Index

A methodology, 122 Abdulrauf, S.I., 139 taurine concentration in glioma biopsies, Acetazolamide, CA inhibitor, 68 124–126 -associated , 84 ligands and effector caspases suppress, 25 Adenomatous polyposis coli (APC), 41 pathways of, 121 Ageing, and cancer, 5 proteins, inhibitors of, 30–31 Agonistic Fas receptors, 25 regulatory function of PTEN, 28 AGT, see O6-methylguanine-DNA methyltransferase repression of Bcl-2 and survivin, 26, 32 (MGMT) role in gliomas, 30, 33 Alkylating agents, 89 TNF-induced, 25 Allograft implantation models, 188 ubiquitination role in, 31 Alpha-carbonic anhydrase family, 65 Aquaporin-1 (AQP1), 240 Altinoz, M.A., 60 Argon lasers, 174 5-Aminolevulinic acid (5-ALA), 239 Aronica, E., 271 Anaplastic astrocytomas, 36–37, 135, 213 Assimakopoulou, M., 61 CBV measurements, 216 Asthagiri, A.R., 247 MGMT IHC of, 92 Astrocytic tumors, see Astrocytoma(s) p16/INKa4 , relation with p53, 27–28 Astrocytoma(s), 57–58, 70, 135, 213–214, 259 Angiogenesis, 135–136 anaplastic astrocytoma, 36 Angiogenesis-related proteins, 137–138 antagonist RU486 role in, 60 Antiapoptotic proteins, see Astrocytoma(s) antiapoptotic proteins role in Antisera, 108 Bcl-2 proteins family, 29–30 ANXA1 (annexin 1), 49 death ligands, 23–26 Aphasia, 224 IAPs, activation in gliomas, 30–32 Apolipoprotein Apia-I, 191 p53, and cell cycle progression E2F role, 26–27 Apoptosis, 136, 146, 153 PTEN relationship with p53, 28–29 activation, and signaling pathways, 23–24 receptors and messengers role, 23–26 Bcl-2 controls, 29–30 survivin and cell cycle progression, 32–33 biological significance, 23 TNF-induced NF-κB activation in, 25 caspases role in, 30 biopsy, analysis of, 122–126 defined, 23, 121–122 carbonic anhydrase IX FasL and TRAIL mediated, 25 diagnostic tool in grading astrocytomas, studies, in gliomas, study using MRS 69–70 apoptotic cell density, 123 evaluation in tumors, 68 ca 2.8 ppm Lip/MM peak from PUFAs, prognostic significance of, 68–69 125–126 role, 68–70

M.A. Hayat (ed.), Tumors of the Central Nervous System, Volume 5, 275 DOI 10.1007/978-94-007-2019-0, © Springer Science+Business Media B.V. 2012 276 Index

Astrocytoma(s) (cont.) therapy, synemin and other IF proteins prospects, CBV/rCBV measurements 86–87 predictive role, in survival and recurrence, see treatments, depending factors, 58 Cerebral blood volume (CBV) See also Gliomas cell motility, IF proteins role Autism, 149–150, 154 GFAP, 85–86 Axin, tumor suppressor, 40–41 , 81, 85–86 synemin, 82–85 B , 81, 85–86 Bannykh, S.I., 199 cerebellar, spontaneous regression of, see Bcl-2 protein family, 23 Cerebellar astrocytomas (CA) controls apoptosis, action mechanism, 29–30 diffuse astrocytoma, 36 groups, 29 doppel protein functionality Bigner, S.H., 111 biochemical features, and cellular localization, Biomarker discovery, methods 18–20 cytogenetic method, 111–112 distinguishing subtypes of, 16 digital karyotyping technique, 114–115 functional pathways analysis, 19–20 EGFR amplification technique, 111–112 gene expression analysis, tumor marker, 13, EGFRvIII expression, 112 15–17 genomic characterization technique, 116–117 glial tumors, gene expression, 16, 18 immunologic methods, 108–109 interaction analysis, 19–20 integrated genomic analysis, 115–116 over-expression, 16–17 karyotypic analysis, 111 glioblastoma multiforme, 35 large-scale array analysis, 113 higher MVD in p53 mutated low-grade, 140 using double-minute (DM) , 111 high recurrence rate of, factors, 81 using gangliosides, 109–110 hormonal therapy for, 58, 62 using gene expression arrays, 114 Human Angiogenesis Array, 137–138 using GLI transcript, 112–113 IF proteins role in cell motility, 85–86 using tenascin, 110 IHC for MVD, 136–137 Bisdas, S., 216–218 Laser-Induced Fluorescence Spectroscopy (LIFS) Bisulfite DNA treatment, 6–7 for, 162 Bjerkvig, R., 109 low grade, p53 involvement, 135 Bleier, A.R., 180 pilocytic astrocytoma, 36 Blood brain barrier (BBB), 188 P53 mutation, 138 Bonéy-Montoya, J., 60 association with MVD, 138–139 Borit, A., 143 characterization, 137 Bourdon, M.A., 110 higher number of vessels, 138 Bouvier, C., 199 PR isoforms Bovenzi, V., 60 expression regulation, and malignancy grades, Bovine spongiform encephalopathy (BSE), 13 59–60, 62 Bowers, D.C., 201 function in growth of, 57, 60–61 Bown, S.G., 173–174 progesterone (P) Brain Cancer, nanotechnology based therapy genomic mechanism of action, 58 methods to increase targeting specificity, 191–192 role in cell growth and proliferation of, 57, 60 nanomaterials delivery, 190–191 regression, 143 convection-enhanced delivery (CED), 192–193 SEGA, see Subependymal giant cell astrocytomas systemic delivery, 190–191 (SEGAs) nanoparticle formulations, 189–190 statistical analyses, 138 strategies to overcome BBB, 192 taurine role, in apoptosis, see Apoptosis See also Cancer Index 277

