NIBP在胃癌组织中的表达及其与胃癌发生发展的关系

目的:检测NIBP（NIK and IKKβ binding protein,NIBP）在胃癌组织中的表达水平,探讨其与胃癌发生发展及预后之间的关系。方法:应用免疫组织化学染色法检测组织芯片中123例胃癌和123例相匹配的癌旁良性胃组织中NIBP蛋白的表达水平。结果:胃癌组织中肿瘤细胞NIBP蛋白表达水平明显高于癌旁良性胃组织上皮细胞（P=0.000）,NIBP蛋白在正常胃黏膜和浅表性胃炎、萎缩性胃炎伴肠上皮化生及胃癌组织中的表达水平逐渐升高（P=0.000）。NIBP蛋白表达水平与Lauren分型（P=0.000）、WHO分型（P=0.000）和肿瘤的侵犯深度（P=0.002）显著相关,与年龄、性别、淋巴结转移、远处转移、临床分期无关。生存分析显示NIBP蛋白表达水平与总生存期无明显相关（P=0.552）。结论:NIBP可能参与胃癌的发生发展,在胃炎向胃癌发展的级联过程中发挥重要作用。NIBP可能是胃癌治疗新的潜在的分子靶点。     

结肠癌中NIBP阳性肿瘤浸润免疫细胞的数量与患者预后的关系

目的:分析结肠癌组织肿瘤浸润的免疫细胞NIBP（NIK and IKKβ binding protein,NIBP）的表达水平,探讨其与临床病理学特征和预后之间的关系。方法:应用免疫组织化学染色法,在组织芯片中检测133例结肠癌组织肿瘤浸润的免疫细胞和92例相匹配的癌旁良性结肠组织中免疫细胞NIBP蛋白的表达水平。结果:结肠癌组织肿瘤浸润免疫细胞与癌旁结肠组织黏膜腺体间免疫细胞的NIBP蛋白表达水平无明显差别（P=0.207）。结肠癌组织肿瘤浸润免疫细胞NIBP蛋白表达水平与性别、年龄、肿瘤侵袭深度、淋巴结转移、远处转移、临床分期、组织学类型、组织学分级无关。单因素生存分析显示结肠癌组织肿瘤浸润免疫细胞NIBP蛋白阳性表达较阴性表达者总生存期明显延长（P=0.031）。多因素分析结果表明肿瘤浸润免疫细胞NIBP蛋白表达水平是结肠癌患者独立的预后因素（HR=0.281,95%CI=0.111~0.714,P=0.008）。结论:结肠癌中NIBP阳性肿瘤浸润免疫细胞的数量增加的患者预后较好,NIBP可能是结肠癌免疫治疗新的分子靶点。     

NIBP在结肠癌组织中的表达及临床意义

目的:探讨NIK和IKKβ连接蛋白（NIK and IKKβ binding protein,NIBP）在结肠癌组织中的表达及其与临床病理和预后之间的关系。方法:应用免疫组织化学染色法检测组织芯片中133例结肠癌和92例相匹配的癌旁正常结肠组织中NIBP蛋白的表达水平。结果:结肠癌组织中肿瘤细胞NIBP蛋白表达水平明显高于癌旁正常结肠组织上皮细胞（P=0.000）。NIBP蛋白表达水平与临床分期显著相关（P=0.044）,与性别、年龄、肿瘤侵袭深度、淋巴结转移、远处转移、组织学类型、组织学分级无关。单因素生存分析显示NIBP蛋白高水平表达者较低水平表达者总生存期明显延长（P=0.006）,多因素分析结果表明NIBP蛋白表达水平是结肠癌患者独立的预后因素（HR=0.461,95%CI=0.229-0.925,P=0.029）。结论:NIBP可能参与结肠癌的发生发展,可能是预测结肠癌预后的新的生物学标志物。     

核因子-κB中介的TNF-α与胃癌细胞侵袭力的相关性

目的 探讨肿瘤坏死闪子(TNF-α)诱导胃癌细胞侵袭力的相关机制.方法 体外培养人胃癌细胞株SGC-7901,采用免疫组化方法检测其在TNF-α不同浓度、时间诱导下的NF-κB活性、uPA蛋白表达强度;采用噻唑蓝(MTT)比色法检测SGC-7901细胞在不同浓度的TNF-α、PDTC(吡咯烷二硫代氨基甲酸盐,NF-κB特异性抑制剂)孵育下的细胞增殖情况;构建侵袭小室,检测不同浓度TNF-α对SGC-7901细胞侵袭力影响,并用PDTC预先处理细胞后.检测其对细胞侵袭力的改变.结果 随着TNF-α浓度的增加和时间延长,SGC-7901细胞NF-κB活性明显增强,90 min为高峰;TNF-α明显上调SGC-7901细胞中的uPA蛋白表达水平;一定范围浓度的TNF-α、PDTC对SGC-7901细胞增殖无明显影响;随着TNF-α浓度增加SGC-7901细胞侵袭数也随之增加,具有明显浓度依赖性(TNF-α5、10、20 μg//L vs 0μg/L,84.33±3.786、108.33±6.110、121.330±4.163 vs 63.330±4.933,F=126.282,P＜0.001),PDTC明显抑制TNF-α诱导的SGC-7901细胞侵袭力(42.330±4.041 vs 63.330±4.933,F=126.282,P＜0.05).结论 TNF-α能够增强胃癌细胞的侵袭力,可能是通过NF-κB信号转导路径,激活uPA等蛋白水解酶而实现的.     

