Shark Cartilage

Last Editorial Review: 6/11/2021
Other Name(s):

AE-941, Cartilage de Requin, Cartilage de Requin du Pacifique, Cartilago de Tiburon, Collagène Marin, Extrait de Cartilage de Requin, Liquide de Cartilage Marin, Marine Collagen, Marine Liquid Cartilage, MSI-1256F, Neovastat, Pacific Shark Cartilage, Poudre de Cartilage de Requin, Shark Cartilage Powder, Shark Cartilage Extract, Sphyrna lewini, Squalus acanthias.

Overview

Shark cartilage (tough elastic tissue that provides support, much as bone does) used for medicine comes primarily from sharks caught in the Pacific Ocean. Several types of extracts are made from shark cartilage including squalamine lactate, AE-941, and U-995.

Shark cartilage is most famously used for cancer, including a type of cancer called Kaposi's sarcoma, that is more common in people with HIV infection. Shark cartilage is also used for arthritis, psoriasis, wound healing, damage to the retina of the eye due to diabetes, and inflammation of the intestine (enteritis).

Some people apply shark cartilage directly to the skin for arthritis and psoriasis.

How does work?

Shark cartilage might help prevent tumor growth.

QUESTION

Next to red peppers, you can get the most vitamin C from ________________. See Answer

Uses

Likely Ineffective for...

  • Cancer. Most research shows that taking shark cartilage by mouth does not benefit people with advanced, previously treated cancers of the breast, colon, lung, prostate, and brain or advanced, previously treated non-Hodgkin's lymphoma. Studies of shark cartilage in people with less advanced cancer have not been published.

Insufficient Evidence to Rate Effectiveness for...

  • Age-related vision loss (age-related macular-degeneration). Early research suggests that taking a specific shark cartilage extract (AE-941, Neovastat) for 24 weeks might improve or stabilize vision in people with age-related vision loss.
  • Cancerous tumor called Kaposi sarcoma. There are reports that shark cartilage might decrease tumors called Kaposi sarcoma.
  • Osteoarthritis. When applied to the skin, products containing shark cartilage in combination with chondroitin sulfate, glucosamine sulfate, and camphor reportedly reduce arthritis symptoms. However, any symptom relief is most likely due to the effect of camphor and not the other ingredients. Additionally, there is no research showing that shark cartilage is absorbed through the skin.
  • Psoriasis. Developing research suggests that a specific shark cartilage extract (AE-941, Neovastat) might improve appearance and decrease itching of plaque psoriasis when taken by mouth or applied to the skin.
  • Kidney cancer. Taking a specific shark cartilage extract (AE-941, Neovastat) by mouth seems to increase survival in patients with advanced kidney cancer (renal cell carcinoma). This product has FDA “Orphan Drug status” for renal cell carcinoma. The Orphan Drug law gives drug makers special incentives to study drugs for rare conditions.
  • Arthritis.
  • Eye complications.
  • Wound healing.
  • Other conditions.
More evidence is needed to rate shark cartilage for these uses.

Side Effects

Shark cartilage is POSSIBLY SAFE for most people when taken appropriately by mouth for up to 40 months or when applied to the skin for up to 8 weeks.

It can cause a bad taste in the mouth, nausea, vomiting, stomach upset, constipation, low blood pressure, dizziness, high blood sugar, high calcium levels, and fatigue. Some products have an unpleasant odor and taste.

Precautions

Pregnancy and breast-feeding: There is not enough reliable information about the safety of taking shark cartilage if you are pregnant or breast-feeding. Stay on the safe side and avoid use.

High calcium levels (hypercalcemia): Shark cartilage might increase calcium levels, so it should not be used by people whose calcium levels are already too high.

SLIDESHOW

Vitamin D Deficiency: How Much Vitamin D Is Enough? See Slideshow

Interactions


Medications that decrease the immune system (Immunosuppressants)Interaction Rating: Moderate Be cautious with this combination.Talk with your health provider.

Shark cartilage might increase the immune system. By increasing the immune system, shark cartilage might decrease the effectiveness of medications that decrease the immune system.

