p16、survivin、cyclin D1 在膀胱尿路上皮癌中的表达及意义

目的:探讨抑癌基因p16、细胞周期蛋白cyclin D1和凋亡抑制基因survivin在膀胱移行细胞癌中的表达及意义。方法:膀胱移行细胞癌组67例,10例正常正常膀胱粘膜作为对照,采用免疫组织化学方法检测p16和cyclin D1、survivin蛋白表达,然后分析上述三种蛋白在膀胱癌组织中的表达情况,以及随着不同临床分期和病理分级表达的变化。结果:所有膀胱癌患者平均年龄58.16岁,其中男性患者38例。免疫组织化学分析表明,p16和cyclin D1、survivin蛋白均表达在细胞的细胞核。膀胱癌组织中P16表达明显低于正常对照组,而cyclin D1和survivin表达明显高于正常对照组。随着临床分期的进展,p16表达明显下降,cyclinD1表达明显上升;而随着膀胱癌病理分级升高,p16表达明显下降,survivin表达上升。此外,膀胱癌组织中,p16与cyclin D1p16之间存在着明确的负相关。结论:p16、cyclin D1、survivin在膀胱移行细胞癌的生物学行为中起重要作用,p16,cyclin D1和survivin与膀胱移行细胞癌的恶性进展有关。     

膀胱移行细胞癌中EphA2的表达和肿瘤MVD计数的关系

目的:探讨膀胱移行细胞癌中EphA2的生物学意义以及EphA2与微血管密度(MVD)的关系。方法:应用免疫组织化学技术检测85例膀胱移行细胞癌及10例正常膀胱粘膜中EphA2的表达,采用CD31染色标记微血管,行肿瘤微血管密度计数。结果:膀胱移行细胞癌和正常膀胱粘膜EphA2表达阳性率分别为89.4%(76/85)、40%(4/10),两组间差异有统计学意义(P<0.01);EphA2表达程度与膀胱癌的病理分级、临床分期和淋巴结转移均有相关性(P<0.05);膀胱移行细胞癌EphA2阴性组与EphA2阳性纽间肿瘤微血管密度(MVD)计数差异有统计学意义(P<0.05),EphA2不同阳性程度组之间MVD计数差异没有统计学意义(P>0.05)。结论:EphA2可作为判定膀胱癌恶性程度的参考指标,与肿瘤微血管生成相关,有望成为膀胱癌治疗的新靶向。     

STAT3及下游基因Cyclin D1在膀胱癌中的表达及意义

目的 探讨STAT3及下游基因CyclinD1在膀胱癌中的表达及临床意义.为膀胱癌的基因治疗提供理论依据.方法 收集武汉大学人民医院病理科2004-2006年膀胱移行细胞癌存档蜡块50例,其中男性38例,女性12例,平均年龄50.3岁,另取5例癌旁组织做对照.标本均经HE染色,光镜观察诊断,按WHO病理分级标准,G1:30例,G2:15例,G3:5例;运用免疫组织化学染色方法检测STAT3和CyclinD1在以上各组中的表达.利用HPIAS-2000图像分析系统测定STAT3和CyclinD1在以上各组中表达的平均光密度和平均阳性面积率.结果 1.STAT3的表达:STAT3在膀胱移行细胞癌中呈高表达;STAT3在癌旁组织中呈低表达.膀胱移行细胞癌与癌旁组织比较,STAT3的表达差异有显著性(P＜0.05);2.CyclinD1的表达:CyclinD1在膀胱移行细胞癌中呈高表达;CyclinD1在癌旁组织中呈低表达.膀胱移行细胞癌与癌旁组织比较,CyclinD1的表达差异有显著性(P＜0.05).结论 1.STAT3可能参与了膀胱癌细胞的增殖分化、细胞周期等的调节;2.STAT3的活化促进了抗凋亡基因CyclinD1的表达;3.STAT3及其下游基因CyclinD1在膀胱癌的形成中起了一定作用.     

