The expression of TNFAIP8 in gastric cancer and its clinical significance

目的通过检测胃癌组织中肿瘤坏死因子α诱导蛋白8(TnfAIP8)的表达,探讨其与胃癌临床病理参数的关系及与胃癌发生发展的关系,揭示胃癌的发病机制。方法采用免疫组化SP法,检测50例胃癌以及50例正常胃粘膜中TnfAIP8的表达。结果 50例正常胃粘膜组织中TnfAIP8无表达,而在50例胃癌组织中TnfAIP8阳性表达13例,TnfAIP8阳性率为26%。低分化胃癌组TnfAIP8阳性表达率明显高于中分化腺癌组(P<0.05);Ⅲ期胃癌组TnfAIP8阳性表达率明显高于Ⅱ期胃癌组(P<0.05);有淋巴结转移组TnfAIP8阳性表达明显高于无淋巴结转移组;TnfAIP8在不同性别和年龄的胃癌组织中无差异。结论 TnfAIP8的表达与患者的性别和年龄无关,而与胃癌的组织学分级、胃癌的TnM分期和淋巴结转移有相关性。TnfAIP8在胃癌组织中表达率较正常胃粘膜升高,差异有统计学意义(P<0.05),提示TnfAIP8可能参与了胃癌的发生、发展。Tumor necrosis factor-α induced protein-8(TNFAIP8) is a recently discovered antiapoptotic molecule.Recent data have demonstrated that TNFAIP8 is involved in the regulation of apoptosis,cellular signaling cascade,tumor proliferation and invasion,as well as metastasis.In this study,we aimed to investigate the expression of TNFAIP8 in patients with gastric cancer and their relationships with clinicopathology.We detected the expression of TNFAIP8 in 50 cases of gastric cancer and 50 cases of normal gastric tissues with SP immunohistochemical.In gastric cancer,the expression of TNFAIP8 was located in cytoplasm and/or nucleolus of tumor cells;the expression of TNFAIP8 in patients with gastric cancer(26%) was higher than that in the normal gastric tissues(0%,P﹤0.05).And the expression of TNFAIP8 in poor differentiated adenocarcinoma of gastric was higher compared with that in well differentiated(P < 0.05),the same difference was fund between Ⅲ andⅡ stages of adenocarcinoma.However,the expression of TNFAIP8 was on significant difference among different person with different age and gender.The results suggest that the expression of TNFAIP8 is not related with patient gender or age,but related with the stage of disease.And the expression of TNFAIP8 may be involved in the generation and development of gastric cancer.福建省自然基金(2010D009

多药耐药对肝癌细胞增殖、凋亡、侵袭活性、耐药机制及丝裂原活化蛋白激酶表达的影响

目的:通过化疗药物诱导建立多株人肝癌多药耐药细胞模型,探讨多药耐药获得对细胞增殖、凋亡、侵袭能力的影响,耐药机制及与丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路表达的相关性。方法:采用多柔比星(adriamycin,ADM)高浓度冲击和小剂量缓升2种方法诱导建立人肝癌细胞(HepG2、SMMC-7721和BEL-7402)耐药模型。比较耐药细胞株与亲本细胞株间的差异,主要包括采用生物发光法进行药物敏感实验并计算耐药指数;RT-PCR法和免疫组织化学法检测相关耐药基因(P-糖蛋白、多药耐药相关蛋白1、肺癌耐药蛋白、乳腺癌耐药蛋白、蛋白激酶C、谷胱甘肽-S-转移酶-π和拓扑异构酶Ⅱ)mRNA及相应蛋白的表达。免疫组织化学法检测与细胞增殖活性相关的Ki-67和增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达;FCM法检测细胞周期、细胞凋亡率的改变;Transwell小室法检测细胞体外侵袭能力的改变;最后,分别采用RT-PCR和蛋白质印迹法检测MAPK信号通路中ERK1、ERK2、ERK5、JNK1、JNK2和p38α基因及相应蛋白的表达。结果:共建立6株ADM耐药细胞株;与亲本细胞株相比,耐药细胞株耐药指数均>5,并对多种化疗药耐受性增强,多药耐药相关基因及蛋白的表达均上调2～10倍,以高浓度冲击法诱导的细胞中蛋白表达上调明显。耐药细胞中Ki-67及PCNA蛋白的表达量均升高20倍以上,细胞周期被阻滞在S期,体外侵袭能力增强1.3～2.5倍;ADM干预后,细胞凋亡率减少60%以上。MAPK信号通路中不同基因和蛋白表达量均有不同比例升高,以ERK1、ERK2升高明显。结论:ADM能够诱导多株人肝癌细胞产生多药耐药,导致细胞增殖活性升高、细胞周期改变、抗凋亡能力及侵袭能力增强。MAPK信号通路中相关蛋白表达的上调与细胞多药耐药有一定关系

Mirk/Dyrk1b在上皮性卵巢癌组织中的表达及意义

目的:探讨Mirk/Dryk1b(Minibrain-related kinase/Dual specificity tyrosine-phosphorylation-regulated kinase1B)在卵巢组织中的表达及其临床意义。方法:利用免疫组化检测Mirk/Dyrk1b在30例上皮性卵巢癌、20例上皮性卵巢囊腺瘤、10例正常卵巢组织中的表达。结果:Dyrk1b在上皮性卵巢癌中的表达明显高于上皮性卵巢囊腺瘤及正常卵巢组织(P0.05)。结论:Dyrk1b在上皮性卵巢癌中高表达,提示其可能参与了肿瘤的发生和发展,并有望成为临床早期诊断的肿瘤标志物和新的卵巢癌治疗的靶基因