Some medications that decrease the immune system include azathioprine (Imuran), basiliximab (Simulect), cyclosporine (Neoral, Sandimmune), daclizumab (Zenapax), muromonab-CD3 (OKT3, Orthoclone OKT3), mycophenolate (CellCept), tacrolimus (FK506, Prograf), sirolimus (Rapamune), prednisone (Deltasone, Orasone), corticosteroids (glucocorticoids), and others.

Dosing

The appropriate dose of shark cartilage depends on several factors such as the user's age, health, and several other conditions. At this time there is not enough scientific information to determine an appropriate range of doses for shark cartilage. Keep in mind that natural products are not always necessarily safe and dosages can be important. Be sure to follow relevant directions on product labels and consult your pharmacist or physician or other healthcare professional before using.

Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, and Insufficient Evidence to Rate (detailed description of each of the ratings).

FDA Logo

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

References

Aeterna Laboratories Inc. Phase II study of AE-941 (Neovastat; Shark Cartilage) in patients with early relapse or refractory multiple myeloma. 2001. Information Contact Number 1-888-349-3232.

Aeterna Laboratories Inc. Phase III randomized study of AE-941 (Neovastat; Shark Cartilage Extract) in patients with metastatic renal cell carcinoma refractory to immunotherapy. 2001.

Anonymous. Angiostatic and antitumoral activity of AE-941 (neovastat-R), a molecular fraction derived from shark cartilage (meeting abstract). Proc Annu Meet Am Assoc Cancer Res 1997;38:A1530.

Arnheim, K. [From shark cartilage to hypnosis. Conservative medicine against cancer?]. MMW.Fortschr.Med 4-22-2004;146(17):8, 10. View abstract.

Barber, R., Delahunt, B., Grebe, S. K., Davis, P. F., Thornton, A., and Slim, G. C. Oral shark cartilage does not abolish carcinogenesis but delays tumor progression in a murine model. Anticancer Res 2001;21(2A):1065-1069. View abstract.

Bargahi, A., Hassan, Z. M., Rabbani, A., Langroudi, L., Noori, S. H., and Safari, E. Effect of shark cartilage derived protein on the NK cells activity. Immunopharmacol.Immunotoxicol. 2011;33(3):403-409. View abstract.

Beliveau, R., Gingras, D., Kruger, E. A., Lamy, S., Sirois, P., Simard, B., Sirois, M. G., Tranqui, L., Baffert, F., Beaulieu, E., Dimitriadou, V., Pepin, M. C., Courjal, F., Ricard, I., Poyet, P., Falardeau, P., Figg, W. D., and Dupont, E. The Antiangiogenic Agent Neovastat (AE-941) Inhibits Vascular Endothelial Growth Factor-mediated Biological Effects. Clin Cancer Res 2002;8(4):1242-1250. View abstract.

Bhargava P, Trocky N Marshall J et al. A phase I safety, tolerance and pharmacokinetic study of rising dose, rising duration continuous infusion of MSI-1256F (Squalamine Lactate) in patients with advanced cancer. Proc Am Soc Clinical Oncol 1999;18(A698):1.

Blanchard, V., Chevalier, F., Imberty, A., Leeflang, B. R., Basappa, Sugahara, K., and Kamerling, J. P. Conformational studies on five octasaccharides isolated from chondroitin sulfate using NMR spectroscopy and molecular modeling. Biochemistry 2-6-2007;46(5):1167-1175. View abstract.

Boivin, D., Provencal, M., Gendron, S., Ratel, D., Demeule, M., Gingras, D., and Beliveau, R. Purification and characterization of a stimulator of plasmin generation from the antiangiogenic agent Neovastat: identification as immunoglobulin kappa light chain. Arch Biochem.Biophys. 11-15-2004;431(2):197-206. View abstract.

Brem, H. and Folkman, J. Inhibition of tumor angiogenesis mediated by cartilage. J Exp.Med 2-1-1975;141(2):427-439. View abstract.

Bukowski, R. M. AE-941, a multifunctional antiangiogenic compound: trials in renal cell carcinoma. Expert.Opin.Investig.Drugs 2003;12(8):1403-1411. View abstract.

Cataldi, JM and Osborne, DL. Effects of shark cartilage on mammary tumor neovascularization in vivo and cell proliferation in vitro (meeting abstract). FASEB Journal 1995;9(3):A135.

