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Gliomas:

Gliomas, which comprise astrocytic, oligodendroglial, and ependymal lesions, are the most frequent primary intracranial tumors. This volume summarizes the enormous advances in our knowledge of gliomas that have occurred during recent years.

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Bibliographic Details
Format:	Book
Language:	English
Published:	Berlin [u.a.] Springer 2009
Series:	Recent results in cancer research 171
Subjects:	Gene Therapy Glioma > diagnosis Glioma > therapy Gliomas Gliom Aufsatzsammlung
Online Access:	Inhaltsverzeichnis
Summary:	Gliomas, which comprise astrocytic, oligodendroglial, and ependymal lesions, are the most frequent primary intracranial tumors. This volume summarizes the enormous advances in our knowledge of gliomas that have occurred during recent years.
Physical Description:	XV, 259 S. Ill., graph. Darst.
ISBN:	9783540312055

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adam_text	Contents Part I Gliomas 1 Astrocytic Tumors .......................................................................................................... 3 Markus J. Ríemenschneider and Guido Reifenberger 1.1 Introduction ..................................................................................................... З 1.2 Epidemiological, Neuroradiologicai, and Clinical Features ........................... 4 1.3 Histopathology ................................................................................................ 6 1.4 Immunohistochemistry ................................................................................... 9 1.5 Molecular Genetics ......................................................................................... 10 1.6 Molecular Diagnostics .................................................................................... 13 1.7 Pathways to Astrocytoma and Targeted Therapies .......................................... 15 1.8 Novel In Vitro and In Vivo Astrocytoma Models ............................................ 18 1.9 Conclusion ...................................................................................................... 20 References ....................................................................................................... 21 2 Molecular Pathology of Oligodendroglial Tumors ...................................................... 25 Christian Hartmann and Andreas von Deimling 2.1 Epidemiological, Neuroradiologicai, and Clinical Features ........................... 25 2.2 Pathology ......................................................................................................... 26 2.2.1 Oligodendrogliomas WHO Grade II ............................................................... 27 2.2.2 Anaplastic Oligodendrogliomas WHO Grade III ............................................ 27 2.2.3 Oligoastrocytomas WHO Grade II .................................................................. 27 2.2.4 Anaplastic Oligoastrocytomas WHO Grade III .............................................. 29 2.2.5 Glioblastomas with Oligodendroglioma Component WHO Grade IV ........... 29 2.3 Immunohistochemistry ................................................................................... 29 2.4 Molecular Genetics ......................................................................................... 30 2.4.1 Combined Losses on Chromosome lpand 19q in Oligodendroglial Tumors ............................................................................ 30 Contents 2.4.2 Isolateci and Combined Losses of lp and 1 9q Oligodendroglial and Astrocytic Tumors ..................................................................................... 31 2.4.3 Mechanism for Combined Losses of 1 ρ and 19q ............................................ 32 2.4.4 Methods for Detection of Allelic Losses on Chromosome lp and 19q .......... 32 2.4.5 Tumor Suppressor Gene Identification on lp and 19q ................................... 33 2.4.6 Candidate Genes on lp ................................................................................... 35 2.4.7 Candidate Genes on 19q ................................................................................. 36 2.4.8 ЮШ Mutations in Oligodendroglial Tumors ................................................. 36 2.4.9 Progression-Associated Genetic Alterations ................................................... 37 2.5 The Origin of Oligodendrogliomas ................................................................. 38 2.5.1 Phenotype and Genotype of Gliomas .............................................................. 38 2.5.2 Progenitor Cells of Oligodendrocytes and Oligodendroglial Tumors ............. 38 2.6 Prognosis ......................................................................................................... 