Myeloid-derived suppressor cells (MDSCs) accumulate in the spleen and tumors and contribute to tumor growth, angiogenesis and progression. In this study, we examined the effects of curcumin on the activation and differentiation of MDSCs, their interaction with human cancer cells and related tumor growth. Treatment with curcumin in the diet or by i.p. injection significantly inhibited tumorigenecity and tumor growth, decreased the percentages of MDSCs in the spleen, blood and tumor tissues, reduced IL-6 levels in the serum and tumor tissues in a human gastric cancer xenograft model and a mouse colon cancer allograft model. Curcumin treatment significantly inhibited cell proliferation and colony formation of cancer cells and decreased the secretion of murine interleukin (IL)-6 by MDSCs in a co-culture system. Curcumin treatment inhibited the expansion of MDSCs, the activation of Stat3 and NF-κB in MDSCs, and the secretion of IL-6 by MDSCs when MDSCs were cultured in the presence of IL-1β, or with cancer cell- or myofibroblast-conditioned medium. Furthermore, curcumin treatment polarized MDSCs toward a M1-like phenotype with an increased expression of CCR7 and decreased expression of dectin 1 in vivo and in vitro. Our results demonstrate that curcumin inhibits the accumulation of MDSCs and their interaction with cancer cells and induces the differentiation of MDSCs. The induction of MDSC differentiation and inhibition of the interaction of MDSCs with cancer cells are potential strategies for cancer prevention and therapy.
To evaluate the prognostic significance of Wilms' tumor gene 1 (WT1) expression for monitoring minimal residual disease and predicting relapse in patients with acute leukemia (AL) following allogeneic hematopoietic SCT (allo-HSCT), the WT1 expression levels of 138 AL patients were measured using real-time quantitative reverse transcription PCR at designed time points after allo-HSCT. All patients were divided into four groups based on the HSCT outcomes and intervention application. A low level of WT1 expression following HSCT indicated a low risk of relapse, whereas WT1 expression 41.05% was indicative of a higher probability of relapse. Only the advanced stage of disease (hazard ratio (HR) ¼ 2.73; 95% confidence interval (CI) ¼ 1.337-5.573, P ¼ 0.006) and a WT1 expression X0.60% (HR ¼ 4.774; 95% CI ¼ 2.410-9.459, P ¼ 0.000) were associated with lower disease-free survival. Relapse (HR ¼ 0.119; 95% CI ¼ 0.056-0.250, P ¼ 0.000) and a WT1 expression X0.60% (HR ¼ 2.771; 95% CI ¼ 1.316-5.834, P ¼ 0.007) were associated with lower OS. In conclusion, the WT1 expression level is an independent prognostic factor that can predict clinical outcomes for AL patients after HSCT and provide a guide for suitable interventions.
In recent years, the transsphenoidal approach has been extensively used surgically to treat parasellar, suprasellar, clival, and even petrous lesions. Extended pneumatization of the sphenoid sinus (SS) is considered an indispensable element for the extended transsphenoidal (ETS) approach. Because most anatomical studies of the ETS approach use Caucasian subjects, the present study aims to clarify the pneumatic extension types in Chinese individuals as well as any differences from those in Caucasians and analyze these differences with respect to the application of the ETS approach. A total of 200 computed tomography (CT) images of SSs and 18 adult cadaveric heads were selected for observation and measurement. The conchal, presellar, and sellar types comprised 6, 28.5, and 65.5% of subjects, respectively; according to the extra extension, the prevalence of the lateral, clival, lesser wing, and combined extension sinus types was 11.4, 21.4, 0.8, and 48.1% of subjects, respectively. The percentages of pneumatization of the anterior and posterior clinoid processes, pterygoid process, and optic strut were 5.0, 1.0, 22.3, and 7.0%, respectively. Onodi cells were observed in 61.1% of the sides of the cadaveric heads, including 30.6% with good pneumatization with identifiable optical or ICA bulges. These features were related to poor lateral and clival gasification in Chinese compared with Caucasians, which might make extended surgery more dangerous. However, the anterior pneumatization, especially the higher presentation of Onodi cells, ensures that the anterior ETS approach can be performed safely in Chinese patients. In general, measurements showing smaller sinus volumes and thicker bones with identifiable bone landmarks that are hard to find compared with those in Caucasians suggest increased surgical risks in the Chinese population. In this situation, carefully analysis of presurgical CT and magnetic resonance imaging scans is important. Furthermore, in the ETS approach, the use of stricter intraoperative technological devices such as neuronavigation and ultrasound Doppler is advisable.