Chen, J. S., Chang, C. M., Wu, J. C., and Wang, S. M. Shark cartilage extract interferes with cell adhesion and induces reorganization of focal adhesions in cultured endothelial cells. J Cell Biochem 6-6-2000;78(3):417-428. View abstract.

Coppes, M. J., Anderson, R. A., Egeler, R. M., and Wolff, J. E. Alternative therapies for the treatment of childhood cancer. N Engl.J Med 9-17-1998;339(12):846-847. View abstract.

Davis, P. F., He, Y., Furneaux, R. H., Johnston, P. S., Ruger, B. M., and Slim, G. C. Inhibition of angiogenesis by oral ingestion of powdered shark cartilage in a rat model. Microvasc.Res 1997;54(2):178-182. View abstract.

de Mejia, E. G. and Dia, V. P. The role of nutraceutical proteins and peptides in apoptosis, angiogenesis, and metastasis of cancer cells. Cancer Metastasis Rev 2010;29(3):511-528. View abstract.

Deepa, S. S., Yamada, S., Fukui, S., and Sugahara, K. Structural determination of novel sulfated octasaccharides isolated from chondroitin sulfate of shark cartilage and their application for characterizing monoclonal antibody epitopes. Glycobiology 2007;17(6):631-645. View abstract.

Deng, B. and Zhang, Z. [Determination of trace elements in shark cartilage by inductively coupled plasma atomic emission spectrometry]. Guang.Pu.Xue.Yu Guang.Pu.Fen.Xi. 1998;18(5):570-575. View abstract.

Dupont E, Alaoui-Jamali M, Wang T, and et al. Angiostatic and antitumoral activity of AE-941 (Neovastat), a molecular fraction derived from shark cartilage. Proceedings of the American Association for Cancer Research 1997;38:227.

Dupont E, Savard RE, Jourdain C, Juneau C, Thibodeau A, Ross N, and et al. Antiangiogenic properties of a novel shark cartilage extract: potential role in the treatment of psoriasis. J Cutan Med Surg 1998;2(3):146-152.

Dupont, E., Falardeau, P., Mousa, S. A., Dimitriadou, V., Pepin, M. C., Wang, T., and Alaoui-Jamali, M. A. Antiangiogenic and antimetastatic properties of Neovastat (AE-941), an orally active extract derived from cartilage tissue. Clin Exp Metastasis 2002;19(2):145-153. View abstract.

Escudier, B, Patenaude, F, Bukowski, R, and et al. Rationale for a phase III clinical trial with AE-941 (Neovastat (R)) in metastatic renal cell carcinoma patients refractory to immunotherapy. Ann Oncol 2000;11(supplement 4):143-144.

Evans WK, Latreille J, Batist G, and et al. AE-941, an inhibitor of angiogenesis: rationale for development in combination with induction chemotherapy/radiotherapy in patients with non-small-cell lung cancer (NSCLC). Proffered Papers 1999;S250.

FDA grants orphan-drug status to Aeterna's Neovastat for kidney cancer. Expert.Rev Anticancer Ther 2002;2(6):618. View abstract.

Felzenszwalb, I., Pelielo de Mattos, J. C., Bernardo-Filho, M., and Caldeira-de-Araujo, A. Shark cartilage-containing preparation: protection against reactive oxygen species. Food Chem Toxicol 1998;36(12):1079-1084. View abstract.

Feyzi, R., Hassan, Z. M., and Mostafaie, A. Modulation of CD(4)(+) and CD(8)(+) tumor infiltrating lymphocytes by a fraction isolated from shark cartilage: shark cartilage modulates anti-tumor immunity. Int Immunopharmacol. 2003;3(7):921-926. View abstract.

Food and Drug Administration. FDA takes action against firm marketing unapproved drugs. FDA talk paper (December 10, 1999)

Gingras, D., Labelle, D., Nyalendo, C., Boivin, D., Demeule, M., Barthomeuf, C., and Beliveau, R. The antiangiogenic agent Neovastat (AE-941) stimulates tissue plasminogen activator activity. Invest New Drugs 2004;22(1):17-26. View abstract.

Goldman E. Shark cartilage extract tried as a novel psoriasis treatment. Skin All News 1998;29(12):14.

