CNS Cancer: Models, Markers, Prognostic Factors, Targets, and Therapeutic Approaches

Voorkant
Erwin G. Van Meir
Springer Science & Business Media, 15 aug 2009 - 1284 pagina's
Cancers of the central nervous system are among the most lethal of human neoplasms. They are recalcitrant to even intensive multimodality therapies that include surgery, radiotherapy, and chemotherapy. Moreover, especially in children, the consequences of these therapies can itself be devastating and involve serious cognitive and developmental disorders. It is small wonder that such cancers have come under the intense scrutiny of each of the subspecialties of clinical care and investigation as well as attracting some of the best basic research scientists. Their joint efforts are gradually peeling away the mysteries surrounding the genesis and progression of these tumors and inroads are being steadily made into understanding why they resist therapies. This makes it an especially opportune time to assemble some of the best investigators in the field to review the ‘‘state of the art’’ in the various arenas that comprise the assault on CNS tumors. The breadth of this effort by the clinical and basic neuro-oncology community is quite simply amazing. To a large extent, it evolves from the knowledge of the human genome and its regulation that has been hard won over the past two decades.
 

Inhoudsopgave

Modeling Gliomas Using PDGFExpressing Retroviruses
3
Modeling Brain Tumors Using Avian Retroviral Gene Transfer
29
Using Neurofibromatosis Type 1 Mouse Models to Understand Human Pediatric LowGrade Gliomas
44
Using Genetically Engineered Murine Models to Study the Role of p21Ras in Glioblastoma Multiforme
61
PtenDeficient Mouse Models for HighGrade Astrocytomas
77
Dissecting Genetic Susceptibility to Brain Cancer
93
Implications for Preclinical Cancer Drug Development
119
Human Brain Tumor Cell and Tumor Tissue Transplantation Models
146
MicroRNAs in the Central Nervous System and Potential Roles of RNA Interference in Brain Tumors
651
Understanding Glioma Resistance to Temozolomide Therapy
679
Brain Tumor Stem Cell Markers
712
Therapeutic Targets and Targeting Approaches
729
Clinical Agents for the Targeting of Brain Tumor Vasculature
731
Bone MarrowDerived Cells in GBM Neovascularization
748
Vascular Targeting of Brain Tumors Bridging the Gap with Phage Display
775
Impact of the BloodBrain Barrier on Brain Tumor Imaging and Therapy
788

Transformed Human Brain Cells in Culture as a Model for Brain Tumors
163
Rat Glioma Models for Preclinical Evaluation of Novel Therapeutic and Diagnostic Modalities
181
Neurooncogenesis Induced by Nitroso Compounds in Rodents and StrainSpecific Genetic Modifiers of Predisposition
206
The Murine GL261 Glioma Experimental Model to Assess Novel Brain Tumor Treatments
227
Opportunities as Preclinical Model Systems
243
Prognostic Factors and Biomarkers
281
p53 Pathway Alterations in Brain Tumors
282
The PTENPI3 Kinase Pathway in Human Glioma
315
Value of 1p19q and Other LOH Markers for Brain Tumor Diagnosis Prognosis and Therapy
359
Discovery of Genetic Markers for Brain Tumors by Comparative Genomic Hybridization
373
Genomic Identification of Significant Targets in Brain Cancer
395
Oncomodulatory Role of the Human Cytomegalovirus in Glioblastoma
414
Aberrant EGFR Signaling in Glioma
441
Mechanisms of Brain Tumor Angiogenesis
461
The Role of Thrombosis and Tissue Factor
507
Tumor Biology and Treatment Stratification
529
Proteomic Profiling of Human Brain Tumors
552
Proteomic Discovery of Biomarkers in the Cerebrospinal Fluid of Brain Tumor Patients
577
Epigenetic Profiling of Gliomas
614
Targeting CXCR4 in Brain Tumors
813
Molecular Targeting of IL13Ralpha2 and EphA2 Receptor in GBM
846
Molecular Targets for AntibodyMediated Immunotherapy of Malignant Glioma
865
Stat3 Oncogenic Signaling in Glioblastoma Multiforme
899
Inhibition of Ras Signaling for Brain Tumor Therapy
919
HGFcMet Signaling and Targeted Therapeutics in Brain Tumors
933
Combinatorial Therapeutic Strategies for Blocking Kinase Pathways in Brain Tumors
953
Targeting of TRAIL Apoptotic Pathways for Glioblastoma Therapies
976
Implications for Apoptotic and Inflammatory Responses and Exploitation for Therapy
1011
Targeting Endoplasmic Reticulum Stress for Malignant Glioma Therapy
1037
Brain Cancer Stem Cells as Targets of Novel Therapies
1057
The Use of Retinoids as Differentiation Agents Against Medulloblastoma
1076
Herpes Simplex Virus 1 HSV1 for Glioblastoma Multiforme Therapy
1105
The Development of Targeted Cancer GeneTherapy Adenoviruses for HighGrade Glioma Treatment
1137
Harnessing TCell Immunity to Target Brain Tumors
1165
Mechanisms and Therapeutic Challenges
1219
Index
1253
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Over de auteur (2009)