Hepatocellular carcinoma (HCC) is a common malignant tumor that severely threatens human health. The poor prognosis of HCC is mainly attributed to intrahepatic and extrahepatic metastases. HOXD9 proteins belong to a superfamily that regulates the development and control of many cellular processes, including proliferation, apoptosis, cell shape, and cell migration. HOXD9 can also function as an oncogene in several cancer cells. However, its biological function in human HCC requires further investigation. In this study, HOXD9 exhibited high expression in invasive HCC cells. HOXD9 overexpression can significantly enhance HCC cell migration, invasion, and metastasis, whereas silencing HOXD9 inhibits these processes. HOXD9 also promotes the epithelial–mesenchymal transition (EMT) of HCC cells. Microarray analysis suggests that ZEB1 can function as a downstream factor of HOXD9. HOXD9 can interact with the promoter region of ZEB1 and promotes ZEB1 expression. ZEB1 knockdown inhibits HOXD9-induced migration and invasion, as well as EMT in HCC cells. This study helps elucidates the oncogenic functions of HOXD9 in HCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0245-3) contains supplementary material, which is available to authorized users.
Background: Epithelial-mesenchymal transition (EMT) is regulated by induction factors, transcription factor families and an array of signaling pathways genes, and has been implicated in the invasion and progression of gliomas. Methods: We obtained the Clinicopathological data sets from Chinese Glioma Genome Atlas (CGGA). The "limma" package was used to analyze the expression of EMT-related genes in gliomas with different pathological characteristics. We used the "ConsensusClusterPlus" package to divide gliomas into two groups to study their correlation with glioma malignancy. The least absolute shrinkage and selection operator (LASSO) Cox regression was applied to select seven prognosis-associated genes to build the risk signature, and the coefficients obtained from the LASSO algorithm were used to calculate the risk score which we applied to determine the prognostic value of the risk signature. Univariate and multivariate Cox regression analyses were used to determine whether the risk signature is an independent prognostic indicator. Results: We analyzed the differentially expressed 22 common epithelial-mesenchymal transition-associated genes in 508 gliomas graded by different clinicopathological features. Two glioma subgroups (EM1/2) were identified by consistent clustering of the proteins, of which the EM1 subgroup had a better prognosis than the EM2 subgroup, and the EM2 group was associated with cancer migration and proliferation. Significant enrichment analysis revealed that EMT-related transcriptional regulators and signaling pathways genes were highly related to glioma malignancies. Seven EMT-related genes were used to derive risk scores, which served as independent prognostic markers and prediction factors for the clinicopathological features of glioma. And we found the overall survival (OS) was significantly different between the low-and high-risk groups, the ROC curve indicated that the risk score can predict survival rates for glioma patients. Conclusion: EMT-related induction factors, transcriptional regulators and signaling pathways genes are important players in the malignant progression of glioma and may help in decision making regarding the choice of prognosis assessment and provide us clues to understand EMT epigenetic modification in glioma.
The proportion of the velopharyngeal mechanism remains stable in young children and adults so that the motions of the velum and pharyngeal walls are adequate to close the velopharyngeal port completely.
Background Emerging evidence has shown that dysregulated expression of long noncoding RNAs (lncRNAs) is implicated in liver hepatocellular carcinoma (HCC). However, the role and molecular mechanism of differentially expressed lncRNAs in HCC has not been fully explained. Methods The expression profiles of lncRNAs in HCC samples were derived from microarrays analysis or downloaded from The Cancer Genome Atlas (TCGA), and their correlation with prognosis and clinical characteristics were further analyzed. Silencing of lncRNA ZFPM2-AS1 was conducted to assess the effect of ZFPM2-AS1 in vitro. The miRcode and Target Scan databases were used to determine the lncRNA-miRNA-mRNA interactions. The biological functions were demonstrated by luciferase reporter assay, western blotting, PCR and rescue experiments. Results The expression level of lncRNA ZFPM2-AS1 was significantly higher in HCC tissues than in adjacent normal tissues, and higher ZFPM2-AS1 was remarkably related to poor survival. Functionally, silencing of lncRNA ZFPM2-AS1 inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro. Bioinformatics analysis based on the miRcode and TargetScan databases showed that lncRNA ZFPM2-AS1 regulated GDF10 expression by competitively binding to miR-139. miR-139 and downregulated GDF10 reversed cell phenotypes caused by lncRNA ZFPM2-AS1 by rescue analysis. Conclusions ZFPM2-AS1, an upregulated lncRNA in HCC, was associated with malignant tumor phenotypes and worse patient survival. ZFPM2-AS1 regulated the progression of HCC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-139 and regulate GDF10 expression. Our study provides new insight into the posttranscriptional regulation mechanism of lncRNA ZFPM2-AS1 and suggests that ZFPM2-AS1/miR-139/GDF10 may act as a potential therapeutic target and prognostic biomarker for HCC.
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