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An In Vivo Study to Evaluate the Efficacy of Blue Shark (Prionace glauca) Cartilage Collagen as a Cosmetic.

1. Mar Drugs. 2022 Oct 5;20(10):633. doi: 10.3390/md20100633. An In Vivo Study to Evaluate the Efficacy of Blue Shark (Prionace glauca) Cartilage Collagen as a Cosmetic. Lu WC(1), Chiu CS(2), Chan YJ(3), Guo TP(4), Lin CC(5), Wang PC(4), Lin PY(4), Mulio AT(6), Li PH(6). Author information: (1)

[Systematic Review of Case Reports on the Adverse Events Due to Health Food Intake by Cancer Patients].

2. Yakugaku Zasshi. 2019;139(10):1333-1347. doi: 10.1248/yakushi.19-00116. [Systematic Review of Case Reports on the Adverse Events Due to Health Food Intake by Cancer Patients]. [Article in Japanese] Kojima A(1), Sato Y(1), Nishijima C(1), Umegaki K(2), Chiba T(1). Author information: (1)Natio

Biopharmacologic and herbal therapies for cancer: research update from NCCAM.

3. J Nutr. 2001 Nov;131(11 Suppl):3037S-40S. doi: 10.1093/jn/131.11.3037S. Biopharmacologic and herbal therapies for cancer: research update from NCCAM. Richardson MA(1). Author information: (1)National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health, Bet

The analgesic and anti-inflammatory effects of shark cartilage are due to a peptide molecule and are nitric oxide (NO) system dependent.

4. Biol Pharm Bull. 1997 Nov;20(11):1151-4. doi: 10.1248/bpb.20.1151. The analgesic and anti-inflammatory effects of shark cartilage are due to a peptide molecule and are nitric oxide (NO) system dependent. Fontenele JB(1), Araújo GB, de Alencar JW, Viana GS. Author information: (1)Department of

AE 941.

5. Drugs R D. 2004;5(2):83-9. doi: 10.2165/00126839-200405020-00003. AE 941. [No authors listed] AE 941 [Arthrovas, Neoretna, Psovascar] is shark cartilage extract that inhibits angiogenesis. AE 941 acts by blocking the two main pathways that contribute to the process of angiogenesis, matrix me

Occurrence of β-N-methylamino-l-alanine (BMAA) and Isomers in Aquatic Environments and Aquatic Food Sources for Humans.

6. Toxins (Basel). 2018 Feb 14;10(2):83. doi: 10.3390/toxins10020083. Occurrence of β-N-methylamino-l-alanine (BMAA) and Isomers in Aquatic Environments and Aquatic Food Sources for Humans. Lance E(1), Arnich N(2), Maignien T(3), Biré R(4). Author information: (1)UMR SEBIO, Bat 18, Campus du Mou

Evaluation of inflammatory responses induced via intra-articular injection of interleukin-1 in horses receiving a dietary nutraceutical and assessment of the clinical effects of long-term nutraceutical administration.