Erwin G Van Meir is Professor of Neurosurgery and Hematology & Medical Oncology in the School of Medicine at Emory University. A native of Belgium, he obtained Bachelor’s degrees in Biology and Education at the University of Fribourg, Switzerland. He pursued graduate studies in Molecular Virology at the University of Lausanne, Switzerland where he obtained his PhD in 1989. He then became interested in cancer and pursued postdoctoral work at the University Hospital in Lausanne and at the Ludwig Institute for Cancer Research in San Diego. In 1994 he became a Junior Faculty and Director of the Laboratory of Brain Tumor Biology and Genetics in the Neurosurgery Department at the University of Lausanne. In 1998 he joined Emory University in Atlanta, where he now serves as the Leader of the Winship Cancer Institute Molecular Pathways and Biomarkers scientific program and as the co-Director of the brain tumor working group.

For the past 20 years Dr. Van Meir’s research has focused on defining the biological significance of specific genetic alterations for brain tumor development, with particular emphasis on extracellular signaling regulating heterotypic cell communication as in tumor angiogenesis, and translating this knowledge into new therapeutic approaches. His research is described in more than 140 peer-reviewed research papers and review articles in internationally recognized journals that have cumulated over 5,000 citations and received several awards. These contributions were presented in over 100 invited seminars worldwide and have furthered the understanding of cytokine expression for glioma biology, Turcot syndrome, the role of transcription factors p53 and HIF and of pro- and anti-angiogenesis factors IL-8, thrombospondin-1 and brain angiogenesis inhibitor-1 in brain tumor angiogenesis, hypoxia, and pseudopalisade formation. He also discovered novel biomarkers in the cerebrospinal fluid of brain tumor patients and developed novel therapeutic agents including oncolytic hypoxia-activated adenoviruses, pro-apoptotic galectin-3, anti-angiogenic vasculostatins and small molecule HIF/Hsp90/plectin1 inhibitors that are covered by several US and foreign patents. Perhaps most importantly, over his still young 20 year independent career Dr Van Meir has already mentored and trained over 60 postdoctoral fellows, students and visiting scientists, many of which now hold independent leading positions in Academia or Industry.

Dr Van Meir is an active member of the International Neuro-Oncology community and served on the Board of Directors of the Society for Neuro-Oncology from 2004-2008. He organized several international conferences on brain tumors, has served on the Scientific Committee of the European Association for Neuro-Oncology, the Scientific Advisory Board of the Southeastern Brain Tumor Foundation and is a current or former member of several other international cancer societies including the American Association for Cancer Research, the European Association for Cancer Research, and the American Society for Investigative Pathology.

Dr. Van Meir currently serves on the Editorial Board of Neuro-Oncology, Frontiers in Bioscience, and International Journal of Oncology and is a former Associate Editor of the International Journal of Cancer. He has served as a reviewer for over 30 international scientific journals and for grant proposals from public and private agencies including the US National Institutes of Health, the US Department of Defense, the Swiss National Science Foundation, the Swiss Cancer Society, the Wellcome Trust of the UK, Cancer Research UK, the Research Grants Council of Hong Kong, the Israel Science Foundation, The Belgian Fournier-Majoie and Baudouin Foundations and the Italian Association for Cancer Research.

He acknowledges present and past support by multiple funding agencies for his scientific work, including the US National Institutes of Health, the Swiss National Science Foundation, the Goldhirsh Foundation, the Charlotte Geyer Foundation, the Southeastern and National Brain Tumor Foundations, The Brain Tumor Society, the Pediatric Brain Tumor Foundation of the US, the American Brain Tumor Association, the Brain Tumor Foundation for Children, the Al Musella, Wayne O Rollins and Frances Wood Wilson Foundations, the Brain Tumor Trust, the Emory University Research Council and EmTechBio, the Swiss Cancer League and Anti-Cancer Foundations, the San Salvatore, Tossizza, Ott and Chuard-Smith Foundations, and the European Institute of Oncology.

Bibliografische gegevens