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Approximately 15% of human cancers are attributed to viruses. Numerous studies have shown that high-risk human polyomaviruses (HR-HPV) and Merkel cell polyomavirus (MCPyV) are two human tumor viruses associated with anogenetal and oropharyngeal cancers, and with Merkel cell carcinoma, respectively. MCPyV has been found in HR-HPV positive anogenetal and oropharyngeal tumors, suggesting that MCPyV can act as a co-factor in HR-HPV induced oncogenesis. This prompted us to investigate whether the oncoproteins large T-antigen (LT) and small antigen (sT) of MCPyV could affect the transcriptional activity HPV16 and HPV18 and vice versa whether HPV16 and HPV18 E6 and E7 oncoproteins affected the expression of MCPyV LT and sT. Reciprocal stimulation of these viral oncoproteinscould enhance the oncogenic processes triggered by these tumor viruses.
Transient co-transfection studies using a luciferase reporter plasmid with the long control region of HPV16 or HPV18, or the early or late promoter of MCPyV and expressionfactor in the initiation and/or progression of HPV-induced cancers.
These results indicate that the co-infection of MCPyV may act as a co-factor in the initiation and/or progression of HPV-induced cancers.
Some driver oncogenes are still unknown in non-small-cell lung cancer (NSCLC). DNAJC19, a major component of the translocation machinery of mitochondrial membranes, is a disease-associated protein. Herein, we report the role of DNAJC19 in NSCLC cell growth and metastasis.
Immunohistochemistry (IHC) was performed to investigate DNAJC19 expression in NSCLC clinical samples. For knockdown or overexpression assays in A549 or NCI-H1299 lung cancer cells, lentiviral vectors were used. After assessment of cell functions, DNAJC19-knockdown A549 cells were further applied to establish mouse xenograft and metastasis tumor models. Assessments based on the RNA-seq data, western blotting, PCR and IHC were performed for the mechanistic study.
Expression of DNAJC19 was higher in tumors than in noncancerous adjacent tissues. Survival analysis indicated that low DNAJC19 levels were correlated with an increased progression-free survival rate. selleck ShRNA-mediated knockdown of DNAJC19 markedly inhibited cell growth, viability, migration and invasion. Moreover, RNA-seq analysis revealed that the PI3K/AKT signaling pathway was involved in molecular events when A549 cells were treated with shDNAJC19. In addition, DNAJC19 knockdown decreased PI3Kp85a, AKT and p-AKT expression in A549 cells, and cellular functions were greatly rescued in DNAJC19-knockdown A549 cells by ectopic overexpression of AKT. Furthermore, tumor xenograft growth and lung metastasis were markedly repressed in the shDNAJC19 group compared to the control group. As expected, the expression levels of DNAJC19, PI3K and AKT in xenograft mouse samples were also lower in the shDNAJC19 group than in the shCtrl group.
DNAJC19 greatly promotes NSCLC cell growth and lung metastasis by regulating PI3K/AKT signaling, providing a novel therapeutic target for treating NSCLC patients.
DNAJC19 greatly promotes NSCLC cell growth and lung metastasis by regulating PI3K/AKT signaling, providing a novel therapeutic target for treating NSCLC patients.
Hepatocellular carcinoma (HCC) was the sixth common malignancies characteristic with highly aggressive in the world. It was well established that tumor mutation burden (TMB) act as indicator of immunotherapeutic responsiveness in various tumors. However, the role of TMB in tumor immune microenvironment (TIME) is still obscure.
The mutation data was analyzed by employing "maftools" package. Weighted gene co-expression network analysis (WGCNA) was implemented to determine candidate module and significant genes correlated with TMB value. Differential analysis was performed between different level of TMB subgroups employing R package "limma". Gene ontology (GO) enrichment analysis was implemented with "clusterProfiler", "enrichplot" and "ggplot2" packages. Then risk score signature was developed by systematical bioinformatics analyses. K-M survival curves and receiver operating characteristic (ROC) plot were further analyzed for prognostic validity. To depict comprehensive context of TIME, XCELL, TIMER, QUANTbased prognostic prediction.
Collectively, a comprehensive analysis of TMB might provide novel insights into mutation-driven mechanism of tumorigenesis further contribute to tailored immunotherapy and prognosis prediction of HCC.
Collectively, a comprehensive analysis of TMB might provide novel insights into mutation-driven mechanism of tumorigenesis further contribute to tailored immunotherapy and prognosis prediction of HCC.
Provider-initiated HIV testing and counseling (PITC) is a recommended approach to screen for HIV to all pregnant women during antenatal care (ANC) visits, and all with HIV positive results have to be enrolled into prevention of mother-to-child transmission of HIV (PMTCT) program. However, little is known about the relationship between facility readiness and the uptake of PITC to pregnant women attending ANC in Tanzania. Therefore, this study assessed whether the facility readiness promotes the uptake of PITC to the pregnant women attending ANC for the purpose of improving the PMTCT interventions in Tanzania.
This study analyzed data for health facilities obtained from the 2014-2015 Tanzania service provision assessment survey. The Primary outcome measure was a composite variable (with score of 0-5) in which its higher scores indicates provision of high-quality of PITC. Also, facilities scored higher in the PMTCT service readiness index were considered to have high readiness to provide PMTCT services. In Ptrained staffs, diagnostic tools, and ARTs among health facilities in Tanzania.
Understanding the distinct patterns (trajectories) of variation in blood lipid levels before diagnosing cardiovascular disease (CVD) might carry important implications for improving disease prevention or treatment.
We investigated 14,373 participants (45.5% men) aged 45-84 from two large US prospective cohort studies with a median of 23years follow-up. First, we jointly estimated developmental trajectories of lipid indices, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) concentrations using group-based multi-trajectory modeling. Then, the association of identified multi-trajectories with incident CVD, heart failure, and all-cause mortality were examined using Cox proportional hazard model.
Seven distinct multi-trajectories were identified. The majority of participants (approximately 80%) exhibited decreasing LDL-C but rising TG levels and relatively stable HDL-C levels. Compared to the individuals with healthy and stable LDL-C, HDL-C, and TG levels, those in other groups were at significant risk of incident CVD after adjusting for other conventional risk factors.
Homepage: https://www.selleckchem.com/peptide/apamin.html
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