1. Am J Vet Res. 2009 Jul;70(7):848-61. doi: 10.2460/ajvr.70.7.848. Evaluation of inflammatory responses induced via intra-articular injection of interleukin-1 in horses receiving a dietary nutraceutical and assessment of the clinical effects of long-term nutraceutical administration. Pearson W(1), Orth MW, Lindinger MI. Author information: (1)Department of Plant Agriculture, Ontario Agriculture College, University of Guelph, Guelph, ON N1G 2W1, Canada. OBJECTIVE: To evaluate inflammatory responses induced via intra-articular recombinant human interleukin (IL)-1beta treatment in horses receiving a dietary nutraceutical (DN; composed of mussel, shark cartilage, abalone, and Biota orientalis lipid extract) and assess the clinical effects of long-term DN administration. ANIMALS: 22 healthy horses. PROCEDURES: 12 horses were fed 0, 15, 45, or 75 mg of DN (3 horses/treatment) daily for 84 days. General health and clinicopathologic variables were monitored at intervals. Ten other horses received 0 or 15 g of DN/d (5 horses/treatment) for 29 days (beginning day -14). One intercarpal joint in each horse was injected twice with IL-1beta (10 and 100 ng on days 0 and 1, respectively), and the contralateral joint was similarly injected with saline (0.9% NaCl) solution. Synovial fluid prostaglandin E(2) (PGE(2)), sulfated glycosaminoglycan (GAG), nitric oxide (NO), and protein concentrations and leukocyte counts were analyzed before and at intervals after injections. RESULTS: Administration of the DN (up to 75 g/d) to horses for 84 days did not induce any adverse effects. In the other experiment, synovial fluid PGE(2), GAG, and protein concentrations and leukocyte count increased after intra-articular injections of IL-1beta (compared with effects of saline solution injections) in horses that received no DN; NO concentration was not affected. In horses that were fed the DN, intra-articular IL-1beta injections did not induce significant increases in synovial fluid PGE(2) and GAG concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that administration of the DN may be useful in preventing inflammation associated with arthritis and degenerative joint disease in horses. DOI: 10.2460/ajvr.70.7.848 PMID: 19566470 [Indexed for MEDLINE]

Results and lessons from clinical trials using dietary supplements for cancer: direct and indirect investigations.

2. Semin Urol Oncol. 2001 Nov;19(4):232-46. Results and lessons from clinical trials using dietary supplements for cancer: direct and indirect investigations. Moyad MA(1). Author information: (1)Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109-0330, USA. Randomized controlled trials are generally regarded as the standard of study designs to determine potential causality. The inclusion of a placebo group in these trials, when appropriate, is generally needed to access the efficacy of a drug or dietary supplement. The recent increasing use of dietary supplements and herbal medications by patients makes it imperative to reevaluate the past findings of clinical studies. Several large-scale trials of dietary supplements have been tested in various populations to determine their effect on cancer prevention. Other trials have focused on patients already diagnosed with cancer. In the latter case, it is difficult to involve a placebo because of the serious nature of the disease. Nevertheless, much has been gleaned from these trials directly and indirectly. Overall, when analyzing primary endpoints in these trials, the results have been discouraging and even support the nonuse of certain supplements because of potential adverse effects. Other secondary endpoints in these same trials have revealed some potential encouraging and discouraging data. Individuals who currently qualify for the potential use of dietary supplements for cancer may be restricted to those who have a deficiency in a certain compound despite adequate dietary sources or lifestyle changes. Those individuals with a smoking history or other unhealthy lifestyle seem to have the most to gain or lose from taking certain dietary supplements for cancer. The time seems more than ripe to evaluate past adequate trials with supplements, such as beta-carotene, N-acetyl-cysteine, selenium, shark cartilage, vitamin C, vitamin E, and others. Again, these studies have been disappointing, but they provide insight for the clinician and patient of what to potentially expect when using these supplements for cancer. In addition, indirect trials for other conditions (cardiovascular) may provide future insight into possible results for future cancer prevention trials. PMID: 11769876 [Indexed for MEDLINE]

Dietary supplement use by women at risk for breast cancer recurrence. The Women's Healthy Eating and Living Study Group.

