Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.
 ...
PMID:The prognostic molecular markers in hepatocellular carcinoma. 1204 56

Angiogenesis is required for the development and biologic progression of infiltrative astrocytomas and takes the form of "microvascular hyperplasia" in glioblastoma multiforme, the most malignant astrocytoma. This pathologic term refers to an abnormal vascular proliferation that is often associated with necrosis and likely originates in hypoxic zones. Both the physiologic response to hypoxia and genetic alterations contribute to this process. The presence of hypoxic regions within an expanding tumor mass leads to upregulation of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), through increased activity of the transcriptional complex HIF-1 (hypoxia-inducible factor-1). HIF-1 mediated gene expression may be directly or indirectly modulated by alterations in oncogenes/tumor suppressor genes that occur during astrocytoma development, including PTEN, TP53, p16(CDKN2A), p14ARF, EGFR, and PDGFR. Genetic alterations are also believed to influence the HIF-independent expression of pro- and anti- angiogenic factors, such as basic fibroblast growth factor (bFGF) and thrombospondin-1 (TSP-1), respectively. Thus, genetic events that occur during the progression of infiltrating astrocytomas promote angiogenesis, both by modulating hypoxia induced gene expression and by regulating of pro- and anti- angiogenic factors.
 ...
PMID:Genetic modulation of hypoxia induced gene expression and angiogenesis: relevance to brain tumors. 1245 39

All neoplasms require angiogenesis and resulting neovascularity for growth beyond 1 mm(2). Quantitative microvessel density (MVD) has been shown to provide staging and prognostic significance in human prostate cancer (CaP). recently, it has been demonstrated that loss of the wild-type allele of the p53 tumour suppressor gene results in reduced expression of thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis. There is also an increased expression of vascular endothelial growth factor which promotes neovascularization. p53 gene mutation and MVD were investigated in men with prostate cancer. Sections from 103 radical prostatectomy cases were evaluated with immunohistochemistry to detect mutant p53 proteins. Quantitative MVD was performed on the cases exhibiting p53 positive staining and compared with negative fields of similar Gleason grade on the same histologic sections. Twenty of the 103 cases (19.4%) revealed positive p53 staining nuclei. In 19 of these 20 cases, the MVD in p53 positive areas was greater than corresponding control regions (overall P<0.0001). Extent of p53 abnormality, as well as MVD, correlated with pathologic stage. These data suggest that mutations of the p53 tumour suppressor gene may be associated with increased angiogenesis in CaP. In addition to providing staging and prognostic information, this relationship potentially has therapeutic implications.
 ...
PMID:The relation of p53 protein nuclear accumulation and angiogenesis in human prostatic carcinoma. 1249 32

Brain angiogenesis inhibitors (BAI) are putative transmembrane proteins containing an extracellular domain with thrombospondin type-1 repeats which can exhibit anti-angiogenic activity. BAI1 mRNA is expressed mainly in the brain, while BAI2 and BAI3 mRNAs are more widely expressed. We hypothesized that the BAI family might have anti-tumoral properties and studied the expression of BAI1 protein in normal human brain and in glioblastoma multiforme. We generated an anti-BAI1 antibody and showed that BAI1 was widely expressed in normal brain but was absent in 28 glioma cell lines and in the majority of human glioblastoma investigated. BAI1 expression did not correlate with TP53 status and we did not confirm previous findings that p53 regulates BAI1 mRNA expression in glioma cells. The finding that expression of BAI proteins may be lost during tumor formation is of special interest as restoration of their function in tumors may be of therapeutic benefit.
 ...
PMID:Brain angiogenesis inhibitor 1 is differentially expressed in normal brain and glioblastoma independently of p53 expression. 1250 86