Gonzalez, R. P., Soares, F. S., Farias, R. F., Pessoa, C., Leyva, A., Barros Viana, G. S., and Moraes, M. O. Demonstration of inhibitory effect of oral shark cartilage on basic fibroblast growth factor-induced angiogenesis in the rabbit cornea. Biol.Pharm.Bull. 2001;24(2):151-154. View abstract.

Hassan, Z. M., Feyzi, R., Sheikhian, A., Bargahi, A., Mostafaie, A., Mansouri, K., Shahrokhi, S., Ghazanfari, T., and Shahabi, S. Low molecular weight fraction of shark cartilage can modulate immune responses and abolish angiogenesis. Int Immunopharmacol. 2005;5(6):961-970. View abstract.

Horsman, M. R., Alsner, J., and Overgaard, J. The effect of shark cartilage extracts on the growth and metastatic spread of the SCCVII carcinoma. Acta Oncol 1998;37(5):441-445. View abstract.

Imada, K., Oka, H., Kawasaki, D., Miura, N., Sato, T., and Ito, A. Anti-arthritic action mechanisms of natural chondroitin sulfate in human articular chondrocytes and synovial fibroblasts. Biol.Pharm Bull. 2010;33(3):410-414. View abstract.

Jagannath, S., Champagne, P., Hariton, C., and Dupont, E. Neovastat in multiple myeloma. Eur.J.Haematol. 2003;70(4):267-268. View abstract.

Jamali MA, Riviere P, Falardeau A, and et al. Effect of AE-941 (Neovastat), an angiogenesis inhibitor, in the Lewis lung carcinoma metastatic model, efficacy, toxicity prevention and survival. Clin Invest Med 1998;(suppl):S16.

Kalidas M, Hammond LA Patnaik P et al. A phase I and pharmacokinetic (PK) study of the angiogenesis inhibitor, squalamine lactate (MSI-1256F). Proc Am Soc Clinical Oncol 2000;19(A698):1.

Kern, B. E., Balcom, J. H., Antoniu, B. A., Warshaw, A. L., and Fernandez-del Castillo, C. Troponin I peptide (Glu94-Leu123), a cartilage-derived angiogenesis inhibitor: in vitro and in vivo effects on human endothelial cells and on pancreatic cancer. J Gastrointest.Surg. 2003;7(8):961-968. View abstract.

Kim, S., de, A., V, Bouajila, J., Dias, A. G., Cyrino, F. Z., Bouskela, E., Costa, P. R., and Nepveu, F. Alpha-phenyl-N-tert-butyl nitrone (PBN) derivatives: synthesis and protective action against microvascular damages induced by ischemia/reperfusion. Bioorg.Med Chem 5-15-2007;15(10):3572-3578. View abstract.

Koch, A. E. The role of angiogenesis in rheumatoid arthritis: recent developments. Ann Rheum.Dis. 2000;59 Suppl 1:i65-i71. View abstract.

Korman, D. B. [Antiangiogenic and antitumor properties of cartilage]. Vopr.Onkol. 2012;58(6):717-726. View abstract.

Kuettner, K. E. and Pauli, B. U. Inhibition of neovascularization by a cartilage factor. Ciba Found.Symp. 1983;100:163-173. View abstract.

Kusano, S., Igarashi, N., Sakai, S., and Toida, T. [Effect of orally administered chondrosine on uptake of 35S sulfate into rat cartilage]. Yakugaku Zasshi 2006;126(4):297-300. View abstract.

Lane IW and Contreras E. High rate of bioactivity (reduction in gross tumor size) observed in advanced cancer patients treated with shark cartilage material. J Naturopath Med 1992;3(1):86-88.

Lane W and Milner M. A comparison of shark cartilage and bovine cartilage. Townsend Lett 1996;153:40-42.

Langer, R, Conn, H, Vacanti, J, and et al. Control of tumor growth in animals by infusion of an angiogenesis inhibitor. Proc National Acad Sci USA 1980;77.

Langer, R., Brem, H., Falterman, K., Klein, M., and Folkman, J. Isolations of a cartilage factor that inhibits tumor neovascularization. Science 7-2-1976;193(4247):70-72. View abstract.