3. J Am Diet Assoc. 1998 Mar;98(3):285-92. doi: 10.1016/s0002-8223(98)00068-6. Dietary supplement use by women at risk for breast cancer recurrence. The Women's Healthy Eating and Living Study Group. Newman V(1), Rock CL, Faerber S, Flatt SW, Wright FA, Pierce JP. Author information: (1)Department of Family and Preventive Medicine, University of California-San Diego, La Jolla 92093-0901, USA. OBJECTIVE: To develop a method of collecting, organizing, and analyzing information on nutrient and nonnutrient dietary supplement use by women at risk for breast cancer recurrence as a component of nutrition assessment and monitoring, and to describe the characteristics associated with dietary supplement use in this population at enrollment in a clinical trial to prevent breast cancer recurrence. DESIGN: Cross-sectional descriptive study design. SUBJECTS: Women diagnosed with breast cancer within the previous 4 years (n=435). ANALYSIS: Dietary supplements reported in four 24-hour dietary recalls were categorized according to primary nutrient and nonnutrient contents. Prevalence of dietary supplement use is described. Associations between supplement use and demographic and participant characteristics were examined using chi(2) analysis and logistic regression. RESULTS: Dietary supplement use was reported by 80.9% of the women. Increased likelihood of supplement use was associated with demographic (eg, older age, higher level of education, white race vs other ethnic groups) and personal (eg, lower body mass index, moderate alcohol consumption) characteristics. Use of vitamin C and related compounds, other nutrients (eg, n-3 fatty acids, evening primrose oil), and herbal products was inversely associated with months since diagnosis; use of miscellaneous supplements (eg, shark cartilage) was directly associated with more advanced stage at diagnosis. APPLICATIONS: Monitoring dietary supplement use is an important aspect of nutrition assessment, especially in populations with chronic health conditions or medical diagnoses. Demographic and personal characteristics, time passed since diagnosis, and stage of cancer at diagnosis are predictive of dietary supplement use by women at risk for breast cancer recurrence. Associations in this population may be present in other groups that are the object of nutrition intervention efforts. DOI: 10.1016/s0002-8223(98)00068-6 PMID: 9508010 [Indexed for MEDLINE]

Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial.

4. J Natl Cancer Inst. 2010 Jun 16;102(12):859-65. doi: 10.1093/jnci/djq179. Epub 2010 May 26. Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial. Lu C(1), Lee JJ, Komaki R, Herbst RS, Feng L, Evans WK, Choy H, Desjardins P, Esparaz BT, Truong MT, Saxman S, Kelaghan J, Bleyer A, Fisch MJ. Author information: (1)Department of Thoracic/Head & Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 432, Houston, TX 77030-4009, USA. clu@mdanderson.org Comment in J Natl Cancer Inst. 2010 Jun 16;102(12):834-5. doi: 10.1093/jnci/djq196. BACKGROUND AE-941 is a standardized aqueous shark cartilage extract with antiangiogenic properties that has previously been evaluated in phase I and II clinical trials. Our objective was to determine the effect of adding AE-941 to chemoradiotherapy on overall survival of patients with unresectable stage III non-small cell lung cancer (NSCLC). METHODS A randomized, double-blinded, placebo-controlled, phase III clinical trial was designed to test the efficacy of AE-941 in unresectable stage III NSCLC patients who were treated with chemoradiotherapy. Between June 5, 2000, and February 6, 2006, 379 eligible patients were enrolled in community and academic oncology centers across the United States and Canada. In February 2006, the trial was closed to new patient entry before meeting the target sample size because of insufficient accrual. All subjects received induction chemotherapy followed by concurrent chemotherapy with chest radiotherapy. Each participating center administered one of the two chemotherapy regimens, either carboplatin and paclitaxel, or cisplatin and vinorelbine. The primary endpoint was overall survival, and secondary endpoints were time to progression, progression-free survival, tumor response rate, and toxic effects. Event-time distributions were estimated by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS There was no statistically significant difference in overall survival between the chemoradiotherapy plus AE-941 group (n = 188; median survival = 14.4 months, 95% confidence interval = 12.6 to 17.9 months) and the chemoradiotherapy plus placebo group (n = 191; median survival = 15.6 months, 95% confidence interval = 13.8 to 18.1 months) (P = .73). Time to progression, progression-free survival, and tumor response rates were not statistically significantly different between the AE-941 and the placebo groups. No differences between the two groups were observed in common grade 3 or higher toxic effects attributable to chemoradiotherapy. CONCLUSIONS The addition of AE-941 to chemoradiotherapy did not improve overall survival in patients with unresectable stage III NSCLC. This study does not support the use of shark cartilage-derived products as therapy for lung cancer. DOI: 10.1093/jnci/djq179 PMCID: PMC2902826 PMID: 20505152 [Indexed for MEDLINE]

The challenge of rational development of complex natural products as cancer therapeutics.

