Shark Cartilage Research Data

High rate of bioactivity (reduction in gross tumor size)
observed in advanced cancer patients treated with shark cartilage material.

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Seven of 9 (87%) advanced cancer cases exhibited positive response (defined as a reduction gross tumor size) when treated with repeated intrarectal and intravaginal suspensions of shark cartilagenous material. During the study no other form or treatment was employed. Clinical data (7 and 11 week) are Included, and anti- angiogenesis, as the mode of action, is discussed. Shark cartilage, by inhibiting angiogenesis, interferes with tumor growth. Its therapeutic potential in the management of other angiogenesis-dependent diseases such as the spread of cancer, the inflammation and pain or arthritis and Kaposi's sarcoma are also discussed.
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Keywords: cancer( non-standard or experimental treatment); natural products: shark cartilage material; anti-angiogenesis factor; Kaposi's sarcoma

The hypothesis that solid tumors are angiogenesis-dependent and that anti-angiogenesis could be a potential therapeutic treatment was first published in 1987 by Folkman and co-authors (1). They theorized that once a tumor has formed, every increase in tumor size must be preceded by a concurrent increase in the blood supply network that converges on and nourishes the tumor. Evidence was presented showing that tumors of or two cubic millimeters (the size of a pencil point) stopped growing when separated from their capillary bed but resumed rapid growth upon revascularization. At this size the delivery of nutrients and the removal of waste products becomes growth limiting.

In 1988 D'Amore (2) theorized that if vascularization is to essential for the establishment and subsequent growth of metastasis, it seems that the inhibition of vascularization might be a method to prevent the formation of metastasis. The need for a non or low toxicity inhibitor is essential since administration over a prolonged period is necessary. Lee and Langer in 1983 (3) reported that shark cartilage contains a subtance that strongly inhibits the growth of new blood vessels toward solid tumors, thereby restricting junior growth. The abundance of the angiogenesis inhibiting factor was, on a pound for pound basis, one thousand times more concentrated in shark cartilage compared to mammalian cartilage. In 1990 Moses and co-workers (4) identified an inhibitor of neovascularization from cartilage as a macro-protein and also in 1990 Oikawa and co-workers in Japan (5) further identified an inhibitor or series of inhibitors in shark cartilage as guanadine extractable protein. In 1991 Lane (6) published on shark cartilage and its medical potential and also in 1991 a U.S. patent on the use of shark cartilage to inhibit angiogenesis was registered (7).

In 1989 Atassi, at the Institute Jules Bordet (6) showed tumor mass reductions of 36% in xenographs using orally administered shark cartilage, while tumor mass increased by 169% in the controls. All the growth occurred in the 7 days subsequent to the establishment of the blood network, which required about 14 days.

The opportunity to work with advanced cancer patients using cartilagenous material as the sole treatment was offered by the Ernesto Contreras Hospital in Tijuana, Mexico. The results of these preliminary results after 7 and 11 weeks of treatment wherein 7 out of 8 patients all classified as stage III or IV responded via reduced tumor size, reduced pain and improved quality of life are reported here from the medical records of each case as prepared by Ernesto Contreras, Jr., M.D., and his hospital staff.

Eight advanced cancer patients were chosen, all of whom were deemed to be terminal based in experience which predicted survival of between 3 and 6 months. These patients were started on a shark cartilage derived material (Cartilage Technologies Inc. Port Chester, NY) during the month of September 1991.

The eight patients (7 female and 1 male) all received the shark cartilaginous material (91% protein) at the rate of 30gm daily. The seven women received 15 gm daily rectally administered as a retention enema and 15 gms daily as an aqueous suspension administered into the vaginal body cavity. In the one man the 30 gm was administered as two 15 gm retention enemas. The enemas were retained for a minimum of 30 minutes before being expelled. The cartilage material was used as an aqueous suspension and was of a physical size whereby a minimum of 87% passed through a # 140 mesh screen and 66% passed through a #200 mesh screen. Fifteen grams of this material were suspended in 200 to 250 cc of water. The particle size was designed to allow absorption as the preformed protein or polypeptide as a suspension and the location of administration was designed to expedite rapid absorption.

every 15 days by the co-author (E.C.). Medical charts were maintained and updated constantly and are the basis of the results reported here.

The patients were taught how to administer the retention enemas and the

vaginal cavity suspension. Plastic bags each containing 15 gm were used by the patients in making their suspension using regular lap water.

The enemas were self- administered shortly after the patient had had their normal daily bowel movement and again just before bedtime. A reuseable plastic bottle similar to a fleet enema bottle was used on an outpatient basis after preliminary instructions by the medical staff.