CXCR4 和MMP-9 在膀胱移行细胞癌中的表达

目的:探讨CXCR4与MMP-9在膀胱移行细胞癌中表达的相关性及其临床意义.方法:采用免疫组化SP法与半定量RT-PCR检测40例膀胱移行细胞癌组织及10例正常膀胱粘膜组织中CXCR4和MMP-9蛋白及mRNA的表达情况,分析膀胱移行细胞癌组织中CXCR4和MMP-9表达的相关性,分析二者与临床病理特征的关系.结果:膀胱移行细胞癌组织中CXCR4蛋白表达率为77.5％,mRNA相对含量为0,777±0.044;其中浸润深度达肌层者表达率为100％,mRNA相对含量为0.790± 0.049;局限在粘膜下层者表达率为50％,mRNA相对含量为0.660± 0.052;二者之间差异有统计学意义.MMP-9在膀胱移行细胞癌组织中的表达率为80.0％,mRNA相对含量为0.850± 0.079,其中浸润深度达肌层者表达率为95.5％,mRNA相对含量为0.854±0.070,局限在粘膜下层者表达率为61.1％,mRNA相对含量为0.758±0.092,二者之间差异有统计学意义.膀胱移行细胞癌组织中CXCR4及MMP-9蛋白阳性表达呈正相关关系(γ=0.479,P＜0.05).MMP-9与肿瘤组织学分级有关,与患者的性别、年龄无关;而CXCR4的表达与肿瘤组织学分级及患者的性别、年龄均无关.结论:CXCR4和MMP-9表达与膀胱移行细胞癌的发生和浸润密切相关,通过干预CXCR4和MMP-9的活性可能成为治疗膀胱移行细胞癌的新靶点.     

Polι与移行细胞癌发生关系的实验研究

目的:检测DNA聚合酶■(Pol■)在膀胱肿瘤细胞株及移行细胞癌组织中的表达,探讨Pol■在移行细胞癌组织中表达的意义。方法:培养膀胱肿瘤细胞株BIU87细胞、T24细胞株,利用RT-PCR方法检测Pol■在膀胱肿瘤细胞株中的表达;收集人膀胱粘膜正常组织、临床膀胱肿瘤和肾盂癌的移行细胞癌组织标本,利用RT-PCR方法检测组织标本中Pol■的表达。结果:Pol■在膀胱肿瘤细胞株中丰富表达,显著高于膀胱正常粘膜组织(P<0.01);Pol■在膀胱肿瘤及肾盂癌组织的表达显著高于膀胱正常粘膜组织的表达(P<0.01),且与移行细胞癌的分级相关。结论:Pol■在移行细胞癌组织中的高表达可能与膀胱肿瘤的发生、发展相关,为进一步研究Pol■在膀胱肿瘤中表达的意义打下基础。     

VEGF-D的表达与膀胱移行细胞癌LVD及淋巴结转移有关

目的观察血管内皮生长因子D(vascular endothelial growth factor D,VEGF-D)在人膀胱移行细胞癌组织内的表达,探讨VEGF-D在膀胱移行细胞癌组织淋巴管密度(lymphatic vessel density,LVD)及淋巴结转移之间的关系。方法取人膀胱移行细胞癌组织蜡块30例,免疫组化法观察VEGF-D在膀胱移行细胞癌组织内的表达情况。以淋巴管内皮特异性标记物D2-40标记淋巴管,计数癌组织内淋巴管密度。结果VEGF-D蛋白主要表达于癌细胞胞浆内,VEGF-D在淋巴结转移组膀胱移行细胞癌组织内的表达水平明显高于无淋巴结转移组(P0.05);淋巴结转移组膀胱移行细胞癌组织内的淋巴管密度明显高于无淋巴结转移组(P0.05)。VEGF-D表达与膀胱移行细胞癌淋巴管密度及淋巴结转移之间具有显著的相关性。结论VEGF-D表达在膀胱移行细胞癌组织内淋巴管生成及淋巴结转移中起重要作用。     