Latreille, J., Batist, G., Laberge, F., Champagne, P., Croteau, D., Falardeau, P., Levinton, C., Hariton, C., Evans, W. K., and Dupont, E. Phase I/II trial of the safety and efficacy of AE-941 (Neovastat) in the treatment of non-small-cell lung cancer. Clin Lung Cancer 2003;4(4):231-236. View abstract.

Lee, A. and Langer, R. Shark cartilage contains inhibitors of tumor angiogenesis. Science 9-16-1983;221(4616):1185-1187. View abstract.

Lee, S. Y. and Chung, S. M. Neovastat (AE-941) inhibits the airway inflammation via VEGF and HIF-2 alpha suppression. Vascul.Pharmacol 2007;47(5-6):313-318. View abstract.

Leitner SP, Rothkopf MM, Haverstick DD, and et al. Two phase II studies of oral dry shark cartilage powder (SCP) in patients with either metastatic breast or prostate cancer refractory to standard treatment. Amer Soc Clin Oncol 1998;17:A240.

McGuire, T. R., Kazakoff, P. W., Hoie, E. B., and Fienhold, M. A. Antiproliferative activity of shark cartilage with and without tumor necrosis factor-alpha in human umbilical vein endothelium. Pharmacotherapy 1996;16(2):237-244. View abstract.

Merly, L., Simjee, S., and Smith, S. L. Induction of inflammatory cytokines by cartilage extracts. Int Immunopharmacol. 2007;7(3):383-391. View abstract.

Milner M. A guide to the use of shark cartilage in the treatment of arthritis and other inflammatory joint diseases. Amer Chiropractor 1999;21:40-42.

Morris, G. M., Coderre, J. A., Micca, P. L., Lombardo, D. T., and Hopewell, J. W. Boron neutron capture therapy of the rat 9L gliosarcoma: evaluation of the effects of shark cartilage. Br J Radiol. 2000;73(868):429-434. View abstract.

Moses, M. A. A cartilage-derived inhibitor of neovascularization and metalloproteinases. Clin Exp.Rheumatol. 1993;11 Suppl 8:S67-S69. View abstract.

Moses, M. A., Sudhalter, J., and Langer, R. Identification of an inhibitor of neovascularization from cartilage. Science 6-15-1990;248(4961):1408-1410. View abstract.

Moses, M. A., Wiederschain, D., Wu, I., Fernandez, C. A., Ghazizadeh, V., Lane, W. S., Flynn, E., Sytkowski, A., Tao, T., and Langer, R. Troponin I is present in human cartilage and inhibits angiogenesis. Proc Natl.Acad.Sci.U.S.A 3-16-1999;96(6):2645-2650. View abstract.

Neame, P. J., Young, C. N., and Treep, J. T. Primary structure of a protein isolated from reef shark (Carcharhinus springeri) cartilage that is similar to the mammalian C-type lectin homolog, tetranectin. Protein Sci 1992;1(1):161-168. View abstract.

No authors. Neovastat clinical trial abstracts. 2001;

O'Connell, G. D., Fong, J. V., Dunleavy, N., Joffe, A., Ateshian, G. A., and Hung, C. T. Trimethylamine N-oxide as a media supplement for cartilage tissue engineering. J Orthop.Res 2012;30(12):1898-1905. View abstract.

Oikawa, T., Ashino-Fuse, H., Shimamura, M., Koide, U., and Iwaguchi, T. A novel angiogenic inhibitor derived from Japanese shark cartilage (I). Extraction and estimation of inhibitory activities toward tumor and embryonic angiogenesis. Cancer Lett 6-15-1990;51(3):181-186. View abstract.

Ortiz-Delgado, J. B., Simes, D. C., Viegas, C. S., Schaff, B. J., Sarasquete, C., and Cancela, M. L. Cloning of matrix Gla protein in a marine cartilaginous fish, Prionace glauca: preferential protein accumulation in skeletal and vascular systems. Histochem.Cell Biol 2006;126(1):89-101. View abstract.

Parton, A., Forest, D., Kobayashi, H., Dowell, L., Bayne, C., and Barnes, D. Cell and molecular biology of SAE, a cell line from the spiny dogfish shark, Squalus acanthias. Comp Biochem Physiol C.Toxicol Pharmacol 2007;145(1):111-119. View abstract.

