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Query: UMLS:C1519670 (tumor angiogenesis)
 6,052 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor angiogenesis is associated with metastasis in several types of solid tumors, including melanoma, breast, prostate, lung, bladder, and oral-cavity tumors. The purpose of this study was to determine whether tumor angiogenesis could predict recurrence following curative surgery for colorectal cancer. Thirty-five patients were studied, including 13 patients with recurrent tumor and 22 without. Representative formalin-fixed, paraffin-embedded sections of invasive colorectal cancers from these patients were sectioned. The endothelial cells of microvessels within the tumors were highlighted by immunohistochemical staining for CD31. The most active areas were identified and the microvessels counted in a x 400 field (0.152 mm2) by two observers in a blinded fashion. Tumor microvessel count (p = 0.0062). Dukes' staging (p = 0.0004), vascular invasion (p = 0.0280), and tumor grade (p = 0.0559) were all significantly associated with tumor recurrence. Tumor microvessel counts > or = 65 per x 400 field were associated with tumor recurrence (p = 0.0035, relative risk [RR] = 11.3). Controlling for Dukes' stage, a multivariate logistic regression model revealed that a tumor microvessel count > or = 65 is an important predictor of tumor recurrence (p = 0.0783, RR = 6.0). A backwards elimination proportional hazards model revealed that a microvessel count > or = 65 shows a trend toward independent prediction of time to tumor recurrence (p = 0.1203, RR = 2.967) when controlled for Dukes' staging (p = 0.0029, RR = 9.089). Despite the small number of patients studied, these results suggest that the number of microvessels in sections of invasive colorectal adenocarcinoma immunohistochemically stained with CD31 may be an important independent predictor of tumor recurrence and time to recurrence.
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PMID:Tumor angiogenesis predicts recurrence in invasive colorectal cancer when controlled for Dukes staging. 882 33

Neovascularization promotes tumor growth by facilitating nutrient exchange and by the paracrine effect. To investigate the relationship between tumor angiogenesis and patient outcome in colorectal cancer, 133 primary tumors were immunostained for CD34 antigen. Blood vessels within five microscopic fields at x200 were counted, and the mean was assigned. Mean patient age was 62.9 years, mean follow-up was 56.4 months, and mean vessel count was 112 (range, 23-298). Cox proportional hazards model and multivariate logistic regression analyses showed that the vessel count was the most important prognostic factor and correlated significantly with hematogenous, but not peritoneal or lymph node, metastasis.
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PMID:Tumor angiogenesis and mode of metastasis in patients with colorectal cancer. 906 67

To examine the association of vascular endothelial growth factor (VEGF) expression with tumor angiogenesis, survival and thymidine phosphorylase/platelet-derived endothelial cell growth factor (dThdPase/PD-ECGF) expression in human colorectal cancer, immunohistochemical studies were performed on 136 cases of resected colorectal cancer specimens using antibodies for VEGF, KDR, CD34 and dThdPase/PD-ECGF. Fifty-nine cases (43%) were evaluated as positive for VEGF staining and 71 cases (52%) were evaluated as positive for dThdPase/PD-ECGF staining. The expression of VEGF correlated significantly with vessel counts and the expression of dThdPase/PD-ECGF (P = 0.01 and 0.01, respectively). Cox proportional hazards model analysis showed that vessel counts and VEGF expression were significant and independent prognostic factors, but that KDR expression was not.
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PMID:Association of vascular endothelial growth factor expression with tumor angiogenesis, survival and thymidine phosphorylase/platelet-derived endothelial cell growth factor expression in human colorectal cancer. 957 Mar 76

To clarify whether platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) expression in both tumor cells and stromal cells has independent or synergistic effects on tumor angiogenesis and progression and to explore a possible regulator for PD-ECGF/TP expression, immunohistochemical staining was conducted on 148 specimens of colorectal cancer. The microvessel count was significantly correlated with the extent of PD-ECGF/TP expression. Macrophage infiltration in tumors with positive TP was significantly higher than in tumors with negative TP (P < 0.001). The Cox model showed that PD-ECGF/TP expression was an independent prognostic factor, although the microvessel count had a stronger value in determining the patient prognosis.
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PMID:Platelet-derived endothelial cell growth factor/thymidine phosphorylase expression correlated with tumor angiogenesis and macrophage infiltration in colorectal cancer. 965 93

