Neuroblastoma Biology and Therapy

神经母细胞瘤生物学和治疗

基本信息

批准号：
7277179
负责人：
GARRETT M BRODEUR
金额：
$ 221.65万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-30 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7277179
关键词：
11q 14q 17q Accounting Adrenal Glands Adult Adverse effects Affect Affinity Age Age-Years Angiogenesis Inhibitors Angiogenic Factor Animal Model Anthracycline Antibiotics Anthracyclines Apoptosis Behavior Benign Binding Biochemical Pathway Bioinformatics Biological Biological Response Modifier Therapy Biologically Based Therapy Biology Biometry Blood Vessels Brain-Derived Neurotrophic Factor Cardiotoxicity Cell Death Cell Line Cells Cessation of life Child Childhood Children&apos s Cancer Group Children&apos s Oncology Group Chromosome abnormality Chromosomes Chromosomes, Human, Pair 1 Cisplatin Class Classification Clinical Clinical Trials Combined Modality Therapy Commit Complex Critical Pathways Cytogenetics Cytotoxic agent DNA Sequence Rearrangement Data Death Domain Deformity Development Diagnosis Diagnostic Neoplasm Staging Differentiation and Growth Diploidy Disease Disease regression Down-Regulation Drug Kinetics Etoposide Evolution Family Fenretinide Functional disorder Future Gene Proteins Genes Genetic Genetic Models Goals Growth Hand Heterogeneity Histology Histopathology Hypoxia In Vitro Individual Infant Institution International Investigation Isotretinoin Karyotype Lead Length Ligands Light Localized Disease Loss of Heterozygosity MYCN gene Malignant - descriptor Malignant Neoplasms Marrow Mediating Mitotic Molecular Molecular Abnormality Molecular Profiling Mutation NGFR Protein Neoplasm Metastasis Neoplasms in Vascular Tissue Nerve Growth Factor Receptors Nerve Growth Factors Nervous system structure Neural Crest Neuroblastoma Numbers Nutrient Operative Surgical Procedures Other Genetics Outcome Outpatients Pathology Pathway interactions Patients Pattern Personal Satisfaction Pharmaceutical Preparations Play Ploidies Principal Investigator Process Production Program Research Project Grants Progression-Free Survivals Protein Overexpression Protocols documentation Radiation therapy Randomized Clinical Trials Recurrence Refractory Relapse Reliance Resistance Retinoic Acid Receptor Retinoids Risk Role Second Look Surgery Second Primary Cancers Sensitivity and Specificity Signal Transduction Site Solid Neoplasm Staging Staging System Stem cell transplant Stem cells Sterility Stimulus Stratification Sum Sympathetic Ganglia Targeted Radiotherapy Testing Text Therapeutic Therapeutic Agents Thinking Toxic effect Transplantation Tretinoin Tumor Angiogenesis Tumor Angiogenic Factor Tumor Cell Line Tumor Necrosis Factor Receptor Tumor Suppressor Genes Tumor stage Tumor-Derived Tyrosine Kinase Inhibitor Upper arm Virulent alpha-Thalassemia angiogenesis autocrine base cancer therapy cell growth chemotherapeutic agent chemotherapy chromosome 17q gain clinical efficacy cytotoxic deprivation experience gangliocytoma indexing insight interest malignant state member neoplastic neoplastic cell neuroblast neurotrophic factor novel novel strategies novel therapeutics ototoxicity outcome forecast paracrine pre-clinical pre-clinical research programs receptor receptor expression research study response transcriptional coactivator p75 tumor tumor growth tumor progression tumorigenesis

