Correlation of E-and P-cadherin expression with differentiation grade and mode of invasion in gingival carcinoma

The expression pattern of two Ca²⁺-dependent cell-cell adhesion molecules, E-and P-cadherin (CD), in 25 primary gingival squamous cell carcinomas (SCC) was examined immunohistochemically. The occurrence of reduced-type expression of both E-and P-CD increased significantly with the grade of carcinoma differentiation, culminating in a complete loss of P-CD in poorly differentiated SCC. The occurrence of reduced-type P-CD expression also increased significantly with the mode of invasion, as was the case with E-CD. Furthermore, no P-CD molecules were detected in one of the six SCC having a diffuse, cord-like invasion and in three of the six having a diffuse type of invasion. These findings suggest that the down-regulation of these cell adhesion molecules closely correlates with the differentiation grade and mode of invasion of gingival SCC.     

比较蛋白质组学在肝癌中的应用

肝癌的发病机制至今仍不清楚，且缺乏有效的早期诊断和治疗靶点。比较蛋白质组学代表了蛋白质组学中新出现的领域，从蛋白质整体水平上研究肝癌发生与转移，寻找与肝癌发生及转移相关的新蛋白质、肝癌特异性的标志物，对肝癌的早期诊断和治疗起重要作用。     

Knock-down of hepatitis B virus X protein reduces the tumorigenicity of hepatocellular carcinoma cells

Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) in Southeast Asia and Hong Kong. Among the four proteins that are encoded by the HBV genome, HBV X (HBx) is the most potentially oncogenic factor. It is known that HBx plays an important role in hepatocarcinogenesis, but the exact functions and molecular mechanisms of HBx in HCC are not well understood. In this study, we constructed expression vectors for small hairpin RNAs (shRNA) against HBx and investigated their regulatory effects in PLC/PRF/5 HCC cells, which constitutively produce HBx. Our data show that this tool of RNA interference (RNAi) could successfully reduce the HBx mRNA and protein levels by 50-95%. RNAi targeting HBx in PLC/PRF/5 cells demonstrated significant reduction in cell proliferation, cell growth, anchorage-independent growth in soft agar, and tumour development in nude mice. In addition, depletion of HBx expression increased cell sensitivity to TNFalpha-mediated and serum-free-induced apoptosis, and reduced the expression levels of C-myc and Bcl-X(L). These findings suggest that HBx plays an important role in tumorigenicity and anti-apoptotic mechanisms in HCC.     

Histological study of PIVKA-II expression in hepatocellular carcinoma and adenomatous hyperplasia

Although serum concentration of protein induced vitamin K absence or antagonist II (PIVKA-II) has been widely used for diagnosing hepatocellular carcinoma (HCC), little information is available concerning tissue PIVKA-II as an immunohistochemical marker for liver histology. In this study, we examined the expression of PIVKA-II in precancerous nodules (adenomatous hyperplasia) and various differentiation grades of HCC by immunohistochemical study using the monoclonal anti-PIVKA-II antibody (MU-3). We examined the relationship between tissue PIVKA-II staining and serum PIVKA-II level, tumor histology and tumor size. PIVKA-II was mainly detected in the cytoplasm of the HCC cells. The positive rates of PIVKA-II were as follows: adenomatous hyperplasia (AH), 0% (0/9); well-differentiated HCC, 65% (15/23); moderately differentiated HCC, 85% (22/26); poorly differentiated HCC, 54% (7/13). The expression of tissue PIVKA-II staining in moderately differentiated HCC was significantly higher than in well- or poorly differentiated HCC, whereas the serum PIVKA-II level in poorly differentiated HCC was higher than well- or moderately differentiated HCC. There was no relationship between the expression of PIVKA-II in cancer tissues and serum levels of PIVKA-II. Immunohistochemical studies revealed that PIVKA-II was expressed even in small-sized or well-differentiated HCC cells, but expression was not detected in AH. It was concluded that PIVKA-II is a useful immunohistochemical marker, even in small-sized or well-differentiated HCC.     

