B7-H4在胃腺癌中的表达及临床意义

目的研究B7-H4蛋白在胃腺癌中的表达及临床意义。方法应用S-P免疫组化法检测B7-H4蛋白在20例正常胃黏膜、50例胃腺癌中的表达情况。结果 B7-H4在胃癌中的阳性表达率（82%）高于正常胃黏膜组（10%）,差异有显著意义（P〈0.05）。B7-H4在胃腺癌中的表达与年龄、性别无关（P〉0.05）,而与组织学分级、浸润深度及淋巴结转移有关（P〈0.05）。结论 B7-H4在胃腺癌中表达上调,可能与胃腺癌的转移和预后相关。     

人结肠直肠癌组织中B7-H4的表达及其临床意义

目的探讨共刺激分子B7-H4在结肠直肠癌组织中的表达及其意义。方法运用免疫组织化学S-P法检测B7-H4分子在60例结肠直肠癌组织中的表达,并对其表达水平与结肠直肠癌临床病理参数之间的关系进行相关性分析。结果B7-H4在结肠直肠癌组织中高表达,阳性率为83.3%;在结肠直肠癌组织中B7-H4的表达与患者性别、年龄、肿瘤组织的类型、分级和分期无关（P〈0.05）,而与淋巴结是否转移显著相关（P〈0.05）。结论B7-H4在结肠直肠癌组织中的高表达,可成为结肠直肠癌新的诊断标志。B7-H4在肿瘤的发生、进展中起到一定作用,封闭B7-H4有可能成为结肠直肠癌免疫治疗的一个新靶点。     

协同刺激分子B7-H3在自发性流产患者中的表达及生物学意义

目的：研究可溶性B7-H3（sB7-H3）在正常、妊娠、自发性流产和复发性流产外周血血清中的含量,同时研究B7-H3在正常妊娠行人工流产者（孕3个月内）和自发性流产者（流产后3个月内）的绒毛膜和蜕膜表达情况,探讨协同刺激分子B7-H3在妊娠免疫中的生物学意义。方法利用ELISA的方法分析sB7-H3在正常未孕者、正常妊娠者、自发性流产者、复发性流产者血清含量。收集正常妊娠行人工流产术组的绒毛膜和蜕膜以及自发性流产组的绒毛膜和蜕膜,通过免疫组化的方法,分析B7-H3在不同组织中的表达情况。结果 sB7-H3在正常对照组、妊娠组、自发性流产组、复发性流产组的血清标本的平均含量之间差异有统计学意义（ P ＜0倐．05）。人工流产组和自发性流产组中B7-H3在绒毛膜的表达差异无统计学意义（ P ＞0．05）;在蜕膜上的表达人工流产组明显高于自发性流产组（ P＜0．05）;B7-H3在绒毛膜局部表达,在蜕膜组织各处均有表达。结论 B7-H3参与了妊娠免疫,并与自发性流产的发生相关。     

B7-H4基因在直肠癌组织的表达及其临床意义

目的 研究B7-H4基因在直肠癌组织中的表达及其临床意义.方法 采用免疫组织化学SP法检测B7-H4基因分子在65例直肠癌组织中的表达水平.结果 B7-H4基因在直肠癌组织中表达阳性率为78.5％(51/65);B7-H4基因的阳性表达与直肠癌患者的性别、年龄、肿瘤大小无关(P＞0.05),而与肿瘤分期和有无淋巴结转移相关(P＜0.05);BT-H4基因阳性表达的直肠癌患者平均生存时间明显短于阴性表达患者[(36±7)个月比(48±9)个月,P＜0.05].结论 B7-H4基因在直肠癌组织的过表达,可能为直肠癌新的具有诊断价值的肿瘤标志物,可作为直肠癌患者预后不良的参考指标.     

