Mercerschroeder1927

Based on the positive results of these studies, SQ®-HDM SLIT-tablets were approved Europe-wide as registered drug for treating moderate-to-severe allergic rhinitis with or without allergic asthma and not well controlled HDM allergic asthma, associated with allergic rhinitis of any severity. GINA guidelines in 2017 included SLIT-tablet-based immunotherapy as an "add-on" treatment for asthmatic patients sensitized to HDM; indeed, allergen immunotherapy (AIT) is considered to be a complementary treatment option that targets the immunological of allergic diseases, representing the only treatment potentially disease-modifier or, at least, with a long-term efficacy. The availability of a safe, standardized, registered treatment for HDM respiratory allergies is pivotal in the immunotherapy field, pushing it out of a century-long limbo of amatorial interest towards the full dignity deserved by the only casual treatment of respiratory allergies.Background Non-receptor protein tyrosine phosphatases (PTPNs) are a set of enzymes involved in the tyrosyl phosphorylation. The present study intended to clarify the associations between the expression patterns of PTPN family members, and diagnosis as well as the prognosis of digestive tract cancers. Methods Oncomine and Ualcan were used to analyze PTPN expressions. Data from The Cancer Genome Atlas (TCGA) were downloaded through UCSC Xena for validation and to explore the relationship of the PTPN expression with diagnosis, clinicopathological parameters and survival of digestive tract cancers. Gene ontology enrichment analysis was conducted using the DAVID database. The gene-gene interaction network was performed by GeneMANIA and the protein-protein interaction (PPI) network was built using STRING portal coupled with Cytoscape. The expression of differentially expressed PTPNs in cancer cell lines were explored using CCLE. Moreover, by histological verification, the expression of four PTPNs in digestive tractession was associated with increased hazards of death. CCLE analyses showed that in esophagus cancer cell lines, PTPN1, PTPN4 and PTPN12 were highly expressed; in gastric cancer cell lines, PTPN2 and PTPN12 were highly expressed; in colorectal cancer cell lines, PTPN12 was highly expressed while PTPN22 was downregulated. Results of histological verification experiment showed differential expressions of PTPN22 in CRC, and PTPN12 in GC and CRC. Conclusions Members of PTPN family were differentially expressed in digestive tract cancers. Correlations were found between PTPN genes and clinicopathological parameters of patients. DMH1 solubility dmso Expression of PTPN12 was upregulated in both STAD and CRC, and thus could be used as a diagnostic biomarker. Differential expression of PTPN12 in GC and CRC, and PTPN22 in CRC were presented in our histological verification experiment.Background The aberrant expression of microRNA-454 (miR-454) has been confirmed to be involved in the development of cancers. However, the functional role of miR-454 in the progression of ovarian cancer remains unclear. Methods The expression of miR-454 in ovarian cancer cells and serum of ovarian cancer patients was detected by RT-PCR. CCK8, colony formation, transwell, and flow cytometry assays were conducted to assess the effects of miR-454 on ovarian cancer cell proliferation, migration, invasion, and apoptosis, respectively. Dual-luciferase reporter assay was used to confirm the targeting relationship between miR-454 and E2F6. The expression pattern of E2F6 in ovarian cancer tissues was detected using immunohistochemistry (IHC) assay. The relative expression of related proteins was examined using western blot analysis. Results miR-454 was markedly down-regulated by hypoxia in ovarian cancer cells. Compared with normal samples, the expression of miR-454 was up-regulated in the serum of ovarian cancer patients, and correlated with the clinicopathological stages of ovarian cancer. Next, we found that miR-454 overexpression inhibited the proliferation, migration and invasion of OVCAR3 and SKOV3 cells, as well as promoted apoptosis. In addition, the Akt/mTOR and Wnt/β-catenin signaling pathway were inhibited by miR-454 in ovarian cancer cells. Mechanically, bioinformatic analysis and dual-luciferase reporter assay confirmed that E2F6 was a direct target of miR-454 and negatively regulated by miR-454 in ovarian cancer cells. Moreover, IHC analysis showed that E2F6 was highly expressed in ovarian cancer tissues. Finally, we found that the increasing cell proliferation and migration triggered by E2F6 overexpression were abolished by miR-454 overexpression. Conclusion Taken together, these results highlight the role of miR-454 as a tumor suppressor in ovarian cancer cells by targeting E2F6, indicating that miR-454 may be a potential diagnostic biomarker and therapeutic target for ovarian cancer.Background Long noncoding RNA small nucleolar RNA host gene 16 (lncRNA SNHG16) has been revealed to be involved in the tumorigenesis of neuroblastoma. However, the role of SNHG16 in regulating cisplatin sensitivity in neuroblastoma remains largely unknown. Methods The expression of SNHG16, microRNA (miR)-338-3p and polo-like kinase 4 (PLK4) mRNA was measured using quantitative real-time polymerase chain reaction. The protein levels of PLK4, multidrug resistance protein 1 (MRP1), multidrug-resistance gene 1-type p-glycoprotein (P-gp) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related proteins were detected by Western blot. The half maximal inhibitory concentration (IC50) value, cell proliferation, migration and invasion