38 2.6.1 Clinical and Histological/Immunohistological Prognostic Factors ................. 39 2.6.2 Losses on lp and 19 as a Prognostic Factor .................................................... 39 2.6.3 MGMT as a Prognostic Factor ........................................................................ 40 2.6.4 Other Prognostic Molecular Factors ................................................................ 40 2.7 Conclusions ..................................................................................................... 41 References ....................................................................................................... 41 Ependymal Tumors ........................................................................................................ 51 Martin Hasselblatt 3.1 Introduction ..................................................................................................... 51 3.1.1 WHO Classification ........................................................................................ 51 3.1.2 Synonyms .................................................,...................................................... 51 3.1.3 Historical Aspects ........................................................................................... 52 3.2 Epidemiology and Clinical Features ............................................................... 52 3.2.1 Incidence ......................................................................................................... 52 3.2.2 Age and Sex Distribution ................................................................................ 52 3.2.3 Environmental Factors .................................................................................... 53 3.2.4 Tumor Localization ......................................................................................... 53 3.2.5 Typical Clinical Presentation .......................................................................... 54 3.2.6 Neuroradiological Imaging ............................................................................. 54 3.3 Pathology ......................................................................................................... 54 3.3.1 Macroscopic Features ...................................................................................... 54 3.3.2 Histological Features ....................................................................................... 55 3.3.3 Immunohistochemistry ................................................................................... 56 3.4 Genetic Susceptibility and Molecular Genetics .............................................. 57 3.4.1 Genetic Susceptibility ..................................................................................... 57 3.4.2 Molecular Genetics ......................................................................................... 57 3.4.3 Tumor Recurrence and Prognosis ................................................................... 59 3.4.4 Potential Molecular Targets for Therapy ......................................................... 60 References ....................................................................................................... 61 Contents vii 4 Pediatrie Gliomas ........................................................................................................... 67 Stefan Pf ister and Olaf Witt 4.1 Introduction..................................................................................................... 67 4.2 Epidemiology and Clinical Features ............................................................... 68 4.3 Histopathology ................................................................................................ 71 4.4 Molecular Genetics ......................................................................................... 72 4.5 Molecular Diagnostics .................................................................................... 74 4.6 Pathways to Pediatrie Astrocytoma ................................................................. 75 4.7 Pathways to Pediatrie Ependymoma ............................................................... 76 4.8 Novel Therapies for Pediatrie Gliomas........................................................... 76 4.9 Conclusion ...................................................................................................... 78 References ....................................................................................................... 78 5 Hereditary Tumor Syndromes andGliomas ................................................................ 83 David Reuss and Andreas von Deimling 5.1 Neurofibromatosis .......................................................................................... 83 5.1.1 Historic Aspects .............................................................................................. 