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Query: UMLS:C1519670 (tumor angiogenesis)
 6,052 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

We have previously suggested that tumor angiogenesis in human gliomas is regulated by a paracrine mechanism involving vascular endothelial growth factor (VEGF) and flt-1 (VEGF-receptor 1). VEGF, an endothelial-cell-specific mitogen, is abundantly expressed in glioma cells which reside along necrotic areas, whereas flt-1, a tyrosine-kinase receptor for VEGF, is expressed in tumor endothelial cells, but not in endothelial cells in normal adult brain. Recently, a second tyrosine-kinase receptor which binds VEGF with high affinity, designated KDR or flk-1, has been described. We performed in situ hybridization for VEGF mRNA, flt-1 mRNA and KDR mRNA on serial sections of normal brain, low-grade and high-grade glioma specimens. We show that KDR mRNA is co-expressed with flt-1 in vascular cells in glioblastoma but not in low-grade glioma. Since flt-1 and KDR are not expressed in endothelial cells in the normal adult brain, the coordinate up-regulation of 2 receptors for VEGF appears to be a critical event which controls tumor angiogenesis. Immunocytochemistry with a monoclonal anti-VEGF antibody revealed significant amounts of VEGF protein in the same glioma cells that expressed VEGF mRNA. The largest amount of VEGF immunoreactivity, however, was detected on the vasculature of glioblastomas, the site where VEGF exerts its biological functions. These findings suggest that VEGF is produced and secreted by glioma cells and acts on tumor endothelial cells which express VEGF receptors. To further characterize VEGF-producer cells in vivo, we investigated cellular proliferation, immunoreactivity to the p53 tumor-suppressor gene product and epidermal-growth-factor-receptor (EGFR) expression on serial sections by immunocytochemistry. VEGF-producer cells did not show increased cellular proliferation, p53 immunoreactivity or EGFR immunoreactivity as compared with glioma cells which did not express VEGF. Our studies therefore do not demonstrate evidence for a growth advantage of VEGF-producer cells in vivo or VEGF induction by p53 mutation or EGFR over-expression.
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PMID:Vascular endothelial growth factor and glioma angiogenesis: coordinate induction of VEGF receptors, distribution of VEGF protein and possible in vivo regulatory mechanisms. 752 92

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

Many tumor cells produce vascular endothelial growth factor (VEGF), which is thought to be a pivotal mediator of tumor neoangiogenesis. Expression of the VEGF gene can be induced by tumor promoting phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), which activate protein kinase C (PKC). Here we show that in transient transfection assays a mutated form of the murine p53 tumor suppressor gene (ala135-->val) induces expression of VEGF mRNA and potentiates TPA stimulated VEGF mRNA expression. In NIH 3T3 cells which stably overexpress the temperature sensitive p53 (ala135-->val), displaying mutant phenotype at 37 degrees C and wildtype phenotype at 32.5 degrees C, induction of VEGF mRNA and protein by activated PKC is strongly synergistic with mutant, but not wildtype p53. Mutant p53 specifically increases TPA induction of VEGF without affecting the expression of other TPA inducible genes. TPA dependent VEGF expression is also enhanced by human p53 mutated at amino acid 175. Thus, our data link PKC and p53, the gene most frequently altered in human tumors, with the regulation of tumor angiogenesis.
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PMID:Mutant p53 potentiates protein kinase C induction of vascular endothelial growth factor expression. 810 42

Thrombospondin-1 (TSP) is a 450-KD glycoprotein that was initially discovered in the platelet alpha-granule. It now appears that TSP is intimately involved in the regulation of a variety of cellular functions and cell-to-cell interactions. Recently, it has been demonstrated that TSP functions as a p53-dependent inhibitor of angiogenesis in cultured fibroblasts from Li-Fraumeni patients and therefore may be an important factor involved with tumor invasion and metastasis. It has previously been demonstrated that TSP can be detected in frozen tissue sections by immunohistochemical methods. Our objective in this study was to determine the optimal antigen retrieval (AR) protocol for detection of TSP in formalin-fixed, paraffin-embedded tissue by using tissue sections from patients with invasive transitional cell carcinoma of the bladder. The optimal AR protocol was determined utilizing a variety of heating conditions and antigen retrieval buffers. Our results demonstrate that TSP can be reliably detected in paraffin-embedded tissue by immunohistochemical techniques that utilize AR with high-temperature microwave heating and a low-pH Tris-HCI buffer. The importance of this method is that it allows the reliable detection of TSP in archival tissue. This should facilitate further investigation into TSP's role in the regulation of cellular processes, including its influence on tumor angiogenesis and metastasis.
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PMID:Immunohistochemical detection of thrombospondin-1 in formalin-fixed, paraffin-embedded tissue. 867 97

