Surgical therapy and prognosis of sarcomatoid carcinoma of the gallbladder

BACKGROUND:Sarcomatoid carcinoma of the gallbladder is rare and its characteristics are poorly understood.This study aimed to understand the behavior and prognosis of sarcomatoid carcinoma of the gallbladder as well as its clinical manifestations and survival rate of patients after radical or palliative surgery,and to review the reported data worldwide and our 10 patients. METHODS:From 2004 to 2009,ten patients were pathologically diagnosed with sarcomatoid carcinoma of the gallbladder and underwent operati...     

乙酰肝素酶在结肠癌组织中的表达与临床病理特征及预后的关系

[目的]探讨乙酰肝素酶（Heparanase，Hpa）在结肠癌组织中的表达及其与结肠癌临床病理特征和预后的关系。[方法]采用S-P免疫组织化学法检测Hpa和CD34蛋白在结肠癌组织和正常结肠黏膜组织中的表达，并结合病理学分型、组织学分级、微血管密度（MVD）和临床分期探讨其意义。[结果]结肠癌Hpa蛋白的表达显著高于正常结肠黏膜（P〈0．05），结肠癌组织中Hpa蛋白的表达与结肠癌组织血管生成、病理分型、Duke＇s分期、预后有关（P〈0．05）。[结论]Hpa蛋白在结肠癌中呈高表达，并与结肠癌血管生成、病理特征和预后有关，检测其表达可以对判断结肠癌的生物学行为提供指标。     

肝癌组织、缺氧SMMC-7721细胞中HPA的表达变化及机制探讨

目的观察肝癌组织及缺氧培养的肝癌SMMC-7721细胞中乙酰肝素酶（HPA）和缺氧诱导因子-1α（HIF-1α）的表达变化,并探讨其机制。方法免疫组化法检测50例肝癌组织、28例肝癌癌旁组织、14例正常肝组织中的HPA、HIF-1α蛋白。分别采用RT-PCR和Western blot法检测常氧和缺氧培养的人肝癌SMMC-7721细胞中HPA mRNA及其蛋白。结果 HPA、HIF-1α蛋白在肝癌组织中的阳性表达率显著高于癌旁和正常肝组织（P〈0.05）;肝癌组织中HPA、HIF-1α蛋白的表达呈正相关（r=0.295,P〈0.05）。缺氧培养20 h后,SMMC-7721细胞HPA mRNA表达量（6.234±0.457）显著高于常氧培养细胞的表达量（2.910±0.137）,两者相比,P〈0.05;其HPA蛋白表达量（65 kD为1.437±0.067,50 kD为1.706±0.066）也显著高于常氧培养细胞的表达量（65 kD为1.192±0.060,50 kD为1.580±0.265）,两者相比,P〈0.05。结论肝癌组织中HPA蛋白阳性表达率升高,缺氧肝癌SMMC-7721细胞中HPAmRNA及蛋白表达量均升高,可能与缺氧导致的HIF-1α表达上调有关。     

增殖细胞核抗原（PCNA）在原发性胆囊癌中的表达及其预后意义

目的探讨ＰＣＮＡ在原发性胆囊癌的表达及其预后意义。方法３８例原发性胆囊癌石蜡包埋标本，用免疫组织化学方法（ＳＰ）测定。结果ＰＣＮＡ在原发性胆橐癌中的表达阶性率为４５．６±３６．１％，表达呈异质性，且ＰＣＮＡ指数无论是高、中、低分化均显著高于胆囊良性病变组（Ｐ＜０．０５％）。生存期分析表明，ＰＣＮＡ高值组生存划短，预后不佳。ＰＣＮＡ指数与胆囊癌的分化程度、浸润深度，淋巴结转移均显著相关（Ｐ＜０．０５）．在各病理组织类型差异无显著性（Ｐ＞０．０５）。结论ＰＣＮＡ表达在原发性胆囊癌鉴别诊断及预后有一定参考价值。     