83 5.1.2 Neurofibromatosis Type 1............................................................................... 83 5.1.3 Neurofibromatosis Type 2............................................................................... 87 5.2 Tuberous Sclerosis Complex ........................................................................... 90 5.2.1 Molecular Genetics ......................................................................................... 90 5.2.2 Molecular Pathogenesis .................................................................................. 91 5.2.3 Subependymal Giant Cell Astrocytomas ........................................................ 92 5.3 Li-Fraumeni and Li-Fraumeni-Like Syndrome .............................................. 92 5.4 Melanoma-Astrocytoma Syndrome ............................................................... 93 5.5 Turcot Syndrome ............................................................................................. 93 5.6 Familial Gliomas ............................................................................................. 94 References ....................................................................................................... 94 Part II Management of Gliomas 6 Surgical Management of Intracranial Gliomas ........................................................... 105 Matthias Simon and Johannes Schramm 6.1 Surgical Management: Overview .................................................................... 105 6.2 Surgical Therapy for Gliomas: Indications and Results .................................. 106 6.2.1 Low-Grade Gliomas ........................................................................................ 106 6.2.2 Malignant Gliomas .......................................................................................... 108 6.2.3 Rare Gliomas ................................................................................................... 110 v¡¡¡ Contents 6.2.4 Cytoreductive Surgery for Gliomas in Difficult and Eloquent Locations ...... 111 6.2.5 Recurrent Gliomas .......................................................................................... 111 6.2.6 Pediatrie Gliomas ............................................................................................ 113 6.2.7 Stereotactic Biopsy and Interstitial Radiosurgery (Brachytherapy) ................ 114 6.3 Technical Aspects of Glioma Surgery ............................................................. 114 6.3.1 Electrophysiological Mapping and Monitoring of Eloquent Brain Areas ....... 114 6.3.2 Imaging of Functional Brain Areas for Glioma Surgery ................................. 115 6.3.3 Image-Guided Surgery: Neuronavigation ....................................................... 116 6.3.4 Intraoperative Imaging .................................................................................... 118 6.4 Perspectives ..................................................................................................... 119 6.4.1 Technological Progress and Neurosurgery ...................................................... 119 6.4.2 Clinical Research and Socioeconomic Issues ................................................. 119 References ....................................................................................................... 120 7 Radiation Therapy .......................................................................................................... 125 Stephanie E. Combs 7.1 Low-Grade Gliomas ........................................................................................ 125 7.1.1 Dose Prescription: High Versus Low .............................................................. 126 7.1.2 Timing of Radiation Therapy: Early Versus Delayed ...................................... 127 7.2 Anaplastic Gliomas ......................................................................................... 128 7.3 Glioblastoma ................................................................................................... 131 7.4 Re-irradiation .................................................................................................. 134 7.5 Conclusion ...................................................................................................... 135 References ....................................................................................................... 135 8 Adjuvant Therapy ........................................................................................................... 141 Wolfgang Wick and Michael Weiler 8.1 Introduction ..................................................................................................... 141 8.1.1 General Principles ........................................................................................... 141 8.1.2 Current Therapeutic Strategies ........................................................................ 