Additional in vivo studies of the antitumor potential of shark cartilage have been published in the peer-reviewed scientific literature.[10,11,12] In one study, oral administration of powdered shark cartilage (no brand name given) was shown to inhibit chemically induced angiogenesis in the mesenteric membrane of rats. In another study, oral administration of powdered shark cartilage (no brand name given) was shown to reduce the growth of GS-9L gliosarcomas in rats. It was reported in a third study that oral administration of two powdered shark cartilage products, Sharkilage and MIA Shark Powder, did not inhibit the growth or the metastasis of SCCVII squamous cell carcinomas in mice.
A large number of laboratory and animal studies concerning the antiangiogenic potential of cartilage have been published.[2,10,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33] Overall, these studies have revealed the presence of at least three angiogenesis inhibitors in bovine cartilage [14,15,18,19,22,24] Reviewed in [17,34] and at least two in shark cartilage.[2,10,26,27]
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  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  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  and one (CDI) has been shown to inhibit endothelial cell migration in vitro. Reviewed in  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