To catalog factors that may contribute to the completion of myogenesis, we have been looking for molecular differences between BC3H1 and C2C12 cells. Cells of the BC3H1 tumor line, though myogenic, are nonfusing, and withdraw from the cell cycle only reversibly, whereas cells of the C2C12 line fuse, differentiate terminally, and express several muscle-specific gene products that BC3H1 cells do not. Relative to C2C12 cells, BC3H1 cells underaccumulated cyclin-dependent kinase inhibitor p21 and underaccumulated transcripts for p21, GADD45, CDO, decorin, osteopontin, H19, fibronectin, and thrombospondin-1 (tsp-1). Levels of accumulation of H19, tsp-1, and larger isoforms of fibronectin messenger ribonucleic acid (mRNA) were found to increase in response to expression of myogenic regulatory factors as shown by their accumulation in differentiated myogenically converted 10T1/2 cells but not in 10T1/2 fibroblasts. BC3H1s accumulated a temperature-insensitive, geldanamycin-sensitive, misfolded form of p53 incapable of transactivating a p53 responsive reporter, consistent with underexpression of p21, GADD45, and tsp-1. BC3H1 and C2C12 cells were similar with respect to upregulation of p27 protein, downregulation of mitogen-activated protein kinase phosphatase-1 (MKP-1) protein, upregulation of retinoblastoma (Rb) mRNA, and nuclear localization of hypophosphorylated Rb. Cells of both lines expressed the muscle-specific 1b isoform of MEF2D. Although nonfusing in the short term, after more than 18 d in differentiation medium, some cultures of BC3H1 cells formed viable multinucleated cells in which the nuclei did not reinitiate synthesis of DNA in response to serum. Our findings suggest participation of tsp-1 and specific isoforms of fibronectin in myogenesis and suggest additional avenues of research in myogenesis and oncogenesis.
 ...
PMID:Further characterization of BC3H1 myogenic cells reveals lack of p53 activity and underexpression of several p53 regulated and extracellular matrix-associated gene products. 1253 38

Malignant gliomas are distinguished from low-grade gliomas by their intense angiogenesis. In gliomas, p53 is the most frequently altered gene and is involved in the early phase of glioma development. In contrast, homozygous p16 gene deletion is more common in high-grade gliomas. In order to understand the mechanism by which gliomas become more angiogenic during the malignant transformation, we examined the relationship between thrombospondin-1, a negative regulator in angiogenesis, and these tumor suppressor genes in malignant gliomas. Human glioma cell line U-251 MG, which has mutated p53 and deleted p16, was transduced with recombinant replication-defective adenovirus vectors containing the cDNA of wild-type p53, p16, and p21. Only the induction of wild-type p53 enhanced expression of thrombospondin-1 mRNA and the protein in U-251 MG cells. Furthermore, thrombospondin-1 that was secreted in the culture medium was significantly increased (3.8-fold) as compared with that of the viral control 36 h after infection with Ad5CMV-p53. In the presence of wild-type p53 plasmid DNA, the promoter activity was increased 7.4-fold as compared with an empty expression vector control. These studies may suggest that mutation of p53 gene endows gliomas with an angiogenic phenotype by reducing thrombospondin-1 production as well as enhancing the angiogenesis inducers in the early phase of malignant progression.
 ...
PMID:Introduction of wild-type p53 enhances thrombospondin-1 expression in human glioma cells. 1260 16

We have determined the promoter CpG island methylation status of O(6)-methylguanine-DNA methyltransferase (MGMT), glutathione-S-transferase P1 (GSTP1), death-associated protein kinase (DAPK), p14(ARF), thrombospondin-1 (THBS1), tissue inhibitor of metalloproteinase-3 gene (TIMP-3), p73, p16(INK4A), RB1, and TP53 genes in three primary central nervous system lymphomas (PCNSL). Five genes (GSTP1, DAPK, TIMP-3, p16(INK4A), and RB1) were hypermethylated in two samples, whereas MGMT, THBS1, and p73 were aberrantly methylated in only one sample. No case presented CpG island methylation for the p14(ARF) and TP53 genes. These findings concur with previous data suggesting a frequent inactivation of p16(INK4A) and very limited involvement of TP53 in PCNSL and also provide insights into the epigenetic molecular involvement of other tumor-related genes in this neoplasm.
 ...
PMID:CpG island methylation of tumor-related genes in three primary central nervous system lymphomas in immunocompetent patients. 1266 28