143 8.1.3 Alternative Modes of Application ................................................................... 146 8.1.4 Alternative Therapies ...................................................................................... 146 8.1.5 Gene Therapy .................................................................................................. 147 8.2 Astrocytic Tumors ........................................................................................... 147 8.3 Oligodendroglial Tumors ................................................................................ 149 References ....................................................................................................... 150 9 Other Experimental Therapies for Glioma .................................................................. 155 Manfred Westphal and Katrin Lamszus 9.1 Introduction ..................................................................................................... 155 9.2 Surgery ............................................................................................................ 155 Contents ¡x 9.3 Chemotherapy ................................................................................................. 156 9.4 Radiation ......................................................................................................... 157 9.5 New Developments ......................................................................................... 158 9.5.1 Targeted Therapies for Glioma ........................................................................ 158 9.5.2 Targeting New Targets by Convection ............................................................ 158 9.6 Immunotherapy ............................................................................................... 159 9.7 Oncolytic Viruses ............................................................................................ 160 9.8 Gene Therapy .................................................................................................. 160 9.9 Stem Cells ....................................................................................................... 161 9.10 Final Remarks ................................................................................................. 161 References ....................................................................................................... 161 10 Neurotoxicity of Treatment ........................................................................................... 165 Pasquale Calabrese and Uwe Schlegel 10.1 Introduction .................................................................................................... 165 10.2 Radiation ........................................................................................................ 166 10.3 Radiation-Induced Neurotoxicity ................................................................... 166 10.4 Brain Atrophy ................................................................................................. 167 10.5 The Effect of Radiation Dosage ..................................................................... 168 10.6 Neuropsychological Deficits Associated with Radiotherapy ......................... 168 10.7 Quality of Life After Radiotherapy ................................................................ 169 10.8 Other Treatment-Related Parameters Influencing Cognitive Function .......... 170 10.9 Radiotherapy and Chemotherapy ................................................................... 171 10.10 Conclusions .................................................................................................... 171 10.11 Proposed Neuropsychological and Quality of Life Test Battery .................... 172 References ...................................................................................................... 173 11 Neuroimaging ................................................................................................................ 175 R. Klingebiel and G. Bohner 11.1 Introduction .................................................................................................... 175 11.2 MRI and CT- Technique ............................................................................... 176 11.2.1 MRI - General Aspects .................................................................................. 176 11.2.2 Imaging Technique ......................................................................................... 178 11.3 Indications ...................................................................................................... 185 11.3.1 Differential Diagnosis of Cerebral Tumors .................................................... 185 11.3.2 Peritherapeutic Imaging .................................................................................. 