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Endostatin

About: Endostatin is a(n) research topic. Over the lifetime, 1830 publication(s) have been published within this topic receiving 81359 citation(s). The topic is also known as: endostatins.

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Open accessJournal ArticleDOI: 10.1016/S0092-8674(00)81848-6
Michael S. O'Reilly1, Thomas Boehm1, Yuen Shing1, Naomi Fukai2  +6 moreInstitutions (2)
24 Jan 1997-Cell
Abstract: We previously identified the angiogenesis inhibitor angiostatin. Using a similar strategy, we have identified endostatin, an angiogenesis inhibitor produced by hemangioendothelioma. Endostatin is a 20 kDa C-terminal fragment of collagen XVIII. Endostatin specifically inhibits endothelial proliferation and potently inhibits angiogenesis and tumor growth. By a novel method of sustained release, E. coli-derived endostatin was administered as a nonrefolded suspension. Primary tumors were regressed to dormant microscopic lesions. Immunohistochemistry revealed blocked angiogenesis accompanied by high proliferation balanced by apoptosis in tumor cells. There was no toxicity. Together with angiostatin data, these findings validate a strategy for identifying endogenous angiogenesis inhibitors, suggest a theme of fragments of proteins as angiogenesis inhibitors, and demonstrate dormancy therapy.

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Topics: Endostatin (74%), Tumstatin (73%), Angiogenesis inhibitor (67%) ...read more

4,508 Citations


Journal ArticleDOI: 10.1016/0092-8674(94)90200-3
21 Oct 1994-Cell
Abstract: The phenomenon of inhibition of tumor growth by tumor mass has been repeatedly studied, but without elucidation of a satisfactory mechanism. In our animal model, a primary tumor inhibits its remote metastases. After tumor removal, metastases neovascularize and grow. When the primary tumor is present, metastatic growth is suppressed by a circulating angiogenesis inhibitor. Serum and urine from tumor-bearing mice, but not from controls, specifically inhibit endothelial cell proliferation. The activity copurifies with a 38 kDa plasminogen fragment that we have sequenced and named angiostatin. A corresponding fragment of human plasminogen has similar activity. Systemic administration of angiostatin, but not intact plasminogen, potently blocks neovascularization and growth of metastases. We here show that the inhibition of metastases by a primary mouse tumor is mediated, at least in part, by angiostatin.

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Topics: Angiostatin binding (75%), Angiostatin (67%), Endostatin (60%) ...read more

3,459 Citations


Journal ArticleDOI: 10.1016/S0093-7754(02)70065-1
Judah Folkman1Institutions (1)
Abstract: Angiogenesis is required for invasive tumor growth and metastasis and constitutes an important point in the control of cancer progression. Its inhibition may be a valuable new approach to cancer therapy. Avascular tumors are severely restricted in their growth potential because of the lack of a blood supply. For tumors to develop in size and metastatic potential they must make an "angiogenic switch" through perturbing the local balance of proangiogenic and antiangiogenic factors. Frequently, tumors overexpress proangiogenic factors, such as vascular endothelial growth factor, allowing them to make this angiogenic switch. Two strategies used in the development of antiangiogenic agents involve the inhibition of proangiogenic factors (eg, anti-vascular endothelial growth factor monoclonal antibodies) as well as therapy with endogenous inhibitors of angiogenesis, such as endostatin and angiostatin. Therapy with endogenous angiogenic inhibitors such as endostatin and angiostatin may reverse the angiogenic switch preventing growth of tumor vasculature. Preclinical studies have shown that endostatin effectively inhibits tumor growth and shrinks existing tumor blood vessels. Phase 1 clinical trials of endostatin and angiostatin are ongoing, and preliminary results show minimal toxicities.

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Topics: Angiogenic Switch (67%), Endostatin (65%), Angiogenesis (60%) ...read more

2,486 Citations


Journal ArticleDOI: 10.1038/37126
27 Nov 1997-Nature
Abstract: Acquired drug resistance is a major problem in the treatment of cancer. Of the more than 500,000 annual deaths from cancer in the United States, many follow the development of resistance to chemotherapy. The emergence of resistance depends in part on the genetic instability, heterogeneity and high mutational rate of tumour cells. In contrast, endothelial cells are genetically stable, homogeneous and have a low mutational rate. Therefore, antiangiogenic therapy directed against a tumour's endothelial cells should, in principle, induce little or no drug resistance. Endostatin, a potent angiogenesis inhibitor, was administered to mice bearing Lewis lung carcinoma, T241 fibrosarcoma or B16F10 melanoma. Treatment was stopped when tumours had regressed. Tumours were then allowed to re-grow and endostatin therapy was resumed. After 6, 4 or 2 treatment cycles, respectively, no tumours recurred after discontinuation of therapy. These experiments show that drug resistance does not develop in three tumour types treated with a potent angiogenesis inhibitor. An unexpected finding is that repeated cycles of antiangiogenic therapy are followed by prolonged tumour dormancy without further therapy.

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Topics: Drug resistance (55%), Angiogenesis inhibitor (55%), Cancer (55%) ...read more

1,749 Citations


Open accessJournal ArticleDOI: 10.1073/PNAS.87.17.6624
Deborah J. Good1, Peter J. Polverini1, F Rastinejad2, M M Le Beau3  +3 moreInstitutions (4)
Abstract: A secreted inhibitor of angiogenesis that is controlled by a tumor suppressor gene in hamster cells has been found to be similar to a fragment of the platelet and matrix protein thrombospondin. The two proteins were biochemically similar and immunologically crossreactive and could substitute for one another in two functional assays. Human thrombospondin inhibited neovascularization in vivo and endothelial cell migration in vitro, as does the hamster protein, gp140. gp140 sensitized smooth muscle cells to stimulation by epidermal growth factor, as does human thrombospondin. The thrombospondin gene has been localized on human chromosome 15. These results demonstrate a function for the ubiquitous adhesive glycoprotein thrombospondin that is likely to be important in the normal physiological down-regulation of neovascularization. In addition, they raise the possibility that thrombospondin may be one of a number of target molecules through which a tumor suppressor gene could act to restrain tumor growth.

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Topics: Thrombospondin 1 (72%), Thrombospondin-2 (70%), Thrombospondin (69%) ...read more

1,075 Citations


Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202132
202033
201928
201842
201745
201665

Top Attributes

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Topic's top 5 most impactful authors

Judah Folkman

40 papers, 14K citations

Yongzhang Luo

34 papers, 785 citations

Bjorn R. Olsen

28 papers, 8K citations

Taina Pihlajaniemi

26 papers, 2.2K citations

Yan Fu

24 papers, 653 citations

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