TM9SF1 is implicated in promoting the proliferation and invasion of bladder cancer cells

Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth,movement,invasion,and cell cycle advancement.Their results show that TM9SF1 can boost the growth,movement,and invasion of BC cells and their access into the G2/M stage of the cell cycle.This research gives a novel direction and concept for targeted therapy of BC.

TM9SF1 promotes bladder cancer cell growth and infiltration

BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.

Understanding the role of transmembrane 9 superfamily member 1 in bladder cancer pathogenesis

In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein in bladder cancer(BC)carcinogenesis.Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines.These cell lines were then subject to cell counting kit 8,wound-healing assay,transwell assay,and flow cytometry.Proliferation,migration,and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression.TM9SF1 silencing inhibited proliferation,migration and invasion of BC cells.The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.

Erdafitinib and checkpoint inhibitors for first-line and second-line immunotherapy of hepatic,gastrointestinal,and urinary bladder carcinomas:Recent concept

Cancer immunotherapy is administered for first-line,second-line,neoadjuvant,or adjuvant treatment of advanced,metastatic,and recurrent cancer in the liver,gastrointestinal tract,and genitourinary tract,and other solid tumors.Erdafitinib is a fibroblast growth factor receptor(FGFR)inhibitor,and it is an adenosine triphosphate competitive inhibitor of FGFR1,FGFR2,FGFR3,and FGFR4.Immune checkpoint inhibitors are monoclonal antibodies that block programmed cell death protein 1(PD-1)and its ligand that exert intrinsic antitumor mechanisms.The promising results of first-line treatment of advanced and metastatic urothelial carcinoma with PD-1 blockades with single or combined agents,indicate a new concept in the treatment of advanced,metastatic,and recurrent hepatic and gastrointestinal carcinomas.Cancer immunotherapy as first-line treatment will improve overall survival and provide better quality of life.Debate is arising as to whether to apply the cancer immunotherapy as first-line treatment in invasive carcinomas,or as second-line treatment in recurrent or metastatic carcinoma following the standard chemotherapy.The literature in the field is not definite,and so far,there has been no consensus on the best approach in this situation.At present,as it is described in this editorial,the decision is applied on a case-by-case basis.

Expression and significance of B7-H1 in peripheral blood dendritic cells from patients with bladder cancer

Objective： The aim of this study was to study the expression and the clinical significance of B7-H1 on dendritic cells （DCs） in peripheral blood from patients with bladder cancer. Methods： Peripheral blood mononuclear cell were disparted from 30 bladder cancer patients and 7 healthy controls by density gradient centfifugation and then co-cultured. The expres- sion of B7-H1 on DCs were analyzed by flow cytometry. Results： Expression of BT-H1 on DCs in bladder cancer was higher than healthy controls （P 〈 0.01）. And the expression were strongly associated with the pathological grade and clinical stage of bladder cancer （P 〈 0,05）. Conclusion： The up-regulation of B7-H1 on DCs was strongly associated with neoplastic progres-sion of bladder cancer. B7-H1/programmed death （PD）-1 signal pathway may also play an important role in immune escape of bladder cancer during initial phase of T cell immune response.

Procaine Inhibiting Human Bladder Cancer Cell Proliferation by Inducing Apoptosis and Demethylating APAF1 CpG Island Hypermethylated

Studies have shown that aberrant DNA methylation of apoptotic protease activating factor-1（APAF1） is an important epigenetic mechanism of gene regulation in the progression of bladder cancer.In this article,we have proved that procaine,an inhibitor of DNA methyltransferases,could inhibit the proliferation of T24 and 5637 human bladder cancer cells by inducing their apoptosis.The mechanism studies reveal that procaine could induce demethylation of APAF1 gene in T24 or 5637 cells,subsequently activating caspase-3/9.It was also shown that the serum soluble fas ligand（sFasL） was activated,and the expression of matrix metallopeptidase 9（MMP-9） was down-regulated.Procaine seems to induce cell death by different pathways,and it might be used as a potential agent for bladder cancer treatment.

