Neuroblastoma
Conditions
Keywords
disseminated neuroblastoma, localized resectable neuroblastoma, localized unresectable neuroblastoma, regional neuroblastoma, stage 4S neuroblastoma
Brief summary
RATIONALE: Studying samples of blood and tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. PURPOSE: This research trial studies biomarkers in blood and tissue samples from patients with newly diagnosed neuroblastoma.
Detailed description
OBJECTIVES: * Determine the expression of neuropeptide Y (NPY) and its receptors (Rs) in human neuroblastoma (NB) tissues. * Determine whether BDNF/TrkB and TrkAIII stimulate expression of NPY and its Rs. * Determine whether NPY mediates BDNF- and TrkAIII-induced NB proliferation and survival. * Determine neurotrophins' angiogenic actions. * Identify factors released from NB cells upon NPY stimulation (proteomics). * Determine whether NPY upregulates expression of the identified proteins in NB and their Rs in endothelial cells (ECs). * Test whether inhibition of the identified pathways reduces angiogenic activity of NB-conditioned media. * Determine the mechanisms of NYP actions and signaling pathways. * Test whether blocking NPY-Y2/Y5 pathway reduces NB growth and vascularization in vivo. OUTLINE: Archived tumor tissue and serum samples are analyzed for neuropeptide Y and its receptors (Y1, Y2, and Y5) expression, neuroblastoma prognostic factors (MYCN, TrkA, TrkAIII, TrkB, BDNF, and NGF), and angiogenic markers by real-time PCR, IHC, ELISA, radioimmunoassay (RIA), mitogenic assay, caspase 3/7 activity assay, western blots, liquid chromatography, tandem mass spectrometry, proteomic assays, and other assays. Results are then analyzed and compared with patients' clinical data, including stage of disease, its phenotype, prognostic markers, age and gender, and response to treatment.
Interventions
GENETICRNA analysis
GENETICpolymerase chain reaction
GENETICprotein expression analysis
GENETICproteomic profiling
GENETICwestern blotting
OTHERenzyme-linked immunosorbent assay
OTHERimmunohistochemistry staining method
OTHERlaboratory biomarker analysis
OTHERmass spectrometry
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Years to 10 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Children with newly diagnosed neuroblastoma or ganglioneuroblastoma * Samples from the Children's Oncology Group (COG) from patients enrolled in clinical trials in institutions in the USA, Canada, and Australia * Paraffin-embedded tumor specimens, RNA isolated from tumor tissues, and patient serum must be available PATIENT CHARACTERISTICS: * Not specified PRIOR CONCURRENT THERAPY: * Not specified
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Association of high expression of NPY and its Y2/Y5 Rs in NBs with poor outcome of the disease, advanced stage, increased vascularization and other unfavorable prognostic factors, such as TrkB expression and MYCN amplification | — |
| BDNF/TrkB and TrkAIII up-regulate expression of NPY and its Rs | — |
| NPY upregulates expression of the identified proteins in NB and their Rs in endothelial cells (ECs) | — |
| Interaction between Y2 and Y5 receptors in NB and ECs sensitize them to NPY and amplify NPY-induced proliferation | — |
| Blocking the NPY-Y2/Y5 pathway reduces NB growth and tumor vascularization | — |
Outcome results
None listed