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

Angiogenesis is a key prerequisite for the successful establishment, growth, and dissemination of tumors. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity and cyclooxygenase-2 (COX-2) promotes angiogenesis by modulated production of angiogenic factors including VEGF. The current study was designed to investigate the possible roles of COX-2 and VEGF in gastric cancer angiogenesis. In this study, we conducted an immunohistochemical investigation of COX-2 and VEGF expression in 97 patients with gastric cancer. To assess tumor angiogenesis, microvessel density (MVD) was determined by CD34 immunohistochemical staining. Expression of COX-2 and VEGF in gastric cancer tissues, was demonstrated in 63.9% and 75.3% of cases, respectively. The expression of COX-2 correlated significantly with VEGF expression. High MVD was significantly associated with depth of tumor invasion and poor survival. The mean MVD value of VEGF positive tumors was 79.8 +/- 32.0 and significantly higher than that of VEGF negative tumors. The mean MVD value of COX-2 positive tumors was 77.9 +/- 29.9 and not significantly higher than that of COX-2 negative tumor. The mean value of MVD in tumors positive for both COX-2 and VEGF was significantly higher than that in tumors negative for both. However, there was no correlation between COX-2 or VEGF expression and various clinicopathological features including patient survival. These results suggest that COX-2 may play an important role in carcinogenesis by stimulating tumor angiogenesis in concert with VEGF in human gastric cancer.
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PMID:Cyclooxygenase-2 overexpression correlates with vascular endothelial growth factor expression and tumor angiogenesis in gastric cancer. 1281 Dec

It has been a concern that a therapeutic modality recommended as an adjunct to healing and administered to promote proliferation of fibroblasts, epithelial cells and blood vessels in a wound could also lead to proliferation of malignant cells and angiogenesis in a malignant tumor. The first reported concern that hyperbaric oxygen (HBO2) might have cancer growth enhancing effects appeared in a paper by Johnson and Lauchlan in 1966. In a series of patients treated with HBO2 radiosensitization, they reported a more frequent than expected incidence of metastases and an unusual pattern of metastases. The published literature from clinical reports, animal studies and cell culture studies are reviewed. Putative mechanisms whereby HBO2 could have carcinogenic effects are discussed. The processes of angiogenesis in wound healing and in cancer growth are compared and contrasted. In vitro, in vivo and clinical studies strongly suggest no more than a neutral effect of HBO2 on tumor growth. In fact some studies suggest a negative impact of HBO2 on malignant progression or formation. For angiogenesis, similarities in wound healing and cancer are striking but significant differences are found including the relative importance of angiogenic factors and the process of cessation of angiogenesis. Tumors that grow in hypoxic environments are more prone to metastases and more lethal to the patient. They are also more likely to mutate toward resistant genotypes. Discussion of postulated mechanisms of carcinogenesis including free radical and immunosuppressive effects points out why they are not likely to enhance or cause cancer growth or initiation. In conclusion, the published literature on tumor angiogenesis mechanisms and other possible mechanisms of cancer causation or accelerated growth provides little basis for HBO2 to enhance malignant growth or metastases. A history of malignancy should not be considered a contraindication for HBO2 therapy.
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PMID:Hyperbaric oxygen: does it promote growth or recurrence of malignancy? 1284 4

Combined modality therapy represents current standard therapy for locoregionally advanced non-small cell lung cancer. In particular, concomitant chemoradiotherapy has emerged as the preferred approach. At the same time, efforts to increase locoregional and systemic antitumor activity are necessary to further improve long-term survival rates for these patients. In recent years, multiple cellular targets have emerged in the development of novel antitumor therapies. Several of these are of high relevance in the carcinogenesis of lung cancer including the epidermal growth factor receptor (EGFR), the ras signaling pathway, tumor angiogenesis, and cyclooxygenase-2 (COX-2) expression. Novel agents directed against these targets are currently under development with promising early results in non-small cell lung cancer when administered as single agents or in combination with chemotherapy in stage IV or recurrent disease. Similarly their use with concurrent radiation therapy is supported by preclinical models. Selected early clinical trials utilizing these agents in combination with radiotherapy or chemoradiotherapy are discussed.
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PMID:Targeted therapies for stage III non-small cell lung cancer: integration in the combined modality setting. 1286 70

