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)

Following up-regulation of an angiogenesis inhibitor by the wild-type p53 protein proven recently, we have analysed on the one hand the prognostic impact of microvessel count (MC) and p53 protein overexpression in non-small-cell lung carcinoma (NSCLC) progression and, on the other hand, the inter-relation between the microvascular pattern and the p53 protein expression. Moreover, we assessed the expression of vascular endothelial growth factor (VEGF), one of the pivotal mediators of tumour angiogenesis, in order to investigate its relation to p53 protein expression and MC. Tumours from 73 patients resected for NSCLC between March 1991 and April 1992 (median follow-up 47 months, range 32-51 months) were analysed using an immunohistochemical method. In univariate analysis, MC and p53 accumulation were shown to affect metastatic nodal involvement, recurrence and death significantly. Multiple logistic regression analysis showed an important prognostic influence of MC and nodal status on overall (P = 0.0009; P = 0.01) and disease-free survival (P = 0.0001; P = 0.03). Interestingly, a strong statistical association was observed between p53 nuclear accumulation and MC (P = 0.0003). The same inter-relationship was found in non-squamous histotype (P = 0.002). When we analysed the concomitant influence of MC and p53 expression on overall survival, we were able to confirm a real predominant role of MC in comparison with p53. With regard to VEGF expression, p53-negative and lowly vascularized tumours showed a mean VEGF expression significantly lower than p53-positive and highly vascularized cancers (P = 0.02). These results underline the prognostic impact of MC and p53 protein accumulation in NSCLC and their reciprocal inter-relationship, supporting the hypothesis of a wild-type p53 regulation on the angiogenetic process through a VEGF up-regulation.
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PMID:Neoangiogenesis and p53 protein in lung cancer: their prognostic role and their relation with vascular endothelial growth factor (VEGF) expression. 951 69

Like most other normal cells, human endothelial cells possess a limited replicative life span, and, after multiple passages in vitro, develop an arrest in cell division referred to as replicative senescence. For many cell types senescence can be delayed by oncogenes or tumor suppressor genes or prevented altogether by malignant transformation; however, once developed, senescence has been regarded as irreversible. We now report that a cytokine, vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), significantly delays senescence in human dermal microvascular endothelial cells (HDMEC). Typically, VPF/VEGF-treated HDMEC could be cultured for at least 15-20 more population doublings (PD) than control cells. Protection from senescence was reversible in that subsequent withdrawal of VPF/VEGF returned cells to the senescent phenotype. Expression of several cell cycle-related genes (p21, p16 and p27) was significantly reduced in VPF/VEGF-treated cells but p53 expression was not significantly altered. Of particular importance, VPF/VEGF was able to rescue senescent HDMEC, restoring them to proliferation, to a more normal morphology, and to reduced expression of a senescence marker, neutral beta-galactosidase. Taken together, VPF/VEGF delayed the onset of senescence and also reversed senescence in microvascular endothelial cells without inducing cell transformation.
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PMID:Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) delays and induces escape from senescence in human dermal microvascular endothelial cells. 916 Aug 82

Recent studies have demonstrated that the p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis. We examined the expression of p53 and vascular endothelial growth factor (VEGF), a well-characterized angiogenic inducer, together with microvessel density to investigate the role of p53 in the regulation of angiogenesis and its clinical significance in human colorectal carcinoma. Surgically resected specimens of 163 colorectal carcinomas were studied by immunohistochemical staining for p53 protein, VEGF and factor VIII-related antigen. Positive p53 protein accumulation and VEGF expression was found in 41.7% and 49.1% of tumors, respectively. p53 and VEGF staining status was identical in 65.6% of tumors. The incidence of p53- or VEGF-positive tumors was significantly higher in patients with venous invasion and liver metastases than in those without. The microvessel count (MVC) in p53- or VEGF-positive tumors was significantly higher than that in negative tumors, and MVC in both p53- and VEGF-positive tumors was significantly higher than that in the other subgroups. Neither synchronous nor metachronous hepatic metastases were found in patients with p53- and VEGF-negative tumors, while 52.2% of patients with both-positive tumors had liver metastases and had a poorer prognosis than those with both-negative tumors. Our findings suggest the presence of a p53-VEGF pathway regulating tumor angiogenesis in human colorectal carcinoma. Combined analysis of p53 and VEGF expression might be useful for predicting the occurrence of liver metastasis in patients with this disease.
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PMID:Combined analysis of p53 and vascular endothelial growth factor expression in colorectal carcinoma for determination of tumor vascularity and liver metastasis. 935 71