5. J Natl Cancer Inst. 2010 Jun 16;102(12):834-5. doi: 10.1093/jnci/djq196. Epub 2010 May 26. The challenge of rational development of complex natural products as cancer therapeutics. White J. Comment on J Natl Cancer Inst. 2010 Jun 16;102(12):859-65. doi: 10.1093/jnci/djq179. DOI: 10.1093/jnci/djq196 PMID: 20505150 [Indexed for MEDLINE]

[Shark cartilage extract. No effect on bronchial carcinoma].

6. Med Monatsschr Pharm. 2007 Sep;30(9):351. [Shark cartilage extract. No effect on bronchial carcinoma]. [Article in German] [No authors listed] PMID: 17912881 [Indexed for MEDLINE]

Prognostic factors of metastatic renal cell carcinoma after failure of immunotherapy: new paradigm from a large phase III trial with shark cartilage extract AE 941.

7. J Urol. 2007 Nov;178(5):1901-5. doi: 10.1016/j.juro.2007.07.035. Epub 2007 Sep 17. Prognostic factors of metastatic renal cell carcinoma after failure of immunotherapy: new paradigm from a large phase III trial with shark cartilage extract AE 941. Escudier B(1), Choueiri TK, Oudard S, Szczylik C, Négrier S, Ravaud A, Chevreau C, Venner P, Champagne P, Croteau D, Dupont E, Hariton C, Bukowski RM. Author information: (1)Institut Gustave Roussy, Villejuif, France. PURPOSE: We analyzed prognostic factors, described survival and generated a prognostic model in patients with metastatic renal cell carcinoma in whom immunotherapy failed and who were potentially eligible for novel agents. MATERIALS AND METHODS: An analysis of the relationship between clinical features and survival was performed in 300 patients with advanced renal cell carcinoma in whom immunotherapy had failed and who were subsequently treated as part of a single, phase III clinical trial with the anti-angiogenic agent Neovastat (shark cartilage extract AE 941). Clinical features were first examined univariately and a stepwise modeling approach based on Cox proportional hazard regression was then performed to generate a multivariate model. RESULTS: Median and progression-free survival (prognostic factors) for the whole cohort was 12.6 and 2 months, respectively. Prognostic features associated with shorter survival on multivariate analysis were the number of metastatic sites (greater than 1), time from nephrectomy to metastatic disease (less than 2 years), high alkaline phosphatase, abnormal corrected serum Ca and high lactate dehydrogenase (greater than 1.5 x the upper limit of normal). Four prognostic subgroups were identified by counting the number of adverse prognostic factors. Median survival in patients with zero adverse prognostic factors was 15.6 months compared to 11.7 months in patients with 1, 8.5 months in patients with 2 and 3.5 months in patients with 3 or more. CONCLUSIONS: We identified 4 risk groups to predict survival in previously treated patients with renal cell carcinoma. This model was based on data from what is to our knowledge the largest experience in this population. It should be used in clinical trial design, risk stratification and patient counseling. DOI: 10.1016/j.juro.2007.07.035 PMID: 17868728 [Indexed for MEDLINE]

Evaluation of shark cartilage in patients with advanced cancer: a North Central Cancer Treatment Group trial.

