Progressive Neuroblastoma ：Innovation and Novel Therapeutic Strategies ( Pediatric and Adolescent Medicine )

Publication subTitle ：Innovation and Novel Therapeutic Strategies

Publication series ： Pediatric and Adolescent Medicine

Author： Christiansen H.; Christiansen N.M.

Publisher： S. Karger AG‎

Publication year： 2015

E-ISBN: 9783318054972

P-ISBN(Paperback): 9783318054965

Subject： R739.4 systemic tumor

Keyword：外科学,医学遗传学,儿科学,肿瘤学,神经病学,医学免疫学

Language： ENG

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Description

Neuroblastoma is a tumor derived from the sympathetic nervous system. It is the most common extracranial solid tumor occurring in children and exhibits a marked variability in outcome when the disease is categorized by clinical (e.g. age or stage) and biologic characteristics. This book gives an introduction into the clinical features of progressive neuroblastoma and focuses on molecular-targeted therapies and immunotherapies of this disease. It has become increasingly clear that MYCN (v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog) holds a key position in neuroblastic transformation and gene expression in normal and transformed cells. In the 14 chapters important topics such as genomic alterations in neuroblastoma and strategies for indirect molecular targeting of MYCN are discussed. Two chapters, for example, review apoptotic pathways and proapoptotic molecular targets in neuroblastoma, one focusing on the p53 pathway and the extrinsic and intrinsic pathways of apoptosis. Other chapters cover topics related to immunology in neuroblastoma, such as immune regulation in neuroblastoma, immunotherapy related to passive and active vaccination approaches and additional immunotherapy in the treatment of progressive disease. This volume will be essential reading for all clinicians and basic researchers who are involved in delivering health care to patients with progressive neuroblastoma.

Chapter

Clinical Introduction

Clinical Features of Progressive Neuroblastoma

Abstract

Identification of Patients with Progressive Neuroblastoma

Induction Chemotherapy

Stem Cell Transplantation

Surgery

Radiotherapy

MIBG Therapy

Postconsolidation Therapy

Acute and Long-Term Toxicity of Treatment

Disclosure Statement

References

Genomic Alterations

DNA Copy Number Changes and Beyond

Abstract

Evolving Technologies for Assessing DNA Copy Number Alterations in Cancer

DNA Copy Number Alterations Mark Distinct Clinicogenetic Neuroblastoma Subsets

Identifying Driver Genes within the Larger Segmental Recurrent Aberrations Occurring in Neuroblastoma

Evidence for Selection of Focal DNA Copy Number Changes during Tumor Formation

Challenges for Animal Modeling of Neuroblastoma

Conclusions

References

Genomic Alterations and Abnormal Cell Cycle in High-Risk Neuroblastoma

Abstract

Cell Cycle and Mitotic Checkpoints in Neuroblastoma

Novel Neuroblastoma Candidate Genes by Genome-Wide Studies

Cell Cycle Genes and Genome-Wide Studies

Acknowledgements

References

Targeting MYCN

MYCN and MicroRNAs

Abstract

MicroRNAs in Neuroblastoma

MicroRNAs as Blood or Serum Biomarkers

Therapeutic Approaches to Modulate MicroRNA Activity

References

MYCN and Its Posttranslational Regulation in Neuroblastoma

Abstract

Regulation of N-Myc by PI3K Signaling

Regulation of N-Myc by Aurora-A

Regulation of N-Myc by Anaplastic Lymphoma Kinase

Regulation of N-Myc by Histone Deacetylases

Conclusion

Acknowledgements

References

Apoptosis and Angioneogenesis

Neuroblastoma and the p53 Pathway

Abstract

p53

The p53/MDM2/p14 ARF Pathway

p53 Pathway Inactivation and Cancer

p53 and Neuroblastoma

p53 Pathway Polymorphisms in Neuroblastoma

MYCN and p53

Mechanisms of p53 Pathway Inactivation in Neuroblastoma

p53 Pathway Inactivation and Therapy Resistance

p53 Pathway Inactivation and MYCN

MDM2-Mediated MYCN-Driven Neuroblastomagenesis

TWIST1-, BMI1- and PPM1D-Mediated Inhibition of the p53 Pathway

Downregulation of TP53INP1-Mediated p53-Dependent Apoptosis

Strategies of p53 Reactivation in Human Cancers

MDM2-p53 Antagonists

Preclinical Evaluation of MDM2-p53 Antagonists in Neuroblastoma

Acquired Mechanisms of Resistance to MDM2-p53 Antagonists

p53-Independent Functions of MDM2-p53 Antagonists

Restoration of Mutant p53

Kevetrin

Conclusions

Disclosure Statement

References

Targeting Cell Death Pathways in Neuroblastoma

Abstract

Signaling Pathways of Apoptosis

Conclusions

Acknowledgements

References

Neuroblastoma and Angiogenesis

Abstract

Angiogenesis

Lymphangiogenesis

Mechanisms of Angiogenesis in Neuroblastoma

Regulation of Angiogenesis in Neuroblastoma

Lymphangiogenesis in Neuroblastoma

Preclinical Studies of Angiogenesis Inhibitors in Neuroblastoma

Clinical Trials with Antiangiogenic Molecules in Neuroblastoma

Conclusions and Perspectives

Acknowledgements

References

Molecular-Targeted Therapy Studies

The Role of the Anaplastic Lymphoma Kinase Receptor in Neuroblastoma

Abstract

Structure and Function of Anaplastic Lymphoma Kinase

Anaplastic Lymphoma Kinase Signaling Pathways and Mechanistic Relationships

Alterations of Anaplastic Lymphoma Kinase in Neuroblastoma

Therapeutic Strategies for Patients with Anaplastic Lymphoma Kinase-Driven Neuroblastomas

Resistance to Anaplastic Lymphoma Kinase Inhibitors

Conclusion

References

Molecular-Targeted Therapy in Refractory or Relapsed Neuroblastoma

Abstract

Molecular Targets in Neuroblastoma

The MYCN Proto-Oncogene

Tyrosine-Protein Phosphatase Nonreceptor Type 11

Anaplastic Lymphoma Kinase

Molecular-Targeted Therapy

The PI3K/AKT/mTOR Pathway in Neuroblastoma

Development of Resistance

Common Pathways or Individualized Therapy

The Concept of Multimodal Metronomic Trial Designs

The RIST Design: A Multimodal Metronomic Trial Design

Conclusion

References

Immunology

Immune Regulation

Abstract

Immune Regulatory Cells

Immune Regulatory Molecules

Concluding Remarks

References

Approaches to Passive and Active Vaccination against Neuroblastoma

Abstract

Passive Immunotherapy

Approaches to Induce Adaptive Immunity against Neuroblastoma

Conclusion

References

Role of Cell Therapy in Neuroblastoma

Abstract

Myeloablative Therapy and Autologous Stem Cell Rescue

Allogeneic and Haploidentical Stem Cell Transplantation

Adoptive Cellular Immunotherapies

Natural Killer Cells

Clinical Grade Purification, Expansion and Activation of Natural Killer Cells for Adoptive Cell Therapy

Natural Killer Cell-Based Immunotherapy Trials

Natural Killer Cell Immunotherapy Phase I/II Trial Frankfurt-Basel

Limitations

Conclusion

References

Minimal Residual Disease

Minimal Residual Disease in Neuroblastoma

Abstract

References

Author Index

Subject Index

Cover

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