Brain thermal lesions, evolution on MRI, 181–182 diagnostic tool, in grading astrocytomas, 70 Brain tumors, 57, 60, 135, 195 expression cell cultures, 107 in Barrett’s-associated adenocarcinomas, 66 computer-based QOL monitoring, ePROM, and disease prognosis, 67 226–227 ectopic, 66 fluorescence signature and, 170 and hypoxia responsive element (HRE), 67 Laser-Induced Fluorescence Spectroscopy (LIFS) increased, 66–67 for, 162 malignant gliomas, 67 malignant, nanotechnology-based therapy for, in normal tissue, 66 187–189 predominant CA isozyme in tumors, 66 PROM, see electronic Patient-Reported Outcome prognostic significance (studies), as valuable Monitoring (ePROM) marker, 67–70 specific Pros, 225 role in astrocytomas, 68–70 symptoms, 223–224 role in carcinogenesis, function mechanism, 67–68 TR-LIFS, tool for intra-operative diagnosis, see Carboplatin, in treatment of PMAs, 207 Time-resolved laser induced fluorescence Carpentier, A., 175–176, 180, 183 spectroscopy (TR-LIFS) Carroll, R.S., 60 variety of, and treatment possibilities, 223 β-, 35, 37–39, 42–43 Breast cancer, CA IX as tumor biomarker, 67 See also Wnt signaling pathway Brell, M., 92 Cathepsin D, lysosomal proteinase, 74 Britz, G.W., 235 CBV, see Cerebral blood volume (CBV) Brunetaud, J.M., 177 CD95 ligand (CD95L), 23 CD34 protein, 256 C Cellular differentiation, 136 Cabrera-Munoz, E., 61 Central nervous system (CNS), 187–188 Cachexia, 196 and doppel protein expression, 13, 15, 19 CA9 gene, 65, 67 germ cell tumors, 95 Calcifications, 196, 199 arise from pleuropotential embryonic cells, 95 Camacho-Arroyo, I., 58–59 in Asian population, higher incidence, 97 Camptothecin, 146 benign and malignant, 95 Cancer clinical presentation, tumors in, 96–97 ageing and, 5 germinoma and non-germinoma, histological and DNA methylation failure, 5–6 examination, 95–96 ERK/MAPK pathway deregulation, 102 locations, mainly midline, 95–97 importance, of imaging of HIF-1-active tumors, hemangioblastomas, see Hemangioblastomas 129 low-grade neoplasms PAs, pediatric tumors of, see NF-κB in genesis and progression of, 25 Pilocytic astrocytomas (PAs) p16/INKa4 protein role, 27–28 malignant tumors, nanotechnology-based therapy role of synemin in, 83 for, 187–189 -targeted PROs, 225 tumors and EGBs presence diagnosis, 78 types, 223 Ceppa, E.P., 198, 207 Cantharidinare, 147 Cerebellar astrocytomas (CA), 143 Cao, V.T., 93 regression, 144, 147 Capper, D., 92–93 criteria for, 144 Carbonic anhydrase (CAs), 65 CT scans, spontaneous regression, 144 Carbonic Anhydrase IX (CA IX), 65–66 hormonal changes and chances of, 145 diagnostic evaluation imaging surveillance in, 145 monoclonal M75 anti-human CA IX antibody incidence and time course of, 144–145 use, 68 mechanism and multiple factors, 145–146 278 Index