抗氧化剂PDTC对肝癌细胞株Hep3B增殖的影响及机制

目的探讨抗氧化剂二硫代氨基甲酸毗咯烷（PDTC）在肝细胞性肝癌化学预防中的作用及机制。方法将不同浓度PDTC、阿霉素及PDTC联用阿霉素作用于Hep3B细胞。采用MTT法检测细胞存活率;流式细胞术（FCM）检测凋亡率;电泳迁移率变动分析（EMSA）检测NF—KB活性。结果PDTC作用后Hep3B存活率明显降低,呈浓度依赖性,P〈0．01。阿霉素联用PDTC的细胞生长抑制率明显高于单用阿霉素（P〈0．01）。PDTC为10μmol／L时的细胞凋亡率明显低于50μmol／L时（P〈0．01）。EMSA示PDTC作用后NF-κB表达降低,不同浓度PDTC作用两两相比P〈0．01。结论PDTC能抑制肝癌细胞株Hep3B的增殖、促进细胞凋亡、增强阿霉素的细胞毒作用;其作用机制主要是抑制NF-κB激活。PDTC可用于肝癌的化学预防,联用阿霉素可进一步提高疗效。     

Alpha-fetoprotein expression in hepatocellular carcinoma: A clinical study

Alpha-fetoprotein (AFP) levels were studied in 51 consecutive patients with hepatocellular carcinoma that presented to the Surgical Hepatobiliary Unit at Westmead Hospital over 12 years. Twenty-three were hepatitis surface antigen (HBsAg) positive and 13 of those patients were Asian. Thirteen patients drank more than 60 g of alcohol each day. A significantly raised level of AFP was defined as more than 20 ng/mL, and 31 of the 51 patients had AFP levels exceeding this at some stage during surveillance. Twenty-five demonstrated levels above 200 ng/mL. Univariate statistical methods suggested that men were more likely to express raised AFP than women, Asians more likely than other races, patients with chronic active hepatitis more likely than those without and those with chronic hepatitis B infection more likely than those who were HBsAg negative. Those who drank more than 60 g alcohol each day were less likely to demonstrate a raised serum AFP than those who drank less. Multivariate logistic regression demonstrated that HBsAg carriage was the only statistically significant independent determinant of a raised AFP. Age 65 years or more was associated with a chance of a raised AFP.     

低氧诱导因子-1的低氧调节及其信号转导通路

低氧诱导因子-1是调节氧稳态的核转录因子。在缺氧条件下它与相应的靶基因相结合,通过转录及转录后的调控,使机体对缺氧、缺血产生适应,是近年来低氧适应研究的关注焦点。由α和β亚基组成异二聚体,其中α亚基受低氧调节。现就低氧诱导因子-1的低氧调节机制及其低氧信号转导通路作一综述。     

Expression of cyclooxygenase-2, glucose transporter-1 and angiogenesis in gallbladder carcinomas and their impact on prognosis

Objective. To investigate the angiogenic and prognostic role of cyclooxygenase-2 (COX-2) in gallbladder carcinomas. We assume COX-2 overexpression, neoangiogenesis and glucose transporter-1 (GLUT-1) to be involved in disease progression. Material andmethods. The carcinoma tissues of 56 patients with gallbladder carcinomas were studied immunohistochemically for the expression of COX-2, GLUT-1 and micro-vessel density. The results were correlated with clinico-pathological features and survival/prognosis. Results. The overexpression of COX-2 in gallbladder carcinomas was significantly associated with increased angiogenesis and GLUT-1 expression. Neither angiogenesis nor the grade of the tumour correlate significantly with poor survival. Age, gender and a strong GLUT-1 expression were significant factors of adverse prognosis. Conclusions. Next to age and gender of patients, hypoxia of gallbladder tumours is a factor influencing survival. Among hypoxic factors, GLUT-1 expression is an important (significant) denominator of poor prognosis in gallbladder carcinomas, but not COX-2 nor angiogenesis.     

