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

Recent developments in molecular biology have revealed that several oncogenes, suppressor genes and adhesion molecules are involved in the development of oesophageal cancer; however, the role of these genes is still unknown. To evaluate which molecular biological factors are related to patients' prognosis and recurrence, we checked p53, p16, p21/Waf1, cyclin D1, Ki-67, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), Mdm2, Bcl2, E-cadherin and MRP1/CD9 by means of immunohistochemical analysis in 116 cases of oesophageal cancer (R0). We also checked the regrowth capability of the primary cultures of the resected tumours and the effect of post-operative treatment. Although univariate analysis revealed that pN (pTNM), pT (pTNM), sex, cyclin D1, Ki-67, VEGF, E-cadherin and cell regrowth capability were prognostic factors, multivariate analysis revealed that pN (risk ratio (RR) 3.17), sex (RR 8.13), cell regrowth capability (RR 3.03) and E-cadherin (RR 0.30) were prognostic factors. Interestingly, step-wise analysis revealed that the following five factors were prognostic factors: pN (RR 5.74), sex (RR 3.14), cyclin D1 (RR 2.29), E-cadherin (RR 0.26) and cell regrowth capability (RR 1.94). Logistic regression analysis revealed that the risk factors of haematogenous recurrence were pN (odds ratio (OR) 8.97), cyclin D1 (OR 4.52) and EGFR (OR 0.18). On the other hand, the risk factor of lymph node recurrence was pN (OR 5.16). With regard to the effect of postoperative treatment, post-operative radiotherapy was a favourable risk factor (RR 0.43) and reduced the haematogenous recurrence (OR 0.18). Our data indicate that combination analysis using pN, sex, cyclin D1, E-cadherin, EGFR and cell regrowth capability may be useful for the prediction of patient survival and recurrence.
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PMID:Prognostic factors of oesophageal squamous cell carcinoma from the perspective of molecular biology. 1037 85

Fibroadenoma (FA) is the most common benign tumor of the breast in adult women. Some FA have a highly cellular stroma, making it difficult to differentiate from phyllodes tumors (PT). Forty-three FA were grouped into: (i) 27 conventional type (FACT) median stromal cellularity (SC) of highest cellular area (HCA), < or = 125 cells/1 high-power field (HPF); and (ii) 16 cellular variant (FACV) median SC of HCA, > 125 cells/1 HPF. These were studied for the proliferative activity of their stromal cells. Expression of c-fos, p53, basic fibroblast growth factor (bFGF), fibroblast growth factor receptor (FGFR), and vascular endothelial growth factor (VEGF) in the stromal cells were examined in the FA and 12 PT to determine whether it is possible to separate FACV from FACT. The proliferative activity of stromal cells was evaluated by the labeling index (LI) of proliferating cell nuclear antigen (PCNA). Conventional type fibroadenoma stromal cells had the lowest frequency of c-fos, p53, bFGF, FGFR and VEGF protein expression; PT stromal cells had the highest frequency of expression; and FACV stromal cells had an intermediate frequency of expression. Multivariate analysis demonstrated that bFGF and FGFR expression are significantly correlated with SC of FA. Separation of FACV from FACT by SC seems appropriate in revealing the phenotypic and biological differences of FA. The SC of FA seems to be regulated by bFGF and FGFR expression.
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PMID:Proliferative activity and tumor angiogenesis is closely correlated to stromal cellularity of fibroadenoma: proposal fibroadenoma, cellular variant. 1041 87

P53 protein and vascular endothelial growth factor (VEGF) expression, and mean intratumoral microvessel density (IMVD) were studied by immunohistochemistry in 31 salivary gland carcinomas, consisting of 11 adenoid cystic carcinomas (AdCCs), 10 mucoepidermoid carcinomas (MECs), 7 acinic cell carcinomas (AcCCs), and 3 squamous cell carcinomas (SCCs). Cases with p53 protein in more than 20% of tumor cells were detected in one AdCC, four MECs, one AcCC, and two SCCs. Both frequency of p53 and VEGF expression, and mean IMVD, were higher in the MECs and SCCs than in the AdCCs and AcCCs. Similarly, both VEGF expression and mean IMVD were significantly higher (P<0.05) in the eight p53-positive tumors than in the 23 negative tumors. Six cases with survival periods less than 5 years showed significantly higher frequency of p53 and VEGF expression and of mean IMVD than those with longer survival periods. These results indicate that p53 expression might partly correlate with VEGF expression and mean IMVD, and be a factor in the survival of patients with salivary gland carcinomas.
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PMID:Expression of p53 oncoprotein increases intratumoral microvessel formation in human salivary gland carcinomas. 1042 98