SDF-1/CXCR4 expression in bladder cancer tissue and the correlation with negative costimulatory molecule PD-L1, cell apoptosis and invasion

Objective:To study the SDF-1/CXCR4 expression in bladder cancer tissue and the correlation with negative costimulatory molecule PD-L1, cell apoptosis and invasion.Methods: A total of 118 cases of bladder cancer tissue and para-carcinoma tissue surgically removed in our hospital between May 2014 and May 2016 were selected as the research samples, the RNA was extracted and then reverse-transcribed into cDNA, and the expression levels of SDF-1/CXCR4, PD-L1/PD-1, cell apoptosis-related molecules and cell invasion-related molecules were detected.Results: SDF-1 and CXCR4 mRNA expression in bladder cancer tissue were significantly higher than those in para-carcinoma tissue;PD-L1, PD-1, Rec1, Survivin, MRPS5, Nanog, BCAPP2Ac, TRPM8, TRPV2, ILK,β-catenin and GUGBP1 mRNA expression in bladder cancer tissue were significantly higher than those in para-carcinoma tissue and positively correlated with SDF-1 and CXCR4 mRNA expression.Conclusion:Highly expressed SDF-1/CXCR4 in bladder cancer tissue are closely related to the high expression of negative costimulatory molecule PD-L1, pro-proliferation molecules and pro-invasion molecules, and SDF-1/CXCR4 can promote the immune escape, proliferation and invasion of bladder cancer cells.

自然杀伤细胞2组成员A、程序性死亡因子配体1表达检测对PD-L1阻断免疫治疗肌层浸润性膀胱癌反应性的预测价值

目的:探究自然杀伤细胞2组成员A(NKG2A)及程序性死亡因子配体1(PD-L1)表达检测对PD-L1阻断免疫治疗肌层浸润性膀胱癌反应性的预测价值。方法:选取100例肌层浸润性膀胱癌患者作为研究对象,对其行PD-L1阻断免疫治疗后,根据治疗反应性将其分为缓解组和未缓解组;对缓解组患者随访3个月,将其分为复发组和未复发组。比较两组患者NKG2A和PD-L1在CD4^(+)和CD8^(+)上的表达水平,采用ROC曲线分析NKG2A和PD-L1预测膀胱癌患者治疗反应性的价值。结果:100例研究对象中,缓解组患者72例(72.00%),未缓解组患者28例(28.00%),两组性别、年龄比较无统计学差异(均P>0.05),但缓解组患者肿瘤直径小于未缓解组,NKG2A、PD-L1/CD4^(+)和PD-L1/CD8^(+)表达水平均低于未缓解组(均P<0.05)。膀胱癌患者NKG2A、PD-L1/CD4^(+)和PD-L1/CD8^(+)表达预测免疫治疗后缓解的AUC值分别为0.771、0.724、0.710;联合诊断的AUC为0.836。72例缓解患者中,出现复发29例(40.28%),未出现复发43例(59.72%),两组性别、年龄以及肿瘤直径比较无统计学差异(均P>0.05),但复发组NKG2A、PD-L1/CD4^(+)和PD-L1/CD8^(+)表达水平均高于未复发组(均P<0.05)。NKG2A、PD-L1/CD4^(+)和PD-L1/CD8^(+)表达预测膀胱癌患者缓解后复发的AUC值分别为0.775、0.740、0.728;联合诊断的AUC为0.874。结论:NKG2A、PD-L1/CD4^(+)和PD-L1/CD8^(+)在不同治疗反应性肌层浸润性膀胱癌患者外周血中表达水平不同,三者对于膀胱癌患者PD-L1阻断免疫治疗反应性均有一定的预测价值,且三者联合预测效能最佳。

