Search results for " TOXIC"

Ochratoxin A and T-2 Toxin Induce Clonogenicity and Cell Migration in Human Colon Carcinoma and Fetal Lung Fibroblast Cell Lines

2016

T-2 toxin and Ochratoxin A (OTA) are toxic secondary metabolites produced by various fungi, and together they contaminate feedstuffs worldwide. T-2 toxin and OTA may exert carcinogenic action in rodent. Despite the various in vivo experiments, carcinogenicity of these two mycotoxins has not yet been proven for human. In this current study, we proposed to investigate, in Human colon carcinoma cells and fetal lung fibroblast-like cells transfected with MYC, the effect of T-2 toxin and OTA on cell clonogenicity and cell migration. Results of the present investigation showed that T2-toxin as well as OTA has an important clonogenic effect in all cell lines, suggesting that these mycotoxins could…

Impact of novel polymorphisms related to cytotoxicity of cytarabine in the induction treatment of acute myeloid leukemia.

2017

Several novel single nucleotide polymorphisms (SNPs) involved in cytarabine cytotoxicity and related to clinical outcomes have been reported recently in a series of 232 pediatric patients with acute myeloid leukemia (AML). We report the first adult AML cohort in which the influence of these SNPs in cytarabine efficacy and toxicity was analyzed. Six of polymorphisms with clinical significance in the previous study [rs12036333, rs10758713, rs9883101, rs6550826, IRX2: rs2897047, mutated in colorectal cancers (MCC): rs7729269] were analyzed in a cohort of 225 adult patients at initial diagnosis of AML treated with an induction scheme of idarubicin plus cytarabine. The variant alleles of rs12036…

CXC chemokine ligand 4 (CXCL4) is predictor of tumour angiogenic activity and prognostic biomarker in non-small cell lung cancer (NSCLC) patients und…

2016

AbstractObjective: To evaluate the association of CXC chemokine ligand 4 (CXCL4) plasma levels with tumour angiogenesis in non-small cell lung cancer (NSCLC) and to assess association of CXCL4 with clinical outcomes.Patients and methods: Fifty patients with early stage NSCLC who underwent pulmonary resection. CXCL4 levels were analysed by ELISA. Angiogenesis was assessed by immunohistochemistry, and microvessel density (MVD) count.Results: There was positive correlation between MVD and CXCL4 levels. Patients with higher CXCL4 levels had worse overall and disease-free survival.Conclusions: Plasma levels of CXCL4 are associated with tumour vascularity. Increased CXCL4 levels in NSCLC patients…

Correlation between polymorphism of TYMS gene and toxicity response to treatment with 5-fluoruracil and capecitabine

2020

Tumorigenesis is a multiphasic process in which genetic alterations guide the progressive transformation in cancer cells1. In order to evaluate the possible correlation between some gene variants and the risk of the toxicity development onset, two of the polymorphisms of the thymidylate synthase (TYMS), rs34743033 (2R/3R) and rs16430 (DEL/INS) were investigated. We enrolled in our study 47 patients from the Hospital of Sicily. Our preliminary findings suggest that there could be a linkage between the genotypes discussed and the development of the toxicity following the chemotherapy treatment. These results need to be confirmed by further studies, however this short paper offers some initial…

New insights in primary ciliary dyskinesia

2017

Introduction: Primary ciliary dyskinesia (PCD) is a rare genetic disease with an estimated prevalence of 1:20.000 births. It is characterized by abnormal motility of cilia, leading to impaired mucociliary clearance, and subsequent infection and chronic inflammation of the airways. PCD also affects spermatozoa and cilia in the Fallopian tubes, contributing to fertility issues; dyskinesia of embryonic nodal cilia causes a random distribution of the organs. Areas covered: An overview of the history, genetics, clinical manifestations in children and adults, diagnostic tests, treatments, and prognosis are reviewed. We also discuss current research and future prospects of PCD. Expert opinion: As …

Cystic fibrosis treatment: targeting the basic defect

2017

ABSTRACTIntroduction: Cystic Fibrosis (CF) is a disease caused by different class mutations in the CF transmembrane conductance regulator (CFTR) gene. It can therefore benefit from a personalized medicine approach based on the individual genotype of each patient.Areas covered: This review provides a detailed overview of the current major development of new CF treatments that target the basic CF defect. The review summarizes gene therapy, mRNA repair strategies, read-through agents, and CFTR-modulators (potentiators, correctors, stabilizers, amplifiers and different combination therapies).Expert opinion: We are currently perhaps at the most exciting stage in the history of CF, with the poten…

2017

Recently, in vitro anti-cancer properties of beauvericin, a fungal metabolite were shown in various cancer cell lines. In this study, we assessed the specificity of this effect by comparing beauvericin cytotoxicity in malignant versus non-malignant cells. Moreover, we tested in vivo anticancer effects of beauvericin by treating BALB/c and CB-17/SCID mice bearing murine CT-26 or human KB-3-1-grafted tumors, respectively. Tumor size and weight were measured and histological sections were evaluated by Ki-67 and H/E staining as well as TdT-mediated-dUTP-nick-end (TUNEL) labeling. Beauvericin levels were determined in various tissues and body fluids by LC-MS/MS. In addition to a more pronounced …

Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts

2016

The research leading to these results was funded by the Spanish Ministry of Health (FIS-PI11/00610, FIS-PI041436, FIS-PI081151, FIS-PI042018, and FIS-PI09/02311), the European Union (EU) (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), the Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, CP11/00178, FIS-PI06/0867, and FIS-PS09/00090), the Conselleria de Sanitat Generalitat Valenciana, the Generalitat de Catalunya-CIRIT (1999SGR 00241), the Obre Social Cajastur, the Universidad de Oviedo, the Department of Health of the Basque Government (2005111093 and 2009111069),…

Prenatal Air Pollution and Reduced Birth Weight: Decline in Placental Mitochondria as a Potential Mechanism.

2016

Strong epidemiological evidence links prenatal exposure to ambient air pollution and outcomes including low birth weight, intrauterine growth restriction, and preterm birth.1,2 A new study finds evidence that the association between prenatal air pollution exposure and reduced birth weight may be mediated in part by a decline in the mitochondrial content of the placenta.3 During pregnancy, the placenta supports the nourishment, growth, and development of the fetus, and mitochondria within the cells of the placenta are essential to these processes.4 Mitochondria, the cellular organelles that regulate energy production, are easily damaged by reactive oxygen species generated by oxidative stres…

Modeling Chronic Toxicity: A Comparison of Experimental Variability With (Q)SAR/Read-Across Predictions

2018

This study compares the accuracy of (Q)SAR/read-across predictions with the experimental variability of chronic lowest-observed-adverse-effect levels (LOAELs) from in vivo experiments. We could demonstrate that predictions of the lazy structure-activity relationships (lazar) algorithm within the applicability domain of the training data have the same variability as the experimental training data. Predictions with a lower similarity threshold (i.e., a larger distance from the applicability domain) are also significantly better than random guessing, but the errors to be expected are higher and a manual inspection of prediction results is highly recommended.