Neutralization by "antineoplastin" of insulin-activated nitric oxide synthase antibody and its effects in cancers

Abstract

Purpose: The plasma level of nitric oxide (NO), that has been reported to possess various antineoplastic properties, was found to be diminished due to the impairment of insulin-activated nitric oxide synthase (IANOS) as a result of the appearance of a novel antibody (free light chain of IgG, Mr 44 kD) against the enzyme in the circulation in various cancers compared to normal control. Methods: We report here two NO-generating agents, antineoplastin I (a protein, Mr 5000) and antineoplastin II (an inorganic compound), which when applied to the skin of cancer patients were capable of neutralizing the antibody in vivo through the production of NO in the skin cells due to the stimulation of membrane IANOS of these cells and, subsequently, in erythrocytes in the circulation. Results: Neither antineoplastin I nor antineoplastin II itself enters into the circulation but due to the application of these agents on the skin, the NO synthesis in erythrocytes was normalized in these patients through "feedback" activation and amplification of IANOS activity by NO itself. Conclusion: It was found that the resumption of NO synthesis through the neutralization of antibody resulted in favorable modifications of various cancer-associated pathophysiologic consequences.