PD1/PD-L1、中性粒细胞弹性蛋白酶、赖氨酰氧化酶在膀胱癌中的表达及其与膀胱癌预后的关系

目的探讨膀胱癌组织中程序性细胞死亡受体1(PD1)、程序性细胞死亡配体1(PD-L1)、中性粒细胞弹性蛋白酶(NE)、赖氨酰氧化酶(LOX)的表达水平及其表达差异与膀胱癌患者临床病理特征和预后的关系。方法选取2018年1月至2020年12月江西省人民医院收治的56例膀胱癌患者的癌组织作为研究对象,并记录患者的复发和死亡情况进行分析研究。采用免疫组织化学染色法检测PD1、PD-L1、NE、LOX的表达情况,分析PD1、PD-L1、NE、LOX与患者的病理特征和预后的关系。结果免疫组化结果显示PD1在肿瘤相关免疫细胞中存在表达(46/56);TNM分期T2-T3期、高级别肿瘤和出现淋巴结转移的患者PD1和PDL-1的表达阳性率均明显升高,差异有统计学意义(P<0.05)。NE与PD1、PDL-1的表达呈正相关(P<0.05);LOX与PD-L1、PDL-1的表达呈正相关(P<0.05)。PD1阳性表达患者3年无进展生存率为58.70%(27/46),PD-L1阳性表达患者3年无进展生存率为43.48%(10/23),不同PD1、PD-L1表达患者的3年无进展生存率比较差异有统计学意义(P<0.05)。结论膀胱癌组织中PD1、PD-L1表达增加可作为膀胱癌患者潜在的预后预测指标,有助于筛选术后复发的高危患者,并为膀胱癌的免疫学治疗提供新靶点。

术前血清sTim-3、HMGB1水平与肌层浸润性膀胱癌根治术后预后的关系

目的探讨术前血清可溶性T细胞免疫球蛋白黏蛋白分子-3(sTim-3)、高迁移率族蛋白B1(HMGB1)水平与肌层浸润性膀胱癌(MIBC)根治术后预后的关系。方法选取2019年6月至2020年6月该院收治的85例MIBC患者作为MIBC组,另选取同期在该院体检的85例健康者作为对照组。采用酶联免疫吸附试验(ELISA)检测所有受试者血清sTim-3、HMGB1水平;根据血清sTim-3、HMGB1水平均值将MIBC患者分为sTim-3高表达组(≥均值)和sTim-3低表达组(<均值)、HMGB1高表达组(≥均值)和HMGB1低表达组(<均值)。对比各组血清sTim-3、HMGB1水平,以及不同sTim-3、HMGB1水平与MIBC患者病理特征的关系。采用Pearson相关分析MIBC患者血清sTim-3水平与血清HMGB1水平的相关性;采用Kaplan-Meier生存曲线分析不同血清sTim-3、HMGB1水平MIBC患者的生存预后情况。结果MIBC组患者血清sTim-3、HMGB1水平高于对照组(P<0.05)。Pearson相关性分析结果显示,MIBC组患者血清sTim-3水平与血清HMGB1水平呈正相关(r=0.405,P<0.001)。不同年龄、性别、肿瘤最大径及是否发生淋巴结转移MIBC患者的血清sTim-3、HMGB1水平比较,差异均无统计学意义(P>0.05),而不同TNM分期、组织分级、淋巴结状态MIBC患者的血清sTim-3、HMGB1水平比较,差异均有统计学意义(P<0.05)。根据血清sTim-3、HMGB1水平的均值将85例MIBC患者分为sTim-3高表达组(≥3.67 ng/mL,n=44)和sTim-3低表达组(<3.67 ng/mL,n=41)、HMGB1高表达组(≥14.91 ng/mL,n=47)和HMGB1低表达组(<14.91 ng/mL,n=38)。Kaplan-Meier生存曲线结果显示,sTim-3低表达组患者的3年生存曲线高于sTim-3高表达组患者(Log-rankχ^(2)=6.175,P=0.013),HMGB1低表达组患者的3年生存曲线高于HMGB1高表达组患者(Log-rankχ^(2)=4.056,P=0.044)。sTim-3高表达组与sTim-3低表达组MIBC患者的3年生存率分别为52.27%、78.05%,HMGB1高表达组与HMGB1低表达组MIBC患者3年生存率分别为55.32%、76.31%。结论血清sTim-3、HMGB1在MIBC患者中呈高表达,且二者水平呈正相关,可作为评估MIBC患者预后不良的重要指标。

