Tumour Angiogenesis

Fox, Stephen B.; Gatter, Kevin C.; Harris, Adrian L.

doi:10.1002/(sici)1096-9896(199607)179:3<232::aid-path505>3.0.co;2-a

Cited by 137 publications

(112 citation statements)

References 91 publications

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“…Angiogenesis, formation of new microvessels, is critical for the growth and progression of various human solid tumors because it enables delivery of oxygen and nutrients (2). Angiogenesis is regulated by angiogenic factors, such as vascular endothelial growth factor (VEGF) and angiopoietins, which can be secreted by some tumor cells (3). Among the known angiogenic factors, VEGF has emerged as the central regulator of the angiogenic process in physiological and pathological conditions.…”

Section: Hepatocellular Carcinoma (Hcc) Is Becoming One Of the Most Cmentioning

confidence: 99%

Overexpression of VEGF and Angiopoietin 2: A Key to High Vascularity of Hepatocellular Carcinoma?

et al. 2003

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Hepatocellular carcinoma (HCC) is becoming one of the most common malignant tumors worldwide and is characterized by a high vascularity. Angiogenesis, formation of new microvessels, is critical for the growth and progression of various human solid tumors. Vascular endothelial growth factor (VEGF) and angiopoietins (Ang1 and Ang2) are endothelial cell-specific vasculogenic and angiogenic growth factors, but their expression and roles in HCC have not been extensively explored. The aim of this study was to determine the expression and cellular localization of VEGF, Ang1, and Ang2 in specimens of resected human HCC using in situ hybridization and immunohistochemical staining and to examine their relationship to microvessel density (MVD) and tumor size. We also investigated whether mutation of p53 protein might affect the expression of the above angiogenic growth factors. VEGF and Ang2 were strongly expressed and localized predominantly to cancer cells, whereas Ang1 was detected in supportive cells of large blood vessels, stromal cells, endothelial cells, and tumor cells. Expression of the VEGF protein and the Ang2 (but not Ang1) mRNA were strongly correlated with MVD (P < .05, P ‫؍‬ .001) and tumor size (P < .05). There was also a strong correlation between VEGF protein and Ang2 mRNA expression (P < .001). However, no significant correlation was found between overexpression of p53 and the expression of VEGF, angiopoietins, or MVD. These findings suggest that overproduction of the angiogenic growth factors VEGF and Ang2 by HCC cells may increase vascularity and tumor growth in a paracrine manner. Our findings also suggest that interaction between VEGF and Ang2 may play a critical role in tumor angiogenesis in HCC.

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Section: Hepatocellular Carcinoma (Hcc) Is Becoming One Of the Most Cmentioning

confidence: 99%

Overexpression of VEGF and Angiopoietin 2: A Key to High Vascularity of Hepatocellular Carcinoma?

et al. 2003

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“…2, 2014 CONSENSUS DIAGNOSES AND MODE OF ACTION FOR THE FORMATION OF GASTRIC TUMORSeffect of gastrin on oxyntic mucosa may be due to paracrine effects, that is, effects that are mediated by substances from the ECL cell (Burkitt, Varro, and Pritchard 2009;Fossmark, Qvigstad, and Waldum 2008;Waldum, Brenna, and Sandvik 1998) that act locally on other mucosal elements. Substances such as basic fibroblast growth factor (bFGF) and histamine are also produced by ECL cells (Bordi et al 1994;Waldum, Brenna, and Sandvik 1998), and both have an angiogenic effect (Fox, Gatter, and Harris 1996). The production of bFGF in tumors of ECL cell origin may be responsible for the desmoplastic proliferation (Fox, Gatter, and Harris 1996), and along with histamine may promote angioblastic proliferations (Fox, Gatter, and Harris 1996;Waldum, Brenna, and Sandvik 1998).…”

Section: Ecl Cell Paracrine Effectsmentioning

confidence: 99%

Consensus Diagnoses and Mode of Action for the Formation of Gastric Tumors in Rats Treated with the Chloroacetanilide Herbicides Alachlor and Butachlor

Furukawa

Harada²,

Thake³

et al. 2013

Toxicol Pathol

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A panel of pathologists (Panel) was formed to evaluate the pathogenesis and human relevance of tumors that developed in the fundic region of rat stomachs in carcinogenicity and mechanistic studies with alachlor and butachlor. The Panel evaluated stomach sections stained with hematoxylin and eosin, neuron-specific enolase, and chromogranin A to determine the presence and relative proportion of enterochromaffin-like (ECL) cells in the tumors and concluded all tumors were derived from ECL cells. Biochemical and pathological data demonstrated the tumor formation involved a nongenotoxic threshold mode of action (MOA) initially characterized by profound atrophy of the glandular fundic mucosa that affected gastric glands, but not surface epithelium. This resulted in a substantial loss of parietal cells and a compensatory mucosal cell proliferation. The loss of parietal cells caused a marked increase in gastric pH (hypochlorhydria), leading to sustained and profound hypergastrinemia. The mucosal atrophy, together with the increased gastrin, stimulated cell growth in one or more ECL cell populations, resulting in neoplasia. ECL cell autocrine and paracrine effects led to dedifferentiation of ECL cell tumors. The Panel concluded the tumors develop via a threshold-dependent nongenotoxic MOA, under conditions not relevant to humans.

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“…Using standard methods, 6,12 bone marrow MVD was estimated independently by two investigators (SVR and PRG) on all samples using a two-headed microscope. Such a method ensured that microvessel density was estimated on the same field by each investigator.…”

Section: Estimation Of Mvdmentioning

confidence: 99%

“…Persistent angiogenesis may reflect continued stimulus of microvessels by minimal residual disease not detectable by conventional laboratory methods and may involve potent cytokines, such as vascular endothelial growth factor (VEGF) and acidic and basic fibroblast growth factors. 2,12 Further, microvascular endothelial cells probably provide growth factors for the residual neoplastic plasma cells that contribute to relapse.…”

Section: Figurementioning

confidence: 99%

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1999

Leukemia

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Although most of the initial studies in angiogenesis were done on solid tumors, there is now data suggesting the importance of angiogenesis in hematologic malignancies. We estimated bone marrow microvessel density before autologous stem cell transplantation and at the time of response in 13 patients with myeloma (seven complete and six partial responders) using an immunohistochemical stain for factor VIII-related antigen (von Willebrand factor). Baseline microvessel density was significantly different between bone marrow samples from patients with myeloma and morphologically normal, staging marrows from patients with limited stage Hodgkin's disease, mean (± s.d.) 294 (±115)/mm 2 vs 93 (±26)/mm 2 , respectively, P = 0.001. After transplantation, microvessel density continued to be high in myeloma samples compared to samples from control patients with limited stage Hodgkin's disease, mean (± s.d.) 230 (±68)/mm 2 , P = 0.003. There was no difference in microvessel density at the time of complete or partial response compared to values prior to transplantation. This report confirms that increased angiogenesis is found in myeloma bone marrow prior to transplantation, and suggests that increased angiogenesis persists even after complete response.

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Tumour Angiogenesis

Cited by 137 publications

References 91 publications

Overexpression of VEGF and Angiopoietin 2: A Key to High Vascularity of Hepatocellular Carcinoma?

Overexpression of VEGF and Angiopoietin 2: A Key to High Vascularity of Hepatocellular Carcinoma?

Consensus Diagnoses and Mode of Action for the Formation of Gastric Tumors in Rats Treated with the Chloroacetanilide Herbicides Alachlor and Butachlor

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