Abstract
This review presents data on the antitumor properties of antineoplastons - alternative means of treatment for cancer originally isolated from human blood and urine. It was assumed that antineoplastons (derivatives of peptides and amino acids) are natural regulators of cell differentiation. In experimental studies it was showed that synthetic antineoplastons (A10-3-phenyl-acetyl-amino-2,6-piperidinedione and AS2-1 - a mixture of phenylacetic acid and phenylacetylglutamine) were able to prevent the introduction of glutamine into the cell, to block the action of Bcl-2, to activate p53 and p21, to inhibit histone deacetylase, to induce apoptosis. In experiments in vitro and in vivo in several studies it was registered antitumor activity, mainly on models of hepatocellular carcinoma and glioma. Clinical data are limited by reports of individual clinical cases or series of cases and the results of several clinical trials Phase I-II, indicating a possible antitumor activity.References
Asharaf A.Q., Liau M.C., Mohabbat M.O., Burzynski S.R. Preclinical studies on antineoplaston A10 injections // Drugs Exp. Clin. Res. - 1986. - Vol. 12, Suppl. 1. - P. 37-45.
Badria F., Mabed M., El-Awadi V. et al. Immune modulatory potentials of antineoplaston A10 in breast cancer patients // Cancer Lett. - 2000. - Vol. 157. - P. 57-63.
Badria F., Mabed M., Knafagy W., Abou-Zeid L. Potential utility of antineoplaston A10 level in breast cancer // Cancer Lett. - 2000. - Vol. 155. - P. 67-70.
Buckner J.C., Malkin M.G., Reed E. et al. Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with reccurent glioma // Mayo Clin. Proc. - 1999. - Vol. 74. - P. 137-145.
Burzynski S.R., Loo T.L., Ho D.H. et al. Biological active peptides in human urine: III. Inhibitors of the growth of human leukemia, osteosarcoma and Hella cells // Physiol. Chem. Phys. - 1976. - Vol. 8. - P. 13-22.
Burzynski S.R., Stolzmann Z., Szopa B. et al. Antineoplaston A. in cancer therapy (I) // Physiol. Chem. Phys. - 1977. - Vol. 9. - P. 485-500.
Burzynski S.R., Kubove T. Toxicology studies on antineoplaston A10 injections in cancer patients // Drugs Exp. Clin. Res. - 1986. - Vol. 12, Suppl. 1. - P. 47-55.
Burzynski S.R. Antineoplastons: history of the research (I) // Drugs Exp. Clin. Res. - 1986. - Vol. 12, Suppl. 1. - P. 1-9.
Burzynski S.R., Burzynski B., Mohabba M.O. Toxicology studies on antineoplaston AS2-1 injections in cancer patients // Drugs Exp. Clin. Res. - 1986. - Vol. 12, Suppl. 1. - P. 25-35.
Burzynski S.R., Mohabbat M.O., Lee S.S. Preclinical studies on antineoplaston AS2-1 and antineoplaston AS2-5 // Drugs Exp. Clin. Res. - 1986. - Vol. 12, Suppl. 1. - P. 11-16.
Burzynski S.R., Kubove E., Burzynski B. Treatment of hormonally refractory cancer of the prostate with antineoplaston AS2-1 // Drugs Exp. Clin. Res. - 1990. - Vol. 16. - P. 361-369.
Burzynski S.R., Lewy R.L., Weaver R.A. et. al. Phase II study of antineoplaston A10 and AS2-1 in patients with recurrent diffuse intrinsic brain steam glioma: a preliminary report // Drugs R.D. - 2003. - Vol. 4. - P. 91-101.
Burzynski S.R. The present state of antineoplaston research (1) // Integr. Cancer Ther. - 2004. - Vol. 3. - P. 47-58.
Burzynski S.R., Weaver R.A., Lewy R.I. et al. Phase II study of antineoplaston A10 and AS2-1 in children with recurrent and progressive multicentric glioma: a preliminary report // Drugs R.D. - 2004. - Vol. 5. - P. 315-326.
Burzynski S.R., Weaver R.A., Janicki T. et al. Long-term survival of high-risk pediatric patients with primitive neuroectodermal tumors treated with antineoplaston A10 and AS2-1 // Integr. Cancer Ther. - 2005. - Vol. 4. - P. 168-177.
Burzynski S.R., Janicki T.J., Weaver R.A., Burzynski B. Targeted therapy with antineoplastons A10 and AS2-1 of high-grade recurrent and progressive brain steam glioma // Integr. Cancer Ther. - 2006. - Vol. 5. - P. 40-47.
Burzynski S.R., Janicki T.J., Burzynski G.S., Marszalek A. Long-term survival (>13 years) in a child with recurrent diffuse pontine gliosarcoma: a case report // J. Pediatr. Hematol. Oncol. - 2013. - (http://www.ncbi.nim.nih.gov/pubmed/24136026).
Fuju T., Nakamura., Yokoyama G. et al. Antineoplaston induces G1 arrest by PKC alfa and MAPK pathway in SKBR-3 breast cancer cells // Oncol. Rep. - 2005. - Vol. 14. - P. 489-494.