一氧化氮合酶（NOS）在膀胱移行细胞癌中的表达及其意义

目的检测膀胱移行细胞癌中一氧化氮合酶（nitric oxide synthase,NOS）的表达,并分析其表达与肿瘤病理特性的关系.方法采用免疫组织化学技术检测35例膀胱移行细胞癌标本、12例癌旁粘膜标本及8例正常膀胱粘膜标本中一氧化氮合酶三种亚型的表达情况.结果 35例肿瘤标本中nNOS、iNOS、eNOS阳性表达率分别为74.3%、85.7%、42.9%,膀胱移行细胞癌中iNOS表达较正常膀胱粘膜增高.但移行细胞癌、癌旁粘膜、正常粘膜三组间nNOS及eNOS表达无差别.nNOS、iNOS、eNOS表达与膀胱移行细胞癌分期分级可能无相关性.结论 iNOS在膀胱移行细胞癌中表达增高,可能参与膀胱移行细胞癌的发生发展.     

NAC-1在膀胱癌中的表达及其与血管生成的相关性研究

目的:检测NAC-1在膀胱癌及癌旁组织中的表达,及其与膀胱癌临床病理的相关性研究,并进一步探讨其与血管生成的关系,为阐明膀胱癌的发生发展机制提供基础。方法:采用免疫组化法检测88例膀胱癌和30例癌旁组织石蜡块中NAC-1的表达情况,用si-RNA干扰技术下调膀胱癌细胞系T-24中NAC-1的表达,然后通过q RT-PCR方法检测干扰组及对照组中促血管生成因子(VEGF、b FGF、EGFR)的表达。结果:膀胱癌组织和癌旁组织中NAC-1的阳性表达率分别为79.54%和13.33%,膀胱癌组织显著高于癌旁组织(P0.01);NAC-1表达与膀胱癌的肿瘤级别、肌肉浸润程度及淋巴结转移显著相关(P0.05),在高级别、肌肉浸润及淋巴结转移的膀胱癌中呈现高表达,细胞实验发现NAC-1下调能够抑制促血管生成因子(VEGF、b FGF、EGFR)的表达。结论:NAC-1作为肿瘤相关基因在膀胱癌中高表达,并与膀胱癌的临床病理密切相关,其能调节促血管生长因子,可能会在肿瘤的血管生成及转移中具有重要的作用。     

miRNA-125b在膀胱癌中的表达和意义

目的:探讨膀胱癌组织中miR-125b的表达在膀胱癌发生发展中的作用及其临床意义。方法:采用应用茎环RT-PCR的方法检测66例膀胱尿路上皮癌组织标本的miR-125b的表达,另有16例正常膀胱黏膜组织作对照,并结合临床病理资料进行统计学分析。结果:miR-125b在膀胱癌组织中的表达显著高于非肿瘤的正常膀胱黏膜组织(p0.05),miR-125b的水平还与表达水平与膀胱癌的组织学分级、肿瘤转移、术后复发均明显相关性(P0.05)。结论:miR-125b在膀胱癌组织中表达量升高,且与组织学分级、肿瘤转移、术后复发相关,可能作为膀胱癌诊断和预后指标。     

细胞角蛋白20在膀胱癌中的研究进展

膀胱肿瘤是最常见的泌尿系统肿瘤,其中上皮性肿瘤占95％以上,绝大多数为尿路移行上皮细胞癌。膀胱癌的早期症状不明显,复发率较高,早期诊断和治疗对提高其疗效非常重要。近年来,诊断膀胱肿瘤的新方法不断出现,显著提高了膀胱肿瘤诊断及预后预测水平。其中,膀胱肿瘤标记物检测已成为膀胱肿瘤的诊断新方法,具有十分重要的临床意义。研究发现,细胞角蛋白20fcytokeratin20,CK20）是中间纤维家族成员之一,在正常膀胱组织中特异性表达于伞细胞,在膀胱癌中特异性表达于膀胱移行细胞癌,其诊断膀胱肿瘤的特异性和灵敏性均较高,且与膀胱肿瘤的临床分级、病理分期和转移均密切相关,因此可作为辅助诊断膀胱肿瘤的检测标志物及治疗和预后评估指标。本文将就其在膀胱癌中的研究进展综述如下。     