5-Fluorouracil (5FU)-based therapy is given to patients with advanced colorectal cancer and as adjuvant treatment. Thymidylate synthase (TS) is the target for 5FU, and may have a prognostic role for the outcome of 5FU-based therapy together with proliferation markers such as p53 and Ki67. Thymidine phosphorylase (TP, also known as platelet-derived endothelial cell growth factor) may be of importance both in the 5FU drug activation pathway and in tumor angiogenesis, similar to vascular endothelial growth factor (VEGF). TS and TP levels were determined biochemically in fresh-frozen tumor specimens of 32 untreated patients with colorectal cancer, whereas in paraffin-embedded tissue samples, immunohistochemistry was performed for TS, TP, and additional prognostic markers such as p53, Ki67, and VEGF as well as microvessel density. All factors were correlated with patient characteristics such as age, gender, Dukes' stage, angio-invasion, and differentiation grade. TS and TP as measured by various assays were correlated with overall and disease-free survival in this patient group. TP enzyme activity and protein expression correlated with each other. A significant correlation was found between TP enzyme activity and 5-fluoro-2'-deoxyuridine-5'-monophosphate binding activity. VEGF expression correlated significantly with TP immunostaining and Ki67 index. Survival analysis revealed a significant relation of TS levels to the overall survival in this small patient group and a significant correlation between TP activity and disease-free survival. TS and TP both were of prognostic significance in these patients with colorectal cancer. The interesting relationship of TS and TP with angiogenesis and proliferation needs further investigation.
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PMID:Prognostic role of thymidylate synthase, thymidine phosphorylase/platelet-derived endothelial cell growth factor, and proliferation markers in colorectal cancer. 1074 35

Chemically stabilized hammerhead ribozymes are nuclease-resistant, RNA-based oligonucleotides that selectively bind and cleave specific target RNAs. Due to their potential for specifically inhibiting gene expression, ribozymes are being investigated for therapeutic applications as well as for the elucidation of gene function. In particular, we have investigated ribozymes that target the mRNA of the vascular endothelial growth factor (VEGF) receptors because VEGF signaling is an important mediator of tumor angiogenesis and metastasis. Here we report pharmacodynamic studies testing anti-Flt-1 (VEGFR-1) and anti-KDR (VEGFR-2) ribozymes in animal models of solid tumor growth and metastasis. Ribozymes targeting either Flt-1 or KDR significantly inhibited primary tumor growth in a highly metastatic variant of Lewis lung carcinoma. However, only treatment with the anti-Flt-1 ribozyme resulted in a statistically significant and dose-dependent inhibition of lung metastasis in this model. The anti-Flt-1 ribozyme was then tested in a xenograft model of human metastatic colorectal cancer in which significant inhibition of liver metastasis was observed. Taken together, these data represent the first demonstration that synthetic ribozymes targeting VEGF receptor mRNA reduced the growth and metastasis of solid tumors in vivo.
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PMID:Antitumor and antimetastatic activity of ribozymes targeting the messenger RNA of vascular endothelial growth factor receptors. 1081 37

