期刊
CANCER BIOLOGY & THERAPY
卷 12, 期 2, 页码 131-138出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.12.2.15720
关键词
sucrose breath test; mucositis; small intestine; methotrexate; S. thermophilus; DAMA; tumor-model
类别
资金
- Cancer Council South Australia (CCSA)
Preventative or adjunctive agents for the amelioration of small intestinal chemotherapy-induced mucositis are not currently available for clinical use. We have previously demonstrated that oral ingestion of Streptococcus thermophilus (TH-4) partially attenuated chemotherapy-induced mucositis in the rat. Here we assess the effects of TH-4 on small intestinal damage and tumor progression in tumor-bearing rats with experimentally-induced mucositis. Female dark agouti tumor-bearing (mammary adenocarcinoma) rats (n = 36; 139 +/- 1 g) had small intestinal damage induced via the administration of methotrexate (MTX). Rats were administered MTX; (1.5 mg/kg intramuscular) or saline at 0 and 24 h; with daily gavage administration of TH-4 (10(9) cfu/mL) or skim milk from -48 to +96 h post-MTX. Rats were allocated to groups (n = 9): saline control, TH-4 control, MTX control or TH-4+MTX. The non-invasive C-13-sucrose breath test (SBT) was conducted prior to tumor inoculation, pre-MTX (-24 h) and prior to sacrifice (96 h) to monitor gut function. At sacrifice small intestinal segments were excised and assessed for sucrase and myeloperoxidase activity as well as histological damage. Irrespective of TH-4 treatment, MTX-treated rats had a significant decrease in bodyweight, SBT levels, sucrase and myeloperoxidase activity, and histological damage score (p < 0.05) compared to saline and TH-4 control rats. TH-4 treatment did not result in tumor progression (p > 0.05) but failed to alleviate mucositis indices. Although TH-4, at a dose of 10(9) cfu/mL, yielded neither protection nor amelioration of chemotherapy-induced mucositis, progression of mammary adenocarcinoma was unaffected.
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