Tumour vasculature - a potential therapeutic target

Baillie, CT; Winslet, MC; Bradley, NJ

doi:10.1038/bjc.1995.323

Cited by 86 publications

(47 citation statements)

References 122 publications

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“…Tumour angiogenesis can be inhibited by blocking more than one of these steps. Prevention of tumour angiogenesis involves inhibition of synthesis of angiogenic factors and blocking of their receptors (Barillie et al, 1995;O'Brien and Harris, 1995). Until now there have been few reports regarding the inhibition of expression and production of angiogenic factors (Sidky and Borden, 1987;Singh et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma

et al. 2002

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Since it has been widely recognised that renal cell carcinoma is refractory to standard therapies such as chemotherapy and radiotherapy, a new modality of treatment is needed. One of the potential alternative therapies for renal cell carcinoma may be inhibition of angiogenesis. In this study, we analysed the inhibitory effects of several potential agents on expression of angiogenic factors such as vascular endothelial growth factor and basic fibroblast growth factor, which are the main mediators in angiogenesis of renal cell carcinoma. We used medroxyprogesterone acetate, interferon-alpha, interferon-gamma, minocycline hydrochrolide and genistein, which are known to be antiangiogeneic. Northern blot analyses revealed that, among the five agents examined, genistein had a strong inhibitory effect on expression of vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA. Medroxyprogesterone acetate and interferon-alpha did not significantly decrease the level of either vascular endothelial growth factor mRNA or basic fibroblast growth factor mRNA. Interferon-gamma and minocycline had mild inhibitory effects on vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA expression. Genistein also inhibited both vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA expression after treatment with epidermal growth factor and hypoxia. These findings suggest that one of the mechanisms of the inhibition of angiogenesis by genistein is suppression of the expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor in renal cell carcinoma.

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Section: Discussionmentioning

confidence: 99%

Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma

et al. 2002

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“…The tumour vasculature is a promising new target in cancer therapy, and a number of antitumour agents have been identified that either inhibit tumour angiogenesis (Baillie et al, 1995) or destroy the tumour's existing blood supply (Baguley, 2001). Tumour necrosis factor (TNF), a pleiotropic cytokine that is produced mainly by activated monocytes/macrophages, neutrophils, and T cells (Balkwill, 1989), is thought to exert its antitumour effect mainly through an antivascular mechanism.…”

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confidence: 99%

The antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF receptor-1 knockout mice

Zhao

Kestell

et al. 2002

Br J Cancer

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5,6-dimethylxanthenone-4-acetic acid, a novel antivascular anticancer drug, has completed Phase I clinical trial. Its actions in mice include tumour necrosis factor induction, serotonin release, tumour blood flow inhibition, and the induction of tumour haemorrhagic necrosis and regression. We have used mice with a targeted disruption of the tumour necrosis factor receptor-1 gene as recipients for the colon 38 carcinoma to determine the role of tumour necrosis factor signalling in the action of 5,6-dimethylxanthenone-4-acetic acid. The pharmacokinetics of 5,6-dimethylxanthenone-4-acetic acid, as well as the degree of induced plasma and tissue tumour necrosis factor, were similar in tumour necrosis factor receptor-1 7/7 and wild-type mice. However, the maximum tolerated dose of 5,6-dimethylxanthenone-4-acetic acid was considerably higher in tumour necrosis factor receptor-1 7/7 mice (4100 mg kg 71 ) than in wild-type mice (27.5 mg kg 71 ). The antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (25 mg kg 71 ) was strongly attenuated in tumour necrosis factor receptor-1 7/7 mice. However, the reduced toxicity in tumour necrosis factor receptor-1 7/7 mice allowed the demonstration that at a higher dose (50 mg kg 71 ), 5,6-dimethylxanthenone-4-acetic acid was curative and comparable in effect to that of a lower dose (25 mg kg 71 ) in wild-type mice. The 5,6-dimethylxanthenone-4-acetic acid -induced rise in plasma 5-hydroxyindoleacetic acid, used to reflect serotonin production in a vascular response, was larger in colon 38 tumour bearing than in non-tumour bearing tumour necrosis factor receptor-1 7/7 mice, but in each case the response was smaller than the corresponding response in wild-type mice. The results suggest an important role for tumour necrosis factor in mediating both the host toxicity and antitumour activity of 5,6-dimethylxanthenone-4-acetic acid, but also suggest that tumour necrosis factor can be replaced by other vasoactive factors in its antitumour action, an observation of relevance to current clinical studies.

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“…Furthermore, chemotherapy that induces vessel wall or endothelial cell death results in loss of vascular integrity, platelet aggregation and vascular occlusion, denying oxygen delivery and precipitating tumor cell death downstream (23). The identification of molecular markers that differentiate newly formed capillaries from their mature counterparts (24,25) has paved the way for targeted delivery of cytotoxic agents to the tumor vasculature (26). The α V β 3 integrin is one of the most specific of these unique markers.…”

Section: Discussionmentioning

confidence: 99%