JAB1在胆囊癌中的表达及临床病理意义

目的研究C-Jun激活域结合蛋白1(C-Jun activation domain binding protein 1,JAB1)在胆囊癌组织中的表达,探讨其临床病理意义。方法采用免疫组化方法检测JAB1在65例胆囊癌组织和15例慢性胆囊炎组织中的表达情况。结果胆囊癌组织中JAB1蛋白阳性率为60.0%,显著高于慢性胆囊炎组织(13.3%)(P0.05)。结论 JAB1蛋白表达增高与胆囊癌发生、发展密切相关,检测JAB1蛋白有助于胆囊癌的早期诊断及判断患者预后。     

High expression of PDGFA predicts poor prognosis of esophageal squamous cell carcinoma

Platelet-derived growth factor A (PDGFA), the most known member of PDGF family, plays a crucial role in occurrence and progression of different tumors. However, PDGFA expression and its clinical significance in esophageal squamous cell carcinoma (ESCC) are not clear. The present study aimed to assess the expression and prognostic value of PDGFA in ESCC.The Gene Expression Omnibus databases ({"type":"entrez-geo","attrs":{"text":"GSE53625","term_id":"53625"}}GSE53625, {"type":"entrez-geo","attrs":{"text":"GSE23400","term_id":"23400"}}GSE23400, and {"type":"entrez-geo","attrs":{"text":"GSE67269","term_id":"67269"}}GSE67269) and fresh clinical samples were employed for detecting PDGFA messenger RNA expression in ESCC. The associations of PDGFA expression with clinicopathological characteristics were evaluated by chi-square test. Kaplan–Meier analysis and Cox proportional hazard regression model were performed to determine the prognostic value of PDGFA in ESCC patients. PDGFA-related signaling pathways were defined by gene set enrichment analysis based on Gene Expression Omnibus databases.The PDGFA messenger RNA expression was upregulated in ESCC tissues compared with paired adjacent noncancerous tissues (P < .05) and was positively correlated with T stage (P < .05). Kaplan–Meier survival analysis suggested that ESCC patients with high PDGFA expression were associated with poorer overall survival compared to those with low PDGFA expression (P < .05), especially in advanced T stage (P < .05). Cox analyses showed that high expression of PDGFA was an independent predictor for poor prognosis in ESCC patients. Gene set enrichment analysis identified 3 signaling pathways (extracellular matrix receptor interaction, focal adhesion, and glycosaminoglycan biosynthesis chondroitin sulfate) that were enriched in PDGFA high expression phenotype (all P < .01).PDGFA may serve as an oncogene in ESCC and represent an independent molecular biomarker for prognosis of ESCC patients.     

STAT3、Survivin在胆囊癌中的表达及意义

目的探讨胆囊癌中STAT3、p-STAT3和Survivin蛋白表达及其在胆囊癌发生、发展中的意义。方法采用免疫组织化学SP法检测45例胆囊癌及相应45例癌旁胆囊组织、20例慢性胆囊炎组织中STAT3、p-STAT3及Survivin蛋白的表达,并分析其与临床病理特征、预后的关系。结果本组45例胆囊癌组织中STAT3、p-STAT3和Survivin蛋白阳性率分别为66.7%（30/45）、55.6%（25/45）、64%（29/45）,明显高于癌旁正常组织（P〈0.01）和慢性胆囊炎组织（P〈0.01）。在胆囊癌组织中STAT3、p-STAT3的表达与Survivin表达均呈正相关（r=0.558,0.830;P〈0.01）。STAT3、p-STAT3和Survivin蛋白的表达与胆囊癌病理组织分级、Nevin分期、有无淋巴结转移和3年生存率有关（P〈0.01）。结论 STAT3、p-STAT3、Survivin参与了胆囊癌的发生、发展,可能作为判断胆囊癌转移、预后的临床指标。     

NDPK／nm23在人肝癌中的表达及其与预后的关系

目的：探讨肿瘤转移抑制基因ｎｍ２３的表达产物，二磷酸核苷激酶（ＮＤＰＫ）在人肝癌组织中的表达及其与预后的关系。材料和方法：材料取自河南省肿瘤医院１９８７～１９９３年肝癌切除的部分手术标本，共５４例。抗ＮＤＰＫ小鼠单克隆抗体和免疫组化试剂盒购自Ｄａｋｏ公司。研究方法按ＬＳＡＢ法免疫组织化学操作技术常规进行。结果：５４例肝癌组织中，ｎｍ２３表达阳性率为５９．３％（３２／５４），患者年龄、肿瘤的大小、肿瘤的大体分型、肿瘤分期、分级等在ｎｍ２３表达的阳性和阴性组间的分布差异无显著性性（Ｐ＞０．０５）。生存期分析表明，ｎｍ２３表达阴性组的生存期短于阳性组。结论：ｎｍ２３表达阴性与肝癌预后不良有关，但多因素分析显示，ｎｍ２３不能作为判断肝癌预后的独立指标。     