Prognostic significance and anti-proliferation effect of microRNA-365 in hepatocellular carcinoma

MircroRNA functions as tumor suppressor or promoter in hepatocellular carcinoma (HCC). Researchers have found that miR-365 expression was lower in HCC tissues compared with that in adjacent normal tissues. However, its prognostic significance and anti-proliferation effect in HCC remain to be clarified. In this study, we firstly found that miR-365 expression was lower in HCC tissues compared with that in adjacent normal tissues. Then, we analyzed miR-365 expression level and its clinicopathological and prognostic significance. Finally, overexpression of miR-365 inhibits HCC cell proliferation and migration in vitro. Our findings suggest that miR-365 expression was an independent poor prognostic factor for HCC patient overall survival and suppressed tumor cell growth. Therefore, miR-365 may serve as a valuable prognostic marker and promising target for HCC.     

肝癌组织中KLF17的表达及临床意义

目的 检测KLF17在肝癌组织的表达并评价其对肝癌预后的影响.方法 免疫组化法检测KLF17在肿瘤组织中的表达,以及KLF17表达对患者无进展生存和总生存期的影响.比较原代培养的Hep11和Hep12细胞侵袭和迁移的差异,以及KLF表达的差异.干扰KLF17表达后Transwell法检测Hep11迁移和侵袭的能力.结果 36名有随访结果并可评估的患者中,KLF17 0 ～2分19人,3～5分的17人.KLF17 3～5分的患者无进展生存期较0～2分的患者长,有统计学差异,分别为(39.3±4.2)个月和(23.4±4.9)个月(P＜0.05).KLF17 3～5分的患者总生存为(46.9±3.2)个月,KLF17 0 ～2分的患者为(35.2±4.2)个月(P＜0.05).在原代培养肝癌细胞中,来自原发灶的Hep11比来自转移复发灶的Hep12的KLF17表达高,Hep11的KLF17干扰后,迁移和侵袭能力增强(P＜0.05).结论 KLF17表达可能是肝癌患者预后的独立预测因素.     

肝癌相关肿瘤标志物研究新进展

肝细胞癌( hepatocellular carcinoma, HCC )是常见的恶性肿瘤之一,其发病隐匿,恶性程度高,病死率高,因此早期诊断对于提高患者的生存率至关重要.目前临床上主要运用甲胎蛋白(alpha-fetoprotein, AFP )结合影像学及病理学检查进行肝癌的早期诊断;但是AFP对于肝癌筛查的特异性...     

MYH9在人肝癌组织中的表达及其对肝细胞系增殖和凋亡的影响

目的探讨非肌肉肌球蛋白重链(MYH9)在肝癌组织中的表达及通过沉默MYH9基因对肝癌细胞系SMMC-7721的增殖及凋亡的影响。方法收集50组人肝癌组织及癌旁组织,选用人肝癌细胞系SMMC-7721和Hep G2及人正常肝细胞系LO2,免疫组织化学方法及Western blot检测肝癌组织及癌旁组织中MYH9蛋白的表达,Western blot检测SMMC-7721、Hep G2及LO2中MYH9蛋白的表达;将MYH9 siRNA转染SMMC-7721,CKK8法及流式细胞术检测沉默MYH9对肝癌细胞增殖及细胞凋亡的影响。结果 MYH9蛋白在肝癌组织中的表达明显高于癌旁(P0.05);MYH9蛋白在SMMC-7721及Hep G2中的表达均明显高于LO2(P0.05);沉默MYH9基因可抑制细胞增殖(P0.001),促进细胞凋亡(P0.05)。结论 MYH9蛋白在肝癌组织的表达显著高于癌旁组织;MYH9低表达能有效抑制肝癌细胞的增殖,促进其凋亡。     

Adenoid cystic carcinoma of maxillary sinus with metastatic hepatocellular carcinoma. Case report

A case of collision tumor in the left maxillary sinus composed of adenoid cystic carcinoma (ACC) and metastatic hepatocellular carcinoma (HCC) is reported. Radiographic examination revealed masses in the liver and bilateral lung metastases. Histologically, proliferation of tumor cells with resemblance to HCC was observed, in addition to the ACC. For this reason, differential diagnosis between a second primary tumor and metastasis was made. The metastatic lesion immunohistochemically showed positivity for hepatocyte antigen (OCH1E5) and protein induced by vitamin K absence or antagonist II (PIVKA-II), sustaining the HCC diagnosis. Primary ACC and metastatic HCC in the maxillary sinus are rare, and this may therefore be the first case of maxillary sinus tumor with both these elements.     

