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)

A more accurate method of detecting nodal disease in squamous cell carcinoma of the tongue is needed so that treatment of the neck with its associated morbidity can safely be reserved for patients who actually have metastatic disease. Tumor angiogenesis and the expression of the p53 antigen--which have each been shown to be predictive of metastasis in breast and colon cancer, respectively--are examined for their ability to predict neck metastasis in tongue cancer. Fifty-seven patients with T1 and T2 squamous cell carcinoma of the oral tongue, whose neck disease was examined by dissection or by 2-year follow-up, were studied. Twenty-eight patients (49%) were node positive and 29 patients (51%) were node negative. The primary tumors were immunohistochemically stained for the p53 antigen and for factor VIII, which allowed the blood vessels within the tumor to be quantitated. The mean vessel counts per x200 high-power field were 59.8 and 61.5 for node-positive and node-negative patients, respectively (p = 0.8). Node-positive patients showed overexpression of p53 43% of the time, vs. 61% for node-negative patients (p = 0.17). Multivariate analysis confirmed that no difference in tumor angiogenesis or the expression of the p53 antigen was found between tumors that had metastasized and those that had not. Therefore neither tumor angiogenesis nor the p53 tumor marker is clinically useful in determining lymph node metastasis in these patients.
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PMID:Tumor angiogenesis, the p53 antigen, and cervical metastasis in squamous carcinoma of the tongue. 752 5

The value of tumor angiogenesis, EGFR and c-erbB-2 oncoprotein, a long with p 53 protein expression for predicting relapse-free survival was investigated in 110 node-negative breast cancer patients. The grade of neovascularization was assessed by the microvessel density which was obtained by an immunocytochemical staining by factor VIII-related antigen. EGFR, c-erbB-2 oncoprotein and p 53 oncoprotein were also determined by immunocytochemical assay. Univariate analysis showed no statistical significance of EGFR, c-erbB-2 and p53 status as a prognostic indicator. However, the microvessel density was a significant predictor of relapse-free survival. Patients with over 100 counts of factor VIII-RA positive cells per mm2 field in the most active areas of neovascularization showed significantly poorer prognosis compared to those with less than 100 counts (p < 0.005). Multivariate analysis demonstrated that microvessel density was an independent prognostic indicator in node-negative breast cancer patients (p < 0.0005). It was suggested that microvessel density might be of use in selecting the high-risk group in node-negative breast cancer patients needing adjuvant therapies.
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PMID:[Significance of tumor angiogenesis as an independent prognostic factor in axillary node-negative breast cancer]. 753 84

We evaluated the prognostic value of tumor angiogenesis in node negative breast cancer (NNBC). Paraffin-embedded tissues from 87 patients with NNBC were immunostained for factor VIII-related antigen, using one tissue block representative of the invasive edge of the tumor. Sections were scanned at low power to identify "hotspots" of angiogenesis. Microvessel (MV) counts were performed at x200 magnification, using a grid eyepiece graticule. Within each hot spot, three fields (area of field = 0.22 mm2) were counted and averaged. The highest average for a hot spot and the highest single field value was recorded for each case. Patients were stratified into low and high MV groups and their survival compared. There were no differences in disease-free or overall survival between the two groups whether the highest average or the highest single value was used. Microvessel counts did not correlate with other prognostic features, ie, grade, size, estrogen receptor status, c-erb B-2 or accumulated P53 status. Because of the difficulty in assessing angiogenesis that is heterogenous throughout tumors, MV counting may not be suitable for clinical use as a prognostic factor in NNBC. This problem could be addressed in a prospective study involving more extensive tumor sampling.
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PMID:Prognostic significance of microvessel density in lymph node negative breast carcinoma. 759 Jun 87

