ZD55-shMYCN provides a novel agent for treating MYCN-amplified and p53-inactive aggressive neuroblastoma, representing a promising approach for further clinical development.
With the identification of amplified MYCN and the demonstration of a consensus deletion spanning the chromosome 1p36.1-2 region it appears now likely that both amplification of a cellular oncogene and loss of a tumour-suppressor gene play an important role in neuroblastoma.
While the N-myc protein is established as an important regulator of several miRNAs involved in neuroblastoma tumorigenesis, tumor suppressor miRNAs have also been documented to repress MYCN expression and inhibit cell proliferation of MYCN-amplified neuroblastoma cells.
While MDM2 SNP309 status does not affect the risk of developing NB nor disease outcome for localized cancer cases, it significantly correlates with survival in stage 4 NB patients, particularly in the presence of MYCN amplification.
Whereas N-Myc repressed and retinoid activated both TG2 isoforms, repression of TG2-L, but not simultaneous repression of TG2-L and TG2-S, enhanced neuroblastoma cell differentiation due to N-Myc small interfering RNA or retinoid.
We utilized this algorithm to classify NB-patients on the bases of the following risk factors: Age at diagnosis, INSS stage, MYCN amplification and NB-hypo.
We used shotgun LC/MS to compare phosphorylation between a human MYCN amplified neuroblastoma cell line (NB10), modeling a resistant tumor, and a human neural precursor cell line (NPC), modeling a normal baseline neural crest cell.
We used hydroxyurea (HU), which accelerates the expulsion of amplified genes and cytostatics (used in neuroblastoma therapy), to describe MYCN amplification changes after chemotherapy.
We treated a panel of neuroblastoma cell lines with a novel small molecule inhibitor of BET proteins, GSK1324726A (I-BET726), and observed potent growth inhibition and cytotoxicity in most cell lines irrespective of MYCN copy number or expression level.
We then performed transient transfections in two NB cell lines, NLF (MYCN amplified) and SY5Y (MYCN non-amplified), with the reporter plasmid and miRNA mimic, as well as appropriate controls.
We studied the prevalence and degree of tumor cell infiltration (TCI) in bone marrow (BM) aspirates of 89 infants with stage 4/4 S neuroblastoma and correlated them with MYCN gene status and patient outcome.
We studied the expressions of both Mina53, which is a myc target gene and is related to cell proliferation, and Cap43, which is related to metastasis suppression and downregulation of MYCN gene, in neuroblastoma.
We show that PI3K/mTOR inhibitors selectively killed MYCN-expressing neuroblastoma tumor cells, and induced significant apoptosis of transgenic MYCN-driven neuroblastoma tumors concomitant with elimination of MYCN protein in vivo.
We show that in ALK-mutated, MYCN-amplified neuroblastoma cells, crizotinib alone does not affect mTORC1 activity as indicated by persistent RPS6 phosphorylation.
We show that higher expression levels of MIF and DDT in Stage 4 NB samples are associated with a poorer prognosis, independently of the presence of MYCN amplification.
We show that cellular delivery of BLF1 selectively induces apoptosis in neuroblastoma cells that display MYCN amplification but has little effect on non-transformed cells.
We show here that Wig-1 knockdown causes a dramatic inhibition of N-Myc expression and triggers differentiation in neuroblastoma cells carrying amplified N-Myc.
We selected tumor specimen spots of highest proliferation activity, that is, hotspots, for the analysis of MYCN amplification status and proliferation-associated molecular markers, such as nestin, which role in neuroblastoma specimens was evaluated for the first time.