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Endowment angiogenesis-related patents
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In vitro and in vivo studies with neomycin and neamine, the non-toxic derivative, were carried out. At 50 µM, neamine abolishes angiogenin-induced proliferation but does not affect the basal level of proliferation and cell viability. Other aminoglycoside antibiotics have no effect on angiogenin-induced cell proliferation. Neamine completely inhibits angiogenin-induced angiogenesis in the chicken chorioallantoic membrane at a dose as low as 20 ng per egg. In athymic mice, xenograft tumor growth is significantly inhibited.
Continuing study of the underlying mechanism of angiogenin inhibition is under way at Harvard. A unique knowledge base and infrastructure is employed in these studies.
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Angiogenin is an extensively validated target involved in tumor angiogenesis. Angiogenin is prominently increased in multiple cancer cell types, including, prostate, colon, bladder, gastric, brain, cervical, pancreatic, ovarian and breast cancers as well as melanoma and leukemias, and its serum level is elevated in patients affected by several of these cancer types. Angiogenin was validated in animals via multiple approaches, including inhibition by mAbs, antisense, RANi and several types of small molecules. A class of angiogenesis inhibitors has emerged from Vallee and Hu's mechanistic study of the action of angiogenin. Neomycin, an aminoglycoside antibiotic, and neamine, a non-toxic neomycine derivative, inhibit nuclear translocation of human angiogenin in human endothelial cells. Translocation into the nucleus was demonstrated to be an essential step for angiogenin-induced angiogenesis. In addition, inhibition of translocation blocks the induction of rRNA transcription, a rate-limiting step in ribosome biogenenesis, normally mediated by Angiogenin. More importantly, neamine inhibits growth of PC-3 human prostate tumor cells in athymic mice. These results suggest that neamine and other neomycin analogs are a class of agents that may be developed for anti-angiogenin therapy.
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Intellectual Property Status: Issued U.S. patent nos.: 6,482,802
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Inventor(s):
Hu, Guofu
Vallee, Bert L.
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Reference Harvard Case #2580