Gliomas are complex and heterogeneous central nervous system tumors with poor prognosis. Despite the increasing development of aggressive combination therapies, the prognosis of glioma is generally unsatisfactory. Exosomal microRNA (miRNA) has been successfully used in other diseases as a reliable biomarker and even therapeutic target. Recent studies show that exosomal miRNA plays an important role in glioma occurrence, development, invasion, metastasis, and treatment resistance. However, the association of exosomal miRNA between glioma has not been systemically characterized. This will provide a theoretical basis for us to further explore the relationship between exosomal miRNAs and glioma and also has a positive clinical significance in the innovative diagnosis and treatment of glioma.
Metastasis is one of the important biological features of malignant tumors and one of the main factors responsible for poor prognosis. Although the widespread application of newer clinical technologies and their continuous development have significantly improved survival in patients with brain metastases, there is no uniform standard of care. More effective therapeutic measures are therefore needed to improve prognosis. Understanding the mechanisms of tumor cell colonization, growth, and invasion in the central nervous system is of particular importance for the prevention and treatment of brain metastases. This process can be plausibly explained by the “seed and soil” hypothesis, which essentially states that tumor cells can interact with various components of the central nervous system microenvironment to produce adaptive changes; it is this interaction that determines the development of brain metastases. As a novel form of intercellular communication, exosomes play a key role in the brain metastasis microenvironment and carry various bioactive molecules that regulate receptor cell activity. In this paper, we review the roles and prospects of brain metastatic tumor cells, the brain metastatic tumor microenvironment, and exosomes in the development and clinical management of brain metastases.
Objective. Research over the past decade has suggested important roles for pseudogenes in gliomas. Our previous study found that the RPL4P4 pseudogene is highly expressed in gliomas. However, its biological function in gliomas remains unclear. Methods. In this study, we analyzed clinical data on patients with glioma obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Genotype-Tissue Expression (GTEx), and the GEPIA2 databases. We used the R language for the main analysis. Correlations among RPL4P4 expression, pathological characteristics, clinical outcome, and biological function were evaluated. In addition, the correlations of RPL4P4 expression with immune cell infiltration and glioma progression were analyzed. Finally, wound healing, Transwell, and CCK-8 assays were performed to analyze the function of RPL4P4 in glioma cells. Result. We found that RPL4P4 is highly expressed in glioma tissues and is associated with poor prognosis, IDH1 wild type, codeletion of 1p19q, and age. Multivariate analysis and the nomogram model showed that high RPL4P4 expression was an independent risk factor for glioma prognosis and had better prognostic prediction power. Moreover, high RPL4P4 expression correlated with immune cell infiltration, which showed a significant positive association with M2-type macrophages. Finally, RPL4P4 knockdown in glioma cell lines caused decreased glioma cell proliferation, invasion, and migration capacity. Conclusion. Our data suggest that RPL4P4 can function as an independent prognostic predictor of glioma. It also shows that RPL4P4 expression correlates with immune cell infiltration and that targeting RPL4P4 may be a new strategy for the treatment of glioma patients.
Background: To evaluate the role and safety of endostar in cervical cancer by comparing the efficacy and adverse reactions of endostar combined with concurrent chemoradiotherapy in patients with locally advanced cervical carcinoma.Methods: The quality of the included literature was evaluated by searching the database for the comparison of endostar combined with concurrent radiotherapy and chemotherapy in cervical cancer patients; objective response rate (ORR) and disease control rate (DCR) were used as the main outcome indicators, and statistical analysis was performed using RevMan5.3 and State15.3 software.Results: A total of 13 studies were included in this study, including 1057 patients with locally advanced cervical cancer, suggesting that endostar combined with chemoradiotherapy can significantly improve the objective response rate (ORR: odds ratio 3.88, 95% confidence interval 2.77-5.45, P < .00001) and disease control rate (DCR: odds ratio 4.43, 95% confidence interval 2.78-7.04; P < .00001), and there was no significant increase in treatment-related adverse reactions.Conclusions: In this meta-analysis, endostar combined with concurrent chemoradiotherapy significantly improved ORR and DCR in patients with locally advanced cervical cancer without increasing toxicity. However, this study only analyzed the shortterm efficacy of endostar, and its influence on overall survival and progression-free survival needs to be further verified in large randomized controlled trials with long-term follow-up.Abbreviations: CCRT = concurrent chemoradiotherapy, CR = complete response, CI = confidence interval, DCR = disease control rate, NOS = Newcastle-Ottawa Scale, NRCT = non randomized controlled trial, ORR = objective response rate, PDGF = platelet-derived growth factor, PFS = progression-free survival, PRISMA = priority report item for systematic review and metaanalysis, RCT = randomized controlled trial, VEGF = vascular endothelial growth factor.
Purpose. Esophageal squamous cell cancer (ESCC) is a deadly malignant tumor characterized by an overall 5-year survival rate below 20%, with China accounting for approximately 50% of all cases worldwide. Our previous studies have demonstrated that high integrin-linked kinase (ILK) expression plays a key role in development and progression of ESCC both in vitro and in vivo. Here, we employed the drug repurposing approach to identify a novel FDA-approved anticancer inhibitor against ILK-induced tumorigenesis and progression. Methods. We screened the ZINC15 database and predicted the molecular docking ability among FDA-approved and publicly available drugs to ILK and then performed computational docking and visual inspection analyses of the top 10 ranked drugs. Two computer-based virtual screened drugs were evaluated in vitro for their ability to directly bind purified ILK by surface plasmon resonance. Cytotoxicity of the two candidate drugs was validated in vitro using CCK-8 and LDH assays. Results. We initially selected the top 10 compounds, based on their minimum binding energy to the ILK crystal, after molecular docking and subjected them to further screening. Taking the binding energy of −10 kcal/mol as the threshold, we selected two drugs, namely, nilotinib and teniposide, for the wet-lab experiment. Surface plasmon resonance (SPR) revealed that nilotinib and teniposide had equilibrium dissociation constant (KD) values of 6.410E − 6 and 1.793E − 6, respectively, which were lower than 2.643E − 6 observed in ILK-IN-3 used as the positive control. The IC50 values for nilotinib and teniposide in ESCC cell lines were 40 μM and 200–400 nM, respectively. Results of the CCK-8 assay demonstrated that both nilotinib and teniposide significantly inhibited proliferation of cells ( P < 0.01 ). LDH results revealed that both drugs significantly suppressed the rate of cell death ( P < 0.01 ). Conclusion. The drug repositioning procedure can effectively identify new therapeutic tools for ESCC. Our findings suggest that nilotinib and teniposide are efficacious inhibitors of ILK and thus have potential to target ILK-mediated signaling pathways for management of ESCC.
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