Of the 8 patients, 2 had cervical cancer, locally advanced, one had a uterine adenocarcinoma, one had a bone metastasis from a primary cervical

cancer; one had a soft tissue sarcoma, one had a large hemangioma of the vagina; one had a peritonea] carcinoma from a primary colon cancer. one was a breast cancer that had invaded the chest cavity. All prior treatments are listed in the case reports. Other treatments were suspended when or before shark cartilage therapy began.

After 7 weeks of shark cartilagenous material treatment results and case histories are as follows:

L.T.,Age 48. Female. A stage III inoperable locally advanced uterine cervix cancer with invasion to the bladder. Earlier treatment with maximum doses of radiation had not stopped tumor growth. There was ulceration with severe pain related to the tumor. The patient had, after 7 weeks of shark cartilage treatment, an 80% reduction in tumor size and after 11 weeks a 100% tumor reduction with only scar tissue remaining that could be palpitated; pain had disappeared. A gastro-intestinal problem with no cancer or block- age developed at 11 weeks but was not cancer related.

2) V.J., Age 50. Female. This patient had a large vaginal hemangioma measuring 5" x 5" persistent after hysterectomy and partial vaginectomy and maximum doses externally and intracavitory of radiation therapy. Heavy bleeding was a life threatening complication.

Tumor size reduced 60% and bleeding was terminated at seven weeks. This case is considered one of the most significant because of the inhibiting effect of shark cartilage on angiogenesis. After 11 weeks the tumor size was reduced to a 3" by 3" size with no bleeding and tumor reduction appears Io be continuing with ongoing treatment.

3) G.L..Age 32. Female. Stage IV uterine cervical cancer with kidney blockage requiring a permanent catheter in the urethra. A very advanced cachexia. At 7 weeks tumor size had diminished 40%, the catheter was successfully removed and was unnecessary and pain was materially reduced. The patient started eating and was gaining weight. Improvement was both objective and subjective. At 11 weeks tumor size was further reduced by 60%. This case is significant since death was anticipated. With the cartilage treatment recovery is proceeding rapidly and her pain has disappeared.

4) J.G., Age 32, Male. With a stage III inoperable soft tissue sarcoma covering the entire back of the right thigh. It had partially responded to earlier radiation therapy but was still growing. When evaluated at 7 weeks there was no change and the result was considered negative. As a last resort after 9 weeks of cartilage therapy, surgery was undertaken and upon opening the sarcoma the entire center portion was gelatinous and undergoing major necrosis. At least 60% of the tumor was dead and surgically removed. No lung metastasis had developed as normally occurs with such cases. At 11 weeks tumor necrosis was continuing and no complications were observed.

5) G.V., Age 38. Female. With a stage III residual tumor after a total hysterectomy for cervical cancer previously treated with maximum doses of internal and external radiation therapy. She was symptomatic and in very poor general condition and had major pain related to her cancer. After 7 weeks important subjective improvement was seen, pain had disappeared, and she was practically asymptomatic. The patient elected to stop the treatment at 7 weeks and at II weeks tumors had reappeared in both lungs. Cartilage treatment has been reinstated.

6) B.S., Age 62. Female. Is a stage III patient with a bone metastasis to the right sacroiliac region from a previously treated uterine cervix cancer. This metastasis developed on a previously radiated area. 3000 Cgy of Cobalt therapy was delivered and the cartilage therapy started. At 7 weeks there was 80% reduction of the tumor and pain had largely disappeared. At 11 weeks the tumor had completely regressed and the patient was considered cured.

7) G.V., Age 45. Female. Stage IV with a bilateral breast cancer with skin and chest wall invasion. No response at 7 weeks was observed from the cartilage therapy and treatment was stopped at that time.

8) M.T., Age 36. Female. Stage IV with a peritoneal carcinomatosis from a primary colon career, persistent after an exploratory laparatomy which confirmed the diagnosis. The patient was considered inoperable. After 7 weeks on cartilage therapy the patient developed an abdominal wall abscess which required a second laparatomy during which 80% of the tumor was found gelatinized and removed. At 11 weeks the patient was tumor free. This case is considered a "miracle"since death is common with this diagnosis.

The reports of Folkman (1) and D'Amore (2) have theorized that by inhibiting angiogenesis one can control the spread of metastasis. lane (6) reports on a variety of therapeutic benefits of shark cartilage in, various mammals. Populations of mice, dogs and humans all suffering from severe osteoarthritis experienced increased mobility and decreased pain due to the anti-inflammatory effects of shark cartilage. Xenographs were used to further show cessation of experimentally induced melanoma growth in nude mice.