Cerebellar astrocytomas (CA) (cont.) Cottingham, S.L., 206–207 residual tumours, smaller volume and higher CpG islands, 4–5, 90 chances of, 146 Curzerenone, 147 therapy for, surgical resection, 144 CyberKnife SRS, 249 Cerebellar lesions, 195 Cyst, 239–240 Cerebral blood volume (CBV) Cystic tumors, see Pilocytic astrocytomas (PAs) estimation, by MRI Cytogenetic method, 111–112 arterial spin labeling techniques, 215 Cytoskeletal protein, 81 DSC-MRI, 214–215 gradient echo pulse sequence use, 215 D preload approach, problem, 214 Death domain (DD), 24 T1-based methods, 214 Death effector domain (DED), 24 measurements, predictive value, 217–219 Death inducing signaling complex (DISC), 24 biases in prediction, 217 Death ligands, 23 correlation between histopathological grade Death receptors, 23–24 and, 218 De Porter, J., 175, 180 cut-off values, 218 Desmuslin, 82 data collection from longitudinal studies, 219 Devaux, B.C., 176 EORTC criteria, 218 Dhermain, F., 218 rCBV value, after combined radiation and Di, C., 115 temozolamide therapy, 219 Dickkopf family proteins, 35, 39 methodological considerations, and survival rates, Diencephalic syndrome, 204 215–216 Dietary supplements, anti-cancer effects, 146–147 CBV mapping, 215 Diffuse astrocytoma(s), 10, 36 histogram analysis, of rCBV values, 216 main tumor entities, 89–90 hot-spot ROI method, 216 MGMT IHC expression, 89–90 limitations, 216 compared to MGMT promoter methylation, 91 in predicting astrocytoma histopathologic grade, in glioma and non-neoplastic cells, 89, 91–92 214 marker of patient outcome, 92–93 Cerebrospinal fluid (CSF), 149, 203 technical considerations, 90–91 Chang, S.D., 248 MGMT protein and resistance alkylating agents, Chemotherapy, for PMA, 203–204, 206–208 89–90 Chen, Y.Y., 43 Digital karyotyping technique, 114–115 Chikai, K., 207 Digital oscilloscope, 164 Chinese herbs, 146–147 3,3-Diindolylmethane (DIM), 146 ChIP-on-chip method, 9 Diode laser, 176 Choi, Y.J., 47, 51 Dirven, C.M., 200–201 Choroid plexus, 65 Discriminant function analysis (DFA), 165 Cisplatin (CDDP), in treatment of PMAs, 203, 207 Dishevelled (Dvl), 40 Coagulation factor III (CF III), 138, 140 D-54 MG glioma cells, 109 Coagulation factor VIIa, 140 DNA, apoptotic DNA fragmentation, 121 CO2 lasers, 174 DNA methylation, 3–4 Colchicinamide, 147 analysis, methods Colchicine, 146 based on DNA chemical modification, 6 Coley’s vaccine, 145 ChIP-on-chip method, 9 α(II) collagen prolyl-4-hydroxylase, 139 MALDI-TOF mass spectrometry, 8 Comincini, S., 18 methylation-sensitive restriction enzymes Computer-based Health Evaluation System (CHES), usage, 6 227 methylation-specific PCR (MSP), 7 Index 279

