Centre for Paediatric and Adolescent Gastroenterology, Children, Youth and Women's Health Service (CYWHS), North Adelaide, Adelaide, Australia.
Cancer Biol Ther. 2011 Jul 15;12(2):131-8. doi: 10.4161/cbt.12.2.15720.
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 (109 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 ( 13) C-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 109 cfu/mL, yielded neither protection nor amelioration of chemotherapy-induced mucositis, progression of mammary adenocarcinoma was unaffected.
目前尚无可用于临床的预防或辅助药物来改善小肠化疗引起的黏膜炎。我们之前已经证明,口服嗜热链球菌(TH-4)可以部分减轻大鼠化疗引起的黏膜炎。在这里,我们评估了 TH-4 对实验性诱导黏膜炎的荷瘤大鼠小肠损伤和肿瘤进展的影响。雌性黑毛大鼠(乳腺腺癌)荷瘤(n=36;139±1g)通过给予甲氨蝶呤(MTX)诱导小肠损伤。大鼠给予 MTX;(1.5mg/kg 肌肉注射)或 0 和 24 小时时给予生理盐水;在 MTX 后 -48 至+96 小时给予每日灌胃 TH-4(109cfu/mL)或脱脂牛奶。大鼠被分配到以下组(n=9):生理盐水对照组、TH-4 对照组、MTX 对照组或 TH-4+MTX 组。在肿瘤接种前、MTX 前(-24 小时)和处死前(96 小时)进行非侵入性(13)C-蔗糖呼吸试验(SBT),以监测肠道功能。处死时,切除小肠段,评估蔗糖酶和髓过氧化物酶活性以及组织学损伤。无论是否给予 TH-4 治疗,与生理盐水和 TH-4 对照组大鼠相比,MTX 治疗的大鼠体重、SBT 水平、蔗糖酶和髓过氧化物酶活性以及组织学损伤评分均显著下降(p<0.05)。TH-4 治疗并未导致肿瘤进展(p>0.05),但未能缓解黏膜炎指数。尽管 TH-4 剂量为 109cfu/mL,既不能预防也不能缓解化疗引起的黏膜炎,但乳腺腺癌的进展没有受到影响。