Sinha Asru K, Acharya Krishnendu, Bhattacharya Sujoy, Patra Sharmistha Chakraborty, Guha Manti, Ray Udayan, Ray Shyamali Basu, Khan Gausal A, Chakraborty Kushal, Biswas Jaydip, Mazumdar Sahana
Sinha Institute of Medical Science and Technology, Tamluk, WB, India.
J Cancer Res Clin Oncol. 2002 Dec;128(12):659-68. doi: 10.1007/s00432-002-0376-8. Epub 2002 Nov 12.
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.
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.
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.
It was found that the resumption of NO synthesis through the neutralization of antibody resulted in favorable modifications of various cancer-associated pathophysiologic consequences.
据报道,一氧化氮(NO)具有多种抗肿瘤特性,但在多种癌症患者的循环系统中,由于一种新型抗体(IgG的游离轻链,分子量44kD)的出现,胰岛素激活型一氧化氮合酶(IANOS)受损,导致血浆中NO水平降低。与正常对照组相比,该抗体可对抗IANOS。
我们在此报告两种NO生成剂,抗肿瘤素I(一种蛋白质,分子量5000)和抗肿瘤素II(一种无机化合物),当将它们应用于癌症患者的皮肤时,能够通过刺激这些细胞的膜IANOS,随后在循环中的红细胞中产生NO,从而在体内中和抗体。
抗肿瘤素I和抗肿瘤素II本身均不会进入循环系统,但由于将这些试剂应用于皮肤,通过NO自身对IANOS活性的“反馈”激活和放大作用,这些患者红细胞中的NO合成得以恢复正常。
研究发现,通过中和抗体恢复NO合成可对各种癌症相关的病理生理后果产生有利的改变。