TRPV1及其激动剂辣椒素在膀胱癌中的作用

瞬时受体电位香草酸受体1(TRPV1)是物理和化学刺激的外周感受器,在痛觉感知中发挥关键作用。作为一种非选择性阳离子通道,TRPV1可以调节钙离子内流而影响细胞功能,参与体内多种生理病理功能调节。 TRPV1与多种肿瘤相关,在膀胱癌细胞系中的表达随着恶性程度增高而降低,在膀胱癌组织中的表达随着临床分期分级增高而降低,并且与患者预后相关。TRPV1激动剂辣椒素是辣椒属植物中存在的一种天然物质,具有镇痛等作用。近年来发现辣椒素在体外实验中对包括膀胱癌在内的多种肿瘤细胞具有抑制作用,但其具体机制仍不明确。

Potential of metastin and metastin receptor as biomarkers for urological cancers

AIM: To investigate the current state of the research of metastin and metastin receptor in the urological cancer field.METHODS: For analyzing the value of metastin and metastin receptor as molecular biomarkers for the patients with urological cancer, MEDLINE database searches were performed using these terms: metastin, KISS1, kisspeptin, renal(cell) carcinoma(RCC), kidney cancer or urothelial cancer or bladder cancer or prostate cancer or testicular cancer(tumor). Since the articles were evaluated by the validity of the articlesbased on plausibility, credibility, and evidence levels, the articles were graded according to their level of evidence, using the grading system defined by the Oxford Centre for Evidence-based Medicine. RESULTS: A total of six clinical studies published by individual institutions between 2003 and 2013 were included in this review. The article numbers for each of the evidence levels 2a and 2b were three(50%) and three(50%), respectively. Immunohistochemistry and reverse transcriptase-polymerase chain reaction using tumor tissues were performed to analyze in five articles(83%) and in one article(17%). The value of metastin and/or metastin receptor as molecular biomarkers in clear cell RCC, upper tract urothelial carcinoma, and bladder cancer was evaluated by multivariate analysis. Low expression of metastin receptor in clear cell RCC and low expression of metastin in upper tract urothelial carcinoma were significant risk factors for metastasis, and low metastin expression was an independent prognostic factor in bladder cancer. CONCLUSION: Metastin and metastin receptor have potential as suitable molecular biomarkers for urological cancers. However, future studies of metastin and metastin receptor should undergo external validation to ensure consistency across different patient series, since individual institutional studies lack generalization.

层粘连蛋白γ1基因沉默对膀胱癌细胞增殖及细胞周期的影响

目的探讨层粘连蛋白γ1(LAMC1)在膀胱癌细胞中的表达情况,以及沉默LAMC1基因表达对膀胱癌细胞增殖和细胞周期的影响。方法选取河北省邯郸市中心医院2019年1月至2021年12月收治的48例膀胱癌患者的癌及癌旁组织。采用RT-qPCR法检测UMUC3、T24、5637及J82细胞中LAMC1的m RNA表达水平。将LAMC1-si RNA质粒转染至5637细胞中,设置LAMC1沉默组和阴性对照组,RT-qPCR和Western blot验证转染效率;采用CCK-8法、克隆形成实验、流式细胞术检测LAMC1基因沉默对膀胱癌细胞增殖、克隆形成能力及细胞周期的影响,Western blot检测细胞周期相关蛋白cyclin A、cyclin D1、p16和p21的表达水平。结果5637细胞中LAMC1 m RNA表达水平较UMUC3、T24、J82细胞高(P<0.05)。癌旁组织与膀胱癌组织中LAMC1阳性表达率比较,差异无统计学意义(P>0.05)。LAMC1沉默组中LAMC1 m RNA和蛋白表达水平低于阴性对照组(P<0.01)。LAMC1沉默组中细胞增殖活力和克隆形成能力低于阴性对照组(P<0.01)。LAMC1沉默组中细胞中S期细胞所占百分比低于阴性对照组(P<0.01),G1期细胞所占百分比高于阴性对照组(P<0.01)。LAMC1沉默组中的cyclin D1和cyclin A蛋白的表达水平低于阴性对照组(P<0.01),而p16和p21蛋白的表达水平高于阴性对照组(P<0.01)。结论沉默LAMC1基因表达能够抑制细胞周期相关蛋白的表达从而抑制膀胱癌5637细胞增殖能力,提示其可能是膀胱癌潜在的治疗靶点。

