Renal epithelioid angiomyolipoma with malignant features: Histological evaluation and novel immunohistochemical findings

Renal epithelioid angiomyolipoma (EAML) is a potentially malignant tumor type whose characteristics and biomarkers predictive of malignant behavior have not been elucidated. Here, we report three cases of renal EAML with malignant features but without histories of tuberous sclerosis complex. Case 1 involved a 29‐year‐old man with a 12‐cm solid mass in the right kidney who underwent radical right nephrectomy. Case 2 involved a 22‐year‐old woman with a retroperitoneal mass who underwent radical right nephrectomy and retroperitoneal tumorectomy. Local recurrence was detected 7 years post‐surgery. Case 3 involved a 23‐year‐old man with a 14‐cm solid mass in the left kidney who underwent radical left nephrectomy. Microscopically, the tumors in all cases demonstrated proliferation of epithelioid cells with atypia, mitotic activity, necrosis, hemorrhage, and vascular invasion. Epithelioid cells in all cases were immunohistochemically positive for melanocytic and myoid markers and weakly positive for E‐cadherin and β‐catenin. Immunohistochemistry revealed activation of the mammalian target of rapamycin pathway. Here, we report the morphological and immunohistochemical features of clinically or histologically malignant renal EAML.     

Increased extracellular matrix density decreases MCF10A breast cell acinus formation in 3D culture conditions

The extracellular matrix (ECM) contributes to the generation and dynamic of normal breast tissue, in particular to the generation of polarized acinar and ductal structures. In vitro 3D culture conditions, including variations in the composition of the ECM, have been shown to directly influence the formation and organization of acinus‐like and duct‐like structures. Furthermore, the density of the ECM appears to also play a role in the normal mammary tissue and tumour formation. Here we show that the density of the ECM directly influences the number, organization and function of breast acini. Briefly, non‐malignant human breast MCF10A cells were incubated in increasing densities of a Matrigel®–collagen I matrix. Elastic moduli near and distant to the acinus structures were measured by atomic force microscopy, and the number of acinus structures was determined. Immunochemistry was used to investigate the expression levels of E‐cadherin, laminin, matrix metalloproteinase‐14 and ß‐casein in MCF10A cells. The modulus of the ECM was significantly increased near the acinus structures and the number of acinus structures decreased with the increase in Matrigel–collagen I density. As evaluated by the expression of laminin, the organization of the acinus structures present was altered as the density of the ECM increased. Increases in both E‐cadherin and MMP14 expression by MCF10A cells as ECM density increased were also observed. In contrast, MCF10A cells expressed lower ß‐casein levels as the ECM density increased. Taken together, these observations highlight the key role of ECM density in modulating the number, organization and function of breast acini. Copyright © 2013 John Wiley & Sons, Ltd.     

N- cadherin, E- cadherin and β- catenin expressions in human brainstem gliomas

Objective To explore the expression and significance of N - cadherin, E - cadherin and β - catenin in human brainstem gliomas. Methods N - cadherin, E - cadherin and β - catenin proteins and mRNA were detected in 38 cases of brainstem gliomas using immunohistochemistry and RT - PCR Methods. Results There was no significant difference in the expression of N - cadherin between grades Ⅰ ～ Ⅱ and grade Ⅲ ～ Ⅳ ( P ＞ 0. 05) . The expression of N - cadherin mRNA in human brainstem gliomas of grade Ⅰ ～ Ⅱ was significantly lower than that in grade Ⅲ～ Ⅳ ( t = 2. 711, P ＜ 0. 05 ). There was no significant difference in the expression of E - cadherin and E - cadherin mRNA between grade Ⅰ ～ Ⅱ and grade Ⅲ～ Ⅳ ( P ＞ 0. 05 ). The expression of β - catenin in human brainstem gliomas of grade Ⅰ ～ Ⅱ was significantly lower than that in grade Ⅲ ～ Ⅳ ( P ＜ 0. 05 ). As regard to β -catenin mRNA, there was no significant difference between grade Ⅰ ～ Ⅱ and grade Ⅲ ～ Ⅳ ( P ＞ 0. 05 ). Conclusions The over -expressionof N - cadherin and β - catenin may play an important role in the invasion and malignant progression of human brainstem gliomas.     