Recent studies have indicated that the loss of p16 is a frequent event in the progression of malignant gliomas. The loss of p16 promotes the acquisition of malignant characteristics in gliomas, which are among the most angiogenic of all human tumors. High-grade gliomas are distinguished from low-grade gliomas by intense angiogenesis in addition to their frequent loss of p16. New therapeutic strategies aimed at inhibiting tumor angiogenesis on the basis of molecular mechanisms are theoretically attractive. Here we evaluate the effect of p16 gene replacement on the angiogenesis of gliomas. Infection with a recombinant replication-defective adenovirus vector containing the cDNA of wild-type p16 significantly reduced the expression of vascular endothelial growth factor, which is thought to be a pivotal mediator of tumor angiogenesis, in p16-deleted glioma cells. Restoring wild-type p16 expression into p16-deleted glioma cells markedly inhibited angiogenesis induced by tumor cells in vivo. Furthermore, wild-type p16 inhibited neovascularization more potently than did wild-type p53 transfer. These findings indicate that the p16 gene plays an important role in the regulation of glioma angiogenesis, suggesting a novel function of the p16 gene.
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PMID:Restoration of wild-type p16 down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in human gliomas. 1044 96

Recent studies have shown that tumor suppressor genes, particularly p53, may play a crucial regulatory role in the control of angiogenesis. Accordingly, we analyzed the correlation between p53 accumulation and the expression of vascular endothelial growth factor (VEGF) and microvessel counts in a series of human gastric adenocarcinomas by immunohistochemical staining. p53 expression was absent in 35 cases (29.7%), weak in 34 cases (28.8%), moderate in 35 cases (29.7%), and strong in 14 cases (11.8%). The prognosis of patients with both absent and weak expression of p53 was significantly better than that of patients with both moderate and strong expression of p53. VEGF expression was significantly associated with increased p53 expression. Moreover, increasing expression of p53 significantly correlated with an increase in microvessel counts. Nuclear p53 accumulation may correlate with tumor angiogenesis through VEGF upregulation in gastric carcinomas.
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PMID:Neoangiogenesis and relationship to nuclear p53 accumulation and vascular endothelial growth factor expression in advanced gastric carcinoma. 1046 Oct 65

Angiogenesis is a key process in tumour growth and metastasis, and microvessel density has been found to influence the prognosis of endometrial carcinoma patients. Less is known about regulators of angiogenesis. Studies of other tumour types have indicated that the density of tumour-associated macrophages (TAMs) and the expression of vascular endothelial growth factor (VEGF) might stimulate vessel formation, whereas thrombospondin-1 (TSP-1) may inhibit this process. We investigated the influence of TAM (CD68+), VEGF and TSP-1 expression on tumour vascular density and prognosis among endometrial carcinoma patients and compared our findings with clinico-pathological variables and tumour markers. In a prospective study, 60 endometrial carcinoma patients with long (median 11 years) and complete follow-up were included. Intratumour density of TAMs was significantly associated with FIGO stage, histological type, histological grade, DNA index, estradiol receptor concentration, intratumour Ki-67 and p53 protein expression (all p < 0.05). Moderate or strong expression of VEGF was significantly associated with serous papillary/clear cell tumour types, high microvessel density and aneuploidy (p < 0.05). There was a tendency to strong TSP-1 expression among tumours with weak VEGF expression (p=0.09). TAM density influenced survival significantly in univariate survival analysis (Kaplan-Meier method, p<0.05) in contrast to VEGF and TSP-1 expression. In Cox regression analysis, however, no independent prognostic impact remained. In conclusion, moderate or strong VEGF expression was significantly associated with high microvessel density and TAM count was increased in a subgroup of aggressive tumours. High TAM density was significantly associated with reduced survival in univariate analysis.
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PMID:Significance of tumour-associated macrophages, vascular endothelial growth factor and thrombospondin-1 expression for tumour angiogenesis and prognosis in endometrial carcinomas. 1050 35

A new human hepatocellular carcinoma (HCC) cell line with a highly metastatic potential was established from subcutaneous xenograft of a metastatic model of human HCC in nude mice (LCI-D20) by means of alternating cell culture in vitro and growth in nude mice. The line, designated MHCC97, has been cultivated for 18 months and subcultured for more than 90 passages. The line was showed to be of human origin by karyotype analysis. The cells were either grown as compact colonies (in clusters) or as a monolayered sheet with about 31 h of population-doubling time, exhibited typical malignant epithelial in morphology and were positive for alpha-fetoprotein (AFP). Flow cytometric analysis of the cell DNA content showed an aneuploid pattern, and its index was 1.5 as compared to that of normal human peripheral blood lymphocytes. Karyotypic analyses of G- and C-banding techniques revealed that all cells presented chromosome abnormalities in number and structure. The number of cell line MHCC97 chromosome ranged from 59 to 65 with a modal number of 60 and 61. At least two common chromosome markers, i(1q) and der(4)t(4;?)(4pter-->q35::?), were present in all cells, and deletion of Y chromosome also occurred in all cells. The subcutaneous and intrahepatic xenografts were formed and metastatic lesions in lungs were found after the cells were inoculated into nude mice. The rate of metastasis to lungs was 100% using orthotopic inoculation. Reverse transcription polymerase chain reaction products revealed positive expressions of integrin alpha5 and beta1, urokinase type plasminogen activator receptor (uPAR), vascular endothelial growth factor and nm23-H1 mRNAs of cell line MHCC97. Immunostaining of c-Met, uPAR showed strongly positive in both subcutaneous xenografts and lung metastatic lesions; while positive in xenografts and negative in metastatic lesions for integrin alpha5, beta1. E-cadherin and P53 was not expressed either in xenograft or in the metastatic lesions. PCR products of HBsAg and HBxAg were both positive. The cell line MHCC97 still retained some characteristic features of original tumour. Establishment of cell line MHCC97 should be beneficial to the studies of HCC metastatic mechanisms.
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PMID:New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. 1055 51