Lung cancer is the leading cause of cancer mortality. Chemoprevention is an attractive strategy to combat this major public health problem. Pre-clinical and clinical studies have identified diverse candidate chemopreventive agents that affect cellular proliferation, differentiation, apoptosis and tumor angiogenesis, among other pathways. These pharmacological agents are undergoing testing through use of pre-clinical models and clinical trials. These studies have uncovered cyclin D1 as a chemoprevention target and a surrogate marker of chemopreventive response in the lung. Chemoprevention of tobacco-carcinogen transformed human bronchial epithelial (HBE) cells appears to be due at least partly to degradation of cyclin D1. These studies of cultured HBE cells were extended to the in vivo setting by examination of preneoplastic bronchial lesions that established the frequent aberrant expression of cyclin D1 in lung carcinogenesis. Certain retinoids, natural and synthetic derivatives of vitamin A, repress cyclin D1, but activation of the epidermal growth factor receptor (EGFR) induces cyclin D1. Retinoids and specific chemopreventive agents can activate the proteasome-dependent degradation of cyclin D1 and also repress EGFR expression, thereby reducing cyclin D1 levels. These actions oppose the mitogenic effects of cyclin D1. This is hypothesized to trigger G1 arrest and thereby permit repair of carcinogenic damage of genomic DNA. These and other pre-clinical and clinical studies that will be reviewed here indicate that cyclin D1 and perhaps other cyclins are attractive pharmacological targets for lung cancer chemoprevention.
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PMID:Cyclin D1 as a target for chemoprevention. 1286 74

In this issue of Cancer Cell, Zhu and coworkers demonstrate that environmental tobacco smoke (ETS) results in tumor angiogenesis, and provide evidence that the responsible factor in ETS is nicotine. While a weak carcinogen, nicotine promotes carcinogenesis by a number of different mechanisms. The authors' findings provide further evidence of the harmful effects of ETS and indicate the desirability of reducing exposure to it.
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PMID:Environmental tobacco smoke, carcinogenesis, and angiogenesis: a double whammy? 1452 53

The von Hippel-Lindau (VHL) tumor suppressor gene plays a prominent role in the development of renal cell carcinoma (RCC) in humans. VHL functions as a ubiquitin E3 ligase, controlling the stability of hypoxia inducible factor (HIF) and tumor angiogenesis. Alterations in this tumor suppressor gene are rarely observed in spontaneous or chemically induced RCC that arise in conventional strains of rodents and Vhl knockout mice (Vhl+/-) do not develop spontaneous RCC. We tested whether Vhl knockout mice exhibited increased susceptibility to renal carcinogenesis using the well-characterized renal carcinogen streptozotocin. No differences were observed between wild-type and Vhl+/- animals in the frequency or type of renal lesions induced by 50-200 mg/kg streptozotocin. Carcinogen-induced RCC that developed in Vhl heterozygotes and wild-type mice did not contain mutations in the wild-type Vhl, as determined by direct sequencing of the primary tumors. While Vhl+/- mice exhibited no increase in renal lesions in response to streptozotocin, heterozygous animals did develop vascular proliferative lesions of the liver, uterus, ovary, spleen and heart. These lesions, ranging from angiectasis to hemangiosarcoma, were most prominent in the livers of Vhl+/- mice, where they were found in high incidence and high multiplicity. Wild-type mice developed a low-frequency of liver angiectasis (7-15%) only at the highest doses of carcinogen used (150 and 200 mg/kg, respectively) while Vhl+/- mice exhibited angiectasis, hemangioma and hemangiosarcomas with a frequency ranging from 19 to 46% at 50-200 mg/kg streptozotocin. Untreated Vhl+/- mice had a spontaneous incidence of hepatic vascular lesions of 21%. Furthermore, vascular lesions of the uterus, ovary, spleen and heart were observed only in Vhl+/- mice, with an incidence of (5-28%). Taken together, the data indicate that heterozygosity at the Vhl locus predisposes mice to a vascular phenotype ranging from angiectasis to hemangiosarcoma, consistent with the ability of this tumor suppressor gene to control the stability of HIF and regulate key proteins that participate in angiogenesis.
Carcinogenesis 2004 Mar
PMID:Susceptibility to vascular neoplasms but no increased susceptibility to renal carcinogenesis in Vhl knockout mice. 1460 87

Elevated expression of Eph receptors has long been correlated with the growth of solid tumors. However, the functional role of this family of receptor tyrosine kinases in carcinogenesis and tumor angiogenesis has not been well characterized. Here we report that soluble EphA receptors inhibit tumor angiogenesis and tumor progression in vivo in the RIP-Tag transgenic model of vascular endothelial growth factor (VEGF)-dependent multistage pancreatic islet cell carcinoma. Soluble EphA receptors delivered either by a transgene or an osmotic minipump inhibited the formation of angiogenic islet, a premalignant lesion, and reduced tumor volume of solid islet cell carcinoma. EphA2-Fc or EphA3-Fc treatment resulted in decreased tumor volume but increased tumor and endothelial cell apoptosis in vivo. In addition, soluble EphA receptors inhibited VEGF and betaTC tumor cell-conditioned medium-induced endothelial cell migration in vitro and VEGF-induced cornea angiogenesis in vivo. A dominant negative EphA2 mutant inhibited--whereas a gain-of-function EphA2 mutant enhanced--tumor cell-induced endothelial cell migration, suggesting that EphA2 receptor activation is required for tumor cell-endothelial cell interaction. These data provide functional evidence for EphA class receptor regulation of VEGF-dependent tumor angiogenesis, suggesting that the EphA signaling pathway may represent an attractive novel target for antiangiogenic therapy in cancer.
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PMID:Inhibition of VEGF-dependent multistage carcinogenesis by soluble EphA receptors. 1467 Jan 82