187 11.3.3 Posttherapeutic Imaging ................................................................................. 188 11.4 Perspectives .................................................................................................... 189 11.5 Summary ........................................................................................................ 189 Suggested Reading ......................................................................................... 190 Contents Part III Concepts 12 Angiogenesis in Gliomas ............................................................................................... 193 Mareia Machein and Lourdes Sánchez de Miguel 12.1 Introduction.................................................................................................... 193 12.2 The Angiogenic Factors in Gliomas ............................................................... 196 12.3 Growth Factors and Their Cognate Receptors ................................................ 196 12.3.1 VEGF ............................................................................................................. 196 12.3.2 Angiopoietins ................................................................................................. 198 12.3.3 Other Angiogenic Growth Factors .................................................................. 198 12.4 Guidance Molecules ....................................................................................... 199 12.4.1 Ephrins ........................................................................................................... 199 12.4.2 Delta-Like 4 Ligand-Notch ............................................................................ 200 12.4.3 ROBO/Slit ...................................................................................................... 200 12.4.4 Netrins and DCC/UNC Receptors .................................................................. 200 12.4.5 Semaphores ................................................................................................... 201 12.5 Endogenous Inhibitors .................................................................................... 201 12.5.1 Thrombospondin 1 and 2................................................................................ 202 12.5.2 Angiostatin ..................................................................................................... 202 12.5.3 Endostatin ....................................................................................................... 202 12.5.4 Pigment Epithelial-Derived Factor ................................................................. 202 12.5.5 PEX ................................................................................................................ 203 12.6 Strategies for Therapeutic Angiogenesis Inhibition in Glioma Treatment ..... 203 12.6.1 Inhibition of Endothelial Cell Proliferation and Adhesion Cell Molecules ... 204 12.6.2 Blocking Stimulatory Factors ......................................................................... 205 12.6.3 Increase of Endogenous Inhibitors of Angiogenesis ...................................... 206 12.6.4 Inhibition of Invasive Activity ........................................................................ 206 12.7 Perspectives and Unanswered Questions ........................................................ 207 References ...................................................................................................... 207 13 Gene Regulation by Methylation ................................................................................. 217 Wolf С Mueller and Andreas von Deimling 13.1 Epigenetics ..................................................................................................... 217 13.1.1 Methylation in Normal Cells and Tissues ...................................................... 217 13.1.2 Methylation in Cancer: General Aspects ........................................................ 218 13.2 Strategies of Epigenetic Studies in Gliomas .................................................. 219 13.3 Methods of Epigenome Analysis .................................................................... 220 13.3.1 General Aspects of Methylation Analysis ...................................................... 220 13.3.2 Bisulfite Sequencing ...................................................................................... 221 13.3.3 Methylation-Specific PCR ............................................................................. 221 13.3.4 Methods of Gene Identification ..................................................................... 222 13.3.5 Genome-Wide Methylation Profiling Implementing Methylation: Sensitive Restriction Enzymes .................................................. 224 Contents x¡ 13.3.6 MS-MLPA: A Novel Technique for Methylation Analysis That Does Not Require Bisulfite Modification and Can Be Reliably Applied to FFPE Tissues .................................................................. 