喉癌组织中NF-Κb和IκB表达及其意义

目的　探讨NF κB和IκB在喉癌组织中的表达及其意义。方法　采用免疫组织化学染色S P法 ,检测 40例喉癌组织和 2 0例正常喉黏膜组织中NF κBp65和IκBα表达水平。 结果　喉癌组织中NF κBp65表达水平明显高于正常组织 ,IκBα表达水平明显低于正常组织 (P <0 .0 5 )。有颈部淋巴结转移的喉癌组织中NF κB p65表达水平明显较无转移喉癌组织高 ,IκBα表达水平则明显下降 (P <0 .0 5 )。结论　NF κB和IκB在喉癌组织中存在异常表达 ,与喉癌发生、发展及转移有密切的关系 ,抑制NF κB表达可能为喉癌治疗提供了 1个新靶点     

胃癌中FTO表达与TGF-β表达、肿瘤免疫表型的关系及临床意义

目的:分析胃癌组织中FTO表达与TGF-β表达及肿瘤免疫表型的关系及临床意义。方法:采用TIMER数据库分析胃癌组织中FTO和TGF-β mRNA的表达情况。采用GEPIA数据库评估FTO及TGF-β mRNA在胃癌中表达的相关性。利用TIMER数据库分析FTO对胃癌免疫细胞浸润水平的影响。采用免疫组织法检测胃FTO、TGF-β、CD8+T细胞的表达,分析FTO与TGF-β、肿瘤免疫表型的相关性,及其与临床病理特征的关系。结果:胃癌组织中FTO、TGF-β阳性率皆高于癌旁组织(P＜0.05);分析三种免疫表型在胃癌中的表达情况,发现在胃癌组织中以免疫豁免型为主(P＜0.05);在胃癌中,FTO表达水平与TGF-β表达水平、免疫细胞浸润及免疫豁免型呈显著正相关(P＜0.05);FTO表达与淋巴结转移、TNM分期及分化程度密切相关(P＜0.05)。结论:FTO在胃癌中高表达,可影响TGF-β表达水平、免疫细胞浸润水平及肿瘤免疫表型。     

核转录因子κBp65蛋白及其抑制蛋白IκBα表达与食管鳞癌浸润转移的关系

目的:探讨核转录因子κB(NF-κB)p65蛋白及其抑制蛋白IκBα表达与食管鳞癌浸润转移的关系.方法:用免疫组化SP法检测了61例食管鳞癌中NF-κBp65、IκBα蛋白的表达.结果:p65、IκBα蛋白的胞浆表达与食管鳞癌的组织学分级、浸润深度和淋巴结转移无关,但p65蛋白的胞核表达与食管鳞癌的组织学分级、浸润深度和淋巴结转移均呈正相关(P值均＜0.01),IκBα蛋白的胞核表达与食管鳞癌的淋巴结转移有关(P＜0.05).在食管鳞癌中IκBα蛋白的胞浆和胞核阳性率均高于p65蛋白,但差异均无统计学意义,也无相关关系.结论:NF-κBp65蛋白的胞核表达与食管鳞癌的分级、浸润和淋巴结转移有关,IκBα蛋白的胞核表达与食管鳞癌的淋巴结转移有关.     

