Active clinical trials for "Neuroblastoma"

RATIONALE: Studying samples of tissue and bone marrow 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 study studies biomarkers in samples from young patients with neuroblastoma.

RATIONALE: The identification of gene mutations in young patients with pleuropulmonary blastoma syndrome may allow doctors to better understand the genetic processes involved in the development of some types of cancer, and may also help doctors identify patients who are at risk for cancer. PURPOSE: This research study studies gene mutations in samples from young patients with pleuropulmonary blastoma syndrome at risk for developing cancer.

This research trial studies the genes biomarkers in children with neuroblastoma. Studying the genes in a child's cancer cells may help doctors improve ways to diagnose and treat children with neuroblastoma.

RATIONALE: Studying samples of tumor 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 tumor samples from younger patients with neuroblastoma.

This research study is looking at tumor samples from young patients with neuroblastoma. Studying samples of tumor 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

Neuroblastoma (NB) is the most common malignant tumor of infancy. Approximately 60% of NB patients are clinically diagnosed as the stage IV disease and have a very poor prognosis with the 5-year survival rate no more than 30%. Molecular markers of NB have great impacts on the tumor behavior. MYCN amplification is the most well-known marker to predict a poor outcome in NB patients. However, how MYCN affects the NB cell behavior remains unknown. In our preliminary studies, we performed a genome-wide analysis of the differential gene expression in 10 NB tumors with MYCN amplification and 10 with normal MYCN copy number. We found that aromatic hydrocarbon receptor (AHR) reversely correlated with the MYCN expression. This relationship was verified in 83 NB tumor samples. In addition, positive AHR expression by immunostaining of NB tumors predicted a favorable prognosis. These lines of evidence demonstrate that AHR not only relates to the MYCN expression but also plays an important role in the tumorigenesis of NB. Therefore in this project we aim at further studying the relationship between AHR and MYCN. In addition, the possible role of AHR in the tumorigenesis of NB will be clarified. Specifically, we propose a 3-year project with the following three aims: Aim I. Determine the molecular relationship between AHR and MYCN expression. AHR has been shown to suppress the E2F1 expression. E2F1 reversely has been found to upregulate the expression of MYCN. In our preliminary microarray study, we also found that the expression E2F1 positively correlated with the MYCN expression but inversely correlated with the expression of AHR. Therefore, NB cells will be transfected with AHR expression vector or AHR siRNA, then the associated E2F1 and MYCN expression will be examined to clarify if AHR could regulate MYCN expression via E2F1. Furthermore, the E2F1 levels will also be manipulated to determine if the effect of AHR on MYCN depends on E2F1. In addition, the E2F1 expression in NB tumor samples will also be examined to clarify its in vivo role. Aim II. Determine the effect of AHR expression on the NB cell behavior. The baseline AHR expression levels in several NB cell lines will be examined. AHR is then overexpressed by gene transfection in NB cells. The cell proliferation, migration, and differentiation after AHR overexpression are evaluated. Furthermore the AHR expression in normal neuron cells is also examined, and suppressed by siRNA to if downregulation of AHR could lead to cancer development. Aim III. Determine if AHR could be a target of gene therapy for NB. NB cells with either normal MYCN or MYCN amplification before and after AHR gene transfection are inoculated into nude mice to demonstrate the effect of AHR expression on NB cells behavior in vivo. AHR is then transfected into the wild type NB tumor to see if the tumor growth could be suppressed by AHR expression. Then wild type tumor and tumors transfected with AHR are subjected microarray analysis to compare with the human tumor data set for evaluation of gene expression changes along with differential AHR expression. Altogether, our studies will not only establish the relationship between AHR and MYCN, but also allow us to depict the functional role of AHR-MYCN interaction in the tumorigenesis of NB.