Patnaik A, Rowinsky E Hammond L et al. A phase I and pharmacokinetic (PK) study of the unique angiogenesis inhibitor, squalamine lactate (MSI-1256F). Proc Am Soc Clinical Oncol 1999;18(A622):1.

Patra, D. and Sandell, L. J. Antiangiogenic and anticancer molecules in cartilage. Expert.Rev Mol.Med 2012;14:e10. View abstract.

Pearson, W., Orth, M. W., Karrow, N. A., Maclusky, N. J., and Lindinger, M. I. Anti-inflammatory and chondroprotective effects of nutraceuticals from Sasha's Blend in a cartilage explant model of inflammation. Mol Nutr Food Res 2007;51(8):1020-1030. View abstract.

Pivnenko, T. N., Sukhoverkhova, G. I., Epshtein, L. M., Somova-Isachkova, L. M., Timchenko, N. F., and Besednova, N. N. [Experimental morphological study of the therapeutic effect of shark cartilage preparation in a model of infective allergic arthritis]. Antibiot Khimioter. 2005;50(5-6):20-23. View abstract.

Pomin, V. H., Piquet, A. A., Pereira, M. S., and Mourao, P. A. Residual keratan sulfate in chondroitin sulfate formulations for oral administration. Carbohydr.Polym. 10-1-2012;90(2):839-846. View abstract.

Porter, M. E., Koob, T. J., and Summers, A. P. The contribution of mineral to the material properties of vertebral cartilage from the smooth-hound shark Mustelus californicus. J Exp Biol 2007;210(Pt 19):3319-3327. View abstract.

Pothacharoen, P., Kalayanamitra, K., Deepa, S. S., Fukui, S., Hattori, T., Fukushima, N., Hardingham, T., Kongtawelert, P., and Sugahara, K. Two related but distinct chondroitin sulfate mimetope octasaccharide sequences recognized by monoclonal antibody WF6. J Biol Chem 11-30-2007;282(48):35232-35246. View abstract.

Prudden JF. Cartilage as therapy. Adjuvant Nutrition in Cancer Treatment Symposium, Tampa, Florida (September 27-30, 1995).

Ratel, D., Glazier, G., Provencal, M., Boivin, D., Beaulieu, E., Gingras, D., and Beliveau, R. Direct-acting fibrinolytic enzymes in shark cartilage extract: potential therapeutic role in vascular disorders. Thromb.Res. 2005;115(1-2):143-152. View abstract.

Renckens, C. N. and van Dam, F. S. [The national cancer fund (Koningin Wilhelmina Fonds) and the Houtsmuller-therapy for cancer]. Ned.Tijdschr.Geneeskd. 7-3-1999;143(27):1431-1433. View abstract.

Riviere M, Alaoui-Jamali M, Falardeau P, and et al. Neovastat: an inhibitor of angiogenesis with anti-cancer activity. Proc Amer Assoc Cancer Res 1998;39:46.

Riviere M, Latreille J, and Falardeau P. AE-941 (Neovastat), an inhibitor of angiogenesis: phase I/II cancer clinical trial results. Cancer Invest 1999;17(suppl 1):16-17.

Rosenbluth, RJ, Jennis, AA, Cantwell, S, and et al. Oral shark cartilage in the treatment of patients with advanced primary brain tumors. A phase II pilot study (meeting abstract). Proc Annu Meet Am Soc Clin Oncol 1999;18:A554.

Roudebush, P., Davenport, D. J., and Novotny, B. J. The use of nutraceuticals in cancer therapy. Vet.Clin North Am Small Anim Pract. 2004;34(1):249-69, viii. View abstract.

Saad F, Klotz L, Babaian R, Lacombe L, Champagne P, and Dupont E. Phase I/II trial on AE-941 (Neovastat) in patients with metastatic refractory prostate cancer (abstract presentation). Canadian Urological Association Annual Meeting (June 24-27, 2001).

Saunder DN. Angiogenesis antagonist as treatment for psoriasis: Phase I clinical trial results with AE-941. American Academy of Dermatology Conference, New Orleans, Louisiana, March 19-24, 1999.

