MicroRNAs involved in the EGFR/PTEN/AKT pathway in gliomas

Gliomas are the most common type of malignant primary brain tumor. Despite advances in surgery, radiation therapy, and chemotherapy, the prognosis of patients with gliomas has not significantly improved. MicroRNAs (miRNAs), a class of non-coding RNAs, 21–25 nucleotides long, negatively regulate the expression of target genes by interacting with specific sites in mRNAs, and play a critical role in the development of gliomas. The EGFR/PTEN/AKT pathway is a promising target for anti-glioma therapy. Recent studies have showed that regulation of the EGFR/PTEN/AKT pathway by miRNAs plays a major role in glioma progression, indicating a novel way to investigate the tumorigenesis, diagnosis, and therapy of gliomas. Here, we focus on recent findings of miRNAs with respect to the EGFR/PTEN/AKT pathway in gliomas.     

Downregulated Dicer expression predicts poor prognosis in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Alterations in microRNAs (miRNAs) expression have been proposed to play a role in CLL pathogenesis. Dicer and Drosha are the main regulators of miRNA biogenesis, and deregulation of their expression has been indicated as a possible cause of miRNA alterations observed in various cancers. To investigate the role of Dicer and Drosha in CLL, we assessed the expression of Dicer and Drosha and their correlation with other prognostic factors, including Binet stages, immunoglobulin heavy chain variable gene (IGHV) mutation status, TP53 mutation status, ZAP-70 protein and CD38 expression level in 165 CLL patients by using real-time polymerase chain reaction methods. Patients with unmutated IGHV genes had significantly lower expression of Dicer than patients with IGHV mutations. The lower expression level of Dicer was also significantly associated with higher level of CD38 and ZAP-70, and more aggressive Binet stage. We also analyzed Dicer expression in different cytogenetic subgroups. Lower Dicer level was found in patients with unfavorable cytogenetic aberrations (deletion in 17p13 or 11q22.3) in contrast to higher level in good risk cytogenetics (deletion in 13q14 as the sole abnormality). Furthermore, the lower expression of Dicer in CLL shows a strong association with shorter overall survival (OS) (P = 0.0046) as well as with reduced treatment free survival (TFS) (P = 0.0006). By contrast, no differences in the expression of Drosha among these groups of patients were observed. Our data suggest that Dicer expression may play an important role in the progression and prognosis of CLL.     

Distinctive microRNA signature is associated with the diagnosis and prognosis of acute leukemia

MicroRNAs (miRNAs) are of great importance in pathogenesis, diagnosis and prognosis of acute leukemia (AL). We studied five AL-related miRNAs to confirm the significance of these miRNAs in AL. Samples tested included acute myeloid leukemia (AML), 107 cases; acute lymphoblastic leukemia (ALL), 40 cases. Five AL-related miRNAs: miR-128, let-7b, miR-223, miR-181a and miR-155 expression were detected by qRT-PCR. Analysis showed that miRNA-128 expression was significantly higher in ALL (P?相似文献   

Molecular classification of gliomas based on whole genome gene expression: a systematic report of 225 samples from the Chinese Glioma Cooperative Group

Defining glioma subtypes based on objective genetic and molecular signatures may allow for a more rational, patient-specific approach to molecularly targeted therapy. However, prior studies attempting to classify glioma subtypes have given conflicting results. We aim to complement and validate the existing molecular classification system on a large number of samples from an East Asian population. A total of 225 samples from Chinese patients was selected for whole genome gene expression profiling. Consensus clustering was applied. Three major groups of gliomas were identified (referred to as G1, G2, and G3). The G1 subgroup correlates with a good clinical outcome, young age, and extremely high frequency of IDH1 mutations. Relative to the G1 subgroup, the G3 subgroup is correlated with a poorer clinical outcome, older age, and a very low rate of mutations in the IDH1 gene. Correlations of the G2 subgroup with respect to clinical outcome, age, and IDH1 mutation fall between the G1 and G3 subgroups. In addition, the G2 subtype was associated with a higher percentage of loss of 1p/19q when compared with G1 and G3 subtypes. Furthermore, our classification scheme was validated on 2 independent datasets derived from the cancer genome atlas (TCGA) and Rembrandt. With use of the TCGA classification system, proneural, neural, and mesenchymal, but not classical subtype, associated gene signatures were clearly defined. In summary, our results reveal that 3 main subtypes stably exist in Chinese patients with glioma. Our classification scheme may reflect the clinical and genetic alterations more clearly. Classical subtype–associated gene signature was not found in our dataset.     

