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

1为了评价Ghrelin对癌细胞增殖的影响，我们将Ghrelin加入食管癌细胞株（TE 3、TE 8）和胃癌细胞株（MKN-45、KATO-Ⅲ）的培养液中，进行MTT法和癌细胞计数，发现Ghrelin对癌细胞的增殖没有影响。这一结果证实了手术后给予上消化道癌症患者Ghrelin的安全性。2我们在口服营养液（Racol）后立即向三名健康供体给予Ghrelin，并向三名健康供体给予生理盐水作为对照，并检查血清中Ghrelin、生长激素和胰岛素水平以及血糖水平。采用呼气试验测定13-C醋酸盐含量，检测胃排空功能。结果发现，与对照组相比，Ghrelin组的血清生长激素随着血清Ghrelin的增加而显著增加，并且Ghrelin组的血清胰岛素和血糖比对照组更迅速地增加。胃排空时间缩短。这些结果表明，向健康供体施用Ghrelin促进胃排空功能和葡萄糖吸收。3在大坂大学医院伦理委员会批准向因胃癌接受胃切除术的患者施用Ghrelin的II期研究后，2006年8月至2007年3月期间有10名患者入组本研究。术后第5 ~ 15天静脉滴注Ghrelin 3μ g/kg，2次/d，观察患者经口进食量、小肠运动、小肠吸收功能及血清生长激素、Ghrelin、瘦素等指标的变化。我们计划详细分析从本研究中获得的患者数据。

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.