乳腺癌组织CXCR7及NF-κB表达临床意义研究

目的观察趋化因子CXCL12的特异性受体CXCR7及核转录因子-κB(nuclear factor kappa B,NF-κB)在乳腺癌组织中的表达情况,探讨其与各临床病理指标的意义,研究其与乳腺癌的发生及淋巴结转移的关系。方法收集甘肃省人民医院2003-01-01-2006-01-01手术切除的102例浸润性乳腺癌标本,以癌旁正常组织作为对照组,应用免疫组织化学及荧光定量PCR的方法,检测CXCR7及NF-κB在乳腺癌组织及癌旁正常组织中的表达水平的差异;应用χ2检验比较乳腺癌组织及癌旁正常组织中CXCR7及NF-κB的表达差异,Spearman秩相关分析CXCR7及NF-κB的表达与各临床病理指标之间的相关性。结果荧光定量PCR结果显示,乳腺癌组织CXCR7mRNA的表达水平明显高于癌旁正常组织,P=0.017。免疫组化结果显示,CXCR7在乳腺癌和癌旁正常组织中的表达水平分别为86.3%(88/102)和14.7%(14/102),差异有统计学意义,χ2=28.00,P<0.001;NF-κB在乳腺癌和癌旁正常组织中的表达水平分别为89.2%(91/102)和10.8%(11/102),差异有统计学意义,χ2=22.00,P<0.001。CXCR7和NF-κB的表达水平与患者年龄、分化程度和肿瘤大小等无关,与淋巴结转移有关,P值分别为0.023和0.003;CXCR7及NF-κB的表达水平呈正相关性,r=0.628,P=0.048。结论 CXCR7和NF-κB在乳腺癌组织中具有相关性高表达,在乳腺癌的发生中可能起着重要作用,且与淋巴结的转移存在密切相关,对评估预后具有重要意义。     

肿瘤浸润免疫细胞及其量化分析方法的研究进展

近年来,随着肿瘤微环境（tumor microenvironment,TME）和免疫治疗的研究不断深入,TME 中肿瘤浸润免疫细胞 （tumor infiltrating immune cell,TIC）已成为研究人员关注的热点。对TIC进行量化分析有助于了解免疫系统在人类恶性肿瘤中 的作用及其机制,并对肿瘤免疫治疗提供新的见解和帮助。在传统的肿瘤组织测序分析结果中,基因表达往往忽略了组织中的 细胞组成和类型,因此肿瘤组织中低丰度细胞的基因表达情况会被掩盖。随着分析算法的不断发展,越来越多的工具被开发应 用于分析肿瘤组织中免疫细胞的基因表达情况,实现对肿瘤组织中免疫细胞的成分进行计算和量化。     

分化型甲状腺癌组织中浸润免疫细胞的类型及其与临床特征的关系

目的:探讨分化型甲状腺癌(DTC)组织中浸润免疫细胞的类型,分析其与肿瘤临床病理特征和风险分期的关系.方法:利用TCGA数据库中转录本数据,通过CIBOSORT反卷积法计算22种免疫细胞在DTC组织中的浸润情况,比较DTC组织与正常甲状腺组织之间的免疫细胞差异,并对DTC按照不同临床病理特征和不同肿瘤分期进行分组,比较...     

胃癌组织中血管内皮生长因子C与肿瘤浸润性树突状细胞的相关性

目的: 探讨胃癌组织中血管内皮细胞生长因子C(vascular endothelial growth factorc, VEGFC)与肿瘤浸润性树突状细胞( tumor infiltrating dendritic cells，TIDC)在胃癌浸润转移中的作用及两者的关系。方法：52例胃癌石蜡标本选自重庆医科大学附属第一医院外科2004年9月至     

Study on the Relationship between P-glycoprotein and CD44 Expression in Gastric Carcinoma

Objective： Investigation of the relationship between P-glycoprotein （P-gp） and adhesion molecule CD44 as well as their clinical significance in gastric carcinoma. Methods： To examine the expressed level of P-gp and CD44 in 98 cases with gastric carcinoma by flow eytometry and evaluate their relationships with elinieopathologieal factors. Results： Among the 98 gastric carcinomas, 40 cases （40.8%） were P-gp negative （positive cells 〈25%）; 14 cases （14.2%） were 25%-40% expression of P-gp positive cells; 17 cases （17.3%） were 41%-60% expression of P-gp positive cells; 27 cases （27.5%） were the high expression （positive cells 〉60%） of P-gp in all patients with gastric carcinoma. When the tumor sizes were more than 6 cm, the P-gp positive of CD44 showed a significant difference （P〈0.05） in 35 cases with P-gp positive, compared with it in 24 cases with P-gp negative. When the tumors were in low-moderate differentiated gastric carcinoma, the expression of CD44 showed a significant difference （P〈0.05） in 44 cases with P-gp positive, as compared with it in 30 cases with P-gp negative. When the patients were in clinical Ⅲ-Ⅳ stage, the expression of CD44 showed a significant difference （P〈0.05） in 42 cases with P-gp positive, as compared with it in 30 cases with P-gp negative. When the patients with lymph node metastasis, their CD44 expression showed a significant difference （P〈0.05） in 46 cases with P-gp positive, compared with it in 32 cases with P-gp negative. When the tumors P-gp expressed positive, their CD44 expression will be increase. Conclusion： When the CD44 and P-gp both have the positive high expression, it will be significantly associated with the gastric carcinoma progression and metastasis, so both were a positive expression in gastric carcinoma, it might suggest a poor and unfavorable prognosis result.     

