Age-Related Macular Degeneration
PURPOSE. Oxidative stress seems to be an important factor in the development of age-related macular degeneration (AMD). The role of DNA repair mechanisms has also received attention recently in AMD pathogenesis. This case-control study was conducted to determine the frequency of polymorphisms in two DNA repair enzyme genes, xeroderma pigmentosum complementation group D (XPD), codons 312 and 751, and x-ray cross-complementing group 1 (XRCC1), codons 194 and 399, in patients with AMD and in disease-free control subjects
Structural Chromosomal Abnormalities in Couples with Recurrent Pregnancy Loss
Objective: Recurrent pregnancy loss is an important problem affecting couples trying to conceive. Genetic factors, particularly chromosomal abnormalities appear to be highly associated with reproductive loss. The frequency of presence of at least one partner, who is a carrier of a structural chromosome rearrangement, varies from 3% to 11% among couples with a history of recurrent pregnancy loss. The aim of this study was to introduce the cytogenetic data of couples that referred with recurrent pregnancy loss to our center. Material and Methods: Chromosome analyses were performed in 449 couples with more than one pregnancy loss using GTL banding. Results: Chromosome abnormalities were detected in one partner in 19 of 449 couples. All chromosome abnormalities were structural, and 18 of them were balanced. Autosomal reciprocal translocations were the most frequent type (2.9%) of abnormalities. The unique Robertsonian translocation found in our study was t(13;14), which was observed in two patients. Chromosomal heteromorphisms were determined in 19.59% of patients. Conclusion: The frequency of chromosomal abnormalities were found as 4.23% in our series. Cytogenetic investigation of couples with recurrent pregnancy loss is necessary as chromosomal abnormalities constitute a very important part of factors that cause pregnancy loss
Additional file 2: Figure S1. of Identification of microRNA profile specific to cancer stem-like cells directly isolated from human larynx cancer specimens
(A) Relative expression levels of miR-223 in each CD133+ and CD133− sample pairs, and (B) mean relative expression levels miR-223 in CD133+ cells with respect to CD133− cells. (C) Relative expression levels of miR-328 in each CD133+ and CD133− sample pairs, and (D) mean relative expression levels miR-328 in CD133+ cells with respect to CD133− cells. (E) Relative expression levels of miR-574-3p in each CD133+ and CD133− sample pairs, and (F) mean relative expression levels miR-574-3p in CD133+ cells with respect to CD133− cells. (JPG 392 kb