CD133和B7-H4在非小细胞肺癌中的表达及其临床意义

目的检测CD133和B7-H4在非小细胞肺癌(NSCLC)标本中的表达,并探讨两者的关系及其临床意义。方法采用流式细胞术检测CD133及B7-H4在NSCLC患者胸水中的表达;采用免疫组化SP法检测103例NSCLC手术标本、25例癌旁组织及24例肺部良性病变组织中CD133及B7-H4的表达。结果 CD133和B7-H4在NSCLC胸水中均见表达。肺癌组织CD133表达率49.51%(51/103),B7-H4表达率66.99%(69/103),均高于良性病变组织及癌旁组织(P<0.01)。CD133表达与肿瘤分化程度有关(P<0.01),并且与B7-H4表达相关(P<0.01)。COX回归分析显示CD133阳性表达与NSCLC患者的预后不良有关。结论 CD133与B7-H4在NSCLC中过度表达,可能参与肿瘤逃避宿主的免疫监视过程;CD133可能是NSCLC患者独立的风险因子。     

B7-H4的研究进展

B7-CD28家族的共刺激信号分子在免疫应答与调节中发挥重要作用,其作为共刺激或共抑制信号决定最终免疫应答。B7-H4作为B7家族(家族成员20%~40%蛋白质相同)中的负向调节分子,它的发现扩展了人们对细胞介导的免疫应答和耐受调控机制的理解。     

膀胱癌来源外泌体携带程序性死亡配体1和共刺激分子B7-H4的表达及初步鉴定

目的 提取并鉴定膀胱癌BIU-87和T24细胞来源的外泌体,检测膀胱癌细胞来源外泌体中程序性死亡配体1(PD-L1)和共刺激分子B7-H4的表达,验证膀胱肿瘤通过外泌体在微环境中传递PD-L1和B7-H4.方法 体外培养膀胱尿路上皮癌BIU-87和T24细胞,超速离心法提取细胞上清液中外泌体,透射电子显微镜(TEM)观...     

SERPINB7对乳腺癌细胞增殖、凋亡、迁移和侵袭的影响

目的 探讨丝氨酸蛋白酶抑制剂B7(SERPINB7)对乳腺癌细胞增殖、凋亡、迁移和侵袭的作用及其可能机制。方法 将人乳腺癌细胞系MCF-7分为sh-SERPINB7组、空白对照组(BC组)和阴性对照组(NC组);其中,sh-SERPINB7组和NC组分别转染SERPINB7 RNA干扰慢病毒和阴性对照慢病毒。采用qRT-PCR法检测SERPINB7 mRNA表达,CCK-8法、流式细胞术、细胞划痕实验和Transwell实验分别检测细胞增殖、凋亡、迁移和侵袭,Western blot法检测SERPINB7、Bax、Bcl-2、Snail、Slug、转化生长因子β(TGF-β)、Smad3和磷酸化Smad3(p-Smad3)的蛋白表达。结果 MCF-7细胞中SERPINB7蛋白表达高于人正常乳腺上皮细胞系MCF-10A(P<0.05)。与BC组和NC组相比,sh-SERPINB7组MCF-7细胞中SERPINB7 mRNA表达以及Bcl-2、Snail、Slug、TGF-β、p-Smad3蛋白表达降低,细胞凋亡率升高,细胞划痕愈合率和侵袭细胞数减少,Bax蛋白表达增加(P<0...     

B7-H4与糖尿病关系的研究进展

1型糖尿病(Type 1 diabetes mellitus,T1DM)是一种T细胞介导的胰岛β细胞选择性破坏的自身免疫病,2型糖尿病(Type2 diabetes mellitus,T2DM)存在一种慢性的低度炎症状态,阐明免疫系统活化机制对糖尿病(DM)及相关代谢紊乱防治具有十分重要的意义。该文探讨糖尿病患者共刺激因子B7-H4的表达及其与疾病发生发展的关系,并为寻找糖尿病肾病的合理的诊断与治疗提供新的途径。     

