Neutralization by "antineoplastin" of insulin-activated nitric oxide synthase antibody and its effects in cancers
Asru K Sinha1, Krishnendu Acharya, Sujoy Bhattacharya
1Sinha Institute of Medical Science and Technology, Tamluk, WB, India. asruksinha@yahoo.com
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, M(r) 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, M(r) 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.
Insights
This study introduces novel agents that restore nitric oxide (NO) synthesis in cancer patients by neutralizing an antibody against insulin-activated nitric oxide synthase (IANOS). This restoration normalized NO levels and improved cancer-associated conditions.
Area of Science:
- Biochemistry
- Immunology
- Oncology
Background:
- Plasma nitric oxide (NO) levels are diminished in various cancers due to impaired insulin-activated nitric oxide synthase (IANOS).
- A novel antibody (free light chain of IgG) against IANOS contributes to this impairment in cancer patients compared to healthy individuals.
Purpose of the Study:
- To investigate the efficacy of two novel NO-generating agents, antineoplastin I and antineoplastin II, in neutralizing the anti-IANOS antibody.
- To assess the impact of restored NO synthesis on cancer-associated pathophysiological consequences.
Main Methods:
- Topical application of antineoplastin I (protein) and antineoplastin II (inorganic compound) to the skin of cancer patients.
- Monitoring of NO production in skin cells and erythrocytes, and assessment of IANOS activity.
- Evaluation of cancer-associated pathophysiological modifications.
Main Results:
- Antineoplastins I and II, applied topically, stimulated NO production in skin cells and erythrocytes by neutralizing the anti-IANOS antibody.
- Neither agent entered systemic circulation, yet NO synthesis in erythrocytes was normalized via feedback activation of IANOS by NO.
- The resumption of NO synthesis led to favorable modifications in cancer-associated pathophysiological consequences.
Conclusions:
- Topical application of NO-generating agents can effectively neutralize anti-IANOS antibodies in vivo.
- Restoration of NO synthesis through antibody neutralization offers a potential therapeutic strategy for managing cancer-associated conditions.
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