PDGF-B released from colon tumor cells regulated tumor growth in athymic mice in a paracrine manner by inducing blood vessel formation. A positive correlation was found between expression of PDGF B-chain in cells grown in vitro and the number of factor VIII-positive blood vessels in tumors induced by three classes of colon carcinoma cell lines. Elevated expression of PDGF-B was also correlated with tumor size. Each cell line had the same mutations in the colon cancer genes APC, DCC, and p53 and had wild type c-K-ras genes (Huang et al. [1994] Oncogene, 9:3701-3706.) eliminating the possibility that any differences in tumor blood vessel formation were due to mutations and/or deletions in these genes. Colon carcinoma cells released biologically active PDGF capable of stimulating the growth of NIH3T3 cells, which was inhibited by neutralizing antisera to PDGF-AB chains. An inverse correlation was found between induction of factor VIII-positive blood vessels and expression of vascular endothelial growth factor (VEGF), while no correlation was seen with expression of either TGF alpha or k-FGF. Basic fibroblast growth factor (FGF) expression was not detected in these tumor cells. TGF beta 1 was capable of inducing PDGF-B expression in the undifferentiated U9 colon carcinoma cell line, but this sensitivity was not seen in differentiated cells. In contrast, TGF beta 1 inhibited VEGF expression in both undifferentiated cells and differentiated colon cancer cells. Thus, TGF beta 1 has two roles in the growth of undifferentiated U9 colon carcinoma cells in vivo: direct stimulation of cell proliferation as we have showed in earlier studies, and an increase in angiogenesis by inducing PDGF-B.
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PMID:Platelet-derived growth factor-B increases colon cancer cell growth in vivo by a paracrine effect. 759 1

Bovine subcultures (second passage) of glomerular endothelial cells (GEN) isolated from one-year-old kidney were successfully transfected by recombinant plasmids containing the simian virus (SV)-40 T antigen (Tag) using a lipofectin-mediated procedure. One cell clone was selected, propagated and characterized. This clone can be grown in RPMI 1640 medium supplemented with 10% fetal calf serum. The advantage of this cell line is the cultivation of bovine GEN without the addition of fibroblast growth factor or a coating of fibronectin or gelatin on the culture plate. More than 80 passages were achieved and the doubling time was 32 h. The Tag was easily identified in transfected-GEN by indirect immunofluorescence. These cells weakly expressed factor VIII-related antigen, slightly took up acetylated-low density lipoprotein and secreted a detectable amount of angiotensin-converting enzyme. Immunocytochemical staining for UAE-1 was also positive. Moreover, oncoproteins, such as Ki-67 and p53, were expressed in these cells. Cell cycle analysis by flow cytometry revealed that the percentages of G1, S, and G2/M stages in cycling transfected-GEN culture in RPMI 1640 medium supplemented with 10% fetal calf serum were 34%, 52.9%, and 13.1%, respectively. The conditioned medium from confluent transfected-GEN stimulated [3H]thymidine incorporation into glomerular mesangial cells. This cell line may provide a useful tool for examining modulators of mesangial cell growth. Thus this cell line is the first immortalized bovine GEN that retain the morphologic, phenotypic, and functional characteristics of bovine GEN.
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PMID:Establishment and characterization of an immortalized bovine glomerular endothelial cell line. 793 62

Microwave oven (mwo) is used to stimulate tissue fixation and to retrieve antigens damaged by fixation. Heavy metal salt solutions, water, and citric acid buffer (cab) have been suggested for this purpose. A serie of tumors treated with cab and phosphate-buffered saline (pbs) with mwo were studied immunohistochemically with 24 antibodies. Controls were treated in the same way, except for microwaving. The antibodies were directed against antigens of the following tumors: breast and prostate carcinoma, carcinoid, lymphoma and melanoma. The results showed that cab enhanced the immunoreactivity of the following antigens: estrogen receptors (AMAC), progesterone receptors (Novocastra), HMB45, vimentin, leukocyte common antigen, PCNA, p53, MIB-1 (Ki-67) and prostatic specific antigen. The antigens that did not improve their immunoreactivity, when compared with the control series were: factor VIII, keratin, Leu 22, L26, neuron-specific enolase, CEA, chromogranin, HBME-1, smooth muscle actin and EMA. Microwaving equally improved protein S100 and desmin either with cab or pbs. The only antigen that improved with pbs was actin. The results with B72.3 and NKI/C3 were poor and not reliable. In conclusion microwaving with cab enhances the immunoreactivity of the antibodies mentioned above leading to an increase in sensibility without loosing specificity.
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PMID:[Antigen retrieval by microwave oven with buffer of citric acid]. 799 28