We previously reported that vascular endothelial growth factor (VEGF) expression correlates with vessel density in human esophageal squamous cell carcinomas. However, tumor angiogenesis is not controlled simply by the presence of VEGF, and is likely regulated by several angiogenic factors produced by tumor and host cells. The goal of the present study was to determine the angiogenic profile of precancerous and cancerous lesions of the esophagus. Expression of mRNAs for VEGF, platelet derived endothelial cell growth factor (PD-ECGF), basic fibroblast growth factor (bFGF), and interleukin (IL)-8 was examined in six esophageal carcinoma cell lines and fresh biopsy specimens from 16 patients with invasive esophageal carcinoma by RT-PCR. Immunohistochemical analyses with antibodies against VEGF, PD-ECGF, bFGF, and IL-8 were performed on archival specimens of 60 normal esophageal mucosa, 11 dysplasias and 49 carcinomas of the esophagus. Microvessels were stained with anti-CD34 antibody and quantified by counting the number of vessels in a x200 field in the most vascularized areas of the tumor. Esophageal carcinoma cell lines and tumor tissues expressed mRNAs for one or more these angiogenic factors at various levels. An initial increase in vessel density and enhanced expression of PD-ECGF and VEGF were observed in dysplastic epithelium. Vessel density was significantly higher in more advanced lesions. bFGF and IL-8 were not expressed in dysplasias and mucosal carcinomas, but expression was increased in late stage squamous cell carcinoma. These findings suggest that the angiogenic switch is a very early event in the development of invasive carcinoma. Several different angiogenic factors produced by tumor cells and host cells may regulate angiogenesis during different steps of esophageal carcinogenesis.
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PMID:Angiogenic switch occurs during the precancerous stage of human esophageal squamous cell carcinoma. 1471 61

Inducible nitric oxide (NO) synthase (iNOS) appears to be a marker of tumor progression in colon carcinogenesis. Here we investigated effects of NO on selected chemokines that differentially regulate angiogenesis, namely pro-angiogenic interleukin (IL)-8 as well as tumor-suppressive interferon-inducible protein-10 (IP-10) and monokine induced by interferon-gamma (MIG). These chemokines are expressed by DLD-1 colon carcinoma cells after stimulation with IL-1beta/interferon-gamma. Expression of IL-8 was markedly upregulated by NO. Moreover, NO enhanced expression of vascular endothelial growth factor (VEGF). In contrast, expression of IP-10 and MIG was suppressed by NO. The present data are consistent with previous observations that link NO to enhanced tumor angiogenesis and imply that NO-mediated upregulation of IL-8 and VEGF as well as downregulation of IP-10 and MIG may contribute to this phenomenon.
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PMID:Nitric oxide differentially regulates pro- and anti-angiogenic markers in DLD-1 colon carcinoma cells. 1506 30

Edpm5 is one member of a group of quantitative trait loci that are responsible for the difference in susceptibility to estrogen-induced prolactinoma between the Fischer 344 (F344) and Brown Norway (BN) strains. Upon chronic estrogen treatment F344 rats develop large, hemorrhagic and invasive pituitary tumors, which exhibit both tumor angiogenesis and neoplasia. In contrast, BN rats do not develop a tumor despite an estrogen-induced increase in lactotroph density. To investigate the role of Edpm5 in the development of these tumors, we have generated a novel congenic rat strain F344.BN-Edpm5BN by introgressing the segment of rat chromosome bearing Edpm5 from BN into the F344 strain background. Phenotypic differences between F344 and F344.BN-Edpm5BN must be due to a gene(s) within the chromosomal interval encompassing Edpm5. Through use of these strains, we find that Edpm5 specifically regulates the switch to angiogenic phenotype, independent of neoplasia. The F344.BN-Edpm5BN rats developed tumors, which exhibited significant growth, 7-fold greater mass than the pituitary of untreated rats, and neoplasia indistinguishable from that of the F344 strain. However, the F344.BN-Edpm5BN rat tumor had a non-angiogenic phenotype. After chronic estrogen treatment, there was no increase in microvessel count over untreated controls in F344.BN-Edpm5BN tumors, whereas F344 rat tumors showed a significant increase (P < 0.0005). The ultrastructural morphology of the pituitary blood vessels also did not show significant angiogenesis associated changes in F344.BN-Edpm5BN rat pituitary tumors. In contrast the parental strain F344 had pronounced angiogenic activity. The F344.BN-Edpm5BN strain also fails to express VEGF at the high levels seen in the F344 rat pituitary after estrogen treatment. Hence at least one gene that has a large impact, directly or indirectly, on the switch to angiogenic phenotype must reside within the chromosomal interval that is the Edpm5 quantitative trait locus.
Carcinogenesis 2004 Oct
PMID:The Edpm5 locus prevents the 'angiogenic switch' in an estrogen-induced rat pituitary tumor. 1516 88


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