Neovascularization and increased glycolysis, two universal characteristics of solid tumors, represent adaptations to a hypoxic microenvironment that are correlated with tumor invasion, metastasis, and lethality. Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding glucose transporters, glycolytic enzymes, and vascular endothelial growth factor. HIF-1 transcriptional activity is determined by regulated expression of the HIF-1alpha subunit. In this study, HIF-1alpha expression was analyzed by immunohistochemistry in 179 tumor specimens. HIF-1alpha was overexpressed in 13 of 19 tumor types compared with the respective normal tissues, including colon, breast, gastric, lung, skin, ovarian, pancreatic, prostate, and renal carcinomas. HIF-1alpha expression was correlated with aberrant p53 accumulation and cell proliferation. Preneoplastic lesions in breast, colon, and prostate overexpressed HIF-1alpha, whereas benign tumors in breast and uterus did not. HIF-1alpha overexpression was detected in only 29% of primary breast cancers but in 69% of breast cancer metastases. In brain tumors, HIF-1alpha immunohistochemistry demarcated areas of angiogenesis. These results provide the first clinical data indicating that HIF-1alpha may play an important role in human cancer progression.
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PMID:Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. 1058 6

The switch to an angiogenic phenotype is a fundamental determinant of neoplastic growth and tumor progression. We demonstrate that homozygous deletion of the p53 tumor suppressor gene via homologous recombination in a human cancer cell line promotes the neovascularization and growth of tumor xenografts in nude mice. We find that p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1alpha subunit of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that regulates cellular energy metabolism and angiogenesis in response to oxygen deprivation. Loss of p53 in tumor cells enhances HIF-1alpha levels and augments HIF-1-dependent transcriptional activation of the vascular endothelial growth factor (VEGF) gene in response to hypoxia. Forced expression of HIF-1alpha in p53-expressing tumor cells increases hypoxia-induced VEGF expression and augments neovascularization and growth of tumor xenografts. These results indicate that amplification of normal HIF-1-dependent responses to hypoxia via loss of p53 function contributes to the angiogenic switch during tumorigenesis.
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PMID:Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. 1064 Feb 74

The angiogenic factor vascular endothelial growth factor (VEGF) predicts outcome in primary breast carcinoma. Alteration of the p53 gene causes down-regulation of the expression of thrombospondin-1, a natural inhibitor of angiogenesis. This study was conducted to investigate the association between mutant p53 protein and VEGF expression, and the prognostic value of these factors. VEGF165 and p53 protein were measured in tumour cytosols by enzyme immunoassays. Recurrence-free survival (RFS) and overall survival (OS) were estimated in 833 consecutive patients, 485 node-negative (NNBC) and 348 node-positive (NPBC) with primary invasive breast cancer. A significant association was found between mutant p53 protein and VEGF expression. Univariate analysis showed both p53 and VEGF to be significant predictors of survival. Similar correlation was seen when p53 was combined with VEGF. Univariate analysis of NNBC showed significant prognostic value of p53 for OS, also when combined with VEGF expression; for NPBC, significant reductions in RFS and OS were seen for p53-positive patients, and these findings were enhanced when combined with VEGF, also in the sub-group receiving adjuvant endocrine treatment. Multivariate analysis showed both p53 and VEGF as independent predictors of OS in all groups. When the 2 factors were combined, an increased relative risk of 2.7 was seen for OS in the group with both p53 positivity and high VEGF content, as compared with 1.7 in the group with one risk factor. The results suggest an association between loss of wt-p53 and increased VEGF expression, indicating that angiogenic activity may depend, at least partly, on altered p53-protein function. Combination of these 2 biological markers appears to give additional predictive information of survival. A high-risk group of patients was associated with p53 positivity and higher VEGF content.
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PMID:p53 and vascular-endothelial-growth-factor (VEGF) expression predicts outcome in 833 patients with primary breast carcinoma. 1071 31


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