Biomarkers in Blood and Tissue Samples From Patients With Newly Diagnosed Neuroblastoma
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.
Genetic: RNA analysis
Genetic: polymerase chain reaction
Genetic: protein expression analysis
Genetic: proteomic profiling
Genetic: western blotting
Other: enzyme-linked immunosorbent assay
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: liquid chromatography
Other: mass spectrometry
|Official Title:||Neuropeptide Y and Its Receptors in Neuroblastoma|
- 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 [ Designated as safety issue: No ]
- BDNF/TrkB and TrkAIII up-regulate expression of NPY and its Rs [ Designated as safety issue: No ]
- NPY upregulates expression of the identified proteins in NB and their Rs in endothelial cells (ECs) [ Designated as safety issue: No ]
- Interaction between Y2 and Y5 receptors in NB and ECs sensitize them to NPY and amplify NPY-induced proliferation [ Designated as safety issue: No ]
- Blocking the NPY-Y2/Y5 pathway reduces NB growth and tumor vascularization [ Designated as safety issue: No ]
|Study Start Date:||June 2011|
|Estimated Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
- 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.
|Principal Investigator:||Joanna Kitlinska, PhD||Lombardi Cancer Research Center|