8. Cancer. 2005 Jul 1;104(1):176-82. doi: 10.1002/cncr.21107. Evaluation of shark cartilage in patients with advanced cancer: a North Central Cancer Treatment Group trial. Loprinzi CL(1), Levitt R, Barton DL, Sloan JA, Atherton PJ, Smith DJ, Dakhil SR, Moore DF Jr, Krook JE, Rowland KM Jr, Mazurczak MA, Berg AR, Kim GP; North Central Cancer Treatment Group. Author information: (1)Department of Oncology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 56301, USA. cloprinzi@mayo.edu BACKGROUND: Shark cartilage has been a popular complementary or alternative medicine intervention. The basis for this popularity is the claim that sharks rarely get cancer because of the high proportion of cartilage in the shark's body. However, early studies were equivocal. Therefore, a clinical trial was conducted to look at the impact of shark cartilage in patients with advanced cancer. The primary goal of this trial was to determine whether a shark cartilage product improved overall survival for patients with advanced cancer who were getting standard care. Secondary research goals were to evaluate toxicities, tolerability, and quality of life associated with this shark cartilage product. METHODS: The study was a two-arm, randomized, placebo-controlled, double-blind, clinical trial. Patients with incurable breast or colorectal carcinoma had to have good performance status and organ function. Patients could be receiving chemotherapy. Patients were all to receive standard care and then to be randomly selected to receive either a shark cartilage product or an identical-appearing and smelling placebo 3 to 4 times each day. RESULTS: Data on a total of 83 evaluable patients were analyzed. There was no difference in overall survival between patients receiving standard care plus a shark cartilage product versus standard care plus placebo. Likewise, there was no suggestion of improvement in quality of life for patients receiving the shark cartilage, compared with those receiving placebo. CONCLUSION: This trial was unable to demonstrate any suggestion of efficacy for this shark cartilage product in patients with advanced cancer. DOI: 10.1002/cncr.21107 PMID: 15912493 [Indexed for MEDLINE]

[From shark cartilage to hypnosis. Conservative medicine against cancer?].

9. MMW Fortschr Med. 2004 Apr 22;146(17):8, 10. [From shark cartilage to hypnosis. Conservative medicine against cancer?]. [Article in German] Arnheim K. Comment in MMW Fortschr Med. 2004 May 20;146(21):17. PMID: 15224894 [Indexed for MEDLINE]

Neovastat (AE-941), an inhibitor of angiogenesis: Randomized phase I/II clinical trial results in patients with plaque psoriasis.

10. J Am Acad Dermatol. 2002 Oct;47(4):535-41. doi: 10.1067/mjd.2002.124702. Neovastat (AE-941), an inhibitor of angiogenesis: Randomized phase I/II clinical trial results in patients with plaque psoriasis. Sauder DN(1), Dekoven J, Champagne P, Croteau D, Dupont E. Author information: (1)Department of Dermatology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21287, USA. There is considerable evidence to support an immunopathogenic basis of psoriasis. However, changes such as altered angiogenesis have also been implicated in the pathogenesis of psoriasis. AE-941 (Neovastat; Aeterna Laboratories, Quebec City Quebec, Canada) is a naturally occurring product currently in clinical investigation that blocks two main mechanisms of angiogenesis activation, namely, vascular endothelial growth factor and matrix metalloproteinase. We hypothesized that psoriasis could be modulated by inhibiting the neovascularization of psoriatic plaques. We conducted a randomized dose-comparison trial to evaluate the safety and potential therapeutic benefit of AE-941, administered orally to patients with psoriasis. Forty-nine patients with psoriasis were enrolled and assigned to receive AE-941 at 30, 60, 120, or 240 mL/d for 12 weeks. Patients were followed up for another 12-week period. Improvement in the Psoriasis Area and Severity Index (PASI) score was observed in 50%, 41.7%, and 30.8% of the patients receiving 240, 120, and 60 mL/d, respectively. No patients receiving a dosage 30 mL/d showed a PASI score improvement. A statistically significant improvement with increasing dose was observed for the PASI score, severity of itch, and the physician's global assessment. The most commonly reported nonserious drug-related adverse events affected the gastrointestinal system in 12 of 49 patients (primarily nausea, diarrhea, vomiting, flatulence, and constipation) and the skin and appendages in 4 of 49 patients (primarily acne and rash). This randomized phase I/II study provides evidence that the antiangiogenic agent AE-941 offers a new therapeutic approach to the management of psoriasis. DOI: 10.1067/mjd.2002.124702 PMID: 12271297 [Indexed for MEDLINE]

Angiogenesis inhibitors in the treatment of lung cancer.

