Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Children with aggressive pediatric solid tumors have poor outcomes and novel treatments are needed. Pediatric solid tumors demonstrate aberrant expression and activity of the fibroblast growth factor receptor (FGFR) family, suggesting FGFR inhibitors may be effective therapeutic agents. AZD4547 is a multikinase inhibitor of the FGFR1-3 kinases, and we hypothesized that AZD4547 would be effective in pediatric solid tumor preclinical models. We evaluated the effects of AZD4547 on neuroblastoma, rhabdomyosarcoma, and Ewing sarcoma cells alone and in combination with STAT3 inhibition. Continuous live cell imaging was used to measure induction of apoptosis and effects on migration. Receptor inhibition and intracellular signaling were examined by western blotting. AZD4547 treatment resulted in decreased cell confluence, increased apoptosis and reduced cell migration in all tested cell lines. AZD4547 treatment led to decreased phosphorylation of signaling proteins involved in cell survival and apoptotic pathways and increased phosphorylation of STAT3, and treatment of cell lines with AZD4547 combined with STAT3 inhibition demonstrated increased efficacy. Sensitivity to AZD4547 appears to be mediated by effects on the Ras/MAPK and JAK/STAT pathways, and AZD4547 represents a potential novel therapeutic agent for children with solid tumors.
 ...
PMID:Mechanisms of Efficacy of the FGFR1-3 Inhibitor AZD4547 in Pediatric Solid Tumor Models. 3243 58

One of the models that best explains the cellular heterogeneity observed in central nervous system (CNS) tumors is the presence of cancer stem cells (CSCs). CSCs can originate from differentiated adult cells that return to an undifferentiated stage through the mechanism known as epithelial-mesenchymal transition (EMT). In this paper, we evaluated cellular and molecular heterogeneity and the participation of the epithelial-mesenchymal transition (EMT) in glioblastoma (U-87 MG and LN-18) and neuroblastoma (KELLY and IMR-32) cell lines cultured in monolayer (2D) and neurosphere (CSC enrichment- 3D) models. For this, after treatment with cisplatin, we studied different cell subpopulations by immunophenotyping using neural stem cell/progenitor markers (ALDH, CD24, CD56, and CD133), mesenchymal stem cell markers (CD73, CD90, CD105, and CD146) and hematopoietic markers (CD14, CD19, CD34, CD45, and HLA-DR) and mRNA expression profiles of genes related to EMT, such as ZEB1, TWIST1, TGFB1, STAT3, and lncRNA HOTAIR. In addition, we evaluated the growth capacity of residual cells when treated with cisplatin using the chorioallantoic membrane (CAM) model to study disease relapse. After treatment with cisplatin, we found that the expression of STAT3 and TGFB1 genes markedly increased in the neurosphere of the IMR-32 cell line, and TWIST1 was upregulated in the neurosphere of LN-18. Only the nontreated monolayer of LN-18, KELLY, and IMR-32 amplified the lncRNA HOTAIR. The IMR-32 cell line exhibited an enrichment of CD24+/ALDH+ and this cell subset decreased after cisplatin treatment. We observed the loss of CD146+/CD73+ cell subpopulations in U-87 MG monolayer and neurosphere models, after cisplatin treatment, while in LN-18 monolayer cisplatin-treated cells, CD73+/CD90+ cell subpopulations increased. Neuroblastoma cell lines showed CD14+/HLA-DR- cell subpopulations representative of myeloid-derived suppressor cells (MDSCs). Tumors generated from residual cells, after exposure to cisplatin, grafted on CAM showed patterns of organization different from those of the controls. Thus, our findings strongly supported the idea that definitions of tumor phenotypic characteristics may help to establish better therapeutic strategies for the development of new drug targets.
 ...
PMID:Central nervous system (CNS) tumor cell heterogeneity contributes to differential platinum-based response in an in vitro 2D and 3D cell culture approach. 3282 40

Neuroblastoma is a common malignancy and frequently affects children, leading to a low survival rate. Long noncoding RNAs (lncRNAs) are reported to be closely related to cancer progression. The purpose of this study was to explore a novel mechanism of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in neuroblastoma. NEAT1 was upregulated in neuroblastoma cell lines (IMR32 and SK-N-SH). Overexpression of NEAT1 increased proliferation inhibited by cisplatin and decreased apoptosis promoted by cisplatin. MicroRNA-326 (miR-326) was a target of NEAT1 and miR-326 reintroduction abolished the effects of NEAT1 overexpression on cell proliferation and apoptosis. Moreover, NEAT1 overexpression activated Janus kinase/signal transducer and activator of transcription 3 (JAK1/STAT3) signaling pathway through absorbing miR-326. Besides, NEAT1 overexpression promoted tumor growth in vivo through stimulating the expression of p-JAK1 and p-STAT3 but inhibiting miR-326 expression. NEAT1 accelerated proliferation and weakened apoptosis of neuroblastoma cells treated by cisplatin by targeting miR-326 through activating JAK1/STAT3 signaling pathway, suggesting that NEAT1 was a potential biomarker against neuroblastoma.
 ...
PMID:Long noncoding RNA nuclear-enriched abundant transcript 1 regulates proliferation and apoptosis of neuroblastoma cells treated by cisplatin by targeting miR-326 through Janus kinase/signal transducer and activator of transcription 3 pathway. 3304 24


<< Previous 1 2 3 4 5 6 7 8