Search results for "p53"

P53 Aggregates and Interacts with Tau in Alzheimer's Disease

2020

Sperm p53 concentration: a potential new biomarker for environmental pollution. Preliminary data.(EcoFoodFertility Project)

2019

Study question:We evaluated the p53 protein concentration in spermcells to test whether environmental pollution can affect expression levels of this protein. Summary answer:We found a significant difference in p53 levels between two homogeneous groups by age and lifestyle, residents in two areas with different environmental impact. What is known already:TheWorld HealthOrganization (WHO) has placed among its priority objectives the understanding of the relationships between the sources of pollution and the effects on human health, which they represent a cause of surprisingly high mortality and morbidity. International scientific literature shows that strong environmental impact may jeopardiz…

Bridge-Induced Translocation between NUP145 and TOP2 Yeast Genes Models the Genetic Fusion between the Human Orthologs Associated With Acute Myeloid …

2017

In mammalian organisms liquid tumors such as acute myeloid leukemia (AML) are related to spontaneous chromosomal translocations ensuing in gene fusions. We previously developed a system named bridge-induced translocation (BIT) that allows linking together two different chromosomes exploiting the strong endogenous homologous recombination system of the yeast Saccharomyces cerevisiae. The BIT system generates a heterogeneous population of cells with different aneuploidies and severe aberrant phenotypes reminiscent of a cancerogenic transformation. In this work, thanks to a complex pop-out methodology of the marker used for the selection of translocants, we succeeded by BIT technology to preci…

“Super p53” Mice Display Retinal Astroglial Changes

2013

Tumour-suppressor genes, such as the p53 gene, produce proteins that inhibit cell division under adverse conditions, as in the case of DNA damage, radiation, hypoxia, or oxidative stress (OS). The p53 gene can arrest proliferation and trigger death by apoptosis subsequent to several factors. In astrocytes, p53 promotes cell-cycle arrest and is involved in oxidative stress-mediated astrocyte cell death. Increasingly, astrocytic p53 is proving fundamental in orchestrating neurodegenerative disease pathogenesis. In terms of ocular disease, p53 may play a role in hypoxia due to ischaemia and may be involved in the retinal response to oxidative stress (OS). We studied the influence of the p53 ge…

Primary glioblastomas with and without EGFR amplification: Relationship to genetic alterations and clinicopathological features

2009

Glioblastomas express a notable heterogeneity in both the histological and cell patterns with glial astrocytic differentiation. Primary glioblastoma, which is the most frequent presentation (90-95%), occurs mainly in older patients and arises de novo, without any clinical or histological evidence of a less malignant precursor lesion. EGFR amplification has been identified as a genetic hallmark of primary glioblastomas and occurs in 40-60% of cases. However, there exist primary glioblastomas without EGFR amplification/overexpression. The purpose of this study was to stabilize the association between cases with and without EGFR gene amplification with clinical and genetic parameters in 45 cas…

Usefulness of immunohistochemical staining for p53 in the prognosis of breast carcinomas: correlations with established prognosis parameters and with…

1995

Mutations of the p53 gene often result in the overexpression of p53 protein. Previous studies have suggested that the function of p53 and its mutant protein forms may be linked with the disease course of patients with a breast carcinoma. In the present study, we tested 462 primary breast carcinomas for the presence of p53 antigen using immunohistochemical methods employing antibodies against the clone, DO-1. These tumors were also immunohistochemically stained using the monoclonal antibody, MIB-1, in order to demonstrate the presence of Ki67. Comparison of the presence of p53 with other prognostic parameters revealed highly significant negative correlations with estrogen- and progesterone-r…

Evaluation of p53, Caspase-3, Bcl-2, and Ki-67 markers in oral squamous cell carcinoma and premalignant epithelium in a sample from Alava Province (S…

2013

Objectives: The objective of this study was to determine whether alterations in the expression of p53, caspase-3 Bcl-2, and ki-67 appear early in premalignant oral epithelium and show clonal behavior. Study Design: Samples from 41 tumors with their adjacent non-tumor epithelia were immunohistochemically analyzed using monoclonal antibodies that recognize p53, caspase-3, Bcl-2, and Ki-67 Results: A statistically significant association was found between the expression in tumor and adjacent epithelium of p53, caspase-3, and Bcl-2 but not of k-67. A significant association was observed between the expression of ki-67 and p53 in both localizations. In non-tumor (premalignant) epithelium samples…

DNA strand breaks induced by nuclear hijacking of neuronal NOS as an anti-cancer effect of 2-methoxyestradiol

2015

2-Methoxyestradiol (2-ME) is a physiological metabolite of 17β-estradiol. At pharmacological concentrations, 2-ME inhibits colon, breast and lung cancer in tumor models. Here we investigated the effect of physiologically relevant concentrations of 2-ME in osteosarcoma cell model. We demonstrated that 2-ME increased nuclear localization of neuronal nitric oxide synthase, resulting in nitro-oxidative DNA damage. This in turn caused cell cycle arrest and apoptosis in osteosarcoma cells. We suggest that 2-ME is a naturally occurring hormone with potential anti-cancer properties.

Differential gene expression in p53-mediated G(1) arrest of human fibroblasts after gamma-irradiation or N-phosphoacetyl-L-aspartate treatment.

2000

In human fibroblasts, N:-phosphoacetyl-L-aspartate (PALA) and gamma-radiation induce reversible and irreversible p53-mediated G(1) cell cycle arrest, respectively. By coupling the premature chromosome condensation technique to fluorescence in situ hybridization, we found no evidence of DNA damage after PALA treatment. We used representational difference analysis (cDNA-RDA) to study changes in gene expression after PALA treatment and gamma-radiation in normal human fibroblasts. The mammary-derived growth inhibitor (MDGI) gene was expressed in PALA-treated cells. Ectopic MDGI expression arrested PALA-treated but not irradiated RKO cells. Expression of an antisense RNA against MDGI resulted in…

“Mitotic Slippage” and Extranuclear DNA in Cancer Chemoresistance: A Focus on Telomeres

2020

Mitotic slippage (MS), the incomplete mitosis that results in a doubled genome in interphase, is a typical response of TP53-mutant tumors resistant to genotoxic therapy. These polyploidized cells display premature senescence and sort the damaged DNA into the cytoplasm. In this study, we explored MS in the MDA-MB-231 cell line treated with doxorubicin (DOX). We found selective release into the cytoplasm of telomere fragments enriched in telomerase reverse transcriptase (hTERT), telomere capping protein TRF2, and DNA double-strand breaks marked by γH2AX, in association with ubiquitin-binding protein SQSTM1/p62. This occurs along with the alternative lengthening of telomeres (ALT) and DNA repa…