微小RNA与肝癌发生发展的研究进展

微dxRNA（microRNAs,miRNA）是一类内源性非编码小RNA分子,miRNA不仅参与各种细胞生理活动（如细胞增殖、分化、凋亡等）,还与肿瘤发生发展关系密切。研究表明miRNA可通过与靶mRNA的3’非编码区互补配对,使得靶mRNA降解或翻译抑制,从而在转录后水平调控基因表达。肝细胞癌是威胁人类健康的恶性肿瘤之一,深入了解miRNA及其在肝细胞癌进程中的作用,将为HCC的分子机制研究提供新的思路。     

Subcutaneous tumor seeding following needle core biopsy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary hepatic tumor and one of the most common cancers worldwide. At present, there are two widely used and accepted methods for obtaining diagnostic material for establishing the likelihood of malignancy in a hepatic mass, namely fine-needle aspiration (FNA) cytology and needle core biopsy (NCB). In recent years, however, tumor cell seeding along the needle tract has been shown to be a risk associated with using these procedures to obtain a pathologic diagnosis. We report a case of a patient who presented with a nodule in the anterior abdominal wall at the expected location of the previous NCB tract. FNA biopsy of the abdominal wall lesion confirmed the presence of malignant cells consistent with HCC. The finding of tumor seeding within a NCB tract raises the question of the role of NCB in the diagnostic workup of focal liver lesions.     

Functional implication of truncated P-cadherin expression in malignant melanoma

Cadherins comprise Ca(2+)-dependent homophilic cell-cell adhesion molecules which are responsible for correct location of cells and for tissue integrity. They are crucial factors for the development and maintenance of epithelial architecture. Aberrantly expressed cadherins are known to be involved in malignant transformation of different types of tissues. In a previous study, we determined the expression of a short truncated 50 kDa form of P-cadherin only consisting of the N-terminal part in malignant melanoma. Further analysis revealed that this short 50 kDa form of P-cadherin representing the N-terminal, extracellular region, is secreted by melanoma cells in contrast to the membrane bound form in melanocytes. In order to define the functional relevance of expression of the 50 kDa P-cadherin variant in malignant melanoma, antisense P-cadherin cell clones were generated. The clones in which P-cadherin expression is reduced show no changes in proliferation or in attachment-independent growth when compared to controls. However, a strong reduction of migratory and invasive properties was observed in these cells, suggesting that truncated P-cadherin promotes melanoma cell invasion and migration and therefore has an important role in the progression of malignant melanoma. Functionally, the secreted form of P-cadherin could play a role as regulator of the homophilic interaction between P-cadherin molecules by antagonizing their biological role acting as a dominant negative form to interrupt cell-cell attachment.     

HAX-1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation

Hepatocellular carcinoma (HCC) is the most common primary liver tumor. Due to the asymptomatic nature of early HCC and lack of effective screening strategies, 80% of patients present with advanced HCC at the time of diagnosis. Novel molecular marker identification will be valuable for effective diagnosis and treatment. In this study we reported HCLS1-associated protein X-1 (HAX-1) is overexpression in HCC in human HCC sample. Furthermore, we provided evidence that HAX-1 expression positively correlated with that of Ki67 in patient sample. Statistic analysis indicated that HAX-1 expression level significantly correlated with clinic outcome of HCC. Cell based assay revealed that knockdown of HAX-1 inhibits cell proliferation. This result suggests that HAX-1 can be a novel molecular marker for HCC.     