224 13.3.7 Novel Platforms for Genome-Wide, High-Throughput Methylation Analyses in Cancer Samples .......................................................................... 225 13.4 DNA: Methyltransferases and Methylation Pattern Maintenance .................. 225 13.5 Epigenetically Regulated Genes of Interest in Gliomas ................................. 226 13.6 Diagnostic and Prognostic Value of Epigenetic Analyses: MGMT Promoter Methylation in Glioblastomas, Current Concepts, and Possible Future Developments .................................. 228 13.7 Current Therapeutic Strategies to Overcome TSG Silencing ......................... 228 13.7.1 Chromatin Remodeling Agents ...................................................................... 228 13.7.2 Gene Replacement Therapy as a Vision for Restoring Expression of Silenced Genes ........................................................................................... 230 13.7.3 Artificial Transcription Factors in Gliomas ................................................... 230 13.8 Conclusion and Perspective ............................................................................ 231 References ...................................................................................................... 231 14 Brain Tumor Stem Cells ............................................................................................... 241 Christian Nern, Daniel Sommerlad, Till Acker and Karl H. Plate 14.1 The Concept of Cancer Stem Cells ................................................................ 241 14.2 Neural Stem Cells in the Adult CNS .............................................................. 243 14.3 Phenotypic and Functional Characterization of Neural Stem Cells ............... 245 14.4 Identification and Enrichment of Brain Tumor Stem Cells ............................ 247 14.5 Brain Tumor Histogenesis .............................................................................. 249 14.6 Signaling Pathways of Neural Stem Cells and Brain Tumor Cells ................. 251 14.7 The (Cancer) Stem Cell Niche ....................................................................... 252 14.8 Therapeutical Aspects .................................................................................... 253 14.9 Outlook ........................................................................................................... 254 References ...................................................................................................... 254
adam_txt	Contents Part I Gliomas 1 Astrocytic Tumors . 3 Markus J. Ríemenschneider and Guido Reifenberger 1.1 Introduction . З 1.2 Epidemiological, Neuroradiologicai, and Clinical Features . 4 1.3 Histopathology . 6 1.4 Immunohistochemistry . 9 1.5 Molecular Genetics . 10 1.6 Molecular Diagnostics . 13 1.7 Pathways to Astrocytoma and Targeted Therapies . 15 1.8 Novel In Vitro and In Vivo Astrocytoma Models . 18 1.9 Conclusion . 20 References . 21 2 Molecular Pathology of Oligodendroglial Tumors . 25 Christian Hartmann and Andreas von Deimling 2.1 Epidemiological, Neuroradiologicai, and Clinical Features . 25 2.2 Pathology . 26 2.2.1 Oligodendrogliomas WHO Grade II . 27 2.2.2 Anaplastic Oligodendrogliomas WHO Grade III . 27 2.2.3 Oligoastrocytomas WHO Grade II . 27 2.2.4 Anaplastic Oligoastrocytomas WHO Grade III . 29 2.2.5 Glioblastomas with Oligodendroglioma Component WHO Grade IV . 29 2.3 Immunohistochemistry . 29 2.4 Molecular Genetics . 30 2.4.1 Combined Losses on Chromosome lpand 19q in Oligodendroglial Tumors . 30 Contents 2.4.2 Isolateci and Combined Losses of lp and 1 9q Oligodendroglial and Astrocytic Tumors . 31 2.4.3 Mechanism for Combined Losses of 1 ρ and 19q . 32 2.4.4 Methods for Detection of Allelic Losses on Chromosome lp and 19q . 32 2.4.5 Tumor Suppressor Gene Identification on lp and 19q . 33 2.4.6 Candidate Genes on lp . 35 2.4.7 Candidate Genes on 19q . 36 2.4.8 ЮШ Mutations in Oligodendroglial Tumors . 36 2.4.9 Progression-Associated Genetic Alterations . 37 2.5 The Origin of Oligodendrogliomas . 38 2.5.1 Phenotype and Genotype of Gliomas . 38 2.5.2 Progenitor Cells of Oligodendrocytes and Oligodendroglial Tumors . 38 2.6 Prognosis . 38 2.6.1 Clinical and Histological/Immunohistological Prognostic Factors . 39 2.6.2 Losses on lp and 19 as a Prognostic Factor . 39 2.6.3 MGMT as a Prognostic Factor . 40 2.6.4 Other Prognostic Molecular Factors . 40 2.7 Conclusions . 41 References . 41 Ependymal Tumors . 51 Martin Hasselblatt 3.1 Introduction . 51 3.1.1 WHO Classification . 51 3.1.2 Synonyms .,. 51 3.1.3 Historical Aspects . 52 3.2 Epidemiology and Clinical Features . 52 3.2.1 Incidence . 52 3.2.2 Age and Sex Distribution . 52 3.2.3 Environmental Factors . 53 3.2.4 Tumor Localization . 