Meta-analysis on the association between nonsteroidal anti-inflammatory drug use and lung cancer risk

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs), especially aspirin, have emerged as the most potential chemopreventive agents. However, epidemiologic studies reported a controversial association between NSAID use and lung cancer risk. We conducted a meta-analysis to summarize the evidence for such relationship.MethodsEligible studies were identified by searching the electronic literature PubMed, Medline, Embase, and ScienceDirect databases for relevant reports and bibliographies. Studies were included if they designed as cohort study, case-control study, or clinical trial on the NSAID exposure and lung cancer with sufficient raw data to analyzes. Relative risk (RR) or odds ratio (OR) was used to evaluate the association between NSAIDs and lung cancer. Stratified analysis was also performed.ResultsA total of 19 studies including 20,266 lung cancer cases met the inclusion criteria. To the effect of aspirin on lung cancer, the combined RR for cohort studies was 0.96 (95%confidence interval [CI]: 0.78-1.19) and OR for case-control studies was 0.87 (95%CI: 0.69-1.09). When restricted in exposure of aspirin use to 7 tablets per week, the OR was 0.80 (95%CI: 0.67-0.95). The summary risk estimates showed no significant association between non-aspirin NSAID or overall NSAID use and lung cancer risk.ConclusionsAspirin use with a dose of 7 tablets per week can significantly reduce lung cancer risk, whereas non-aspirin NSAIDs showed no chemopreventive value. Greater attention should be paid to identifying appropriate individuals for this new indication of aspirin and the optimal dose and duration as a chemopreventive agent.     

成人下腹壁厚度测量及其对根据指南针原理设计的排尿报警装置的意义

目的　了解正常成人下腹壁厚度,并探讨其相关因素及其对根据指南针原理设计的排尿报警装置的意义。 方法　应用B超连续测量l00例成人的下腹壁及其浅层和深层的厚度,膀胱的前后径、上下径及左右径,并测量身高、体质量、测量点到脐部的距离,计算体质量指数（BMI）和膀胱容量,分析影响下腹壁厚度的相关因素。 结果　本组成人的下腹壁厚度(23.4±6.6)mm,95%可信区间为22.1～24.7　mm,与下腹壁深层厚度、浅层厚度和BMI、体质量、测量点到脐部的距离呈正相关(P<0.05),与膀胱容量、膀胱的上下径和左右径呈负相关(P<0.05),而与性别、身高、年龄、膀胱的前后径无相关性(P>0.05)。 结论　应用超声测量的成人下腹壁厚度为(23.4±6.6)mm,营养状态是最重要的影响因素,这为根据指南针原理设计的排尿报警装置的可行性提供了新的证据,对该装置的进一步研究具有重要的参考意义。     

中医序贯疗法对溃疡性结肠炎维持缓解的疗效观察

目的?观察中医序贯疗法对溃疡性结肠炎维持缓解的疗效,比较其与美沙拉嗪在远期抗复发及不良反应等方面的差异,并探求UC复发的危险因素。方法?采用多中心随机对照方法观察204例活动期UC患者,经规范治疗后155例进入缓解期,继予中医序贯疗法或美沙拉嗪维持治疗。结果?随访半年,完成随访者共105例,中药组复发率为8.1%,美沙拉嗪组复发率为23.3%,2组相比有统计学差异（P<0.05）。结论?中医分期序贯治疗在UC维持缓解的远期疗效上具有显著优势。      

特异性免疫治疗对单核细胞及其来源的树突状细胞表型的早期影响

目的探讨抗原特异性免疫治疗对单核细胞及其来源的树突状细胞表达与免疫相关的重要表型的早期影响。方法 20名接受黄蜂毒液免疫治疗的患者,在治疗前(day0)和治疗后第1天(day1)、第3天(day3)和第5天(day5)抽取外周静脉血分离单核细胞(Mo),其中10名患者的单核细胞在体外培养6d诱导分化为单核细胞来源的树突状细胞(MoDC),流式细胞仪检测其表面ILT3,ILT4,B7H1,B7H2,MHCⅠ,MHCⅡ,CD80和CD86的表达。结果单核细胞和MoDC表面ILT3和ILT4表达显著增高,B7H1和CD86表达显著降低,与治疗前比较,差异有统计学意义(P<0.01)。未观察到B7H2,MHCⅠ,MHCⅡ和CD80的显著性改变(P>0.05)。结论单核细胞和MoDC表面的ILT3,ILT4,B7H1和CD86分子参与抗原特异性免疫治疗的早期耐受。