沙利度胺对胃癌外周血微转移的影响

背景：沙利度胺具有明显抗血管生成作用。前期研究发现较高的胃癌组织和血浆血管内皮生长因子（VEGF）水平能促使胃癌外周血微转移发生以及在远处形成转移灶。目的：探讨沙利度胺对胃癌外周血微转移发生和转归的影响及其可能机制。方法：40例经病理检查确诊的初治胃癌患者随机分为试验组和对照组，每组20例。术前一周准备时间内，试验组口服沙利度胺50mg tid，对照组不予任何干预。分别于试验前后抽取外周血，密度梯度离心分离单个核细胞，以免疫磁珠分选技术（抗CD45抗体阴性分选和Ber-EP4阳性分选）结合形态学观察检测外周血微转移，ELISA方法检测血浆VEGF水平。结果：试验组与对照组问胃癌病理学特征以及试验前外周血微转移率和血浆VEGF水平无明显差异。试验后，对照组外周血微转移率和血浆VEGF水平较试验前显著增高90．0％对50．0％，P〈0．05；（14．89±3．36）pg/mL对（8．28±1．63）pg/mL，P〈0．05]，试验组则较试验前显著降低10．0％对45．0％，P〈0．05；（4．13±1．08）pg／mL对（8．11±1．69）pg/mL，P〈0．05]，且显著低于对照组试验后（P〈0．05）。外周血微转移率与血浆VEGF水平呈正相关（r=0．602，P〈0．05）。结论：沙利度胺可能通过降低血浆VEGF水平延缓甚至逆转胃癌外周血微转移的发生。

Effect of Thalidomide on Peripheral Blood Micrometastasis of Gastric Cancer

Background:Thalidomide has notable antiangiogenic effect.Preliminary study showed that high cancer tissue and plasma levels of vascular endothelial growth factor(VEGF) promoted the occurrence of peripheral blood micrometastasis and formation of distant metastasis in gastric cancer.Aims:To investigate the effect of thalidomide on occurrence of peripheral blood micrometastasis in gastric cancer and its outcome and possible mechanism.Methods:Forty initially treated gastric cancer patients proved by pathology were randomized into intervention group(n= 20) and control group(n = 20).Patients in intervention group received thalidomide 50 mg tid orally in one week period for preparation prior to surgery,while those in control group did not take any medicine.Peripheral blood samples were obtained before and after intervention,the mononuclear cells were isolated by density gradient centrifugation and then sorted by immunomagnetic beads sorting technique(including depletion of mononuclear cells with anti-leukocyte antibody CD45 and positive selection of epithelial cells with antiepithelial antibody Ber-EP4) and examined by light microscope for detection of peripheral blood micrometastasis.ELISA was used to determine the plasma level of VEGF.Results:Pathological characteristics of gastric cancer,as well as baseline peripheral blood micrometastasis rate and plasma VEGF level in intervention group were comparable to those in control group.After one week intervention,the peripheral blood micrometastasis rate and plasma VEGF level increased significantly in control group90.0%vs.50.0%,P<0.05;(14.89±3.36) pg/mL vs.(8.28±1.63) pg/mL,P<0.05],while decreased significantly in intervention group10.0%vs.45.0%,P <0.05;(4.13±1.08) pg/mL vs.(8.11±1.69) pg/mL,P <0.05];significant differences were also seen between intervention group and control group after intervention(P <0.05).A positive correlation was found between peripheral blood micrometastasis rate and plasma VEGF level(r = 0.602,P < 0.05).Conclusions;Thalidomide may delay and even reverse the occurrence of peripheral blood micrometastasis of gastric cancer by lowering the plasma VEGF level.