Patients who are being considered for participation in a NCI Pediatric Oncology Branch research study will be screened for eligibility under this protocol. For every NCI research study, patients must meet defined medical criteria in order to ensure the integrity of the research study and to maximize patient safety. Tests and procedures required for determining eligibility depend on the specific study for which the patient is being considered. Some of the more common tests and procedures are: History and physical examination Blood and urine samples for routine laboratory tests and possibly research studies Quality of life assessment questionnaire Magnetic resonance imaging (MRI) scan uses a magnetic field and radio waves to produce pictures of body structures, including tumors Computerized tomography (CT) scan uses radiation to produce multiple detailed pictures of body structures X-rays uses radiation to provide a single picture of a body part Nuclear medicine scans uses a chemical tagged with a radioactive substance to detect tumors, measure kidney or heart function, or monitor the flow of cerebrospinal fluid (fluid that bathes the brain and spinal cord) Electrocardiogram (EKG) uses electrodes placed on the skin to evaluates heart rate and rhythm by measuring electrical impulses from the heart Echocardiogram uses high-frequency sound waves to evaluate heart structure and function Lumbar puncture tests for cancer cells and other substances in cerebrospinal fluid. Involves placing a needle into the lower back between the bones of the spine and withdrawing a fluid sample from the fluid-containing space below the spinal cord Ommaya reservoir surgically implanted catheter inserted into the fluid-filled ventricles of the brain, used to withdraw spinal fluid samples and to give medication Eye examination vision test and eye examination Biopsies removal of a small piece of tissue, by needle or by surgery, for examination under the microscope. An area of skin over the biopsy site is numbed with an anesthetic. For a needle biopsy, a needle is inserted into the tumor, tissue or bone marrow to pull out a small sample. A surgical biopsy may be done in the operating room, clinic, or hospital room, depending on the biopsy location. The tissue or tumor is removed by cutting a small piece of it with a sharp knife or scalpel and the area will be closed with sutures or staples.

RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in RNA and predict how patients will respond to treatment. It may also help doctors find better ways to treat cancer. PURPOSE: This research trial studies gene expression in predicting outcomes in samples from patients with high-risk neuroblastoma.

This research studies chromosomes in samples from younger patients with neuroblastoma. Studying samples of tumor 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.

Neuroblastoma (NB) is the most common malignant tumor of infancy. Approximately 60% of NB patients are clinically diagnosed as the stage IV disease and have a very poor prognosis with a 5-year survival rate of no more than 30%. The mechanism underlying the tumorigenesis of NB remains largely unclear. It has been suggested that the pathogenesis of NB is due to a failure of differentiation or apoptosis of the embryonic NB cells. Well-regulated glycosylation is essential for the normal development of the nervous system. Altered expression of glycosyltransferases with resulting dysregulated glycosylation of neuroblastic cells might lead to the development of NB. The β1,4-N-acetylgalactosaminyltransferase III (B4GALNT3) exhibits GalNAc transferase activity to form the GalNAcβ1,4GlcNAc (LacdiNAc or LDN) structure. The Drosophila B4GALNTA, homolog of human B4GALNT3, has been suggested to regulate the neuronal development. By immunohistochemical studies, we demonstrated that the expression of B4GALNT3 correlated well with histological grade of differentiation in 87 NB tumor samples. In addition, positive B4GALNT3 expression predicted a favorable patient's outcome. These evidences suggest that the regulation of glycosyltransferases is critical for the development of NB. To further explore the role of glycosyltransferases in the differentiation and development of NB, we propose a 3-year project with the following 3 major aims: Aim Ⅰ: Clarifying the effects of B4GALNT3 on NB cell behavior in vitro and in vivo. For further understanding the effects of B4GALNT3 on NB cells, NB cells with stable overexpression of B4GALNT3 are to be selected. Then NB cell phenotype and behavior changes after overexpression of B4GALNT3 are evaluated by in vitro assays as well as by a nude mice xenograft model. In addition, the expression of B4GALNT3 will be suppressed by siRNA, then the response of NB cells to ATRA-induced differentiation is evaluated. Aim Ⅱ: Clarifying the target proteins glycosylated by B4GALNT3 as well as their associated downstream pathways in vitro and in vivo. The possible proteins glycosylated by B4GALNT3 are evaluated by comparing differential protein expressions between B4GALNT3-transfected and mock-transfected NB cells using proteomics analysis. NB tumor samples with low and high B4GALNT3 expression levels are also subjected to proteomics analysis to explore the possible target proteins glycosylated by B4GALNT3 in vivo. After identifying the target proteins modified by B4GALNT3, the downstream pathways to affect NB cell differentiation will also be evaluated. Aim Ⅲ: Clarifying whether B4GALNT4, a family member of B4GALNT, plays a similar role as B4GALNT3, as well as how the expression of these enzymes are controlled epigenetically in human NB cell lines and tumor samples. The expression levels of B4GALNT4 in human NB samples are evaluated by RT-PCR and immunohistochemistry. The methylation status of the promoter sites of both B4GALNT3 and B4GALNT4 are examined in various NB cell lines as well tumor samples. Furthermore, NB tumor samples exhibiting high and low B4GALNT levels are subjected to microRNA array. Altogether, our studies will not only establish the functional role of the family of glycosyltransferases in the cell behavior of NB, but also illustrate how the expression of glycosyltransferases are regulated epigenetically and how the glycosyltransferases affect NB cell behavior. Therefore, our results might shed light to the oncogenesis of NB as well as target therapy of NB.