D2-40 and podoplanin are highly specific and sensitive immunohistochemical markers of epithelioid malignant mesothelioma

Recent investigations have shown that podoplanin and the D2-40 monoclonal antibody, which reacts with an oncofetal antigen present in fetal germ cells, are highly reliable lymphatic endothelial markers. The observation that both of these markers are also expressed in normal and reactive mesothelial cells prompted an investigation into their potential value in the diagnosis of mesotheliomas. To determine whether podoplanin and D2-40 had any use in the diagnosis of these tumors, 40 mesotheliomas (29 epithelioid, 5 biphasic, and 6 sarcomatoid), 34 carcinomas of the lung (24 adenocarcinomas, 10 squamous carcinomas), 80 nonpulmonary adenocarcinomas (17 ovary, 10 breast, 10 colon, 10 kidney, 5 endometrium, 5 stomach, 5 pancreas, 5 prostate, 3 thyroid), 12 synovial sarcomas (6 biphasic and 6 monophasic), 5 angiosarcomas, and 2 adenomatoid tumors were immunostained with a monoclonal antibody to podoplanin and with the D2-40 antibody. Reactivity for both D2-40 and podoplanin was obtained in 25 (86%) of the 29 epithelioid mesotheliomas but in none of the carcinomas or sarcomatoid mesotheliomas. Positivity for D2-40 and podoplanin was also seen in the epithelioid components of 4 of 5 biphasic mesotheliomas and 4 of 6 synovial sarcomas, whereas the spindle cell components of these tumors were negative as were the monophasic synovial sarcomas. Two (40%) of the 5 angiosarcomas expressed these markers, thus confirming previous reports suggesting that some angiosarcomas may have lymphatic endothelial differentiation. Both of the adenomatoid tumors were also positive for D2-40 and podoplanin, a finding which provides further support for the mesothelial derivation of these tumors. It is concluded that, because of their high specificity and sensitivity for epithelioid mesotheliomas, D2-40 and podoplanin are very useful markers for the diagnosis of these tumors. When compared with the other markers that are currently available, in my opinion, they appear to be the best.     

麻杏石甘汤对哮喘模型小鼠气道重塑及肺组织MMP-9和TIMP-1表达的影响

目的:观察麻杏石甘汤对哮喘模型小鼠气道重塑及肺组织基质金属蛋白酶9(MMP-9)和金属蛋白酶组织抑制物1(TIMP-1)表达的影响,探讨其治疗哮喘的可能机制。方法:将72只健康雌性BALB/c小鼠随机分为:空白对照组,模型组,麻杏石甘汤低剂量组、中剂量组和高剂量组,阳性对照组。采用卵清蛋白致敏激发建立小鼠哮喘模型。空白对照组和模型组于激发前30 min以生理盐水灌胃;麻杏石甘汤低剂量组、中剂量组和高剂量组分别于激发前30 min以麻杏石甘汤按5.0 g/kg、10.0 g/kg和20.0 g/kg剂量灌胃;阳性对照组于激发前30 min以地塞米松按0.005 g/kg剂量灌胃。连续给药7 d后,观察气道反应性、支气管肺泡冲洗液(BALF)中嗜酸性粒细胞(EOS)计数、杯状细胞百分比和胶原沉积的变化;ELISA法检测MMP-9和TIMP-1水平;Western blot法检测MMP-9和TIMP-1的蛋白表达;RT-qPCR法分析检测MMP-9和TIMP-1的mRNA表达。结果:与空白对照组比较,模型组的气道反应性、杯状细胞百分比、胶原沉积、BALF中EOS计数及肺组织MMP-9和TIMP-1的mRNA和蛋白水平均显著升高(P 0.01);与模型组比较,麻杏石甘汤低剂量组、中剂量组和高剂量组及阳性对照组上述指标则明显降低(P 0.05或P 0.01)。结论:麻杏石甘汤可能通过降低MMP-9和TIMP-1的表达改善哮喘模型小鼠气道重塑状态。     

Elevated expression of E-cadherin and α-, β-, and γ-catenins in metastatic lesions compared with primary epithelial ovarian carcinomas

E-cadherin and catenins play key roles in cell adhesion and motility. Little is known about the changes in expression of these molecules in the progression of ovarian carcinomas. In the present study, the immunohistochemical expression of E-cadherin and α-, β-, and γ-catenins was examined in 77 cases of ovarian carcinoma. In addition, the expression of these molecules was evaluated in 26 matched pairs of primary and metastatic lesions of advanced ovarian carcinomas. Of the 77 primary lesions, positive staining for E-cadherin and α-, β-, and γ-catenin was observed in 75 (97%), 63 (82%), 71 (92%) and 57 (74%) cases, respectively. Positivity for E-cadherin and α-, β-, and γ-catenin was significantly decreased in stage III and IV tumors compared with stage I and II tumors, suggesting that expression of the cadherin-catenin complex is reduced with the advancing stages of a tumor. Interestingly, expression of E-cadherin and α-, β-, and γ-catenin in the lesions of peritoneal dissemination was significantly increased compared with the primary lesions. These findings suggest that expression of the cadherin-catenin complex changes markedly and that reexpression may occur during the peritoneal dissemination of ovarian carcinoma cells.     

Anti-viral immune responses in a primitive lung: Characterization and expression analysis of interferon-inducible immunoproteasome subunits LMP2, LMP7 and MECL-1 in a sarcopterygian fish,the Nigerian spotted lungfish (Protopterus dolloi)

Lungfishes (Dipnoi) represent the closest ancestor of tetrapods. Dipnoi have dual breathing modes extracting oxygen from water and air. The primitive lungs of lungfishes are exposed to external antigens including viruses. To date, the immune response of lungfishes against viruses has not been investigated. During viral immune responses, cell exposure to type I interferon induces the replacement of the constitutive proteasome with LMP2, LMP7 and MECL-1 beta subunits forming the immunoproteasome and enhancing antigen presentation to MHC class I molecules. In order to study the immune defense system of the lungfish lung, we have characterized for the first time the three immunoproteasome subunits in the sarcopterygian fish, the Nigerian spotted lungfish (Protopterus dolloi). LMP2, LMP7 and MECL-1 were identified in P. dolloi and their sequences encoded predicted proteins of 216, 275 and 278 amino acids, respectively. The mRNA of these three genes was expressed in multiple tissues, including the lung, with the highest abundance observed in kidney and post-pyloric spleen. In vitro stimulation of lungfish lung and kidney primary cell cultures with PolyI:C for 4 and 12 h resulted in increased LMP2, LMP7 and MECL-1 expression in both tissues. These results suggest a central role of these genes in the activation of an antiviral immune response in lungfish. Importantly, they indicate that the primitive lung of the common ancestor of all tetrapods is capable of inducing the expression of these genes in response to viral stimulation.