Hamer M.R., Jonas W.B. Managing social conflict in complementary and alternative medicine research: the case of antineoplastons // Integr. Cancer Ther. - 2004. - Vol. 3. - P. 59-65.
Harrison L.E., Woiciechovicz D.C., Brennan M.E., Paty P.B. Phenylacetate inhibits isoprenoid biosynthesis and suppresses growth of human pancreatic carcinima // Surgery. - 1998. - Vol. 124. - P. 541-550.
Kumabe T., Tsuda H., Ushida M. et al. Antineoplaston treatment for advanced hepatocellular carcinoma // Oncol. Rep. - 1998. - Vol. 5. - P. 1363-1367.
Lehner A.F., Burzynski S.R., Hedry L.B. 3-phenylacetyl-amino-2,6-piperidinedion; a naturally occuring peptide analogue with apparent antineoplastic activity, may bind to DNA // Drugs Exp. Clin. Res. - 1986. - Vol. 12, Suppl. 1. - P. 57-72.
Liau M.C., Szopa M., Burzynski B., Burzynski S.R. Quantitative assay of plasma and urinary peptides as an aid for evaluation of cancer patients undergoing antineoplaston therapy // Drugs Exp. Clin. Res. - 1987. - Vol. 13, Suppl. 1. - P. 61-70.
Matono K., Ogata Y., Tsuda H. et el. Effects of antneoplaston AS2-1 against post-operative lung metastasis in or-thotopically implanted colon cancer in nude rat // Oncol. Rep. - 2005. - Vol. 13. - P. 389-395.
Michalska D. Theoretical investications on the structure and potential binding sites of antineoplsaston A10 and experimental findings // Drugs Exp. Clin. Res. - 1990. - Vol. 16, Suppl. 1. - P. 343-349.
NCI Drug dictionary, definitions of antineoplastons A10 and AS2-1 // http://cancer.gov/Templates/drugdictionary.aspy?searchTxt=antineoplaston.
Ogata Y., Tsuda H., Matono K. et al. Long-term survival following treatment with antineoplastons for colon cancer with unresectable multiple liver metastases: a report of a case // Surg. Today. - 2003. - Vol. 33. - P. 448 -453.
Ram Z., Samid D., Walbredge S. et al. Growth inhibiton, tumor maturation and extended survival in experimental brain tumors in rats treated with phenylacetate // Cancerf Res. - 1994. - Vol. 54. - P. 2923-2027.
Qu X.J., Cui S.X., Tian Z. et al. Induction of apoptosis in human hepatocellular carcinoma cells by syntetic anti-neoplaston A10 // Anticancer Res. - 2007. - Vol. 27 - P. 2427-2431.
Samid D., Ram Z., Hudgins W.R. et al. Selective activity of phenylacetate against malignant glioma: resemplance to fetal brain damage in phenylketonuria // Cancer Res. - 1994. - Vol. 54. - P. 841-849.
Soltisiak-Pawluczak D., Burzynski S.R. Celleular accumulation of antineoplaston AS2-1 in human hepatoma cells // Cancer Lett. - 1995. - Vol. 88. - P. 107-112.
Sugita Y., Tsuda H., Maruiwa H. et al. The effect of antineoplaston, a new anticancer agent on malignant brain tumors // Kurume Med. J. - 1995. - Vol. 42. - P. 133 -140.
Tsuda H. Inhibitory effect of antineoplaston A10 on breast cancer transplanted to athymic mice and human hepatocellular carcinomsa cell lines. The members of antineoplaston study group // Kurume Med. J. - 1990. - Vol. 37. - P. 97-104.
Tsuda H., Sugihara S., Nishiada H. et al. The inhibitory effect of the combination of antineoplaston A10 injections with small dose of cis-diaminedichloro platinum on cell and tumor growth of human hepatocellular carcinoma // Jpn. J. Cancer Res. - 1992. - Vol. 83. - P. 527-531.
Tsuda H., Hara H., Erigushi N. et al. Toxicological study on antineoplastons A10 and AS2-1 in cancer patients // Kurume Med. J. - 1995. - Vol. 42. - P. 241-249.
Tsuda H., Iemura H., Sata M. et al. Inhibitory effect of antineoplastons A10 and AS2-1 on human hepatocellular carcinoma // Kurume Med. J. - 1996. - Vol. 43. - P. 137-147.
Tsuda H., Sata M., Kumabe T. et al. Qick response of advanced cancer to chemoradiation therapy with antineoplastons // Oncol. Rep. - 1998. - Vol. 5. - P. 597-600.
Tsuda H., Sata M., Kumabe T. et al. The preventive effect of antineoplaston AS2-1 on HCC recurrence // Oncol. Rep. - 2003. - Vol. 10. - P. 391-397.
Ushijima M., Ogata Y., Tsuda H. et al. Demethylation effect of the antineoplaston AS2-1 on genes in colon cancer cells // Oncol. Rep. - 2014. - Vol. 31. - P. 19-26.
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