11. Lung Cancer. 2001 Dec;34 Suppl 3:S81-9. doi: 10.1016/s0169-5002(01)00377-4. Angiogenesis inhibitors in the treatment of lung cancer. Shepherd FA(1). Author information: (1)Division of Medical Oncology, Department of Medicine, Princess Margaret Hospital, 610 University Avenue, 5-104, University of Toronto, Ont., Toronto, Canada, M5G 2M9. frances.shepard@uhn.on.ca Numerous inhibitors of angiogenesis are currently under study in lung cancer. Four trials of adjuvant interferon after chemotherapy for small cell lung cancer (SCLC) were negative. Several metalloproteinase inhibitors (MMPIs) are now in study in SCLC and non-small cell lung cancer (NSCLC). Two large randomized trials have closed recently in which Marimastat 10 mg bid was compared to placebo in responding patients with SCLC. Two randomized studies of Prinomastat versus placebo with combination chemotherapy in advanced NSCLC have also completed accrual. The results of these trials are not yet available, but should be reported in mid-2001. A Phase III trial of BMS-275291, a broad-spectrum MMPI in combination with paclitaxel and carboplatin is open for patients with advanced NSCLC. Neovastat, a standardized shark cartilage extract is under study in inoperable Stage III NSCLC. VEG-F gene expression is increased in many tumors including NSCLC, and may act as a paracrine mediator of growth. A randomized Phase II trial of paclitaxel and carboplatin with or without a recombinant humanized anti-VEG-F has been undertaken in NSCLC. Modestly better response and survival were seen with anti-VEG-F and a large Phase III trial is planned. Numerous receptor tyrosine kinases (TK) have been found to be directly or indirectly involved in angiogenesis including Flk-1, Flt-l, Tie-1 and Tie-2. SU5416 is a small molecular TK inhibitor and potent inhibitor of VEG-F-mediated Flk-1 receptor signaling. Another TK inhibitor SU6668 blocks VEG-F, bFGF and PDGF receptor signaling. It is orally available, and it may be evaluated in lung cancer trials in the near future. ZD4190 is an inhibitor of KDR/Flk-1 that may be evaluated in SCLC. Thalidomide has recently been shown in pre-clinical models to be anti-angiogenic. A randomized trial of paclitaxel/carboplatin and radiation with or without thalidomide is open for patients with Stage IIIB NSCLC in the United States. Numerous other anti-angiogenesis agents are in early clinical trials, but have not been evaluated in lung cancer yet. DOI: 10.1016/s0169-5002(01)00377-4 PMID: 11740999 [Indexed for MEDLINE]

A primer of complementary and alternative medicine commonly used by cancer patients.

12. Med J Aust. 2001 Jan 15;174(2):88-92. doi: 10.5694/j.1326-5377.2001.tb143161.x. A primer of complementary and alternative medicine commonly used by cancer patients. Ernst E(1). Author information: (1)School of Postgraduate Medicine and Health Sciences, University of Exeter, UK. E.Ernst@exeter.ac.uk Comment in Med J Aust. 2001 Jun 4;174(11):611-2. doi: 10.5694/j.1326-5377.2001.tb143462.x. Med J Aust. 2001 Sep 17;175(6):342-3. doi: 10.5694/j.1326-5377.2001.tb143610.x. Complementary and alternative medicine (CAM) is frequently used by cancer patients, and many oncologists have limited knowledge of CAM. This article provides a brief, evidence-based introduction to several CAM treatments relevant in the context of cancer. "Alternative" diets, chiropractic, coffee enemas, ozone therapy, and shark cartilage seem to have little to offer cancer patients. The evidence for or against homoeopathy and spiritual healing is at present inconclusive. Acupuncture, aromatherapy, and meditation may be useful for nausea/vomiting, for mild relaxation, and for pain/anxiety, respectively. Herbal treatments offer no reasonable prospect of a cure (mistletoe), but could be useful as palliative treatments (eg, for depression [St John's wort] or anxiety [kava]). Our knowledge regarding the potential benefit and harm of CAM is insufficient. DOI: 10.5694/j.1326-5377.2001.tb143161.x PMID: 11245510 [Indexed for MEDLINE]