were analyzed using Cell Counting Kit-8 assays or Transwell assay. Apoptotic cells were measured by Flow cytometry. The interaction between miR-338-3p and SNHG16 or PLK4 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assay. In vivo experiments wernd cisplatin resistance in neuroblastoma possibly through miR-338-3p/PLK4 pathway, indicating a novel insight for overcoming chemoresistance in neuroblastoma patients.Background Aberrant DNA methylation patterns are involved in the pathogenesis of papillary renal cell carcinoma (pRCC). This study aimed to investigate the potential of methylation-driven genes as biomarkers in determining the prognosis of pRCC by bioinformatics analysis. Methods DNA methylation and transcriptome profiling data were downloaded from The Cancer Genome Atlas database. Methylation-driven genes (MDGs) were obtained using MethylMix R package. A Cox regression model was used to screen for pRCC prognosis-related MDGs, and a linear risk model based on MDG methylation profiles was constructed. A combined methylation and gene expression survival analysis was performed to further explore the prognostic value of MDGs independently. Results A total of 31 MDGs were obtained. Univariate and multivariate Cox regression analysis identified eight genes (CASP1, CD68, HOXD3, HHLA2, HOXD9, HOXA10-AS, TMEM71, and PLA2G16), which were used to construct a predictive model associated with overall survival in pRCC patients. Combined DNA methylation and gene expression survival analysis revealed that C19orf33, GGT6, GIPC2, HHLA2, HOXD3, HSD17B14, PLA2G16, and TMEM71 were significantly associated with patients' survival. Conclusion Through the analysis of MDGs in pRCC, this study identified potential biomarkers for precision treatment and prognosis prediction, and provided the basis for future research into the molecular mechanism of pRCC.Background A comprehensive investigation of ubiquitin-conjugating enzyme E2I (UBE2I) in cancer is still insufficiency. In this study, we aimed to analyze its role and mechanism in cancer by combination of bioinformatic analysis and experimental validation. Methods The expression profile of UBE2I in human cancers were obtained using GEPIA. link2 Kaplan-Meier plotter was used to assess the prognostic values of UBE2I in diverse types of cancer. ROC curve analysis was employed to determine the diagnostic role of UBE2I in hepatocellular carcinoma (HCC). The expression differences based on various clinicopathological features was evaluated by UALCAN. Wound healing assay and transwell invasion assay were used to detected the effects of UBE2I on migration and invasion of HCC cells, respectively. The miRNA regulatory mechanism of UBE2I was successively investigated by binding prediction, expression analysis, survival analysis and dual-luciferase reporter assay. The correlation of UBE2I mRNA expression and UBE2I promoter methylation level was assessed using cBioPortal. STRING was finally introduced to perform co-expression analysis and enrichment analysis for UBE2I. Results UBE2I was upregulated in HCC, correlated with cancer progression and poor prognosis of HCC. We also found a significant diagnostic value of UBE2I in HCC. Functional experiments revealed that knockdown of UBE2I significantly inhibited HCC migration and invasion. Further research on mechanism suggested that loss of inhibition of hsa-miR-195-3p and dysregulation of UBE2I promoter methylation might account for UBE2I overexpression in HCC. Analysis of UBE2I-invovled regulatory network identified six key genes (NSMCE2, SAE1, UBA2, RANGAP1, SUMO1 and SUMO2) whose expression linked to poor prognosis in HCC. Conclusions In conclusion, UBE2I may be a promising therapeutic target and biomarker in cancer, especially HCC.Background Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cell lung cancer (NSCLC). Methods KIF21B expression in 72 cases of NSCLC tissues was measured by immunohistochemical staining (IHC). We used shRNA-KIF21B interference to silence KIF21B in NSCLC H1299 and A549 cells and normal lung epithelial bronchus BEAS-2B cells. The biological roles of KIF21B in the growth and metastasis abilities of NSCLC cells were measured by Cell Counting Kit-8 (CCK8), colony formation and Hoechst 33342/PI, wound-healing, and Transwell assays, respectively. Expression of apoptosis-related proteins was determined using western blot. link3 The effect of KIF21B on tumor growth in vivo was examined using nude mice model. Results KIF21B was up-regulated in NSCLC tissues, and correlated with pathological lymph nodefor NSCLC.Background Dysregulation of long non-coding RNAs (lncRNAs) results in development of human diseases including hepatocellular carcinoma (HCC). Although several HCC related lncRNAs have been reported, the biological functions of many lncRNAs during the development of HCC remains unknown. Methods The expression of ST8SIA6-AS1 was studied by realtime PCR (RT-qPCR) and bioinformatic analysis. The biological functions of ST8SIA6-AS1 was examined by CCK-8 assay and flow cytometry analysis. The target of ST8SIA6-AS1 was analyzed by bioinformatic analysis and validated by dual luciferase reporter assay, western blotting and RT-qPCR. Results In this study we demonstrated that ST8SIA6-AS1 was an upregulated lncRNA in hepatocellular carcinoma. SiRNA-mediated knockdown of ST8SIA6-AS1 repressed cell proliferation and induced cell apoptosis in HCC cells. Bioinformatic analysis and RT-qPCR further showed that ST8SIA6-AS1 mainly located in cytoplasm. Dual luciferase reporter assay further revealed that ST8SIA6-AS1 interacted with miR-4656 in HCC cells.