Bladder cancer is one of the malignancies for which considerable information is available regarding molecular pathogenesis and genetic predictors of natural history, as well as response to treatment. Loss of heterozygosity of chromosome 9 appears to be essential to the genesis of superficial bladder cancer, and mutation of the p53 suppressor gene frequently is associated with progression to invasive and metastatic disease. Many oncogenes, gene products, and suppressor gene mutations, including those of Ras, Myc, p53, Rb, p16, p21, thrombospondin-1, glutathione, and factors controlling expression and function of the epidermal growth factor receptor, have been shown to be involved in the biology of this disease. Retrospective studies have demonstrated that some of these factors have important roles as independent prognostic determinants or predictors of response to chemotherapy, and clinical trials have now been established to validate the utility of molecular prognostication in bladder cancer. Paradigms developed from the treatment of colorectal malignancy, in which the metabolism of cytotoxic agents is affected by genetic and racial factors, now are being applied to the management of bladder cancer. This review summarizes current knowledge in these evolving domains.
 ...
PMID:Molecular targeting and pharmacogenomics in the management of advanced bladder cancer. 1267

Aberrant hypermethylation occurs in tumour cell CpG islands and is an important pathway for the repression of gene transcription in cancers. We investigated aberrant hypermethylation of 11 genes by methylation-specific polymerase chain reaction (PCR), after treatment of the DNA with bisulphite, and correlated the findings with MYCN amplification and allelic status at 1p in a series of 44 neuroblastic tumours. This tumour series includes five ganglioneuromas (G), one ganglioneuroblastoma (GN) and 38 neuroblastomas (six stage 1 tumours; five stage 2 tumours; six stage 3 cases; 19 stage 4 tumours, and two stage 4S cases). Aberrant methylation of at least one of the 11 genes studied was detected in 95% (42 of 44) of the cases. The frequencies of aberrant methylation were: 64% for thrombospondin-1 (THBS1); 30% for tissue inhibitor of metalloproteinase 3 (TIMP-3); 27% for O6-methylguanine-DNA methyltransferase (MGMT); 25% for p73; 18% for RB1; 14% for death-associated protein kinase (DAPK), p14ARF, p16INK4a and caspase 8, and 0% for TP53 and glutathione S-transferase P1 (GSTP1). No aberrant methylation was observed in four control normal tissue samples (brain and adrenal medulla). MYCN amplification was found in 11 cases (all stage 4 neuroblastomas), whereas allelic loss at 1p was identified in 16 samples (13 stage 4 and two stage 3 neuroblastomas, and one ganglioneuroma). All but one case with caspase 8 methylation also displayed MYCN amplification. Our results suggest that promoter hypermethylation is a frequent epigenetic event in the tumorigenesis of neuroblastic tumours, but no specific pattern of hypermethylated genes could be demonstrated.
 ...
PMID:Aberrant methylation of multiple genes in neuroblastic tumours. relationship with MYCN amplification and allelic status at 1p. 1282 52

This study for the first time demonstrates a physical and functional interaction between the Ca(2+)-binding protein Mts1/S100A4 and tumor suppressor p53 protein. Using different in vitro and in vivo approaches, we have found that Mts1 can bind to the C-terminal regulatory domain of p53. The Mts1 binding to p53 promotes activation of the reporter gene transcription in vivo. A modulation of the p53 target gene (p21/WAF, bax, mdm-2, and thrombospondin-1) expression was observed upon Mts1 induction in the cells expressing the wild-type p53. These results suggest that the ability of Mts1 to enhance p53-dependent apoptosis of tumor cells leads to the decrease/disappearance of the tumor cells expressing the wild-type p53. Thus, Mts1 promotes selection of more aggressive, metastatic phenotype during tumor progression.
 ...
PMID:[Activator of metastasis in cancer cells, Mst1/S100A4 protein binds to tumor suppressor protein p53]. 1294 74


<< Previous 1 2 3 4 5 6 7 8 Next >>