Department of Gastroenterology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Int J Colorectal Dis. 2011 May;26(5):575-82. doi: 10.1007/s00384-010-1127-y. Epub 2011 Jan 18.
BACKGROUND/AIM: In order to define future chemoprevention strategies for adenomas or carcinomas in the pouch of patients with familial adenomatous polyposis (FAP), a 4-weeks intervention with (1) sulindac, (2) inulin/VSL#3, and (3) sulindac/inulin/VSL#3 was performed on 17 patients with FAP in a single center intervention study. Primary endpoints were the risk parameters cell proliferation and glutathione S-transferase (GST) detoxification capacity in the pouch mucosa; secondary endpoints were the short chain fatty acid (SCFA) contents, pH, and cytotoxicity of fecal water.
Before the start and at the end of each 4-week intervention period, six biopsies of the pouch were taken and feces was collected during 24 h. Cell proliferation and GST enzyme activity was assessed in the biopsies and pH, SCFA contents, and cytotoxicity were assessed in the fecal water fraction. The three interventions (sulindac, inulin/VSL#3, sulindac/inulin/VSL#3) were compared with the Mann-Whitney U test.
Cell proliferation was lower after sulindac or VSL#3/inulin, the combination treatment with sulindac/inulin/VSL#3 showed the opposite. GST enzyme activity was increased after sulindac or VSL#3/inulin, the combination treatment showed the opposite effect. However, no significance was reached in all these measures. Cytotoxicity, pH, and SCFA content of fecal water showed no differences at all among the three treatment groups.
Our study revealed non-significant decreased cell proliferation and increased detoxification capacity after treatment with sulindac or VSL#3/inulin; however, combining both regimens did not show an additional effect.
背景/目的:为了确定家族性腺瘤性息肉病(FAP)患者的 pouch 中腺瘤或癌的未来化学预防策略,在一项单中心干预研究中,对 17 名 FAP 患者进行了为期 4 周的干预,干预措施包括(1)舒林酸、(2)菊粉/VSL#3 和(3)舒林酸/菊粉/VSL#3。主要终点是 pouch 黏膜中的细胞增殖和谷胱甘肽 S-转移酶(GST)解毒能力的风险参数;次要终点是粪便水中的短链脂肪酸(SCFA)含量、pH 值和细胞毒性。
在每个 4 周干预期开始前和结束时,从 pouch 中采集 6 个活检样本,并在 24 小时内收集粪便。在活检中评估细胞增殖和 GST 酶活性,并在粪便水部分评估 pH 值、SCFA 含量和细胞毒性。将三种干预措施(舒林酸、菊粉/VSL#3、舒林酸/菊粉/VSL#3)与 Mann-Whitney U 检验进行比较。
舒林酸或 VSL#3/菊粉治疗后细胞增殖降低,舒林酸/菊粉/VSL#3 联合治疗则相反。舒林酸或 VSL#3/菊粉治疗后 GST 酶活性增加,联合治疗则相反。然而,所有这些措施都没有达到显著性。粪便水中的细胞毒性、pH 值和 SCFA 含量在三组治疗中均无差异。
我们的研究表明,舒林酸或 VSL#3/菊粉治疗后细胞增殖减少和解毒能力增加,但联合两种方案并未显示出额外的效果。