Shimizu-Suganuma, Masum, Mwanatambwe, Milanga, Iida, Kazum, and et al. Effect of shark cartilage on tumor growth and survival time in vivo (meeting abstract). Proc Annu Meet Am Soc Clin Oncol 1999;18:A1760.

Simard, B., Bouamrani, A., Jourdes, P., Pernod, G., Dimitriadou, V., and Berger, F. Induction of the fibrinolytic system by cartilage extract mediates its antiangiogenic effect in mouse glioma. Microvasc.Res 2011;82(1):6-17. View abstract.

Talks, K. L. and Harris, A. L. Current status of antiangiogenic factors. Br J Haematol. 2000;109(3):477-489. View abstract.

Turcotte P. Phase I dose escalation study of AE-941, an antiangiogenic agent, in age-related macular degeneration patient. Retina Society Conference (Hawaii, December 2, 1999).

Volpi, N. Oral absorption and bioavailability of ichthyic origin chondroitin sulfate in healthy male volunteers. Osteoarthritis.Cartilage. 2003;11(6):433-441. View abstract.

Weber, M. H., Lee, J., and Orr, F. W. The effect of Neovastat (AE-941) on an experimental metastatic bone tumor model. Int J Oncol 2002;20(2):299-303. View abstract.

Wilson JL. Topical shark cartilage subdues psoriasis. Altern Comp Ther 2000;6:291.

Zheng, L., Ling, P., Wang, Z., Niu, R., Hu, C., Zhang, T., and Lin, X. A novel polypeptide from shark cartilage with potent anti-angiogenic activity. Cancer Biol Ther 2007;6(5):775-780. View abstract.

Zhuang, L, Wang, B, Shivji, G, and et al. AE-941, a novel inhibitor of angiogenesis has significant anti-inflammatory effect on contact hypersensitivity. J Invest Derm 1997;108(4):633.

Anon. AEterna announces the commencement of patient enrollment for the NIH - sponsored phase III clinical trial of AE-941/Neovastat in the treatment of lung cancer. Aeterna 2000 News Release 2000 May 17.

Ashar B, Vargo E. Shark cartilage-induced hepatitis [letter]. Ann Intern Med 1996;125:780-1. View abstract.

Batist G, Patenaude F, Champagne P, et al. Neovastat (AE-941) in refractory renal cell carcinoma patients: report of a phase II trial with two dose levels. Ann Oncol 2002;13:1259-63.. View abstract.

Berbari P, Thibodeau A, Germain L, et al Antiangiogenic effects of the oral administration of liquid cartilage extract in humans. J Surg Res 1999;87:108-13. View abstract.

Bhargava P, Trocky N, Marshall J, et al. A phase I safety, tolerance and pharmacokinetic study of rising dose, rising duration continuous infusion of MSI-1256F (Squalamine Lactate) in patients with advanced cancer. Proc Am Soc Clinical Oncol 1999;18:A698.

Boivin D, Gendron S, Beaulieu E, et al. The antiangiogenic agent Neovastat (AE-941) induces endothelial cell apoptosis. Mol Cancer Ther 2002;1:795-802.. View abstract.

Cohen M, Wolfe R, Mai T, Lewis D. A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee. J Rheumatol 2003;30:523-8.. View abstract.

Evans WK, Latreille J, Batist G, et al. AE-941, an inhibitor of angiogenesis: rationale for development in combination with induction chemotherapy/radiotherapy in patients with non small cell lung cancer (NSCLC). Proc Am Soc Clinical Oncol 1999;18:A1938.

Falardeau P, Champagne P, Poyet P, et al. Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol 2001;28:620-5.. View abstract.

FDA List of Orphan Designations and Approvals. http://www.fda.gov/orphan/DESIGNAT/list.htm (Accessed 27 October 2003).

Fontenele JB, Araujo GB, de Alencar JW, Viana GS. The analgesic and anti-inflammatory effects of shark cartilage are due to a peptide molecule and are nitric oxide (NO) system dependent. Biol Pharm Bull 1997;20:1151-4. View abstract.

Fontenele JB, Viana GS, Xavier-Filho J, de-Alencar JW. Anti-inflammatory and analgesic activity of a water-soluble fraction from shark cartilage. Braz J Med Biol Res 1996;29:643-6. View abstract.

