Amplification of N-
            <i>myc</i>
            in Untreated Human Neuroblastomas Correlates with Advanced Disease Stage

Gm, Brodeur; Rc, Seeger; Schwab, Manfred; Varmus, HE; Bishop, J. Michael

doi:10.1126/science.6719137

Cited by 2,052 publications

(1,259 citation statements)

References 28 publications

(6 reference statements)

Supporting

Mentioning

1,185

Contrasting

Unclassified

Order By: Relevance

“…17,24 Many poor-prognosis neuroblastomas are characterized by NMYC amplification. 7 A subset of NMYC -amplified neuroblastoma does not express caspase -8 because the CASP -8 gene is either deleted or silenced by methylation. 21,43 Because caspase-8 is part of the DISC initiating TRAIL signaling, TK /GCV will not cooperate with rhTRAIL in these neuroblastoma cells.…”

Section: Discussionmentioning

confidence: 99%

TRAIL enhances thymidine kinase/ganciclovir gene therapy of neuroblastoma cells

et al. 2002

View full text Add to dashboard Cite

The clinical benefit of suicide gene therapy of tumors has been marginal, mostly due to the low gene transfer efficiency in vivo. The death -inducing ligand, TRAIL, effectively kills many tumor cell types, while sparing most normal tissues. We hypothesized that TRAIL may enhance HSV thymidine kinase / ganciclovir ( TK / GCV ) gene therapy of tumor cells by augmenting both target and bystander cell kill. Human SH -EP neuroblastoma cells expressing TK as well as bystander cells were effectively killed by apoptosis, and their clonogenicity was ablated following GCV. Human TRAIL enhanced TK / GCV -induced cell death and decreased clonogenicity of TK -expressing cells and also of bystander cells. Cooperation between TRAIL and TK / GCV depended both on caspase activation and on mitochondrial apoptogenic function because both the broad -spectrum caspase inhibitor zVAD.fmk and overexpression of Bcl -2 decreased enhancement of cell kill by TRAIL. Facilitation of TRAIL signalling by up -regulation of TRAIL receptors did not contribute to enhancement because cell surface expression of the agonistic TRAIL receptors 1 and 2 was not increased by TK / GCV. In conclusion, the concerted activation of caspases and the mitochondrial amplification of caspase activation by TK / GCV may explain the cooperative effect of TK / GCV and TRAIL on the kill of neuroblastoma cells. Because combined treatment also augmented the bystander cell kill, the addition of TRAIL may increase the efficacy of TK / GCV gene therapy of neuroblastoma.

show abstract

Section: Discussionmentioning

confidence: 99%

TRAIL enhances thymidine kinase/ganciclovir gene therapy of neuroblastoma cells

et al. 2002

View full text Add to dashboard Cite

show abstract

“…The original characterization of N-myc as a c-mycrelated gene (Stanton et al, 1986) was soon followed by reports of its ampli®cation in approximately onethird of cases of NBL, as well as by the observation that the degree of ampli®cation correlated inversely with prognosis (Brodeur et al, 1984(Brodeur et al, , 1985. These original ®ndings have generally been con®rmed in subsequent studies (Combaret et al, 1996;Rubie et al, 1997;Tsuda et al, 1997).…”

Section: Neuroblastoma (Nbl)mentioning

confidence: 97%

MYC oncogenes and human neoplastic disease

1999

View full text Add to dashboard Cite

c-myc, N-myc and L-myc are the three members of the myc oncoprotein family whose role in the pathogenesis of many human neoplastic diseases has received wide empirical support. In this review, we ®rst summarize data, derived mainly from non-clinical studies, indicating that these oncoproteins actually serve quite di erent roles in vivo. This concept necessarily lies at the heart of the basis for the observation that the deregulated expression of each MYC gene is reproducibly associated with only certain naturally occurring malignancies in humans and that these genes are not interchangeable with respect to their aberrant functional consequences. We also review evidence implicating each of the above MYC genes in speci®c neoplastic diseases and have attempted to identify unresolved questions which deserve further basic or clinical investigation. We have made every attempt to review those diseases for which signi®cant and con®rmatory evidence, based on studies with primary tumor material, exists to implicate MYC members in their causation and/or progression.

show abstract

“…Loss of chromosome 1p material, occurring predominately through an unbalanced t(1;17) that also results in gain of 17q (Van Roy et al, 1994), is a common chromosomal imbalance found in NB and occurs preferentially in tumors with MYCN amplification (MNA) (Fong et al, 1989). All three of these nonrandom genetic abnormalities, loss of 1p, gain of 17q and MNA, are independently associated with a poor clinical outcome (Brodeur et al, 1984;Spitz et al, 2003;Attiyeh et al, 2005;Vandesompele et al, 2005).…”

mentioning

confidence: 99%

MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells

2007

View full text Add to dashboard Cite

Neuroblastoma (NB) is one of the most common forms of cancer in children, accounting for 15% of pediatric cancer deaths. The clinical course of these tumors is highly variable and is dependent on such factors as age at presentation, stage, ploidy and genomic abnormalities. Hemizygous deletion of chromosome 1p occurs in approximately 30% of advanced stage tumors, is associated with a poor prognosis, and likely leads to the loss of one or more tumor suppressor genes. We show here that microRNA (miRNA)-34a (1p36.23) is generally expressed at lower levels in unfavorable primary NB tumors and cell lines relative to normal adrenal tissue and that reintroduction of this miRNA into three different NB cell lines causes a dramatic reduction in cell proliferation through the induction of a caspase-dependent apoptotic pathway. As a potential mechanistic explanation for this observation, we demonstrate that miR-34a directly targets the messenger ribonucleic acid (mRNA) encoding E2F3 and significantly reduces the levels of E2F3 protein, a potent transcriptional inducer of cell-cycle progression. Furthermore, miR-34a expression increases during retinoic acidinduced differentiation of the SK-N-BE cell line, whereas E2F3 protein levels decrease. Thus, adding to the increasing role of miRNAs in cancer, miR-34a may act as a suppressor of NB tumorgenesis.

show abstract

Amplification of N- myc in Untreated Human Neuroblastomas Correlates with Advanced Disease Stage

Cited by 2,052 publications

References 28 publications

TRAIL enhances thymidine kinase/ganciclovir gene therapy of neuroblastoma cells

TRAIL enhances thymidine kinase/ganciclovir gene therapy of neuroblastoma cells

MYC oncogenes and human neoplastic disease

MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells

Contact Info

Product

Resources

About