Hypoxia-induced neovascularization mediated by vascular endothelial growth factor (VEGF) contributes to tumor progression. Based on its effects when overexpressed in transient transfection assays, p53 has been proposed to repress VEGF transcription. To investigate this hypothesis, we have analyzed endogenous VEGF mRNA levels in Hep3B cells stably expressing an inducible p53-estrogen receptor fusion protein and in irradiated RKO cells expressing endogenous wild-type p53. In both cell lines, VEGF mRNA levels increased in response to hypoxia, either in the presence or absence of functional p53. Our data provide no evidence for a causal relationship between the loss of p53 activity and increased VEGF expression that is observed during tumor progression. Studies that attribute repressor functions to p53 based on analysis of cells transiently overexpressing this protein should be interpreted cautiously.
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PMID:p53 does not repress hypoxia-induced transcription of the vascular endothelial growth factor gene. 937 55

Tumor development is angiogenesis dependent, and vascular endothelial growth factor (VEGF) is a key growth factor in this process. We demonstrate that high expression of VEGF mRNA in 55 superficial bladder cancers was associated with earlier recurrence (P = 0.001; hazard ratio, 3.09) and progression to a more invasive phenotype (P = 0.02; hazard ratio, 5.33). VEGF mRNA expression correlated with protein levels in superficial tumors (r = 0.59, P = 0.003) and normal bladder (r = 0.65, P < 0.05), although the ratio of VEGF protein to mRNA was elevated in tumors compared to normal bladder (P = 0.004), suggesting posttranscriptional regulation. In this study, VEGF is implicated as a major downstream mediator of the effects of the p53 tumor suppressor gene by the association between high p53 protein (determined immunochemically) and high VEGF protein and mRNA expression (P < 0.02), although in cases without high p53 protein expression, high VEGF mRNA also predicts a poor prognosis. The relationship between VEGF and early tumor recurrence suggests that seeding via angiogenesis may be a major mechanism in the pathogenesis of recurrence. These studies indicate that VEGF can predict the behavior of superficial bladder tumors and is a therapeutic target for intravesical therapy.
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PMID:Vascular endothelial growth factor is a predictor of relapse and stage progression in superficial bladder cancer. 939 50

We previously demonstrated an association between vascular endothelial growth factor (VEGF), vessel counts and metastasis in human colon cancer specimens. Mutant p53 has been implicated in the regulation of angiogenesis. Immuno-histochemical detection of p53 protein has been associated with p53 gene mutations. We sought to determine a correlation between p53 protein detection (i.e., mutant p53), VEGF expression and vessel counts in human colon cancer. Surgical specimens from 93 patients with colon cancer were stained immuno-histochemically for p53, VEGF and factor VIII. Vessel counts were greater in metastatic tumors than in nonmetastatic tumors and adenomas, and greater in nonmetastatic tumors than in adenomas. Vessel counts were highest in tumors with the highest VEGF expression. Vessel counts and VEGF expression were greater in p53-positive tumors than in p53-negative tumors. p53 expression correlated with both VEGF expression and vessel count. The association of p53 expression with VEGF and vessel count suggests that the poor prognosis associated with p53 mutations may be due, in part, to the role of mutant p53 in promoting angiogenesis.
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PMID:p53, vessel count, and vascular endothelial growth factor expression in human colon cancer. 949 55

In this article, we introduce our rapid-production model for pancreatic duct adenocarcinomas and describe the mechanisms of pancreatic duct carcinogenesis so far elucidated in Syrian golden hamsters. It is evident that a series of histogenetic steps are involved, leading from hyperplasia through atypical hyperplasia to intraductal carcinoma and invasive carcinoma. As DNA alters, K-ras mutation appears to be an early event, whereas p53 mutations generally occur in the tumor-progression phase. The induced cancer cells may show autocrine growth, secreting TGF-alpha and vascular endothelial growth factor (VEGF), and are immortalized with a shortened TRF length and increased telomerase activity. The rapid-production model of pancreatic duct adenocarcinomas has not only provided a major stimulus to understanding induction mechanisms but should also serve as a bioassay to facilitate the identification of dietary risk factors and the search for appropriate chemopreventive or chemotherapeutic agents or both to help control this deadly disease.
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PMID:Mechanistic analysis of pancreatic ductal carcinogenesis in hamsters. 954 70

