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肿瘤组织中含硫气体化合物的产生和抑制气体扩散作为抗肿瘤治疗。

Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment.

机构信息

FAP Dental Institute, Tokyo, Japan.

出版信息

Gut. 2012 Apr;61(4):554-61. doi: 10.1136/gutjnl-2011-300721. Epub 2011 Aug 11.

Abstract

BACKGROUND AND AIMS

The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation.

METHODS

Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells.

RESULTS

Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect.

CONCLUSIONS

Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.

摘要

背景与目的

癌细胞生长和转移的机制尚未完全阐明,特别是从肿瘤内化学反应的角度来看。癌细胞中的糖酵解代谢明显加速,导致葡萄糖(还原糖)和蛋氨酸(一种氨基酸)的积累,这两种物质可以非酶促反应形成致癌物质。有推测认为,这种反应会在肿瘤组织中产生含硫气体化合物。本研究旨在阐明肿瘤中的产物,并研究其对肿瘤增殖的影响。

方法

使用气相色谱法在体外分析葡萄糖与蛋氨酸或其代谢物反应形成的产物。使用近边缘 X 射线精细吸收结构光谱法分析结肠癌患者的废气样本和肺癌患者的呼气样本,并与健康个体进行比较。将 HT29 人结肠癌细胞植入的小鼠的肿瘤增殖率与将癌细胞包围在透明质酸钠凝胶中以防止气态物质扩散到健康细胞中的小鼠的肿瘤增殖率进行比较。

结果

当允许葡萄糖与蛋氨酸或其代谢物同型半胱氨酸或半胱氨酸反应时,会产生甲硫醇和硫化氢等含硫气体化合物。近边缘 X 射线精细吸收结构光谱法显示,结肠癌患者废气样本和肺癌患者呼气样本中含硫化合物的浓度明显高于健康个体。动物实验表明,防止含硫化合物的扩散具有明显的抗肿瘤作用。

结论

气态含硫化合物是肿瘤中的主要产物,防止这些化合物的扩散可降低肿瘤增殖率,这提示了一种新的癌症治疗方法的可能性。

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