Human papillomavirus tumor infection in esophageal squamous cell carcinoma

The association between human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) has been recognized for over three decades. Recently, multiple meta-analyses have drawn upon existing literature to assess the strength of the HPV-ESCC linkage. Here, we review these analyses and attempt to provide a clinically-relevant overview of HPV infection in ESCC. HPV-ESCC detection rates are highly variable across studies. Geographic location likely accounts for a majority of the variation in HPV prevalence, with high-incidence regions including Asia reporting significantly higher HPV-ESCC infection rates compared with low-incidence regions such as Europe, North America, and Oceania. Based on our examination of existing data, the current literature does not support the notion that HPV is a prominent carcinogen in ESCC. We conclude that there is no basis to change the current clinical approach to ESCC patients with respect to tumor HPV status.     

Upregulated β1-6 branch N-glycan marks early gliomagenesis but exhibited biphasic expression in the progression of astrocytic glioma

Glioma is the world’s commonest primary brain malignancy with much of its biology relating to translational and post-translational events still unknown. In this study, we investigated the clinicopathological significance of N-linked β1-6-GlcNAc branches and GnT-V enzyme in the development and progression of astrocytic glioma. Expression of GnT-V and its GlcNAc-β1-6 oligosaccharides by-product together with Con-A binding sugars were assessed immunohistochemically on tissue microarrays of 16 normal brain and 159 tissue samples of astrocytomas of variable grades and histology. Although tissues of both grade I astrocytomas and normal brain showed considerably higher GnT-V expression, GlcNAc-β1-6 expression was significantly high only in tissues of grade I astrocytomas (p < 0.001), which is attributable to elevated levels of the precursor Con-A binding sugar moieties (p < 0.001). The activity of GnT-V enzyme was found to be dependent on the degree of glioma pathogenesis, as the GlcNAc-β1-6 branched expression diminished with every progressive grade of glioma, reaching minimum in glioblastoma (p < 0.001). Having biphasic activity in gliomagenesis, the role of GnT-V in glioma was deciphered by generating different ectopic GnT-V expressions in U-87 cells, which showed the highest GnT-V expression among selected glioma cell lines. Transient GnT-V rescue was achieved in knockdown clones by transfection with GnT-V expression vector. Suppression of GnT-V in U-87 cells slowed cell proliferation with G0/G1 cell cycle phase arrest. Reduced tumorigenicity, invasiveness and cell-ECM interactions were also associated with suppressed in vitro GnT-V activity suggesting GnT-V may act as an oncoprotein. We report for the first time that GnT-V products are involved in early gliomagenesis but their reduced expression, correlating with low Con-A binding sugars level found in high tumor grades predicts the loss of total N-glycosylation in glioma development and may be of potential diagnostic and/or prognostic value in astrocytoma.     

Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis

Glioma is the most aggressive brain tumor with high invasiveness and poor prognosis. More reliable, sensitive and practical biomarkers to reveal glioma high invasiveness remain to be explored for the guidance of therapy. We herein evaluated the diagnostic and prognostic value of aldehyde dehydrogenase 1A1 (ALDH1A1) in the glioma specimens from 237 patients, and found that ADLH1A1 was frequently overexpressed in the high-grade glioma (WHO grade III-IV) as compared to the low-grade glioma (WHO grade I-II) patients. The tumor cells with ALDH1A1 expression were more abundant in the region between tumor and the borderline of adjacent tissue as compared to the central part of the tumor. ALDH1A1 overexpression was associated with poor differentiation and dismal prognosis. Notably, the overall and disease-free survivals of the patients who had ALDH1A1⁺ tumor cells sparsely located in the adjacent tissue were much worse. Furthermore, ALDH1A1 expression was correlated with the “classical-like” (CL) subtype as we examined GBM specimens from 72 patients. Multivariate Cox regression analysis revealed that ALDH1A1 was an independent marker for glioma patients’ outcome. Mechanistically, both in vitro and in vivo studies revealed that ALDH1A1⁺ cells isolated from either a glioblastoma cell line U251 or primary glioblastoma cells displayed significant invasiveness, clonogenicity, and proliferation as compared to ALDH1A1^- cells, due to increased levels of mRNA and protein for matrix metalloproteinase 2, 7 and 9 (MMP2, MMP7 and MMP9). These results indicate that ALDH1A1⁺ cells contribute to the progression of glioma including invasion, proliferation and poor prognosis, and suggest that targeting ALDH1A1 may have important implications for the treatment of highly invasive glioma.     