Variable Expression of Neural Cell Adhesion Molecule Isoforms in Renal Tissue: Possible Role in Incipient Renal Fibrosis

Rare neural cell adhesion molecule (NCAM) positive cells have been previously described within the normal human adult kidney interstitium, speculating that they could increase in the interstitium with incipient interstitial renal fibrosis (IRF). In the present study, among 93 biopsy samples of various kidney diseases, NCAM⁺ interstitial cells were detected in 62.4% cases. An increased number of NCAM⁺ cells was significantly observed only in incipient IRF compared to normal renal tissues and advanced IRF stages (p<0.001), independently of underlying diseases (p = 0.657). All three major NCAM isoforms’ RT-PCR bands were visible either in normal or in kidneys with incipient IRF, albeit their mRNA expression levels measured by qRT-PCR were different. Applying qRT-PCR on pure NCAM⁺ cells population, obtained by laser capture microdissection, significant mRNA over-expression of NCAM^140kD isoform was found in NCAM⁺ cells within incipient IRF (p = 0.004), while NCAM^120kD and NCAM^180kD isoforms were not changed significantly (p = 0.750; p = 0.704; respectively). Simultaneously, qRT-PCR also showed significant αSMA (p = 0.014) and SLUG (p = 0.004) mRNAs up-regulation within the NCAM⁺ cells of incipient IRF, as well as highly decreased matrix metalloproteinases (MMP) -2 and -9 mRNAs (p = 0.028; p = 0.036; respectively). However, using double immunofluorescence MMP-9 could still be detectable on the protein level in rare NCAM⁺ cells within the incipient IRF. Further characterization of NCAM⁺ cells by double immunofluorescent labeling revealed their association with molecules involved in fibrosis. Fibroblast growth factor receptor 1 (FGFR1) and α5β1 integrin were extensively expressed on NCAM⁺ cells within the incipient IRF areas, whereas human epididymis protein-4 (HE4) was found to be present in few NCAM⁺ cells of both normal and interstitium with incipient fibrosis. Heterogeneity of NCAM⁺ interstitial cells in normal and incipient IRF, concerning molecules related to fibrosis and variable expression of NCAM isoforms, could suggest diverse role of NCAM⁺ cells in homeostasis and in regulation of renal fibrosis in diseased kidneys.     

Molecular pathology of low malignant bladder transitional cell carcinoma: a current perspective

Bladder transitional cell carcinoma (BTCC) actually has two phenotypes: low malignant and aggressive. Most previous molecular and cytogenetic analyses of bladder cancer were focused on aggressive BTCC. Little is known about the events that lead to the development of low malignant BTCC. This review mainly introduces the concept of two types of bladder tumors and then focuses on the molecular pathology of low malignant BTCC in particular. It is hoped that further understanding of the molecular pathology of low malignant BTCC may provide novel therapies and many other clinical benefits in patients with this disease.     