长链非编码RNA PlncRNA-1与肿瘤发生发展的相关性

随着对长链非编码RNA PlncRNA-1研究的深入,逐渐明确了PlncRNA-1在肿瘤发生发展中的作用。在前列腺癌中,PlncRNA-1可以通过雄激素受体(androgen receptor,AR)、人表皮生长因子受体-2(human epidermal growth factor receptor 2,Her-2)、转化生长因子-β1(human transforming growth factor beta-1,TGF-β1)、磷酸酯酶与张力蛋白同源物(phosphatase and tensin homolog,PTEN)等途径发挥癌基因作用。在其他癌症中,PlncRNA-1还可以通过调控细胞周期、上皮间充质转化(epithelial-mesenchymal transition,EMT)等途径,增强细胞增殖、侵袭、转移能力,抑制细胞凋亡,并且还能够在一定程度上预测肿瘤分期及患者预后。因此,PlncRNA-1有望成为癌症生物标志物和治疗靶标。本文对目前PlncRNA-1在相关癌症中的作用及机制进行综述,讨论其在癌症的发生发展中的重要作用。

外周血免疫细胞对PD-1单抗治疗晚期膀胱尿路上皮癌疗效的预测作用

目的探讨晚期膀胱尿路上皮癌(urothelial bladder cancer,UBC)患者外周血免疫细胞数量对程序性死亡受体1(programmed cell death protein 1,PD-1)单抗治疗的疗效预测作用。方法回顾性分析2017年8月至2021年4月复旦大学附属中山医院接受PD-1单抗治疗的晚期UBC患者86例。收集患者临床信息、外周血免疫细胞数据及肿瘤组织PD-1/程序性死亡配体1(programmed cell death ligand 1,PD-L1)表达情况,并分析这些指标与患者生存及对PD-1单抗治疗客观反应率(objective response rate,ORR)的影响。结果TNM分期早(P=0.02)、外周血NK细胞数量高(P=0.009)、CD4^(+)T细胞占总T细胞比例高(CD4^(+)T%,P=0.009)及B淋巴细胞数量高(P=0.038)是晚期UBC患者总体生存期(overall survival,OS)良好的独立预后因子。TNM分期早(P<0.001)、外周血NK细胞水平高(P=0.043)及B淋巴细胞水平高(P=0.027)是晚期UBC患者无进展生存期(progression free survival,PFS)良好的独立预后因子。外周血B淋巴细胞数量高(P=0.011)、CD4^(+)T%高(P=0.041)和总淋巴细胞数量高(P<0.001)的患者对PD-1单抗治疗有更高的ORR。结论晚期UBC患者外周血NK细胞、B淋巴细胞及CD4^(+)T细胞可能在晚期UBC抗肿瘤免疫中发挥重要作用。患者外周血B淋巴细胞数量、CD4^(+)T%和总淋巴细胞数量影响晚期UBC患者对PD-1单抗治疗的ORR,可能参与PD-1单抗疗效发挥的进程。