PRPF19对肝癌细胞Huh7增殖、迁移和侵袭能力的影响

目的:探究PRPF19对肝癌细胞Huh7增殖、迁移和侵袭能力的影响。方法:基于生物信息学分析PRPF19在肝癌中的表达、预后及其药物敏感性,并通过实时荧光定量PCR和免疫组化法验证PRPF19在人体肝癌组织中的表达水平。采用瞬时转染技术在Huh7细胞中敲低PRPF19,并通过实时荧光定量PCR和蛋白免疫印迹试验验证敲低效果。CCK-8和集落形成试验检测敲低PRPF19对Huh7细胞增殖能力的影响。Transwell和划痕试验检测敲低PRPF19对Huh7细胞迁移和侵袭能力的影响。通过蛋白免疫印迹试验检测p-p53(Ser20)、p53等蛋白的表达水平。结果:PRPF19在肝癌中高表达并与患者的预后显著相关(P<0.05)。与对照组相比,敲低PRPF19后,肝癌细胞Huh7的增殖、迁移及侵袭能力明显降低,p-p53(Ser20)、p53等相关蛋白表达量明显上升(P<0.05)。同时,PRPF19高表达的患者对索拉非尼和舒尼替尼有高敏感性(P<0.01)。结论:PRPF19在肝癌中具有良好的预后价值,敲低PRPF19可能通过激活p53通路抑制肝癌细胞Huh7的增殖、迁移及...     

The expression of Rab5 and its effect on invasion,migration and exosome secretion in triple negative breast cancer

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and current therapeutic strategies are limited in their effectiveness. The expressions of Rab5 and the M2 tumor-associated macrophage marker CD163 in tissues were detected by Western blot. The migration and invasion of cells were determined using a Transwell assay. The expressions of the exosome markers were evaluated by Western blot. The polarization of human macrophages (THP-1) was determined by incubation of THP-1 cells with conditioned medium or exosomes collected from MDA-MB-231 cells with indicated transfections or by a coculture system of THP-1 and MDA-MB-231 cells. The M1 and M2 macrophage markers were evaluated by qRT-PCR. The expression of Rab5 in TNBC was significantly higher than that in normal breast tissue. Rab5 expressions in triple-negative and luminal A breast cancer were higher than those in other molecular subtypes. Higher CD163 expression was observed in triple-negative breast cancer and in triple-negative and luminal B subtypes. Rab5 knockdown suppressed but Rab5 overexpression promoted the migration and invasion capacity of MDA-MB-231 cells. The levels of CD63 and CD9 in the medium of Rab5 knockdown cells were lower than those in control cells, whereas higher levels of CD63 and CD9 were observed in Rab5 overexpression cells. Rab5 knockdown decreased the excretion but did not alter the diameter of the exosomes. Knockdown of Rab5 facilitated the anti-tumor polarization of macrophages, which was partially reversed by Rab5 overexpression. Therefore, Rab5 is expected to be a potential therapeutic target for triple-negative breast cancer.     

B7-H4介导肿瘤免疫逃逸机制及临床研究进展

协同刺激分子B7-H4是B7家族中的新成员,能通过抑制T细胞增殖、减少细胞因子产生和减慢细胞周期进程而负性调控T细胞免疫应答。研究表明,B7-H4在多种肿瘤细胞及组织中均呈高表达,与肿瘤免疫逃逸关系密切,在肿瘤的发生、发展和转归中发挥重要作用。研究B7-H4在肿瘤中的表达和意义,有助于阐明肿瘤免疫逃逸机制,也为肿瘤的免疫治疗提供新的靶点和策略。     

Effect of 7-hydroxystaurosporine on glioblastoma cell invasion and migration

AIM: To investigate the effect of 7-hydroxystaurosporine (UCN-01), a selective protein kinase C (PKC) inhibitor, on cell growth, migration, and invasion in invasive human glioblastoma U-87MG cells. METHODS: PKC activity was determined based on the PKC-catalyzed transfer of the (32)P-phosphate group from [g-(32)P]ATP into a PKC-specific peptide substrate. Cell viability was measured by MTT assay. Cell invasion and migration were evaluated by a Boyden chamber assay and scratch wound assay, respectively. Protein expression was analyzed using Western blot assay. The formation of 3-dimensional cellular aggregates was examined by a cell-cell aggregation assay. RESULTS: UCN-01 treatment resulted in concentration- and time-dependent inhibition of U-87MG cell growth at higher doses (>100 nmol/L), and reduced cell invasion and migration capability at less cytotoxic doses (<100 nmol/L). UCN-01 significantly repressed PKC activity. Consistent with this result, UCN-01 blocked cell invasion stimulated by phorbel 12-myristate-13-acetate (PMA) and ethanol (EtOH), 2 PKC activators. Enforced expression of the tumor suppressor genes BRCA1 and PTEN increased the anti-invasion potential of UCN-01. Exposure to UCN-01 caused a dose-dependent increase in cell adhesion molecule E-cadherin. The effect of UCN-01 on the formation of cell-cell aggregation was significantly reduced by the addition of an anti-E-cadherin antibody. CONCLUSION: UCN-01 inhibits the invasion and migration of human glioma cells. Accordingly, UCN-01 can have potential clinical applications for the treatment of human glioma metastasis.     