Factor-inhibiting hypoxia-inducible factor expression in patients with high-risk locally advanced renal cell carcinoma and its relationship with tumor progression

Hypoxia-inducible factor (HIF) plays an important role in renal cell carcinoma (RCC) associated with angiogenesis. Factor-inhibiting HIF (FIH), which is the upstream mediator protein of HIF, is receiving more attention today. In the present study, the role of FIH expression in high-risk locally advanced renal cell carcinoma (LARCC) was explored. Eighty-eight high-risk LARCC cases were divided into two groups based on their prognosis. Using immunohistochemical staining, the correlations of FIH expression along with clinicopathological factors, progression-free survival (PFS), and overall survival (OS) were analyzed. FIH was mainly located in the cytoplasm (34/88) and nucleus (31/88) of the renal tumor cell. Nuclear negative expression or cytoplasmic positive expression of FIH were associated with an increased risk of disease progression (p = 0.007 and p < 0.001, respectively) and worse OS (p = 0.020 and p = 0.008, respectively). Using the group with nuclear and cytoplasmic FIH negative expression as reference, further stratified analysis found that the exclusive nuclear FIH expression group had a better PFS and OS [hazard ratio (HR) = 0.153, p = 0.07 and HR = 0, p = 0.961, respectively], and the exclusive cytoplasmic FIH positive group experienced the worst PFS and OS (HR = 2.876, p = 0.005 and HR = 2.799, p = 0.034, respectively). In addition, nuclear negative expression of FIH was associated with a significant negative predictive value for the effect of interferon-alpha (IFN-α) on PFS (p = 0.045). The nuclear negative and cytoplasmic positive expressions of FIH were identified not only as risk factors for disease progression in high-risk LARCC postoperative patients, but also to be associated with poor OS. Furthermore, the nuclear negative expression of FIH may be a promising biomarker for postoperative adjuvant therapy.     

胆囊癌组织CD15抗原表达意义

目的 探讨CD15抗原的表达及含量与胆囊癌的临床病理意义。 方法 应用微波-LSAB免疫组织化学法和图象分析技术,检测45例胆囊癌,17例胆囊腺瘤和10例慢性胆囊炎组织中CD15抗原表达及含量。 结果 CD15抗原表达阳性率及阳性细胞积分A值,在胆囊癌中(71％,4.0±3.2)显著高于胆囊腺瘤(35％,0.9±0.3)和慢性胆囊炎(20％,0.4±0.1)(P<0.05,P<0.01);胆囊癌Ⅱ,Ⅲ级(90％,5.4±1.7)显著高于Ⅰ级(58％,2.2±3.1)(P<0.05,P<0.01);有转移的肿瘤(88％,6.5±3.5)(P<0.05,P<0.01);显著高于无转移的肿瘤(52％,3.3±2.1)(P<0.01)。 结论 CD15抗原表达与胆囊癌的发生、细胞增殖、分化和转移相关,对判断胆囊癌的恶性程度、预测生物学行为和预后具有一定临床意义。     

Nuclear BAG-1 expression is a biomarker of poor prognosis in esophageal squamous cell carcinoma

Apoptosis is one of the critical biological factors that correlate with the biological behavior of malignant tumors including cancer progression and clinical outcome. The present study was performed to clarify the clinical implications of BAG-1, a bcl-2 binding protein in esophageal squamous cell carcinoma (ESCC). Seventy-one cases with ESCC were investigated. Immunohistochemical study of BAG-1 was performed on resected specimens. The expression pattern of BAG-1 in nuclei and/or cytoplasm was analyzed and correlated with TNM classification, vessel invasion, survival period after surgery. BAG-1 expression in the nuclei was related to the depth of tumor invasion (P = 0.0381) but not to any other clinicopathologic parameters. The cytoplasmic staining pattern of BAG-1 exhibited no correlation with clinicopathologic parameters. Univariate analysis (P < 0.05), but not multivariate analysis, revealed significantly poor prognosis for ESCC cases exhibiting positive nucleic staining for BAG-1. Our data suggests that BAG-1 expression in the nuclei of ESCC plays an important role in tumor development and may be useful for predicting the prognosis after surgery.     