Gingras D, Renaud A, Mousseau N, et al. Matrix proteinase inhibition by AE-941, a multifunctional antiangiogenic compound. Anticancer Res 2001;21:145-55.. View abstract.

Gomes EM, Souto PR, Felzenszwalb I. Shark-cartilage containing preparation protects cells against hydrogen peroxide induced damage and mutagenesis. Mutat Res 1996;367:204-8. View abstract.

Hillman JD, Peng AT, Gilliam AC, Remick SC. Treatment of Kaposi Sarcoma with oral administration of shark cartilage in a Human Herpes virus 8-seropositive, Human Immunodeficiency Virus-Seronegative homosexual man. Arch Dermatol 2001;137:1149-52. View abstract.

Hunt TJ, Connelly JF. Shark cartilage for cancer treatment. Am J Health Syst Pharm 1995;52:1756-60. View abstract.

Kalidas M, Hammond LA, Patnaik P, et al. A phase I and pharmacokinetic (PK) study of the angiogenesis inhibitor, squalamine lactate (MSI-1256F). Proc Am Soc Clinical Oncol 2000;19:A698.

Kim M. Mercury, cadmium and arsenic contents of calcium dietary supplements. Food Addit Contam 2004;21:763-7. View abstract.

Lane IW, Comac L. Sharks don't get cancer. Garden City, NY: Avery Publishing Group; 1992.

Leitner SP, Rothkopf MM, Haverstick L, et al. Two phase II studies of oral dry shark cartilage powder (SCP) in patients (pts) with either metastatic breast or prostate cancer refractory to standard treatment. Proc Am Soc Clinical Oncol 1998;17:A240.

Loprinzi CL, Levitt R, Barton DL, et al. Evaluation of shark cartilage in patients with advanced cancer: a North Central Cancer Treatment Group trial. Cancer 2005;104:176-82. View abstract.

Lu C, Lee JJ, Komaki R, et al. Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial. J Natl Cancer Inst 2010;102:1-7. View abstract.

Mathews J. Media feeds frenzy over shark cartilage as cancer treatment. J Natl Cancer Inst 1993;85:1190-1. View abstract.

Miller DR, Anderson GT, Stark JJ, et al. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol 1998;16:3649-55. View abstract.

Moller HJ, Moller-Pedersen T, Damsgaard TE, Poulsen JH. Demonstration of immunogenic keratin sulphate in commercial chondroitin 6-sulfate from shark cartilage. Implications for ELISA assays. Clin Chim Acta 1995;236:195-204. View abstract.

Natl Cancer Institute CancerNet. Cartilage website: www.cancer.gov (Accessed 18 August 2000).

Neovastat clinical trial abstracts. Presented at the American Association for Cancer Research 92nd annual meeting. March 27, 2001.

Patnaik A, Rowinsky E, Hammond L, et al. A phase I and pharmacokinetic (PK) study of the unique angiogenesis inhibitor, squalamine lactate (MSI-1256F). Proc Am Soc Clinical Oncol 1999;18:A622.

Riviere M, Falardeau P, Latreille J, and et al. Phase I/II lung cancer clinical trial results with AE-941 (Neovastat ®) an inhibitor of angiogenesis. Clin Invest Med (supplement) 1998;S14.

Rosenbluth RJ, Jennis AA, Cantwell S, DeVries J. Oral shark cartilage in the treatment of patients with advanced primary brain tumors. A phase II pilot study. Proc Am Soc Clinical Oncol 1999;18:A554.

Sauder DN, Dekoven J, Champagne P, et al. Neovastat (AE-941), an inhibitor of angiogenesis: Randomized phase I/II clinical trial results in patients with plaque psoriasis. J Am Acad Dermatol 2002;47:535-41. View abstract.

Sheu JR, Fu CC, Tsai ML, Chung WJ. Effect of U-995, a potent shark cartilage-derived angiogenesis inhibitor, on anti-angiogenesis and anti-tumor activities. Anticancer Res 1998;18:4435-41. View abstract.

Wilson JL. Topical shark cartilage subdues psoriasis: research review and preliminary clinical results. Altern Complement Ther 2000;6:291.