Tumor angiogenesis is essential for tumor growth and tumor metastasis, and it depends on angiogenic factors produced by tumor cells and/or infiltrating cells in tumor tissue. In this study, we evaluated the clinical significance of the expression of angiogenin, which is a potent angiogenic protein, and the relationship between its mRNA expression and focal macrophage infiltration in colorectal cancer. Furthermore, we investigated the induction of angiogenin mRNA expression by proinflammatory cytokines mainly produced by inflammatory cells in tumor tissues. When we examined the relationship between the mRNA expression of angiogenin, by semiquantitative reverse transcription-PCR, and clinicopathological features in 65 patients with colorectal cancer, there was a significant difference in the vascular involvement, lymph node metastasis, liver metastasis, and advanced stage in patients with high-expression of angiogenin compared with low expression (P < 0.05). With regard to prognosis, the survival time for subjects in the high angiogenin mRNA group (tumor:normal ratio >1.9) was significantly worse (P < 0.05). When we examined the localization of angiogenin in colorectal cancer, immunohistochemical analysis in 65 patients with colorectal cancer revealed that angiogenin was predominantly expressed in cancer cells compared with stromal cells or normal tissues. The intensity of staining of angiogenin was significantly correlated with microvessel counts and focal macrophage infiltration counts (P < 0.05). In an in vitro study, interleukin-1beta and tumor necrosis factor-alpha induced angiogenin mRNA expression in colon cancer cells in a dose- and time-dependent manner, and these cytokines significantly upregulated the expression of angiogenin mRNA, especially in colon cancer cells rather than in other cells in the stroma of tumor tissues (fibroblasts, tumor infiltrating lymphocytes, macrophages). These results suggest that tumor angiogenesis in colorectal cancer may be advanced, at least in part, by angiogenin induced by proinflammatory cytokines derived from infiltrating macrophages.
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PMID:Angiogenin expression in human colorectal cancer: the role of focal macrophage infiltration. 1099 42

Integrin alpha v-beta 3 is involved in tumor angiogenesis while the clinical significance of beta 3 integrin expression in colorectal cancer and lung metastases. Analysis was performed on 51 colorectal cancer patients (22 with subsequent lung metastasis and 29 without lung metastasis). Fifty-one primary tumors and 22 lung metastases were examined for immunohistochemical detection of integrin beta 3. We found that the antibody VNR 5 to integrin beta 3 prefentially stains the blood vessels of small caliber. Indeed, vascular integrin beta 3 index was significantly higher in tumors of patients with lung metastasis than in those without lung metastasis. In the patients with lung metastases, vascular integrin beta 3 index was significantly lower in lung metastases than in primary tumors. It was immunohistochemically proved that integrin beta 3 is an important vascular endothelial cell market for lung metastasis.
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PMID:Vascular integrin beta 3 and its relation to pulmonary metastasis of colorectal carcinoma. 1129 20

Extracellular matrix (ECM) degradation enzymes, such as matrix metalloproteinases (MMPs) and plasminogen activators, are important factors in cancer invasion and metastasis, because invasion and metastasis of cancer cells require destruction of mesenchymal collagen or the endothelial basement membrane. Moreover, recent studies have shown that ECM degradation enzymes play important roles in cancer cell proliferation, cancer escape from the immune system, and tumor angiogenesis. ECM degradation enzymes, especially some MMPs, are good targets for anticancer metastatic therapy. Numerous anti-MMP agents have been developed and phase III clinical trials in advanced cancers ongoing. Successful control of MMPs induced by cancer cells will prevent liver metastasis of colorectal cancer.
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PMID:[Extracellular matrix degradation enzymes: important factors in liver metastasis of colorectal cancer and good targets for anticancer metastatic therapy]. 1139 99

To investigate the relationship between tumor angiogenesis and hematogenous metastasis in colorectal cancer, an immunohistochemical analysis using antibody against factor VIII was carried out on archival specimens of 35 primary tumors. In addition, we also evaluated the levels of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), by an enzyme-linked immunosorbent assay (ELISA), in tumor specimens and the serum in the drainage venous blood. The levels of VEGF showed no correlation with the microvessel density and also did not increase significantly in patients with hepatic metastasis. On the other hand, the IL-8 levels in the tumor tissue (r=0.45) and the serum IL-8 levels (r=0.49) showed a significant correlation with the microvessel density. The serum IL-8 levels in patients with Dukes' C colorectal cancer and hepatic metastasis were significantly higher than in those without hepatic metastasis (p<0.05). In addition, the serum levels of IL-8 in patients with Dukes' C cancer without hepatic metastasis and those with Dukes' A and B cancer were also closely similar. These results suggest that IL-8 is associated with the microvessel density in primary tumors and thus play an important role in the occurrence of hepatic metastasis in patients with colorectal cancer. As a result, elevated levels of IL-8 in the drainage vein are considered to be a useful predictor for developing hepatic metastasis in patients with resectable colorectal cancer.
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PMID:Elevated IL-8 levels in the drainage vein of resectable Dukes' C colorectal cancer indicate high risk for developing hepatic metastasis. 1174 75


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