Previous studies have shown that reduced glutathione (GSH) inhibits experimental oral carcinogenesis in the hamster buccal pouch model. To gain further understanding of molecular mechanisms in the anticancer effect of GSH, these studies examined levels of p53 protein expression. 7,12-Dimethylbenz[a]anthracene (DMBA) was applied to the buccal pouches of 20 Syrian Golden hamsters (Mesocricetus auratus) in a 0.5% solution in mineral oil thrice weekly for 14 weeks. In 10 animals, 10 mg/kg reduced glutathione (GSH) in 0.5 ml of mineral oil was administered by mouth thrice weekly on days alternate to the DMBA painting. An additional 20 animals served as DMBA-untreated and GSH controls. At the termination of the experimental period, there were fewer tumors in the DMBA-GSH than in the DMBA tumor control group, and the tumors were smaller (tumor burden 315 vs. 3,040 mm3). Histologically, the DMBA-GSH group showed a marked reduction in dysplasia, carcinoma in situ, and invasive epidermoid carcinoma sites. Immunohistochemically, by use of monoclonal antibodies for wild-type p53 (PAb 246), changes were observed in protein expression levels at dysplastic sites and within the malignant tumors. Staining for p53 protein was slightly increased in dysplasia and squamous cell carcinoma in the tumor control animals (painted with DMBA) compared with the untreated controls that were free of tumors. In the GSH and DMBA treatment group, p53 protein expression levels were strongly increased in dysplastic and tumor sites. The significant inhibition of oral carcinogenesis associated with the administration of GSH was correlated with the increased levels of the wild-type p53 tumor suppressor gene, suggesting its possible use as a biomarker for GSH chemoprevention. The inhibition of oral carcinogenesis by reduced GSH was also related to a very significant inhibition of tumor angiogenesis, defined by factor VIII staining. Thus angiogenesis inhibition may be an additional mechanism for antioxidant chemoprevention, and this suggests another possible biomarker for antioxidant chemoprevention.
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PMID:Glutathione inhibits experimental oral carcinogenesis, p53 expression, and angiogenesis. 887 60

Ninety-four cases of early abortion have been studied. Five histological groups of lesion have been identified by routine histological techniques on abortion materials, group I corresponding to partial hydatidiform mole. Cytogenetic analyses have revealed chromosome anomalies in near 50% of cases with a prevalence of triploidies followed by trisomies and monosomies. Normal histological findings are more often associated with normal karyotypes and group I with abnormal karyotypes but a specific correlation between histological pattern and cytogenetic anomalies is lacking. Neither some histochemical reactions nor the well preserved immunohistochemical reactivities of beta-hCG, hPL, PLAP, AFP, cytokeratin, vimentin, desmin, factor VIII, CD 68, MIB1 (growth fraction), EGF-R, p53 and c-erbB-2 oncoproteins have disclosed specific chromosome anomalies. They have only allowed a better definition of histological groups. A simple histological evaluation, although extended to immunohistochemical reaction may not substitute the cytogenetic analyses, not even for purposes of preselection.
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PMID:[Correlation of the histological and cytogenetic pictures in placental tissue from early abortion. Does immunohistochemistry have a role?]. 900 96

Angiogenesis is essential for tumour growth and metastasis. In spite of its relevant biological significance, recent studies have produced conflicting results regarding the capacity of microvessel quantifications in breast carcinomas to predict patients' outcome and the existence of metastasis. In order to provide further information in this issue, we evaluated tumour angiogenesis in a series of 45 primary breast carcinomas (mean age: 55.3 +/- 14.2) and examined their association with established or potentially useful prognostic parameters. Microvessels were highlighted by immunohistochemical staining for factor VIII-related antigen and counted in the three most vascularized areas in a 200 x field (0.74 mm2) by four observers simultaneously. Results were analysed for the average vessel count of each case. The mean intratumoural microvessel count was 57.7 +/- 24.4 (range: 24.3 to 127.7). We found a statistically significant association between angiogenesis and age. The microvessels count in patients younger than 50 years was 67.8 +/- 26.4, from 51 to 70 years, 52.0 +/- 22.8 and over 71 years, 46.1 +/- 14.2 (p = 0.03). Node positive patients had slightly higher microvessel counts (60.3 +/- 25.3) than node negative ones (54.4 +/- 23.5); this difference was not significant (p = 0.42), even when we considered each age group per se. No association was found between angiogenesis and tumour size, histologic grade, estrogen receptor, MIB-1 index, ploidy and expression of p53 and c-erbB-2. Our results suggest that invasive breast carcinoma-induced angiogenesis is age-dependent.
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PMID:Angiogenesis in breast cancer is related to age but not to other prognostic parameters. 925 52

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


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