项目摘要

Neuroblastoma is the most common and deadly solid tumor in children. This tumor accounts for 8-10% of the cancers and 15% of the deaths from cancer in childhood. Although a third of children are diagnosed under the age of 1 year, the majority of children are diagnosed between 1 and 10 years of age, and most of these have metastatic disease and will die from tumor progression. The goal of this Program Project Grant entitled "Neuroblastoma Biology and Therapy" is to investigate specific biological pathways critical to neuroblastoma tumorigenesis and progression and to develop novel approaches to treatment that are aimed at these pathways. This program is organized into 4 projects and 4 Cores: Project 1. P75 and Trk in Neuroblastoma Differentiation and Death (Garrett Brodeur, Leader). Project 2. Antiangiogenic Strategies for Neuroblastoma Therapy (John Maris, Leader) Project 3. Deregulated Apoptosis in MYCN Amplified Neuroblastomas (Michael Hogarty, Leader) Project 4. Integration of Retinoids with Cytotoxic Agents in Neuroblastoma (Peter Adamson, Leader). Core . Animal Model and Pathology Core (John Maris, Core Director; Bruce Pawel, Co-Director) Core . Biostatistics and Bioinformatics Core (Avital Cnaan, Core Director; Eric Rappaport, Co-Director) Core . Pharmacokinetics Core (Peter Adamson, Core Director) There is increasing interest in novel approaches to cancer treatment with tyrosine kinase inhibitors, angiogenesis inhibitors, cell death-promoting agents and retinoids. We plan to develop novel therapies that are biologically based and likely to have clinical efficacy. The successful completion of these studies should identify novel agents and combinations of agents aimed at important growth, differentiation and cell death pathways that should be very effective and far less toxic than conventional therapy. We anticipate moving these treatment approaches rapidly into clinical trials. Furthermore, treatment strategies developed against neuroblastoma may be useful against other tumors in children and adults that are rely on the biological pathways and are affected by these agents.

神经母细胞瘤是儿童中最常见和致命的实体瘤。这种肿瘤占癌症的 8-10%，占儿童期癌症死亡人数的 15%。尽管三分之一的儿童在1岁以下被诊断，但大多数儿童在1岁至10岁之间被诊断，其中大多数患有转移性疾病，并将因肿瘤进展而死亡。该计划项目拨款题为“神经母细胞瘤生物学和治疗”，其目标是研究对神经母细胞瘤肿瘤发生和进展至关重要的特定生物学途径，并开发针对神经母细胞瘤的新治疗方法。在这些路径上。该计划分为 4 个项目和 4 个核心：项目 1. P75 和 Trk 在神经母细胞瘤分化和死亡中的作用（Garrett Brodeur，负责人）。项目 2. 神经母细胞瘤治疗的抗血管生成策略（John Maris，负责人）项目 3. MYCN 扩增神经母细胞瘤中细胞凋亡失调（Michael Hogarty，负责人）项目 4. 类视色素与细胞毒性药物在神经母细胞瘤中的整合（Peter Adamson，负责人）。核。动物模型和病理学核心（John Maris，核心主任；Bruce Pawel，联合主任）核。生物统计学和生物信息学核心（Avital Cnaan，核心总监；Eric Rappaport，联合总监）核。药代动力学核心（Peter Adamson，核心总监）人们对酪氨酸激酶抑制剂、血管生成抑制剂、细胞死亡促进剂和类维生素A治疗癌症的新方法越来越感兴趣。我们计划开发基于生物学且可能具有临床疗效的新疗法。这些研究的成功完成应该确定针对重要生长、分化和细胞死亡途径的新型药物和药物组合，这些药物和药物组合应该非常有效，并且比传统疗法的毒性要低得多。我们预计这些治疗方法将迅速进入临床试验。此外，针对神经母细胞瘤开发的治疗策略可能对治疗儿童和成人中依赖生物途径并受这些药物影响的其他肿瘤有用。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Disrupting polyamine homeostasis as a therapeutic strategy for neuroblastoma.

DOI：
10.1158/1078-0432.ccr-08-3213
发表时间：
2009-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
0
作者：
Evageliou NF;Hogarty MD
通讯作者：
Hogarty MD

Multiple components of the spliceosome regulate Mcl1 activity in neuroblastoma.