Eight case reports on Mexican charity patients, all of whom were given 30 gm daily of a concentrated shark cartilagenous material as the only treatment showed that 7 out of 8 (87%) responded in a highly significant way to the treatment with shark cartilage. It is theorized that the mode of action on stopping tumor growth and bringing about major tumor necrosis was angiogenesis inhibition caused by a large protein molecule identified by Moses et al. (4) and Oikawa et al. (5) as one or more protein molecules found abundantly natural shark cartilagenous material.

These responses in 7 of 8 advanced cancer patients, though preliminary and on a limited number of patients, are considered highly significant and confirmatory work is now underway in Germany (12 patients) and New York (2 patients).

The work in Mexico continues. Other types of cancerous tumors utilizing shark cartilage as the only treatment include lung, renal, colon, breast, pancreatic and prostate cancers. Very preliminary results suggest that rectal administration is more effective than oral administration and most of the re- search is now being conducted rectally with limited oral administration for comparison.

No toxic effects have been reported with shark cartilage at all levels of use including the 30 gm daily used as herein reported. This is supported by the years of experience covered by the wide use of shark cartilage in the form of shark fin soup consumed by the Chinese for ever 100 years and earlier use in the treatment of inflammation and pain of arthritis with dogs and humans.

The experimental results discussed here and the theories reviewed in the introduction suggest a correlation between blood vessel development and tumor growth. Earlier work reported by Lane (6) also suggests a correlation between the pain of arthritis (inflammation), angiogenesis and immune stimulation by the mucopolysaccharides in shark cartilage, working synergistically.

The results of case 2, (V.J.) with a 5" x 5" vaginal hemangioma, the size of a large grapefruit reducing to 3"x 3", the size of an orange, with complete cessation of bleeding, is probably the best direct example of angiogenesis inhibition.

Experimental work about to start with a model of Karposi's Sarcoma with the National Cancer Institute (NCI) in Bethesda, Maryland, will hopefully add to this growing pool of information. The rationale for this study is that angiogenesis inhibition would stop the development of endothial cells needed to form the walls of blood vessels or the walls of a Karposi's sarcoma lesion.

Since cancer and the spread of metastasis, as well as inflammation and the pain of arthritis, have now been shown by preliminary work to be significantly helped through the administration of natural shark cartilage, one can also assume that other angiogenic maladies like psoriasis, diabetic retinopathy, neovascular glaucoma and Karposi's sarcoma may be helped in a similar manner. By either a rectal or oral administration a systemic rather than a local treatment is induced. Thus, utilizing shark cartilage for one malady, other angiogenesis dependent maladies may be automatically treated or prevented. Diseases involving angiogenesis often occur in older patients. Research on shark cartilage is particularly appropriate today as our population is aging.

No research has been done on the preventive benefits of shark cartilage. The only observations have been with a number of women who have been on 7 gms of shark cartilage daily for 3 years following mastectomies or lumpectomies and who have shown no reoccurrence of breast cancer. These limited observations are encouraging since the odds favor a reoccurrence.

These preliminary but significant results (87%) with advanced cancer patients using shark cartilagenous material as the only treatment show major promise. Additional critical trials are underway or starting. Shark cartilage is a non toxic, natural product. It probably can be used as an adjunct to other forms of treatment such as chemotherapy, surgery and radiation. Shark cartilage functions as an angiogenesis inhibitor with a novel mode of action and can therefore be used in acomplimentary manner to other widely used and accepted therapies.

Patients who have recently suffered a heart attack, pregnant women and those recently recovering from deep surgery all need angiogenesis for a period of 1 - 3 months and should not be taking shark cartilage during that time. Adults normally have their blind network in place and will only experience rapid and new angiogenesis if a serious condition like cancer develops.

2. D'Amore PA. Anti- angiogenesis as a strategy for antimetastasis Seminars in Thrombosis and Homeostasis, 1988, 14 73-78

3. Lee, A., Langer, R. Shark cartilage contains inhibitors of tumor angiogenesis. Science 1983, 221 1185-1187

4. Moses MA, Sudhalter J, Langer R. Identification of an inhibitor of neovascularization from cartilage. Science 1990, 248 1408-1410

5. Oikawa, T., Ashino-Fuse, Shimamura, Korde and Iwaguchi: A novel angiogenic inhibitor derived from Japanese shark cartilage. Cancer Letters. 1990, 51; 181-186

6. Lane, IW. Shark cartilage: Its potential medical applications. Journal of Advancement in Medicine. 1991,4(4) 263-271

7. Lane, IW. US Patent #5, 075 112, 1991. Method of and dosage unit for inhibiting angiogenesis or vascularization in an animal using shark cartilage.