生殖器疱疹初发患者外周血淋巴细胞检测结果分析

目的检测生殖器疱疹初发患者（GH）外周血T淋巴细胞亚群、NK细胞和B细胞的表达水平,探讨其发病机制与细胞免疫功能之间的关系。方法应用流式细胞仪检测20例初发生殖器疱疹患者外周血T淋巴细胞亚群、NK细胞和B细胞的表达水平,并与60例复发性生殖器疱疹患者（RGH）、35例健康对照者外周血检测结果相比较。结果（1）初发组和对照组相比,除NK细胞降低差异有显著性外,其他差异无显著性;（2）初发组与复发组相比,初发组T细胞、CD4^＋细胞、CD4^＋／CD8^＋均高于复发组,CD8^＋细胞百分比低于后者,差异有显著性;B细胞、NK细胞比例差异无显著性;（3）复发组与对照组相比,外周血中T细胞、CD4^＋细胞、NK细胞所占比例,CD4^＋／CD8^＋均降低,差异有显著性;CD8^＋细胞百分比升高,差异有显著性;B细胞比例差异无显著性。结论生殖器疱疹初发患者存在细胞免疫功能异常。     

Th1型和Th2型细胞因子在口腔扁平苔藓患者外周血中的表达及临床意义

目的:研究口腔扁平苔藓(OLP1)患者Th1型和Th2型细胞因子的表达及临床意义。方法:选取2013年1月至2014年3月于我院就诊的21例充血糜烂型及14例光滑型OLP患者为研究对象,18例正常人为对照组,采用密度梯度离心法对各组外周血单个核细胞进行分离,酶联免疫吸附剂测定(ELISA)法对各组外周血单个核细胞中的IL-4和IFN-gamma的表达进行检测,逆转录-聚合酶链反应法对各组血清中IL-4 m RNA和IFN-gamma m RNA的表达进行检测。结果:与正常对照组相比,OLP患者IL-4m RNA及蛋白的表达均增高,而IFN-gamma m RNA及蛋白的表达则降低,差异均有显著统计学意义(均P0.01)。充血糜烂型及光滑型OLP患者组间比较发现,IL-4 m RNA和IFN-gamma m RNA及蛋白的表达差异无统计学意义(P0.05)。结论:OLP发病机制与Th1与Th2的表达失衡有关,为临床治疗提供参考。     

Prognostic value of carcinoma-associated antigen MK-1 in urinary bladder carcinoma

BACKGROUND: The present study has been performed to evaluate the expression of MK-1 in schistosomiasis-associated squamous cell carcinoma of the urinary bladder and to correlate this new marker with the conventional histopathological parameters. PATIENTS AND METHODS: Paraffin sections of 5-microm thickness from 81 cases were prepared for hematoxylin and eosin staining and immunohistochemical analysis of MK-1 expression was carried out. RESULTS: Forty-six cases (56.8%) were positive for MK-1 protein expression. Significant correlations between MK-1 expression and tumor grade (p=0.004), schistosoma (p=0.031), DNA ploidy (p=0.001), and tumor recurrence (p<0.001) were observed. MK-1, sex, tumor grade, stage, schistosoma, DNA ploidy, and recurrence were evaluated in relation to outcome. Univariate and multivariate analysis of survival were performed. The overall 5-year survival was 51.85%. In univariate analysis, MK-1 expression, tumor grade, DNA ploidy, and recurrence had a significant impact on the survival of these patients. In a Cox proportional hazards model, recurrence maintained its significant impact on survival. CONCLUSIONS: These findings suggest that MK-1 is a prognostic marker for recurrence: 34 (87.2%) of 39 recurrent cases were positive for MK-1 expression. However, only recurrence was an independent prognostic factor in patients with schistosomiasis- associated squamous cell carcinoma of the bladder.     

Chemotherapy sorting can be used to identify cancer stem cell populations

Cancer stem cells (CSCs) of bladder transitional cell cancers (BTCC) had not been identified by the reported common methods. According to the phenomenon that CSCs were resistant to chemotherapy, BTCC cell lines T24 and 5637 were cultured with mitomycin C respectively. Cell inhibition assay revealed an increased population of drug resistant cancer cells with a concentration gradient of mitomycin C. The maximal and minimal cell inhibition rate in cell line T24 was 92.5?%?±?1.0 versus 64.1?%?±?1.4 (P?相似文献