Neuroblastoma is an embryonal malignancy that commonly affects young children and is remarkably heterogenous in its malignant potential. Recently, the genetic basis of neuroblastoma has come into focus and not only has catalyzed a more comprehensive understanding of neuroblastoma tumorigenesis but also has revealed novel oncogenic vulnerabilities that are being therapeutically leveraged. Neurob...

In human neuroblastoma, amplification of theMYCN gene predicts poor prognosis and resistance to therapy. Because hypoxia contributes to aggressive tumor phenotypes, predominantly via two structurally related hypoxia inducible factors, HIF-1a and HIF-2a, we examined hypoxia responses inMYCN-amplified neuroblastoma cells. We demonstrate here that HIF-1a, but not HIF-2a, is preferentially expresse...

Neuroblastoma, a rapidly growing yet treatment responsive cancer, is the third most common cancer of children and the most common solid tumor in infants. Unfortunately, neuroblastoma that has lost p53 function often has a highly treatment-resistant phenotype leading to tragic outcomes. In the context of neuroblastoma, the functions of p53 and MYCN (which is amplified in ~25% of neuroblastomas) ...

Cancer stem cells (CSCs) have been implicated in many cancers and build up an intratumor heterogeneity bestowing multiple competences on the tumor for metastasis and resistance to anti-cancer drugs [1]. Neuroblastoma is a childhood cancer arising mostly in adrenal gland and sympathetic ganglia [2]. CSCs hypothesis in neuroblastoma recently appeared [3] and was experimentally supported by the ab...

Inneuroblastoma,MYCNgenomicamplificationand segmental chromosomal alterations including1por11q lossofheterozygocity and/or 17q gain are associated with progression and poor clinical outcome. Segmental alterations are the strongest predictor of relapse and result from unbalanced translocations attributable to erroneous repair of chromosomal breaks. Although sequence analysis of affected genomic ...

BACKGROUND The effects of combined valproic acid (VPA) and celecoxib treatment on cancer cells have not been reported. In this study, we examined the effects of VPA and celecoxib, alone and combined, on human SH-SY5Y neuroblastoma cells. MATERIALS AND METHODS The cytotoxicity effects of VPA, celecoxib, and combined VPA and celecoxib treatment on neuroblastoma cells were studied. The apoptotic...

Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with a highly variable prognosis. Activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway in neuroblastoma is correlated with poorpatientprognosis, but theprecisedownstreameffectorsmediating this effect havenotbeendetermined.Here we identify the forkhead transcription factor FOXO3a as a key target of the PI3K...

Neuroblastoma, the major cause of infant cancer deaths, results from fast proliferation of undifferentiated neuroblasts. Treatment of high-risk neuroblastoma includes differentiation with retinoic acid (RA); however, the resistance of many of these tumors to RA-induced differentiation poses a considerable challenge. Human achaete-scute homolog 1 (hASH1) is a proneural basic helix-loop-helix tra...

Neuroblastoma is a childhood cancer that exhibits either a favorable or an unfavorable phenotype. MYCN and MYC are oncoproteins that play crucial roles in determining the malignancy of unfavorable neuroblastoma. The Hsp90 superchaperone complex assists in the folding and function of a variety of oncogenic client proteins. Inhibition of Hsp90 by small molecule inhibitors leads to the destabiliza...

Neuroblastoma is the third most common malignancy of childhood. Nowadays, MIBG has become a central procedure for staging and defining extent and location of neuroblastoma tumors. The recommendations of the International Neuroblastoma Staging System (INSS) indicate that MIBG scintigraphy must be performed in patients with neuroblastoma at the time of initial staging and as a followup tool durin...