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


CONCLUSIONS
It was found that the resumption of NO synthesis through the neutralization of antibody resulted in favorable modifications of various cancer-associated pathophysiologic consequences.
Sinha
Asru K
AK
Sinha Institute of Medical Science and Technology, Tamluk, WB, India. asruksinha@yahoo.com
Acharya
Krishnendu
K
Bhattacharya
Sujoy
S
Patra
Sharmistha Chakraborty
SC
Guha
Manti
M
Ray
Udayan
U
Ray
Shyamali Basu
SB
Khan
Gausal A
GA
Chakraborty
Kushal
K
Biswas
Jaydip
J
Mazumdar
Sahana
S
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000276:immunology* / Q000627:therapeutic use*; D004789:Enzyme Activation; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006801:Humans; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000145:classification / Q000188:drug therapy / Q000276:immunology*; D009500:Neutralization Tests; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000276:immunology*; D010919:Placebos; D011506:Proteins / Q000502:physiology*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007328:Insulin; D010919:Placebos; D011506:Proteins; C472927:antineoplastin I; D019001:Nitric Oxide Synthase