Recently, the importance of tumor angiogenesis in the process of tumor growth, progression and metastasis in solid tumors has been widely accepted. The prognostic value of angiogenesis has been demonstrated in a variety of solid tumors including breast cancer. In this report, we reviewed recent studies investigating on the value of intratumoral microvessel density (MVD), assessed by a sermiquantitative immunohistochemical assay with using factor-VIII related antibody or anti CD-31 antibody, as a prognostic indicator in primary breast cancer patients. Studies using factor-VIII related antibody showed that the average MVD ranged from 67.3 to 84.0 counts per mm2 area. When used by anti CD-31 monoclonal antibody, the average MVD were 120.3 approximately 135 counts per mm2 area in the range. More than 8 clinical investigations have showed that MVD was a potent prognostic indicator for relapse free survival and/or overall survival in both node-negative and -positive patients. Two reports concluded no prognostic value of MVD, however the average MVD of these two studies significantly differed from other reports. Thus, at present, angiogenesis grade seems to provide an independent prognostic value when the MVD was properly assessed. With respect to the relationship with conventional prognostic indicators, several reports showed the tendency that increased MVD was correlated with younger age and increase of tumor size below 3 cm diameter, however, some reports failed to demonstrate the tendency, suggesting that these correlations are still in controversial. Biological markers including ER, p53 and c-erB2 showed no correlation with the MVD in many studies including our investigation. Only a significant correlation we found was that MVD was increased in tumors with the expression of vascular endothelial growth factor and platelet-derived endothelial cell growth factor, which are noted to be potent endothelial growth factor. Since the evaluation of tumor angiogenesis as a prognostic indicator is now widely investigated in a prospective study, MVD might be introduced to the category of the criteria for determining the schedule of postoperative adjuvant therapy of breast cancer.
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PMID:[The importance of tumor angiogenesis as a prognostic indicator in primary breast cancer]. 870 39

A malignant cell population needs the development of microvessels in order to grow and metastasize. Recently, a role for the p53 gene in the regulation of this angiogenic process has been suggested. Wild-type p53 is involved in the secretion of Trombospondin-1 (TSP-1), an angiogenesis inhibitor. Mutations of the p53 gene cause a downregulation of TSP-1 mRNA in cell lines. Mutant p53 also upregulates the expression of vascular endothelial cell growth factor, a potent angiogenic factor. Together with the reported association of p53 protein overexpression and microvessel density (MVD) in head-and-neck squamous-cell carcinoma, these in vitro findings led us to investigate whether this association would also apply in colorectal adenocarcinomas. Structural changes of the p53 gene are the most frequent observed mutations in colorectal carcinoma and are suspected to be involved in the carcinogenesis at a relatively early stage. Parallel tissue sections from primary colorectal adenocarcinomas were immunostained for CD31, an endothelial cell marker, and with DO7, recognizing both mutant and wild-type p53 protein overexpression. The presence of p53 protein overexpression was found to be significantly associated with high MVD in the vascular hot spots. Our results are in accordance with the in vitro studies on the involvement of p53 in angiogenesis. Mutant p53 might stimulate tumor angiogenesis both indirectly, by augmenting the tumor cell proliferation, and directly, by upregulating angiogenic factors and downregulating angiogenic inhibitors.
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PMID:Correlation of intratumoral microvessel density and p53 protein overexpression in human colorectal adenocarcinoma. 877 72

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

Increasing evidence from experimental studies indicates that apoptosis may be related to angiogenesis in tumor progression. To explore how spontaneous apoptosis correlates with tumor angiogenesis, we measured the apoptotic index (AI) using the ApopTag kit (Oncor) and intratumoral microvessel density using an anti-CD34 monoclonal antibody in 101 cases of gastric carcinoma. Immunohistochemical staining for Ki-67 labeling index and the expression of p53 were conducted simultaneously. Statistical analysis revealed an inverse correlation between AIs and intratumoral microvessel densities (r = -0.4066, P < 0.0001) and failed to find significant correlations between AI and Ki-67 labeling index, as well as the expression of p53. The results of this study demonstrated for the first time that the incidence of apoptosis in gastric carcinoma is significantly influenced by the extent of neovascularization and suggests that tumor angiogenesis may contribute to a reduction of apoptosis in tumor cells.
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PMID:Spontaneous apoptosis is inversely related to intratumoral microvessel density in gastric carcinoma. 900 May 58


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