Search results for "Tumor suppressor"
showing 10 items of 401 documents
Prevalence of Autoantibodies to the p53 Protein in Autoimmune Hepatitis
2003
The target antigens of anti-nuclear autoantibodies in autoimmune hepatitis (AIH) are poorly characterised. Since antibodies to the p53 nuclear protein have been reported in various autoimmune diseases, we have assessed the prevalence of these antibodies in patients with AIH (n = 45), primary biliary cirrhosis (n = 60), hepatitis B (n = 22), hepatitis C (n = 55), and in a control group of subjects with various non-liver diseases (n = 56). A significant proportion of patients with AIH (31%) had elevated levels of autoantibodies to the p53 protein. In contrast, the prevalence of these antibodies in primary biliary cirrhosis (8%) and viral hepatitis (6%) was similar to that in the control group…
Study of Proliferation and Apoptosis in Neuroblastoma. Their Relation with Other Prognostic Factors
2002
Abstract Background Our objective was to study the proliferation and apoptotic process in 111 cases of neuroblastoma (NB) and to seek their relationship with other prognostic factors and survival. Methods Immunohistochemistry following ABC peroxidase was carried out for PCNA, Ki-67, bcl-2, and p53 proteins. Apoptosis analysis was performed with in situ detection of chromosomal breakdown. Molecular detection of DNA ladders by electrophoresis and amplification of MYCN was studied with PCR and Southern blot. Statistical study was performed with Pearson χ 2 and Kruskal-Wallis tests and Cox regression. Results Our results indicate that proliferative factors PCNA and Ki-67 were correlated to each…
Hereditary common cancers: molecular and clinical genetics.
2001
This review focuses on the functional role and structural features of the genes involved in common hereditary cancers. Most of these tumors are sporadic and the genetic alterations responsible for their genesis take place over several cell generations; nevertheless, 5 to 10% of the human tumors are hereditary, with a rapid development. Cancer susceptibility genes have been classified as "gatekeepers" (e.g. RB1, ki-ras) and "caretakers" (e.g. hMLH1 and hMSH2, BRCA1). The first step in identifying individuals at high risk of developing a specific inherited form of cancer, and who should therefore undergo genetic tests, is the detailed construction of family history (an accurate cancer family …
Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Modulates N-Methyl-d-aspartate (NMDA) Receptor-dependent Intracellular Signaling and NMDA-i…
2013
The lipoprotein receptor LRP1 is essential in neurons of the central nervous system, as was revealed by the analysis of conditional Lrp1-deficient mouse models. The molecular basis of its neuronal functions, however, is still incompletely understood. Here we show by immunocytochemistry, electron microscopy, and postsynaptic density preparation that LRP1 is located postsynaptically. Basal and NMDA-induced phosphorylation of the transcription factor cAMP-response element-binding protein (CREB) as well as NMDA target gene transcription are reduced in LRP1-deficient neurons. In control neurons, NMDA promotes γ-secretase-dependent release of the LRP1 intracellular domain (LRP1-ICD). However, pul…
The TP53 colorectal cancer international collaborative study on the prognostic and predictive significance of p53 mutation: influence of tumor site, …
2005
Purpose The aims of the TP53 Colorectal Cancer (CRC) International Collaborative Study were to evaluate the possible associations between specific TP53 mutations and tumor site, and to evaluate the prognostic and predictive significance of these mutations in different site, stage, and treatment subgroups. Patients and Methods A total of 3,583 CRC patients from 25 different research groups in 17 countries were recruited to the study. Patients were divided into three groups according to site of the primary tumor. TP53 mutational analyses spanned exons 4 to 8. Results TP53 mutations were found in 34% of the proximal colon tumors and in 45% of the distal colon and rectal tumors. They were assoc…
Head and neck paragangliomas: Report of 175 patients (1989-2010)
2011
Attention of the otorhinolaryngologist needs to be drawn to the versatile aspects of head and neck paragangliomas (PGLs).This study is a retrospective, nonrandomized clinical study of all 175 individuals with PGLs treated in our department between 1989 and 2010. A genetic analysis was performed on 86 patients.The 175 patients presented 224 head and neck PGLs as well as 2 thyroid papillary carcinomas. Genetic analysis resulted in 1 patient positive for a von Hippel-Lindau (VHL) gene mutation and 34 for succinate dehydrogenase (SDH) gene mutations (22 SDHD, 7 SDHC, and 5 SDHB), 12 of the latter carrying a novel mutation. Thirty-three patients (18.9%) had multiple PGLs and 11 patients (6.3%) h…
Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas: results of a 5-year Grupp…
2005
BACKGROUND: Although Ki-ras and TP53 mutations have probably been the genetic abnormalities most exhaustively implicated and studied in colorectal cancer (CRC) progression, their significance in terms of disease relapse and overall survival has not yet clearly been established. PATIENTS AND METHODS: A prospective study was carried out on paired tumor and normal colon tissue samples from a consecutive series of 160 previously-untreated patients, undergoing resective surgery for primary operable sporadic CRC. Mutations within the TP53 (exons 5-8) and Ki-ras (exon 2) genes were detected by PCR-SSCP analyses following sequencing. RESULTS: Mutation analyses of exons 5 to 8 of the TP53 gene showe…
Prognostic relevance of CCN3 in Ewing sarcoma
2009
Ewing sarcoma is a highly aggressive malignant bone tumor occurring preferentially in children and young adults. At present, only clinical features, such as patient age, presence of clinically evident metastases at diagnosis, and poor response to neoadjuvant chemotherapy, are widely accepted as prognostic indicators in Ewing sarcoma. In this study, we assessed the prognostic value of CCN3 (Nov), a matricellular protein that play crucial roles in bone formation. Polyclonal antibodies directed against each of the different CCN3 modules were used to identify variant CCN3 proteins in tumors and to draw potential relationships between the expression of these variants and the outcome of patients …
Deficiency of the promyelocytic leukemia protein fosters hepatitis C-associated hepatocarcinogenesis in mice.
2012
Overwhelming lines of epidemiological evidence have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of hepatocellular carcinoma (HCC). We have recently shown that HCV core protein mediates functional inactivation of the promyelocytic leukemia (PML) tumor suppressor pathway. However, the role of PML in HCC development yet remains unclear. To clarify the function of PML in liver carcinogenesis and HCV-associated pathogenesis we crossed PML-deficient mice with HCV transgene (HCV-Tg) expressing mice and treated the resulting animals with DEN/Phenobarbital, an established protocol for liver carcinogenesis. Seven months after treatment, livers …
BLBP-expression in astrocytes during experimental demyelination and in human multiple sclerosis lesions
2011
Several lines of evidence indicate that remyelination represents one of the most effective mechanisms to achieve axonal protection. For reasons that are not yet understood, this process is often incomplete or fails in multiple sclerosis (MS). Activated astrocytes appear to be able to boost or inhibit endogenous repair processes. A better understanding of remyelination in MS and possible reasons for its failure is needed. Using the well-established toxic demyelination cuprizone model, we created lesions with either robust or impaired endogenous remyelination capacity. Lesions were analyzed for mRNA expression levels by Affymetrix GeneChip® arrays. One finding was the predominance of immune a…