Although scrirrhous cancer has the highest malignant potential among various types of gastric cancer, its pathogenesis is still unclear. The relationship between expression of p53 or vascular endothelial growth factor (VEGF) and clinicopathological variables was investigated by immunohistochemical analysis of archival specimens from 40 patients with scirrhous gastric cancer. Staining for p53 and VEGF was observed in the nuclei and cytoplasm of the tumor cells, respectively. There was no significant association between expression of p53 or VEGF and sex, age, depth of invasion, lymph node metastasis or histological stage. Peritoneal dissemination was the most frequent mode of recurrence, and the depth of tumor invasion was a crucial factor. The recurrence rate was 83.9% (2/9) in patients without serosal invasion. Only 7 out of 40 patients (17.5%) survived without recurrence. Among them, the VEGF-positive rate was 14.3% (1/7), whereas it was 52.6% (10/19) in the patients with recurrence. There was no correlation between p53 and VEGF staining. These findings suggest that the progression of scirrhous gastric cancer may be promoted by VEGF overexpression, which is not upregulated by p53 mutation.
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PMID:Relationship of p53 and vascular endothelial growth factor expression of clinicopathological factors in human scirrhous gastric cancer. 956 47

It has been widely recognized that the vascular structure is an important factor when making a histopathological diagnosis and assessing the malignancy potential, especially of astrocytic tumors. The vascular endothelial growth factor (VEGF), which is thought to be regulated by the p53 gene, is a regulation factor for tumor neovascularization. The relationship between VEGF distribution and neovasculature was studied in 42 cases of astrocytic tumors (grades 1-4), which were obtained from surgical material, and the St Anne-Mayo grading system was applied. The relationship between the labeling indices (LI) of VEGF and LI of p53 protein in tumor cells was also studied using immunohistochemistry. The VEGF LI in high-grade malignancy potential tumors, such as grade 3 and grade 4 tumors, was significantly higher than those that were low grade. In grade 4 tumors, a significant correlation between the VEGF LI and the proliferation indices of endothelial cells of neovasculatures was observed. No significant correlation was noted between p53 LI and VEGF LI, as well as p53 LI and histopathological grade. In astrocytic tumors, expression of VEGF may be correlated to tumor neovascularization, and can be considered as an indicator of malignancy potential in astrocytic tumors.
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PMID:Vascular endothelial growth factor and neovascularization in astrocytic tumors. 958 74

Recent studies have indicated that angiogenesis may be regulated, in part, by p53 tumor suppressor gene function. We hypothesized that wild-type p53 replacement would down-regulate vascular endothelial growth factor (VEGF) expression and inhibit angiogenesis. KM12L4 and SW620, human colon cancer cell lines with p53 mutations, were transduced with a replication-defective adenoviral vector containing the wild-type p53 gene (Ad5/CMV/p53). Reverse transcription-PCR confirmed the presence of p53 in Ad5/CMV/p53-transduced cells. Transduction of colon cancer cells with wild-type p53 decreased VEGF RNA expression compared with that of controls. The decrease in VEGF expression in SW620 cells was dose dependent, with a 49% decrease observed at a multiplicity of infection of 50, and a 71% decrease observed at a multiplicity of infection of 100. Similar effects were seen in KM12L4 cells. VEGF supernatant protein levels were significantly reduced compared with those in nontransduced controls 48 h after the introduction of wild-type p53. Ad5/CMV/p53 inhibited tumor cell-induced angiogenesis in vivo. Restoration of wild-type p53 expression may decrease tumor growth by inhibiting the angiogenic response. These findings may explain, in part, the bystander effect seen with p53 tumor suppressor gene therapy.
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PMID:Adenovirus-mediated wild-type p53 gene transfer down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in human colon cancer. 962 60


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