Journal ArticleDOI
Angiostatin induces and sustains dormancy of human primary tumors in mice
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TLDR
It is shown that systemic administration of human angiostatin potently inhibits the growth of three human and three murine primary carcinomas in mice, the first demonstration of dormancy therapy, a novel anticancer strategy in which malignant tumors are regressed by prolonged blockade of angiogenesis.Abstract:
There is now considerable direct evidence that tumor growth is angiogenesis–dependent1–4. The most compelling evidence is based on the discovery of angiostatin, an angiogenesis inhibitor that selectively instructs endothelium to become refractory to angiogenic stimuli5. Angiostatin, which specifically inhibits endothelial proliferation, induced dormancy of metastases defined by a balance of apoptosis and proliferation6. We now show that systemic administration of human angiostatin potently inhibits the growth of three human and three murine primary carcinomas in mice. An almost complete inhibition of tumor growth was observed without detectable toxicity or resistance. The human carcinomas regressed to microscopic dormant foci in which tumor cell proliferation was balanced by apoptosis in the presence of blocked angiogenesis. This regression of primary tumors without toxicity has not been previously described. This is also the first demonstration of dormancy therapy, a novel anticancer strategy in which malignant tumors are regressed by prolonged blockade of angiogenesis.read more
Citations
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Journal ArticleDOI
Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis
TL;DR: The work from the authors' laboratories reviewed herein was supported by grants from the National Cancer Institute.
Journal ArticleDOI
Endostatin: an endogenous inhibitor of angiogenesis and tumor growth.
Michael S. O'Reilly,Thomas Boehm,Yuen Shing,Naomi Fukai,George Vasios,William S. Lane,Evelyn Flynn,James R Birkhead,Bjorn R. Olsen,Judah Folkman +9 more
TL;DR: This work has identified endostatin, an angiogenesis inhibitor produced by hemangioendothelioma, a 20 kDa C-terminal fragment of collagen XVIII that specifically inhibits endothelial proliferation and potently inhibitsAngiogenesis and tumor growth.
Journal ArticleDOI
Microenvironmental regulation of metastasis
TL;DR: Experimental data demonstrating the role of the microenvironment in metastasis is described, areas for future research are identified and possible new therapeutic avenues are suggested.
Journal ArticleDOI
Role of angiogenesis in tumor growth and metastasis
TL;DR: Preclinical studies have shown that endostatin effectively inhibits tumor growth and shrinks existing tumor blood vessels and therapy with endogenous inhibitors of angiogenesis, such asendostatin and angiostatin may reverse the angiogenic switch preventing growth of tumor vasculature.
Journal ArticleDOI
Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance
TL;DR: It is shown that drug resistance does not develop in three tumour types treated with a potent angiogenesis inhibitor, and an unexpected finding is that repeated cycles of antiangiogenic therapy are followed by prolonged tumour dormancy without further therapy.
References
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What is the evidence that tumors are angiogenesis dependent
TL;DR: Method of treating a wound or burn which comprises directly dressing its surface with non-woven fabric comprising staple fibers of spun, regenerated collagen substantially free of telopeptides is disclosed.
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Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo
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Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a lewis lung carcinoma
Michael S. O'Reilly,Michael S. O'Reilly,Lars Holmgren,Lars Holmgren,Yuen Shing,Yuen Shing,Catherine Chen,Catherine Chen,Rosalind A. Rosenthal,Rosalind A. Rosenthal,Marsha A. Moses,Marsha A. Moses,William S. Lane,Yihai Cao,E. Helene Sage,Judah Folkman +15 more
TL;DR: It is shown that the inhibition of metastases by a primary mouse tumor is mediated, at least in part, by angiostatin, and a corresponding fragment of human plasminogen has similar activity.