53 3.2.5 Typical Clinical Presentation . 54 3.2.6 Neuroradiological Imaging . 54 3.3 Pathology . 54 3.3.1 Macroscopic Features . 54 3.3.2 Histological Features . 55 3.3.3 Immunohistochemistry . 56 3.4 Genetic Susceptibility and Molecular Genetics . 57 3.4.1 Genetic Susceptibility . 57 3.4.2 Molecular Genetics . 57 3.4.3 Tumor Recurrence and Prognosis . 59 3.4.4 Potential Molecular Targets for Therapy . 60 References . 61 Contents vii 4 Pediatrie Gliomas . 67 Stefan Pf ister and Olaf Witt 4.1 Introduction. 67 4.2 Epidemiology and Clinical Features . 68 4.3 Histopathology . 71 4.4 Molecular Genetics . 72 4.5 Molecular Diagnostics . 74 4.6 Pathways to Pediatrie Astrocytoma . 75 4.7 Pathways to Pediatrie Ependymoma . 76 4.8 Novel Therapies for Pediatrie Gliomas. 76 4.9 Conclusion . 78 References . 78 5 Hereditary Tumor Syndromes andGliomas . 83 David Reuss and Andreas von Deimling 5.1 Neurofibromatosis . 83 5.1.1 Historic Aspects . 83 5.1.2 Neurofibromatosis Type 1. 83 5.1.3 Neurofibromatosis Type 2. 87 5.2 Tuberous Sclerosis Complex . 90 5.2.1 Molecular Genetics . 90 5.2.2 Molecular Pathogenesis . 91 5.2.3 Subependymal Giant Cell Astrocytomas . 92 5.3 Li-Fraumeni and Li-Fraumeni-Like Syndrome . 92 5.4 Melanoma-Astrocytoma Syndrome . 93 5.5 Turcot Syndrome . 93 5.6 Familial Gliomas . 94 References . 94 Part II Management of Gliomas 6 Surgical Management of Intracranial Gliomas . 105 Matthias Simon and Johannes Schramm 6.1 Surgical Management: Overview . 105 6.2 Surgical Therapy for Gliomas: Indications and Results . 106 6.2.1 Low-Grade Gliomas . 106 6.2.2 Malignant Gliomas . 108 6.2.3 Rare Gliomas . 110 v¡¡¡ Contents 6.2.4 Cytoreductive Surgery for Gliomas in Difficult and Eloquent Locations . 111 6.2.5 Recurrent Gliomas . 111 6.2.6 Pediatrie Gliomas . 113 6.2.7 Stereotactic Biopsy and Interstitial Radiosurgery (Brachytherapy) . 114 6.3 Technical Aspects of Glioma Surgery . 114 6.3.1 Electrophysiological Mapping and Monitoring of Eloquent Brain Areas . 114 6.3.2 Imaging of Functional Brain Areas for Glioma Surgery . 115 6.3.3 Image-Guided Surgery: Neuronavigation . 116 6.3.4 Intraoperative Imaging . 118 6.4 Perspectives . 119 6.4.1 Technological Progress and Neurosurgery . 119 6.4.2 Clinical Research and Socioeconomic Issues . 119 References . 120 7 Radiation Therapy . 125 Stephanie E. Combs 7.1 Low-Grade Gliomas . 125 7.1.1 Dose Prescription: High Versus Low . 126 7.1.2 Timing of Radiation Therapy: Early Versus Delayed . 127 7.2 Anaplastic Gliomas . 128 7.3 Glioblastoma . 131 7.4 Re-irradiation . 134 7.5 Conclusion . 135 References . 135 8 Adjuvant Therapy . 141 Wolfgang Wick and Michael Weiler 8.1 Introduction . 141 8.1.1 General Principles . 141 8.1.2 Current Therapeutic Strategies . 143 8.1.3 Alternative Modes of Application . 146 8.1.4 Alternative Therapies . 146 8.1.5 Gene Therapy . 147 8.2 Astrocytic Tumors . 147 8.3 Oligodendroglial Tumors . 149 References . 150 9 Other Experimental Therapies for Glioma . 155 Manfred Westphal and Katrin Lamszus 9.1 Introduction . 155 9.2 Surgery . 155 Contents ¡x 9.3 Chemotherapy . 156 9.4 Radiation . 157 9.5 New Developments . 158 9.5.1 Targeted Therapies for Glioma . 158 9.5.2 Targeting New Targets by Convection . 158 9.6 Immunotherapy . 159 9.7 Oncolytic Viruses . 160 9.8 Gene Therapy . 160 9.9 Stem Cells . 161 9.10 Final Remarks . 161 References . 161 10 Neurotoxicity of Treatment . 165 Pasquale Calabrese and Uwe Schlegel 10.1 Introduction . 165 10.2 Radiation . 166 10.3 Radiation-Induced Neurotoxicity . 166 10.4 Brain Atrophy . 167 10.5 The Effect of Radiation Dosage . 168 10.6 Neuropsychological Deficits Associated with Radiotherapy . 168 10.7 Quality of Life After Radiotherapy . 169 10.8 Other Treatment-Related Parameters Influencing Cognitive Function . 170 10.9 Radiotherapy and Chemotherapy . 171 10.10 Conclusions . 171 10.11 Proposed Neuropsychological and Quality of Life Test Battery . 172 References . 173 11 Neuroimaging . 175 R. Klingebiel and G. Bohner 11.1 Introduction . 175 11.2 MRI and CT- Technique . 176 11.2.1 MRI - General Aspects . 176 11.2.2 Imaging Technique . 178 11.3 Indications . 185 11.3.1 Differential Diagnosis of Cerebral Tumors . 185 11.3.2 Peritherapeutic Imaging . 187 11.3.3 Posttherapeutic Imaging . 188 11.4 Perspectives . 189 11.5 Summary . 189 Suggested Reading . 190 Contents Part III Concepts 12 Angiogenesis in Gliomas . 193 Mareia Machein and Lourdes Sánchez de Miguel 12.1 Introduction. 193 12.2 The Angiogenic Factors in Gliomas . 196 12.3 Growth Factors and Their Cognate Receptors . 196 12.3.1 VEGF . 196 12.3.2 Angiopoietins . 198 12.3.3 Other Angiogenic Growth Factors . 198 12.4 Guidance Molecules . 199 12.4.1 Ephrins . 199 12.4.2 Delta-Like 4 Ligand-Notch . 200 12.4.3 ROBO/Slit . 200 12.4.4 Netrins and DCC/UNC Receptors . 200 12.4.5 Semaphores . 201 12.5 Endogenous Inhibitors . 201 12.5.1 Thrombospondin 1 and 2. 202 12.5.2 Angiostatin . 202 12.5.3 Endostatin . 