Evaluation of effect of Ghrelin to patients who undergo surgery for upper gastrointestinal cancers and its clinical appliacation

1为评价Ghrelin对癌细胞增殖的影响，采用四甲基偶氮唑盐比色法，对加入Ghrelin后的食道癌细胞系(TE3、TE8)和胃癌细胞系(MKN-45、Kato-III)进行细胞计数，发现Ghrelin对癌细胞的增殖无明显影响。这一结果证实了Ghrelin用于上消化道肿瘤术后患者的安全性。2我们对3名健康供者给予Ghrelin，同时对3名健康供者在口服营养液后立即给予生理盐水作为对照，并检测血清Ghrelin、生长激素和胰岛素水平及血糖水平。测定13-C醋酸酯呼气试验检测胃排空功能。结果发现，与对照组相比，Ghrelin组随着血清Ghrelin水平的升高，血清生长激素水平显著升高，且Ghrelin组血清胰岛素和血糖升高的速度比对照组更快。格列林组的胃排空时间也明显缩短。这些结果表明，给健康的供者服用Ghrelin可以促进胃排空功能和葡萄糖吸收。3在大阪大学医院伦理委员会批准对胃癌切除患者使用Ghrelin的第二阶段研究后，在2006年8月至2007年3月期间，有10名患者参加了这项研究。术后第5~15天静脉滴注Ghrelin 3μg/kg，每日2次，观察患者的口服摄入量、肠动力、小肠吸收功能及血样生长激素、白蛋白、瘦素等指标的变化。我们计划对从这项研究中获得的患者数据进行详细分析。

1 In order to evaluate the effect of Ghrelin to proliferation of cancer cells, we performed MTT assay and counted the number of cancer cells after adding Ghrelin to culture medium of esophageal cancer cell lines (TE3,TE8) and gastric cancer cell lines (MKN-45,KATO-III), and found that Ghrelin did not affect proliferation of cancer cells. This result confirmed the safety of administering Ghrelin to patients with uppergastrointestinal cancers after surgery.2 We administered Ghrelin to three healthy donors and also did saline as control to three healthy donors immediately after orally taking nutrition liquid (Racol), and examined Ghrelin, growth hormone and insulin levels in serum and blood glucose levels. We also examined gastric emptying function using breath test of measuring 13-C acetate. As a result, we found that serum growth hormone significantly increased as serum Ghrelin increased in Ghrelin group compared with control group and that serum insulin and blood glucose increased more immediately in Ghrelin group than control group. We also found that gastric emptying time shortened in Grhelin group. These results indicated that administrating Ghrelin to healthy donors facilitates gastric emptying function and glucose absorption.3 After a phase II study of administrating Ghrelin to patients who undergo gastrectomy for gastric cancers was approved by the ethics committees at Osaka University Hospital, ten patients were enrolled in this study between August 2006 and March 2007. Ghrelin at a dose of 3μ g/kg were administrated to patients twice a day via drip infusion on days 5 to 15 after surgery, and we evaluated oral intake, intestinal motility, absorption function of small intestine and change of various blood sample data, such as growth hormone, albumin ghrelin and leptin. We plan to analyze patients data obtained from this study in detail.