SiRNA干扰LI-cadherin对荷人肝癌裸鼠移植瘤的影响

目的 研究肝肠粘连蛋白(liver intestine cadherin,LI-cadherin)在荷瘤裸鼠体内对肝癌细胞Hep3B侵袭转移能力的作用.方法 体外培养肝癌细胞株Hep3B,并进行针对LI-cadherin的SiRNA转染.将Hep3B细胞及转染后的肿瘤细胞接种入裸鼠脾脏,建立裸鼠荷瘤模型.观察成瘤及转移效果,免疫组化检测转移灶组织结构,Western blot方法检测转染前后荷瘤裸鼠体内肿瘤转移灶中LI-cadherin的表达.结果 (1)SiRNA质粒转染入Hep3B肝癌细胞,转染率达到80％.(2)建立裸鼠荷人肝癌模型,30只裸鼠移植手术后均成活,荷瘤率达到60％以上.SiRNA转染组荷瘤率为80％,转移灶个数为26个,明显高于空白对照组和空质粒转染组.(3)裸鼠体内转移灶中Ll-cadherin 的含量SiRNA转染组明显低于空白对照组和空质粒转染组.结论 LI-cadherin对肝癌细胞的黏附能力有重要作用,对LI-cadherin进行SiRNA干扰可增强肝细胞癌在裸鼠体内的侵袭转移能力.     

Human oral keratinocyte E‐cadherin degradation by Candida albicans and Candida glabrata

J Oral Pathol Med (2010) 39 : 275–278 Background: E‐cadherin (E‐Cad) is a 120‐kDa adhesive protein found in adherens junctions of the digestive tract epithelium. We tested the ability of two Candida strains to degrade human E‐Cad in the Candida virulence factor perspective. Materials and methods: We set out to study oral mucosal E‐Cad degradation by clinical and reference strains of Candida albicans and Candida glabrata. We also included hyphal and secreted aspartic proteinase (Sap) mutants of C. albicans to test the effect of yeast/hyphal transition on the ability to degrade E‐Cad. The tests were performed at pH 4 and pH 6 to determine the effect of local tissue acidity on the activation of Saps. The C. albicans strains used were: CCUG 32723; clinical strain SC5314 which is known to be strongly invasive; hyphal mutants of SC5314: HLC52 (efg1/efg1), HLC54 (cph1/cph1 efg1/efg1) and JKC19 (cph1/cph1); clinical strain B1134; Sap 1–3 and Sap 4–6 mutants of SC5314. The C. glabrata strains used were ATCC 90030, and the clinical strains 5WT and G212. Results: The sonicated yeast cells of C. albicans JKC19 and SC5314, both in hyphal form, degraded E‐Cad at pH 4. The 10× concentrated growth media of the strains HLC‐52, HLC‐54, 32723 and B1134; all in yeast form, caused degradation at pH 4, HLC‐52 and HLC‐54 also at pH 6. The C. glabrata strains did not degrade E‐Cad. Conclusions: pH is a strain dependent triggering factor in activating yeast or hyphal form related Candida Saps in degrading epithelial cell associated E‐Cads.     

