Search results for "TP53"

Rol del complejo RUNX1-CBF-β/HIPK2/p300/p53 en la evolución leucémica de las neoplasias mieloproliferativas crónicas

2019

Las neoplasias mieloproliferativas crónicas (NMPs) son procesos cancerígenos en los que se produce una expansión clonal de una o varias poblaciones de progenitores hematopoyéticos de estirpe mieloide. En las fases iniciales de la enfermedad, éstos presentan una adecuada diferenciación celular, lo que conlleva una descompensación final de los diferentes tipos celulares en médula ósea y sangre periférica y la consiguiente aparición de una serie de síntomas asociados que pueden llegar a producir importantes citopenias o complicaciones vasculares. A pesar de que las NMPs pueden mantenerse relativamente controladas en su fase crónica mediante un tratamiento adecuado, éstas patologías tienen una …

MAD2 depletion triggers premature cellular senescence in human primary fibroblasts by activating a P53 pathway preventing aneuploid cells propagation.

2012

The spindle assembly checkpoint (SAC) is a cellular surveillance mechanism that ensures faithful chromosome segregation during mitosis and its failure can result in aneuploidy. Previously, it was suggested that reduction of the MAD2 gene, encoding a major component of the SAC, induced aneuploidy in human tumor cells. However, tumor cell lines contain multiple mutations that might affect or exacerbate the cellular response to Mad2 depletion. Thus, the scenario resulting by Mad2 depletion in primary human cells could be different and more complex that the one depicted so far. We used primary human fibroblasts (IMR90) and epithelial breast cells (MCF10A) to gain further insight on the effects …

Allogeneic Stem Cell Transplantation for Myelodysplastic Syndrome Patients with a 5q Deletion

2018

The deletion (5q) karyotype (del [5q]) in patients with myelodysplastic syndrome (MDS) is the most common karyotypic abnormality in de novo MDS. An increased number of blasts and additional karyotypic abnormalities (del [5q]+) are associated with a poor outcome. We analyzed the outcome of allogeneic hematopoietic cell transplants (HCT) in patients suffering from MDS with only del (5q) or del (5q)+ . A total of 162 patients, of median age 54 years (range, 9 to 73), having MDS and del (5q) abnormalities received HCT from identical siblings (n = 87) or unrelated donors (n = 75). The cumulative incidence of nonrelapse mortality and relapse incidence at 4 years was 29% (95% CI, 22 to 36) and 46%…

TP53 mutations and S-phase fraction but not DNA-ploidy are independent prognostic indicators in laryngeal squamous cell carcinoma

2005

To prospectively evaluate the prognostic significance of TP53, H-, K-, and N-Ras mutations, DNA-ploidy and S-phase fraction (SPF) in patients affected by locally advanced laryngeal squamous cell carcinoma (LSCC). Eight-one patients (median follow-up was 71 months) who underwent resective surgery for primary operable locally advanced LSCC were analyzed. Tumor DNA was screened for mutational analysis by PCR/SSCP and sequencing. DNA-ploidy and SPF were performed by flow cytometric analyses. Thirty-six patients (44%) had, at least, a mutation in the TP53 gene. Of them, 22% (8/36) had double mutations and 3% (1/36) had triple mutations. In total, 46 TP53 mutations were observed. The majority (41…

Analysis of TP53, Ki-Ras and P16INK4A promoter methylation as potential prognostic factors in patients with colorectal cancer

2007

Human papillomavirus:Its identikit and controversial role in oral oncogenesis,premalignant an malignant lesions(Review)

2007

Human papillomaviruses (HPVs) are a group of host-specific DNA viruses, with a remarkable epithelial cell specificity: they have been reported principally in the ano-genital tract, urethra, skin, larynx, tracheo-bronchial and oral mucosa. More than 100 different HPV types have been identified and classified as high (e.g. 16, 18, 31) or low (e.g. 11, 42, 36) -risk (HR and LR), based on their association with cervical carcinoma. The carcinogenic role of HR-HPV revolves mainly around two of its oncoproteins: HPV-E6 which promotes degradation of the p53 tumour suppressor gene product and HPV-E7 which modifies the pRb tumour suppressor gene product, inhibiting the activity of TGF-beta2. Since th…

Biomarkers for vascular ageing in aorta tissues and blood samples.

2019

Abstract Objectives Functional and quantitative alterations and senescence of circulating and expanded endothelial progenitor cells (EPC), as well as systemic and tissue modifications of angiogenetic and inflammatory molecules, were evaluated for predicting age-related vessel wall remodeling, correlating them to intima media thickness (IMT) in the common carotid artery (CCA), a biomarker of early cardiovascular disease and aortic root dilation. Populations and methods A homogenous Caucasian population was included in the study, constituted by 160 healthy subjects (80 old subjects, mean age 72 ± 6.4, range 66–83 years; and 80 younger blood donors, mean age 26.2 ± 3.4, range 21–33 years), and…

Impact of somatic mutations in myelodysplastic patients with isolated partial or total loss of chromosome 7

2020

Monosomy 7 [-7] and/or partial loss of chromosome 7 [del(7q)] are associated with poor and intermediate prognosis, respectively, in myelodysplastic syndromes (MDS), but somatic mutations may also play a key complementary role. We analyzed the impact on the outcomes of deep targeted mutational screening in 280 MDS patients with -7/del(7q) as isolated cytogenetic abnormality (86 with del(7q) and 194 with -7). Patients with del(7q) or -7 had similar demographic and disease-related characteristics. Somatic mutations were detected in 79% (93/117) of patients (82% in -7 and 73% in del(7q) group). Median number of mutations per patient was 2 (range 0-8). There was no difference in mutation frequen…

Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.

2006

Item does not contain fulltext BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified ac…

TP53 in gastric cancer: mutations in the l3 loop and LSH motif DNA-binding domains of TP53 predict poor outcome.

2004

The aim of this study was to clarify whether specific p53 mutations may have biological relevance in terms of disease relapse or death in gastric carcinomas (GC). Resected specimens from a consecutive series of 62 patients with GC undergoing potentially curative surgery were prospectively studied. The mutational status of exons 5-8 of the p53 gene was investigated in 62 cases using the PCR-SSCP and sequencing. Presence of microsatellite instability (MSI) was evaluated in 56 cases by analyzing loci highly sensitive of MSI. Twenty mutations of p53 were detected in 17 of the 62 cases analyzed (27%). Ten mutations (50%) occurred in highly conserved domains. According to the p53 specific functio…