胃癌细胞P-gp与C-erbB-2表达相关性研究

Objective:To understand the relationship between C-erbB-2 and multidrug resistance(MDR)as well as its clinical significance.Methods:P-gp level was detected by flow cytometry and simultaneously to examine the C-erbB-2 expression level by immunohistochemistry assay in the operating samples.Their relationship was analyzed from 59 cases with gastric carcinoma. Results:The P-gp positive expression was 38/59(64.4%)cases with gastric carcinoma.The C-erbB-2 positive expression was 21/59(35.6%)cases with gastric carcinoma From the analysis of the P-gp and C-erbB-2 relationship,which was involving,range in the gastric carcinoma,that involving two or three sites were more than the site one,in the cases with C-erbB-2 negative.Compared this two groups,there was a significant difierence(P=0.026).When the C-erbB-2 was positive,the P-gp expression had a significant difierence(P=0.04)in comparing the Ⅲ-Ⅳ stage(lymph node metastasis)with Ⅰ-Ⅱ stage(without lymph node metastasis).The lumor's size,differentiation degree,ages and sex were not related to the C-erbB-2 and P-gp expression.Conclusion:High level of p-gp expression was related to the C-erbB-2 positive expression in clinical Ⅲ-Ⅳ stage patient with gastric carcinoma (lymph node metastasis).It suggested that the double positive patient might be a poor prognosis.However,when the C-erbB-2 was negative expression,the clinical staging(with lymph node metastasis)was not related to the p-gp expression in gastric carcinoma patients.     

Study on the relationship between P-glycoprotein （P-gp） and C-erbB-2 expression in gastric carcinoma

Objective： To understand the relationship between C-erbB-2 and multidrug resistance （MDR） as well as its clinical significance. Methods： P-gp level was detected by flow cytometry and simultaneously to examine the C-erbB-2 expression level by immunohistochemistry assay in the operating samples. Their relationship was analyzed from 59 cases with gastric carcinoma. Results： The P-gp positive expression was 38/59 （64.4%） cases with gastric carcinoma. The C-erbB-2 positive expression was 21/59 （35.6%） cases with gastric carcinoma. From the analysis of the P-gp and C-erbB-2 relationship, which was involving, range in the gastric carcinoma, that involving two or three sites were more than the site one, in the cases with C-erbB-2 negative. Compared this two groups, there was a significant difference （P = 0.026）. When the C-erbB-2 was positive, the P-gp expression had a significant difference （P = 0.04） in comparing the Ⅲ-Ⅳ stage （lymph node metastasis） with Ⅰ-Ⅱ stage （without lymph node metastasis）. The tumor＇s size, differentiation degree, ages and sex were not related to the C-erbB- 2 and P-gp expression. Conclusion： High level of P-gp expression was related to the C-erbB-2 positive expression in clinical Ⅲ-Ⅳ stage patient with gastric carcinoma （lymph node metastasis）. It suggested that the double positive patient might be a poor prognosis. However, when the C-erbB-2 was negative expression, the clinical staging （with lymph node metastasis） was not related to the P-gp expression in gastric carcinoma patients.     

The prognostic landscape of genes and infiltrating immune cells in cytokine induced killer cell treated-lung squamous cell carcinoma and adenocarcinoma

Objective:Patients with non–small cell lung cancer (NSCLC) respond differently to cytokine-induced killer cell (CIK) treatment. Therefore, potential prognostic markers to identify patients who would benefit from CIK treatment must be elucidated. The current research aimed at identifying predictive prognostic markers for efficient CIK treatment of patients with NSCLC.Methods:Patients histologically diagnosed with NSCLC were enrolled from the Tianjin Medical University Cancer Institute and Hospital. We performed whole-exome sequencing (WES) on the tumor tissues and paired adjacent benign tissues collected from 50 patients with NSCLC, and RNA-seq on tumor tissues of 17 patients with NSCLC before CIK immunotherapy treatment. Multivariate Cox proportional hazard regression analysis was used to analyze the association between clinical parameters and prognostic relevance. WES and RNA-seq data between lung squamous cell carcinoma (SCC) and adenocarcinoma (Aden) were analyzed and compared.Results:The pathology subtype of lung cancer was the most significantly relevant clinical parameter associated with DFS, as analyzed by multivariate Cox proportional hazard regression (P = 0.031). The patients with lung SCC showed better CIK treatment efficacy and extended DFS after CIK treatment. Relatively low expression of HLA class II genes and checkpoint molecules, and less immunosuppressive immune cell infiltration were identified in the patients with lung SCC.Conclusions:Coordinated suppression of the expression of HLA class II genes and checkpoint molecules, as well as less immune suppressive cell infiltration together contributed to the better CIK treatment efficacy in lung SCC than lung Aden.