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

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.

Improvement of FR901379 production by mutant selection and medium optimization.

FR901379 (WF11899A) is a novel echinocandin type of lipopeptide antibiotic produced by Coleophoma empetri F-11899. Micafungin (FK463) is derived from the chemical modification of deacylated FR901379. In the present paper, we performed seven generation's strain-breeding, beginning with a wild type, was performed. Selection medium for screening and production medium for high FR901379 production were designed. Sodium chloride content in the selection plate was affected to FR901379 production and shrinkage of the colony size was observed in high producing strains. As selection markers, large colony-shrinking rate and large inhibition circle in the agar-piece method using C. albicans was selected. Using CMA medium with high sodium chloride, 3 mutants, M-1 to M-3, have achieved a high FR901379 production and M-3 showed 5.0 U/mL, while 1.0 U/mL of production was achieved in wild type strain. A-2 medium supplemented with 6% of soluble starch as a carbon source and 0.6% of ammonium sulfate as nitrogen source was also further effective for mutant screening. The FR901379 production of mutant M-4 (fourth generation) increased until 16.0 U/mL. The concentration of the phosphate salt in the medium seemed to inhibit the growth so as to extend the culture period. When the A-3 medium supplemented with low concentration of phosphate salt and magnesium sulfate as a sulfate source was designed and used, mutants with improved production were successively obtained. Finally, variant strain M-7 showed 30.0 U/mL of production, which was about 30 times higher than that of the wild strain.

Confirmation of the antispasmodic effect of shakuyaku-kanzo-to (TJ-68), a Chinese herbal medicine, on the duodenal wall by direct spraying during endoscopic retrograde cholangiopancreatography.

The purpose of the study was to evaluate the suppressive effect of TJ-68 on duodenal spasms during endoscopic retrograde cholangiopancreatography (ERCP). At the point when the duodenal papilla was confirmed after insertion of the endoscope during ERCP, 5.0 g TJ-68 (Tsumura Co., Tokyo, Japan) was dissolved in 50 ml of saline at 36 degrees C, and the whole volume was sprayed slowly using a spray tube from the orifice of the forceps to the duodenal papilla of the 50 patients who demonstrated peristalsis of the digestive tract ("duodenal spasm"). The endoscopic procedure was not performed during that time, and the time until the spasm was suppressed was determined. After the arrest of the spasm, the intended tests and treatment were conducted, and the time until the duodenal spasm started again was determined. The suppressive effect on duodenal spasm was observed in 38 (76%) of 50 patients. The duration from the spraying of TJ-68 of the patients who observed the suppressive effect on duodenal spasm was 50-182 s (mean 122 +/- 21 s). The spasm arrest duration was 7.2-21 min (mean 9.6 +/- 1.2 min). Direct spraying of TJ-68 on the duodenal mucosa suppressed duodenal spasm, and it may be useful during ERCP when anticholinergic agents are contraindicated.