Tumor metastasis and the reciprocal regulation of heparanase gene expression by nuclear factor kappa B in human gastric carcinoma tissue

AIM: To investigate whether NF-kB is activated in human gastric carcinoma tissues and, if so, to study whether there is any correlation between NF-kB activity and heparanase expression in gastric carcinoma. METHODS: NF-kB activation was assayed by immunohistochemical staining in formalin-fixed, paraffin-embedded specimens from 45 gastric carcinoma patients. Electrophoretic mobility shift assay (EMSA) method was used for nuclear protein from these fresh tissue specimens. Heparanase gene expression was quantified using quantitative RT-PCR. RESULTS: The nuclear translocation of RelA (marker of NF-kB activation) was significantly higher in tumor cells compared to adjacent and normal epithelial cells [(41.3±3.52)% vs (0.38±0.22) %, t=10.993, P= 0.000<0.05; (41.3±3.52)% vs(0±0.31)%, t=11.484, P= 0.000<0.05]. NF-kB activation was correlated with tumor invasion-related clinicopathological features such as lymphatic invasion, pathological stage, and depth of invasion (Z= 2.148, P= 0.032<0.05; t = 8.758, P= 0.033<0.05; t = 18.531, P = 0.006<0.05). NF-KB activation was significantly correlated with expression of heparanase gene (r= 0.194, P=0.046<0.05). CONCLUSION: NF-KB RelA (p65) activation was related with increased heparanase gene expression and correlated with poor clinicopathological characteristics in gastric cancers. This suggests NF-kB as a major controller of the metastatic phenotype through its reciprocal regulation of some metastasis-related genes.     

肿瘤相关糖蛋白-72抗原在原发性胆囊癌中的表达及其临床意义

目的探讨抗肿瘤相关糖蛋白-72(TAG-72)抗原的表达及其与原发性胆囊癌(PGC)病理特征的关系。方法用原核表达获得抗TAG-72单链抗体,并用聚丙烯酰胺凝胶电泳(SDS-PAGE)和Western blot得以验证;用免疫组化方法检测TAG-72抗原在PGC的表达。结果通过原核表达获取大小为31 kDa的抗TAG-72单链抗体并得以证实。TAG-72抗原在胆囊良、恶性组织阳性率分别为59.6%、6.7%(P<0.05)。高分化PGC的TAG-72抗原表达显著低于中低分化PGC(P<0.05);肿瘤直径≤2 cm者TAG-72表达显著低于>2 cm者(P<0.05);在PGC Nevin临床分期~期与~期间则无显著性差异(P>0.05)。结论获得了抗TAG-72单链抗体的原核表达方法。TAG-72抗原可以作为一个肿瘤标志物在临床中应用,为抗TAG-72单链抗体在PGC诊治中的应用奠定实验基础。     

PTEN和P16基因蛋白在胆囊癌组织中的表达

[目的]探讨PTEN和P16基因蛋白在胆囊癌组织中表达的意义。[方法]应用免疫组织化学技术检测58例胆囊腺癌、20例胆囊腺瘤和20例慢性胆囊炎组织中PTEN和P16基因蛋白表达。[结果]胆囊癌患者PTEN和P16表达阳性率分别为43．1％（25／58）和37．9％（22／58），其表达阳性率均明显低于胆囊腺瘤和慢性胆囊炎（P〈0.05）。PTEN和P16表达与胆囊癌的分化程度、浆膜浸润和转移相关（P〈O．05）。[结论]检测PTEN和P16基因蛋白表达可作为评估胆囊癌生物学行为和预后的参考指标。