表没食子儿茶素没食子酸醋对人胃癌细胞迁移、袭和FoxM1基因表达的影响

目的观察表没食子儿茶素没食子酸醋（表没食子儿茶素没食子酸醋,EGCG）对人胃癌细胞迁移、侵袭的影响,并探讨其可能机制。方法采用不同浓度的EGCG处理人胃癌BGC823细胞后,以划痕试验方法检测癌细胞迁移能力,以Transwell方法检测癌细胞侵袭能力,采用蛋白质印迹方法检测FoxM1基因蛋白水平变化。结果人胃癌BGC823细胞经EGCG处理后,迁移和侵袭能力均明显下降,且呈剂量依赖性（P〈0.01）。EGCG处理组FoxM1基因蛋白水平明显下调,且呈浓度依赖性。结论 EGCG可降低人胃癌细胞侵袭能力,下调FoxM1基因表达,是其重要机制之一。     

Therapeutic targeting of B7-H1 in breast cancer

Introduction: Breast cancer is the most common form of malignancy occurring in women worldwide. B7-H1 is a co-inhibitory molecule expressed by several types of tumors, including breast cancer. The aberrant expression of B7-H1 in breast cancer cells has been determined, its role in recruiting regulatory T cells into the tumor microenvironment has been elucidated and a strong link to B7-H1 induction in highly proliferative breast cancer has been provided. It has also been demonstrated that doxorubicin, a drug commonly used for breast cancer treatment, downregulates the cell surface expression of B7-H1 and upregulates its nuclear expression, which therefore suggests an anti-apoptotic role of B7-H1 in breast cancer.

Areas covered: This review illustrates the various factors involved in the induction of B7-H1 and its role in immune evasion and chemoresistance. It also provides potential therapeutic strategies for targeting B7-H1 in breast cancer.

Expert opinion: B7-H1 should be considered as a potential therapeutic target for breast cancer. Indeed, there is increasing evidence for the potential efficacy of B7-H1 blockade in the prevention of immune evasion by cancer cells. Additionally, B7-H1 targeting can be used in conjunction with other therapeutic modalities for improved efficacy and reduced toxicity. We expect that B7-H1 blockade in combination with other therapeutics will be a prime therapeutic strategy in the future.     

二甲双胍抑制前列腺癌细胞的增殖、迁移、侵袭及其机制

目的 体外实验研究二甲双胍(Met)对前列腺癌DU145增殖、迁移、侵袭的影响及可能的作用机制。方法 0、5、20、50 mmol·L^-1 Met处理细胞后,CCK8法检测细胞增殖,Transwell实验检测细胞迁移和侵袭能力,实时荧光定量PCR和Western Blot实验在mRNA和蛋白水平检测人抗原R(HuR)的表达变化;分别过表达和敲低HuR后,用上述相同实验方法检测DU145的增殖、迁移、侵袭的能力;Western Blot法检测Met处理,过表达HuR或敲低HuR后对AKT/mTOR通路的影响。结果 Met处理细胞后,DU145的增殖、迁移、侵袭能力降低,并呈现出浓度依赖性,同时在mRNA和蛋白水平降低了HuR的表达;敲低HuR对细胞增殖、迁移、侵袭有一定抑制作用,而过表达HuR对细胞则有相反的作用;Met和低表达HuR组抑制了细胞中AKT、mTOR的磷酸化,而过表达HuR则促进了AKT、mTOR的磷酸化。结论 Met可抑制前列腺癌细胞DU145的增殖、迁移、侵袭;其作用机制可能是Met通过降低HuR表达进而抑制AKT/mTOR通路的异常激活,从而抑制...