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Laboratory / Animal / Preclinical Studies

    continued...

    Aqueous Extracts of Cartilage

    A liquid (i.e., aqueous) extract of shark cartilage called AE-941/Neovastat has also been reported to inhibit the growth of a variety of cancer cell types in vitro. Reviewed in [5] These results have not been published in a peer-reviewed scientific journal and are not consistent with other results obtained by the same group of investigators.[28,35]

    Three angiogenesis inhibitors in bovine cartilage have been very well characterized.[14,15,18,19,22,24] Reviewed in [17,34] They are relatively small proteins with molecular masses that range from 23,000 to 28,000.[14,15,24] Reviewed in [17] These proteins, called cartilage-derived inhibitor (CDI), cartilage-derived antitumor factor (CATF), and cartilage-derived collagenase inhibitor (CDCI) by the researchers who purified them,[14,15,22] have been shown to block endothelial cell proliferation in vitro and new blood vessel formation in the chorioallantoic membrane of chicken embryos.[15,18,19,22,24] Reviewed in [17,34] Two of the proteins (CDI and CDCI) have been shown to inhibit matrix metalloproteinase activity in vitro,[14,15,19] Reviewed in [17] and one (CDI) has been shown to inhibit endothelial cell migration in vitro.[15] Reviewed in [17] These proteins do not block the proliferation of normal cells or of tumor cells in vitro.[15,18,22] Reviewed in [17,34] When the amino acid sequences of CDI, CATF, and CDCI were determined, it was discovered that they were the same as those of proteins known otherwise as tissue inhibitor of matrix metalloproteinases 1 (TIMP-1), chondromodulin I, and TIMP-2, respectively.[14,15,19,24] Reviewed in [34]

    A possible fourth angiogenesis inhibitor in bovine cartilage has been purified not from cartilage but from the culture fluid of bovine chondrocytes grown in the laboratory.[16] This inhibitor, which has been named chondrocyte-derived inhibitor (ChDI), is a protein that has a molecular mass of approximately 36,000.[16] It has been reported that ChDI and CDI/TIMP-1 have similar antiangiogenic activities,[16] Reviewed in [17,34] but the relationship between these proteins is unclear because amino acid sequence information for ChDI is not available. Thus, whether CDI/TIMP-1 is a breakdown product of ChDI or whether ChDI is truly the fourth angiogenesis inhibitor identified in bovine cartilage is unknown.

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