202 12.5.4 Pigment Epithelial-Derived Factor . 202 12.5.5 PEX . 203 12.6 Strategies for Therapeutic Angiogenesis Inhibition in Glioma Treatment . 203 12.6.1 Inhibition of Endothelial Cell Proliferation and Adhesion Cell Molecules . 204 12.6.2 Blocking Stimulatory Factors . 205 12.6.3 Increase of Endogenous Inhibitors of Angiogenesis . 206 12.6.4 Inhibition of Invasive Activity . 206 12.7 Perspectives and Unanswered Questions . 207 References . 207 13 Gene Regulation by Methylation . 217 Wolf С Mueller and Andreas von Deimling 13.1 Epigenetics . 217 13.1.1 Methylation in Normal Cells and Tissues . 217 13.1.2 Methylation in Cancer: General Aspects . 218 13.2 Strategies of Epigenetic Studies in Gliomas . 219 13.3 Methods of Epigenome Analysis . 220 13.3.1 General Aspects of Methylation Analysis . 220 13.3.2 Bisulfite Sequencing . 221 13.3.3 Methylation-Specific PCR . 221 13.3.4 Methods of Gene Identification . 222 13.3.5 Genome-Wide Methylation Profiling Implementing Methylation: Sensitive Restriction Enzymes . 224 Contents x¡ 13.3.6 MS-MLPA: A Novel Technique for Methylation Analysis That Does Not Require Bisulfite Modification and Can Be Reliably Applied to FFPE Tissues . 224 13.3.7 Novel Platforms for Genome-Wide, High-Throughput Methylation Analyses in Cancer Samples . 225 13.4 DNA: Methyltransferases and Methylation Pattern Maintenance . 225 13.5 Epigenetically Regulated Genes of Interest in Gliomas . 226 13.6 Diagnostic and Prognostic Value of Epigenetic Analyses: MGMT Promoter Methylation in Glioblastomas, Current Concepts, and Possible Future Developments . 228 13.7 Current Therapeutic Strategies to Overcome TSG Silencing . 228 13.7.1 Chromatin Remodeling Agents . 228 13.7.2 Gene Replacement Therapy as a Vision for Restoring Expression of Silenced Genes . 230 13.7.3 Artificial Transcription Factors in Gliomas . 230 13.8 Conclusion and Perspective . 231 References . 231 14 Brain Tumor Stem Cells . 241 Christian Nern, Daniel Sommerlad, Till Acker and Karl H. Plate 14.1 The Concept of Cancer Stem Cells . 241 14.2 Neural Stem Cells in the Adult CNS . 243 14.3 Phenotypic and Functional Characterization of Neural Stem Cells . 245 14.4 Identification and Enrichment of Brain Tumor Stem Cells . 247 14.5 Brain Tumor Histogenesis . 249 14.6 Signaling Pathways of Neural Stem Cells and Brain Tumor Cells . 251 14.7 The (Cancer) Stem Cell Niche . 252 14.8 Therapeutical Aspects . 253 14.9 Outlook . 254 References . 254
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genre_facet	Aufsatzsammlung
id	DE-604.BV022364148
illustrated	Illustrated
index_date	2024-07-02T17:04:34Z
indexdate	2024-07-09T20:56:01Z
institution	BVB
isbn	9783540312055
language	English
oai_aleph_id	oai:aleph.bib-bvb.de:BVB01-015573440
oclc_num	295001071
open_access_boolean
owner	DE-355 DE-BY-UBR DE-19 DE-BY-UBM DE-29 DE-12 DE-20
owner_facet	DE-355 DE-BY-UBR DE-19 DE-BY-UBM DE-29 DE-12 DE-20
physical	XV, 259 S. Ill., graph. Darst.
publishDate	2009
publishDateSearch	2009
publishDateSort	2009
publisher	Springer
record_format	marc
series	Recent results in cancer research
series2	Recent results in cancer research
spelling	Gliomas Andreas von Deimling (ed.) Berlin [u.a.] Springer 2009 XV, 259 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Recent results in cancer research 171 Gliomas, which comprise astrocytic, oligodendroglial, and ependymal lesions, are the most frequent primary intracranial tumors. This volume summarizes the enormous advances in our knowledge of gliomas that have occurred during recent years. Gene Therapy Glioma diagnosis Glioma therapy Gliomas Gliom (DE-588)4157618-4 gnd rswk-swf (DE-588)4143413-4 Aufsatzsammlung gnd-content Gliom (DE-588)4157618-4 s DE-604 Deimling, Andreas von 1959- Sonstige (DE-588)103034115X oth Erscheint auch als Online-Ausgabe 978-3-540-31206-2 Recent results in cancer research 171 (DE-604)BV000000043 171 Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=015573440&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis
spellingShingle	Gliomas Recent results in cancer research Gene Therapy Glioma diagnosis Glioma therapy Gliomas Gliom (DE-588)4157618-4 gnd
subject_GND	(DE-588)4157618-4 (DE-588)4143413-4
title	Gliomas
title_auth	Gliomas
title_exact_search	Gliomas
title_exact_search_txtP	Gliomas
title_full	Gliomas Andreas von Deimling (ed.)
title_fullStr	Gliomas Andreas von Deimling (ed.)
title_full_unstemmed	Gliomas Andreas von Deimling (ed.)
title_short	Gliomas
title_sort	gliomas
topic	Gene Therapy Glioma diagnosis Glioma therapy Gliomas Gliom (DE-588)4157618-4 gnd
topic_facet	Gene Therapy Glioma diagnosis Glioma therapy Gliomas Gliom Aufsatzsammlung
url	http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=015573440&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA
volume_link	(DE-604)BV000000043
work_keys_str_mv	AT deimlingandreasvon gliomas

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