三氧化二砷对肝细胞癌组织ezrin基因表达的影响

目的探讨三氧化二砷（As2O3）对肝细胞癌（HCC）组织ezrin基因表达及血清甲胎蛋白（AFP）水平的影响。方法 24例可切除HCC患者,其中男性20例,女性4例;年龄42～74岁,平均年龄为58.6岁。术前接受As2O3治疗14d（10mg/d,静脉滴注）。取治疗前的病灶活组织检查标本和治疗后手术切除标本,采用免疫组织化学方法均行ezrin表达检测,同时比较治疗前、后血清AFP水平的变化,并分析血清AFP水平与ezrin基因表达的相关性。结果治疗前ezrin表达强阳性、弱阳性和阴性例数分别为6例、7例和11例,而As2O3治疗后分别为2例、5例和17例,两组比较差异有统计学意义（χ2=5.619,P〈0.05）。治疗前血清AFP为325.5ng/L,治疗后AFP为278.6ng/L,前后比较差异有统计学意义（Z=-2.360,P〈0.05）。结论 As2O3可明显下调HCC肿瘤细胞ezrin表达,有抑制HCC细胞生长、抑制复发转移的作用。     

MDA-7/IL-24真核表达载体的构建和重组腺病毒的制备及其对肝癌细胞生长抑制作用的研究

目的:构建含有MDA-7基因的的真核表达载体并制备重组腺病毒,转染/感染肝癌细胞后,观察其对细胞增殖的影响.方法:构建MDA-7的真核表达载体,将表达质粒转染肝癌细胞,利用平板克隆形成实验观察MDA-7分子对肿瘤细胞系克隆形成能力的影响.利用Adeasy-1腺病毒重组系统构建、包装并扩增含有MDA-7基因的重组腺病毒.利用MTT实验检测Ad-MDA-7对肿瘤细胞增殖的影响.结果:成功构建了MDA-7真核表达载体,利用平板克隆形成实验证实其可抑制肝癌细胞的克隆形成能力.成功地构建并包装了含有MDA-7基因的重组腺病毒,利用MTT实验证明其可抑制肝癌细胞的增殖.结论:MDA-7对肝癌细胞的增殖具有显著的抑制作用,为进一步研究其在肝癌细胞中的功能提供了重要的实验依据.     

Enhanced CD34 expression of sinusaid-like vascular endothelial cells in hepatocellular carcinoma

The immunohistochemlcal expression of CD34 (human hematopoletic stem cell and endothelial cell marker) and laminin were studied In chronic liver diseases and hepate cellular carcinoma (HCC) to elucidate whether their expression reflected phenotypic differences between non-cancerous slnusoids and sinusoid-like tumor vessels. In normal liver, hepatic sinusoids were always negative for CD34 and lami-nin. In chronic hepatitis and cirrhosis, the two antigens were sparsely expressed in capillarized sinusoids at periportal and petinodular area. In advanced HCC, CD34 was strongly and diffusely expressed by the endothelial lining of sinusoid-like tumor vessels. However, early-stage HCC showed a wide spectrum of CD34 expression from negative to focal and diffuse, strongly positive staining in sinusoid-like vessels. Laminin was strongly expressed in advanced HCC but not in early-stage HCC. The results Indicate that the enhanced expression of CD34 by sinusoidal endothelial cells may reflect the phenotypic change of endothellal cells in chronic liver diseases and HCC, and that the expression may correlate with the processes of angiogenesis induced by hepatocarcinogenesis.     

Expression of Girdin in primary hepatocellular carcinoma and its effect on cell proliferation and invasion

Girdin has been proven to play a vital role in the process of proliferation, apoptosis, and invasion in various cancer cells, yet the underlying molecular mechanism in primary hepatocellular carcinoma (HCC) has not yet been clarified. Thereafter, we performed immunohistochemistry to detect the expression of Girdin in 40 primary HCC tissues and 30 matched adjacent tissues using hepatic carcinoma tissue microarray. Our data showed that the positive expression rate of Girdin in hepatocellular carcinoma tissues was 67.5%, higher than that found in adjacent tissues of 16.7% (P < 0.05). It closely correlates to tumor size, T stage, TNM stage and Edmondson-Steiner stage (P < 0.05) of HCC patients. After specific small interfering RNA of Girdin was transfected into HepG2 and Huh7.5.1 cells, the proliferation and invasion ability of tumor cells were significantly inhibited. In summary, we suggest that the oncogenic role of Girdin could provide new molecular target for the treatment of HCC.