肿瘤干细胞标记物ALDH1在非浸润性膀胱癌组织中的表达及其临床意义

目的:探讨肿瘤干细胞标记物乙醛脱氢酶1(ALDH1)在非浸润性膀胱癌组织中的表达,初步了解肿瘤干细胞与膀胱癌生物学特征的关系。方法:采用免疫组织化学法检测118例非浸润性膀胱癌组织及30例癌旁正常膀胱组织中ALDH1的表达,并结合临床病理及预后资料进行关联性分析。结果:在非浸润性膀胱癌组织中ALDH1阳性表达率为24.58%,在癌旁正常膀胱组织中为6.67%,2组比较差异有统计学意义(P<0.05);在低级别和高级别非浸润性膀胱癌组织中ALDH1阳性表达率分别为18.18%(14/77)和36.59%(15/41),二者比较差异有统计学意义(P<0.05);在pTa期和pT1期非浸润性膀胱癌组织中ALDH1阳性表达率分别为16.92%(11/65)和33.96%(18/53),二者比较差异有统计学意义(P<0.05);在初发和复发的非浸润性膀胱癌组织中ALDH1阳性表达率分别为19.77%(17/86)和37.50%(12/32),差异有统计学意义(P<0.05);ALDH1表达与非浸润性膀胱癌患者性别、年龄及肿瘤大小无明显关联性(P>0.05)。术后随访4～52个月,ALDH1阳性表达组和阴性表达组无瘤生存率分别为55.17%和61.80%,Kaplan-Merier曲线及Log-rank检验,2组患者累积无瘤生存时间比较差异有统计学意义(P<0.05)。结论:ALDH1表达与膀胱癌病理分级、分期及肿瘤复发有关联。肿瘤干细胞可能在非浸润性膀胱癌的发生和复发中具有重要作用。

PD-1/PD-L1在膀胱癌患者外周血T细胞和肿瘤细胞表达

【目的】探讨PD-1/PD-L1在膀胱肿瘤患者外周血T细胞和膀胱肿瘤细胞上表达的特点及临床意义。【方法】选取我科收治的64例原发性膀胱癌患者作为实验组(浅表性46例,浸润性18例),对照组为正常人群,共15例。分别取外周血,通过流式细胞仪检测CD8^+T淋巴细胞表明PD-1的表达量;另外取肿瘤患者膀胱癌组织和正常人群的膀胱肿瘤行免疫组化检测膀胱细胞或膀胱肿瘤细胞表面PD-L1的表达情况。【结果】膀胱癌患者外周血中CD8^+T淋巴细胞PD-1的表达量明显高于对照组[(2.25±0.60)%vs(0.68±0.17)%,P<0.001],其中浸润性膀胱癌患者外周血T细胞PD-1的表达高于浅表性膀胱癌患者[(3.04±0.46)%vs(0.68±0.17)%,P<0.001];膀胱肿瘤细胞和正常膀胱组织细胞PD-L1的表达率分别为:40.6%(26/64)和0(0/15,P<0.001),其中浸润性膀胱肿瘤细胞与浅表性膀胱肿瘤细胞PD-L1的表达率无明显差异(41.3%vs38.8%,P>0.01)。【结论】外周血中PD-1在CD8^+T细胞的表达水平可间接反映膀胱癌的进展程度,膀胱肿瘤细胞表面高表达PD-L1,但与肿瘤的进展无相关。

辣椒素通过下调COX-2和mPGES-1抑制IL-1β诱导的NCI-H460细胞PGE_2含量的实验研究

目的观察辣椒素对IL-1β诱导的人肺腺癌NCI-H460细胞PGE_2含量的影响,并且进一步观察其对COX-2和mPGES-1的影响,探讨其抗非小细胞肺癌(NSCLC)的可能机制。方法体外培养NCI-H460细胞,采用MTT比色分析法,观察辣椒素对NCI-H460细胞增殖抑制作用,计算IC50;采用IL-1β刺激的方法构建炎症模型,ELISA法检测辣椒素对NCI-H460细胞PGE_2含量和COX-2活性的影响;Western blot法检测辣椒素对NCI-H460细胞COX-2、mPGES-1蛋白表达的影响;Real-time PCR法检测辣椒素对NCI-H460细胞COX-2mRNA和mPGES-1mRNA表达的影响。结果 MTT比色分析结果表明,辣椒素对NCI-H460细胞增殖具有明显抑制作用,与对照组比较,差异具有统计学意义(P<0.05或P<0.01)。辣椒素明显降低NCI-H460细胞COX-2活性和PGE_2浓度,而且明显降低NCIH460细胞COX-2、mPGES-1蛋白及其mRNA的表达,且呈剂量依赖性,与模型组比较,差异具有统计学意义(P<0.05)。结论辣椒素通过降低NCI-H460细胞COX-2和mPGES-1 mRNA表达从而抑制PGE_2释放,可能是其抗NSCLC的机制之一。