The impact of displayed awards on the credibility and retention of Web site information.

13. Proc AMIA Symp. 2000:794-8. The impact of displayed awards on the credibility and retention of Web site information. Shon J(1), Marshall J, Musen MA. Author information: (1)Stanford Medical Informatics, Stanford University School of Medicine, Stanford, CA 94305-5479, USA. Ratings systems and awards for medical Web sites have proliferated, but the validity and utility of the systems has not been well established. This study examined the effect of awards on the perceived credibility and retention of health information on a Web page. We recruited study participants from Internet newsgroups and presented them with information on the claimed health benefits of shark cartilage. Participants were randomized to receive health information with and without a medical award present on the page. We subsequently asked them to evaluate the credibility of the Web page and posed multiple-choice questions regarding the content of the pages. 137 completed responses were included for analysis. Our results show that the presentation of awards has no significant effect on the credibility or retention of health information on a Web page. Significantly, the highly educated participants in our study found inaccurate and misleading information on shark cartilage to be slightly believable. PMCID: PMC2243820 PMID: 11079993 [Indexed for MEDLINE]

Antiangiogenic effects of the oral administration of liquid cartilage extract in humans.

14. J Surg Res. 1999 Nov;87(1):108-13. doi: 10.1006/jsre.1999.5698. Antiangiogenic effects of the oral administration of liquid cartilage extract in humans. Berbari P(1), Thibodeau A, Germain L, Saint-Cyr M, Gaudreau P, Elkhouri S, Dupont E, Garrel DR, Elkouri S. Author information: (1)Hôtel-Dieu Hospital, University of Montreal Medical School, Montreal, Canada. Erratum in J Surg Res 2000 Apr;89(2):197. El-Khouri S [corrected to Elkouri S]. BACKGROUND: The antiangiogenic properties of shark cartilage extracts have been demonstrated in animal models but there are no data in human subjects. MATERIALS AND METHODS: A placebo or one of two doses of a liquid shark cartilage extract was orally administered daily, from Day 1 to Day 23 of the study protocol, to 29 healthy male volunteers randomized into three groups. On Day 12, a polyvinyl alcohol sponge threaded in a perforated silicone tubing was inserted subcutaneously on the anterior side of the arm and removed on Day 23. Evaluation of endothelial cell density, with factor VIII immunostaining, an indirect measurement of angiogenesis, was performed on histological sections of the implant using a semiquantitative numerical scale ranging from 1 (low density) to 5 (high density). The hydroxyproline content of the sponges was measured by HPLC. RESULTS: The mean endothelial cell density was significantly lower in groups that had received the liquid cartilage extract: grades 2.24 +/- 0.10, 2.47 +/- 0.10, and 3.15 +/- 0.11 for 7 and 21 ml liquid cartilage extract and placebo, respectively (P < 0.01 for both comparisons). No grade 1 was observed in the placebo group, whereas 9 treated subjects received a grade 1. Hydroxyproline content of the sponges did not differ between groups and there was no significant correlation between hydroxyproline content and endothelial cell density in the sponges. CONCLUSIONS: These results demonstrate that the liquid cartilage extract contains an antiangiogenic component bioavailable in humans by oral administration. This is the first report of an inhibition of wound angiogenesis in healthy men. Copyright 1999 Academic Press. DOI: 10.1006/jsre.1999.5698 PMID: 10527711 [Indexed for MEDLINE]