MicroRNA-320a inhibits proliferation and invasion of breast cancer cells by targeting RAB11A

MicroRNAs (miRNAs) are deregulated in many types of cancer including breast cancer (BC). miR-320a dysregulation has been associated with different malignancies although its prognostic significance remains unclear. Here, we examined the role of miR-320a in BC and explored the underlying mechanisms. Our results showed that miR-320a was significantly downregulated in BC cell lines and tissues, and its ectopic expression inhibited cell proliferation, migration, and invasion in vitro and tumor growth in a mouse xenograft model. We identified Rab11a as a direct target of miR-320a and showed that its expression was upregulated in tumor samples and inversely correlated with the expression of miR-320a. In BC cells, the downregulation of Rab11a through miR-320a was concomitant with the inactivation of Akt. Overexpression of Rab11a abrogated miR-320a-induced inhibition of BC growth and invasion. These results suggest that miR-320a may act as a tumor suppressor in BC through a mechanism involving the modulation of Rab11a expression and the activation of the Akt signaling pathway. miR-320a may therefore serve as a biomarker for BC, and the modulation of its expression may represent a novel therapeutic strategy in BC treatment.     

A vaccine against Alzheimer`s disease: anything left but faith?

Introduction: Alzheimer’s disease looms as a profound and growing threat to future human health. The disease is thought to be primarily driven by aberrant proteolysis of the amyloid precursor protein (APP) and amyloid beta (Aβ) plaque deposition.

Areas covered: We provide an overview of the molecular pathology that leads to an increase in Aβ peptide accumulation, of the mechanism of action for antibody mediated therapies and of the therapeutic vaccines that target Aβ under development. We also discuss the rationale for using vaccines in the early stages of the disease.

Expert opinion: The major components of β-amyloid plaques are Aβ_1-42 and Aβ_1-40 peptides derived from the APP. Reducing these plaques by means of passive or active vaccination against Aβ-peptides has been a long-running endeavor but with disappointing results as the impact on disease progression has been minimal. The data gathered to date could suggest that antibodies do not work, mainly because the studies have not been performed in an optimal fashion. The emerging views are that patients should be treated earlier, ideally in the prodromal or symptom free stage, antibody levels have to be high and the correct epitope must be targeted. More clinical trials to fully explore the potential of vaccines are therefore warranted.     

急性心肌梗死患者血浆BNP、ET、CRP、ANP水平变化与临床观察分析

目的　观察急性心肌梗死 (AMI)患者血浆中B型钠尿肽 (BNP)、内皮素 (ET)、C 反应蛋白 (CRP)、A型钠尿肽 (ANP)水平变化 ,为治疗及预后判断提供依据。方法　应用酶联免疫法及免疫放射分析法对 4 6例AMI患者治疗前后和 30名正常对照者血浆中BNP、ET、CRP、ANP水平进行检测。结果　AMI患者血浆中BNP、ET、CRP、ANP治疗前后比较差异有显著性 (P <0 .0 0 1) ,正常对照组与AMI治疗前比较差异有显著性 (P<0 .0 0 1) ,BNP与CRP在AMI治疗前水平呈正相关 (r =0 .874 ) ,治疗后呈明显的下降趋势 (r =0 .6 5 4 ) ,AMI治疗前后ANP与ET呈正相关 ,但AMI经溶栓和相应的支持治疗后ANP基本恢复到正常水平 (P >0 .0 5 ) ,而BNP、ET、CRP水平虽然下降明显 ,但与正常组比较差异仍有显著性 (P <0 .0 5 )。结论　AMI患者血浆中BNP、ANP、ET、CRP水平的变化说明其参与了AMI的发生、发展 ,特别是冠状动脉粥样斑块的形成和 (或 )破裂及血栓形成 ,其炎症因子是主要因素。因此 ,4项指标的观察分析对AMI治疗、预后判断具有重要意义     

黄芩甙对肾盂肾炎大鼠肾脏表面活性蛋白A表达的影响

目的：探讨正常及肾盂肾炎大鼠肾脏表面活性蛋白A（SP-A）的表达变化及黄芩甙对SP-A表达的影响。方法：将24只雄性Wistar大鼠随机分成4组,每组6只,A组：假手术＋生理盐水;B组：假手术＋黄芩甙;C组：模型＋生理盐水;D组：模型＋黄芩甙。用致肾盂肾炎大肠杆菌（uropathogenic E．coli）制备Wistar大鼠急性肾盂肾炎模型。采用免疫组化方法观察肾组织SP-A的表达,用逆转录聚合酶链反应（RT-PCR）方法观察SP-A mRNA的表达变化。结果：假手术组肾组织SP-A蛋白主要表达于肾小管上皮细胞,以外髓质处较为明显。模型组中SP-A表达的肾小管数量明显增多,染色变深,其阳性表达率于造模后显著高于假手术组,SP-A mRNA表达显著增强（P〈0．05）,模型＋黄芩甙组中SP-A的表达较模型＋生理盐水组增强（P〈0．05）。结论：本实验证实了肾组织SP-A蛋白主要表达于小管上皮细胞,以外髓质处明显。急性肾盂肾炎模型大鼠的SP-A蛋白表达增高,SP-A mRNA表达增强。SP-A可能在急性肾盂肾炎的发病过程中起着重要的防御作用。