Lysophosphatidic acid regulates adhesion molecules and enhances migration of human oral keratinocytes

Oral keratinocytes are connected via cell‐to‐cell adhesions to protect underlying tissues from physical and bacterial damage. Lysophosphatidic acids (LPAs) are a family of phospholipid mediators that have the ability to regulate gene expression, cytoskeletal rearrangement, and cytokine/chemokine secretion, which mediate proliferation, migration, and differentiation. Several forms of LPA are found in saliva and gingival crevicular fluid, but it is unknown how they affect human oral keratinocytes (HOK). The aim of the present study was therefore to examine how different LPA forms affect the expression of adhesion molecules and the migration and proliferation of HOK. Keratinocytes were isolated from gingival biopsies obtained from healthy donors and challenged with different forms of LPA. Quantitative real‐time RT‐PCR, immunocytochemistry, and flow cytometry were used to analyze the expression of adhesion molecules. Migration and proliferation assays were performed. Lysophosphatidic acids strongly promoted expression of E‐cadherin and occludin mRNAs and translocation of E‐cadherin protein from the cytoplasm to the membrane. Occludin and claudin‐1 proteins were up‐regulated by LPA. Migration of HOK in culture was increased, but proliferation was reduced, by the addition of LPA. This indicates that LPA can have a role in the regulation of the oral epithelial barrier by increasing the expression of adhesion molecules of HOK, by promotion of migration and by inhibition of proliferation.     

复方藤梨根制剂对PG荷瘤裸鼠Cx43基因表达水平及E-钙粘附素影响的研究

Objective： To study the anticancer effect of Chinese compound recipe FuFangTengLiGen （FFTLG） against transplantation tumor of PG cell and preliminarily explore the connection with connexin43 （Cx43） and epithelial cadherin （E-cad）. Methods： Model rats of transplantation tumor of human large cell cancer PG were established. The low, medium and high dose groups of FFTLG, the blank control group were set up. After 21 days medication of FFTLG through gastrogavage, the antitumor effect of each group was compared. The gene expressions of Cx43 and E-cad in each group were quantitatively detected and compared by the application of immunohistochemistry technique. Results： FFTLG could significantly inhibit the growth of transplantation tumor. FFTLG could obviously up-regulate the expressions of Cx43 and E-cad, which in the low/medium and high dose groups were separately higher than that in the blank group. Conclusion： FFTLG has definite antitumor effect against human large cell cancer and can obviously up-regulate the expressions of Cx43 and E-cad, which may be correlated with its effect of anti-tumor.     

E-cad与ICAM-1在泌尿生殖系统肿瘤中的研究进展

细胞粘附分子（cellular adhesion molecules，CAMs）是位于细胞表面的糖蛋白。它通过介导细胞与细胞、细胞与外基质间的相互作用，参与多细胞生物的多种生理及病理过程。E-钙粘附素（E-cad）与细胞间粘附分子-1（ICAM-1）是两种重要的细胞粘附分子，与多种肿瘤的发生发展以及浸润转移关系十分密切，近年来正成为研究的重点和热点。现就E-cad、ICAM-1在泌尿生殖系统肿瘤中的研究现状特别是与肿瘤的侵袭、浸润与转移关系作一综述。     

可溶性上皮型钙黏附蛋白在大肠癌患者血清中检测的临床意义

目的检测大肠癌患者血清可溶性上皮型钙黏附蛋白（sE—cad）与癌胚抗原（CEA）含量的变化及临床意义。方法采用酶联免疫吸附法分别检测125例大肠癌患者（大肠癌组）、33例炎症性肠病患者（炎症性肠病组）及30例健康志愿者（正常组）血清sE—cad与CEA的含量，并分别检测大肠癌患者术后各亚组血清sE—cad与CEA的含量；同时观察sE—cad含量与大肠癌病理特征的关系。结果与正常组比较，大肠癌组、术后1周亚组及肿瘤复发亚组血清sE—cad与CEA含量显著升高（P〈0．01），术后1周亚组、术后1个月亚组、术后6个月亚组、术后1年亚组血清sE—cad与CEA含量较大肠癌组显著降低（P〈0．01），而肿瘤复发亚组与大肠癌组比较差异无统计学意义（P〉0．05），炎症性肠病组与正常组比较差异无统计学意义（P〉0．05）。大肠癌组血清sE—cad含量与分化程度、临床Duke分期均呈显著正相关。结论血清sE—cad含量变化与大肠癌的发生、发展密切相关，可作为一种新的大肠癌标志物，对判断预后与复发有一定价值。