细胞粘附分子-1抑制膀胱癌细胞侵袭转移的机制研究

目的:探讨细胞粘附分子-1(cell adhesion molecule-1,CADM1)过表达和干扰前后对人膀胱癌T24细胞恶性行为的影响及其机制。方法:利用前期构建的Ad-CADM1-T24、Ad-GFP1-T24、Ad-sh1-T24、Ad-GFP2-T24稳转细胞株,以T24细胞作为对照,Western blot检测细胞周期相关蛋白p27、cyclin D1、cyclin E1、CDK2,上皮-间充质转化(epithelial-mesenchymal transition,EMT)相关蛋白E-cadherin、β-catenin、Vimentin,凋亡相关蛋白caspase-3、bcl-2、bax的表达情况;MTT法检测细胞增殖能力;Transwell侵袭实验检测细胞侵袭能力。结果:Western blot结果显示Ad-CADM1-T24细胞与其他细胞相比,凋亡相关蛋白caspase-3、bax表达量升高,bcl-2表达量降低;细胞周期相关蛋白p27表达量明显上调,cyclin D1、CDK2、cyclin E1表达量明显下调;EMT相关蛋白E-cadherin、β-catenin表达量明显上调,Vimentin表达量明显下调;MTT结果显示Ad-CADM1-T24细胞与其他细胞相比,细胞增殖明显受到抑制,差异具有统计学意义(P<0.05);Transwell侵袭实验结果显示,Ad-CADM1-T24细胞与其他细胞相比,24 h细胞穿膜数量明显降低,差异具有统计学意义(P<0.05)。结论:CADM1过表达可明显抑制膀胱癌细胞的侵袭转移,其机制可能与抑制细胞增殖和EMT及促进细胞凋亡有关。

肿瘤干细胞标记蛋白ALDH1在浸润性膀胱癌组织中的表达及其与临床病理和预后的关系

目的：探讨肿瘤干细胞标记物乙醛脱氢酶1（ALDH1）在浸润性膀胱癌组织中的表达,阐明其与膀胱癌生物学行为的关系。方法：采用免疫组织化学方法检测109例浸润性膀胱癌组织和20例癌旁正常膀胱组织（对照组）中ALDH1蛋白的表达,同时检测6例癌转移淋巴结组织及20例未转移淋巴结组织中ALDH1的表达,分析ALDH1蛋白表达与浸润性膀胱癌患者临床病理特征的关系及其对患者总生存率和无瘤生存率的影响。结果：ALDH1蛋白阳性表达率,在膀胱癌与正常膀胱组织中分别为33.94%（37/109）和5.00%（1/20）,差异有统计学意义（P〈0.01）;在非肌层浸润性与肌层浸润性膀胱癌中分别为19.05%（8/42）和43.28%（29/67）,差异有统计学意义（P〈0.01）;在低级别与高级别膀胱癌中分别为13.04%（3/23）和39.53%（34/86）,差异有统计学意义（P〈0.05）;在淋巴转移组与淋巴未转移组膀胱癌组织中分别为50.00%（3/6）和12.90%（4/31）,差异有统计学意义（P〈0.05）;在转移淋巴结及未转移淋巴结组织中分别为50.00%（3/6）和0.00%（0/20）,差异有统计学意义（P〈0.01）。术后随访4-65个月,经Kaplan-Merier分析,ALDH1蛋白阳性表达组患者总生存率为64.9%,阴性表达组为84.7%,差异有统计学意义（P〈0.05）;ALDH1蛋白阳性表达组患者总体无瘤生存率为51.40%,阴性表达组为75.00%,差异有统计学意义（P〈0.05）。结论：肿瘤干细胞标记蛋白ALDH1高表达与浸润性膀胱癌分期和分级及预后有关联,是浸润性膀胱癌预后不良的重要因素。