The tumor microenvironment (tumor cells are located in the internal and external environment) is vital for the occurrence, growth and metastasis of tumors. An increasing number of studies have shown that exosomes are closely related to the tumor microenvironment. The mechanisms involved, however, are unclear. The focus of this review is on the exosome-related tumor microenvironment and other relevant factors, such as hypoxia, inflammation and angiogenesis. Many studies have suggested that exosomes are important mediators of metastasis, angiogenesis, and immune modulation in the tumor microenvironment. Additionally, exosomes can be isolated from bodily fluids of cancer patients, including urine, blood, saliva, milk, tumor effusion, cerebrospinal fluid, amniotic fluid and so on. Consequently, exosomes are potential biomarkers for clinical predictions and are also good drug carriers because they can cross the biofilm without triggering an immune response. Collectively, these findings illustrate that exosomes are crucial for developing potential targets for a new generation of pharmaceutical therapies that would improve the tumor microenvironment.
Prostate cancer (PCa) is the most commonly diagnosed cancer in males in the Western world. Although prostate-specific antigen (PSA) has been widely used as a biomarker for PCa diagnosis, its results can be controversial. Therefore, new biomarkers are needed to enhance the clinical management of PCa. From publicly available microarray data, differentially expressed genes (DEGs) were identified by meta-analysis with RankProd. Genetic algorithm optimized artificial neural network (GA-ANN) was introduced to establish a diagnostic prediction model and to filter candidate genes. The diagnostic and prognostic capability of the prediction model and candidate genes were investigated in both GEO and TCGA datasets. Candidate genes were further validated by qPCR, Western Blot and Tissue microarray. By RankProd meta-analyses, 2306 significantly up- and 1311 down-regulated probes were found in 133 cases and 30 controls microarray data. The overall accuracy rate of the PCa diagnostic prediction model, consisting of a 15-gene signature, reached up to 100% in both the training and test dataset. The prediction model also showed good results for the diagnosis (AUC = 0.953) and prognosis (AUC of 5 years overall survival time = 0.808) of PCa in the TCGA database. The expression levels of three genes, FABP5, C1QTNF3 and LPHN3, were validated by qPCR. C1QTNF3 high expression was further validated in PCa tissue by Western Blot and Tissue microarray. In the GEO datasets, C1QTNF3 was a good predictor for the diagnosis of PCa (GSE6956: AUC = 0.791; GSE8218: AUC = 0.868; GSE26910: AUC = 0.972). In the TCGA database, C1QTNF3 was significantly associated with PCa patient recurrence free survival (P < .001, AUC = 0.57). In this study, we have developed a diagnostic and prognostic prediction model for PCa. C1QTNF3 was revealed as a promising biomarker for PCa. This approach can be applied to other high-throughput data from different platforms for the discovery of oncogenes or biomarkers in different kinds of diseases.
ObjectivesTo evaluate the overall efficacy and safety of endoscopic enucleation of the prostate (EP) vs open prostatectomy (OP) for large benign prostatic hyperplasia (BPH).MethodsWe conducted an electronic search of PubMed/Medline, EMBASE, The Cochrane Library, and Web of Science to detect all relevant randomized controlled trials (RCTs) comparing EP with OP. A meta-analysis was performed using Review Manager 5.3.ResultsSeven RCTs (735 patients) were included. At the 3-, 6- and 12-month follow-up, there were no significant differences in the International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), quality of life (QoL) score and post-void residual urine volume (PVR) between EP and OP. The International Index of Erectile Function (IIEF-5) was higher with EP (weighted mean difference [WMD]: 1.00, 95% confidence interval [CI]: 0.21 to 1.78, p=0.01) at the 12-month follow-up. The catheterization time (WMD: 3.80 d, 95%CI: -5.11 to -2.48, P<0.00001) and hospital stay (WMD: 4.93 d, 95%CI: -5.96 to -3.89, P<0.00001) were shorter with EP. The duration of operation was longer for EP compared with OP (WMD: 16.21 min, 95%CI: 3.72 to 28.70, P=0.01). The resected tissue weight (WMD: -9.63 g, 95%CI: -14.46 to -4.81, P<0.0001) and decrease in hemoglobin (WMD: -1.14 g/dL, 95%CI: -1.81 to -0.47, P=0.0008) were less with EP. EP was associated with fewer blood transfusions (risk ratio: 0.22, 95%CI: 0.10 to 0.47, P=0.0001). There were no significant differences between EP and OP when comparing other complications.ConclusionsAlthough only a limited number of RCTs with relatively limited follow-up are available, EP is shown to have a similar postoperative profile and comparable safety to OP. By contrast, EP may have a more desirable perioperative profile. EP appears to be an effective and safe minimally invasive option for treating large prostates that requires only brief convalescence.
Background As most lung cancer patients present with invasive, metastatic disease, it is vital to investigate anti-metastatic treatments for non-small cell lung cancer (NSCLC). Houttuynia cordata is commonly used as a Chinese anticancer medicine in the clinic, and sodium new houttuyfonate (SNH), a main compound of this herb, has long been found to have antibiotic effects, although its anticancer effects have not been investigated. Here, we tried to address this lack of research from the perspective of the competing endogenous RNA (ceRNA) theory. Methods The effects of SNH on NSCLC cells were analysed with Cell Counting Kit-8 assays and colony formation assays. In addition, transwell assays and wound healing assays were used to determine the effects of SNH on migration and invasion in NSCLC cells. The levels of key genes and proteins were examined by quantitative real-time PCR, western blotting, immunofluorescence staining and IHC staining. Through transcriptome screening and digital gene expression profiling, Linc00668 was identified to be regulated by SNH. Dual-luciferase reporter assays and RNA immunoprecipitation assays verified the binding efficiency between miR-147a and Linc00668 or Slug. Results In the present study, SNH regulated NSCLC cells in multiple ways, the most prominent of which was suppressing the expression of Linc00668, which was indicated to promote migration and invasion in NSCLC cells. Functional studies demonstrated that Linc00668 acted as a ceRNA by sponging miR-147a to further regulate Slug mRNA levels, thereby influencing the progression of the epithelial-mesenchymal transition. Consistently, the results of in vivo animal models showed that SNH depressed Linc00668 and suppressed the metastasis of NSCLC. Conclusions SNH suppressed metastasis of NSCLC cells and the mechanism may involve with the Linc00668/miR-147a/Slug axis. Electronic supplementary material The online version of this article (10.1186/s13046-019-1152-9) contains supplementary material, which is available to authorized users.
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