microarray expression profiling, 8 EORTC QLQ-BN20, 226, 228 primers usage, 8 Eosinophilic granular bodies (EGBs), 73–74 restriction landmark genomic scanning (RLGS) cathepsin D role, in cell apoptosis, 76 method, 8–9 contents and morphologies, in tumor, 74 techniques comparison, 7 H&E (hematoxylin and eosin) staining in astrocytic tumors, for diagnosis and prognosis, and anti-GFAP and anti-CSE1L antibodies, 75 9–10 Mayer’s hematoxylin for staining, 75–76 failure, as cause of disease or cancer, 5–6 observation protocol using immunohistochemistry, hypomethylation, 5–6 77 relevance in normal cells, 4 with antibodies against LAMP-1 and LAMP-2, role in mammalian CNS development and 73–74 function, 9 origin, 75–77 DNA methyltransferases, 4 PAS (periodic acid-Schiff) staining DNA methyltransferases (DNMT) , 4 and anti-GFAP and anti-CSE1L antibodies, 75 DNA repair, 136 relation to lysosomal system, 73 DNMT, see DNA methyltransferases role in cyst development in pilocytic astrocytomas, Doppel gene, discovery, 13–15 73, 75–77 Doppel protein Epidermal growth factor receptor gene (EGFR), biochemical features, 15, 18–19 111–112, 192 cell migration process, contribution in, 13, 20 Epigenetics functional pathways, 19–20 defined, 3 and interaction analysis, 19–20 states, modification, 4–5 post-translational modifications, 18 Epigenetic therapy, 11 and prion proteins, comparison and similarities, Epileptogenicity, of brain tumors 13–15, 18, 20 cellular composition and neurochemical profile, similar exon– architecture, with prion gene, 262–263 14 of peritumoral zone, 263–264 and structural characterization, 15 ERM proteins, 261 Double-minute (DM) chromosomes, 111 European Organization for Research and Treatment of Doxorubicin-loaded, PEG coated PHDCA Cancer core questionnaire (EORTC nanoparticles, 191 QLQ-C30), 225, 229 Dysembryoplastic neuroepithelial tumours (DNETs), Everolimus, 45, 50–51 259, 261 F E FACT-Br Symptom Index (FBrSI), 225–226 E2F family protein, 27 FasL (Fas ligand), 25 EGBs, see Eosinophilic granular bodies (EGBs) Fernandez, C., 207 EGFR, see Epidermal growth factor receptor gene Ferroli, P., 235 (EGFR) Fiber optic probe, 164 EGFRvIII expression, 112 Fisher, B.J., 201 electronic Patient-Reported Outcome Monitoring Fisher, P.G., 195 (ePROM) FLAIR image, 218 implementation of, 226–227 Fluorescence measurements types, 162 software, 227 Fluorescence spectroscopy, 162 tele-monitoring, 227–228 Fluorophores, 162, 169 usage of proxy-rating, 228–229 Foltz, G., 39 Ellmann, S., 60 Franz, D.N., 52 Endostatin, 139 FRAT1 (frequently arranged in advanced T-cell EORTC Brain Cancer Module (BN20), 226 lymphomas-1), 40 280 Index

Freilinger, A., 47 localization, 254 Functional Assessment of Cancer Therapy-Brain macroscopy of, 256 Module (FACT-Br), 225–226 mechanisms of epileptogenesis, 261–264 Functional Assessment of Cancer Therapy general molecular pathogenesis of, 260–261 version (FACT-G), 225 neurophysiological features, 254–256 Functional Assessment of Chronic Illness Therapy origin from, 268–269 (FACIT) measurement system, 225 pathogenesis, 263 Furnari, F.B., 187 perilesional changes, 264 Fusion genes prognostic factors and surgical outcome, BRAF and KIAA1549,inPAs,100–101 259–260 MAPK activation via RAF1, 101 symptoms, 254 in pilocytic astrocytoma, KIAA1549, 100–101 Gangliosides Fuss, M., 218 antigens, 109–110 FVIII-immunostaining, 139 patterns, 109–110 GBM, see Glioblastoma multiforme (GBM) G Genetically engineered mouse models Gajjar, A., 195 (GEMMs), 188 Gamma-glutamyl-Semethylselenocysteine (GGMSC), Genomic characterization technique, 116–117 146 Germ cell tumors Gamma Knife SRS, 247 arise from pleuropotential embryonic cells, 95 Gangliocytoma, 258–259 in Asian population, higher incidence, 97 Gangliogliomas (GG) benign and malignant, 95 alterations in Pi3K-mTOR pathway components, clinical presentation, tumors in 263 basal ganglia region, 96 association with temporal lobe epilepsy (TLE), 267 pineal region, symptoms, 96–97 cellular pathology analysis, 269 predilection for males, during puberty time, 97 coexistence with cortical dysplasia, 259 suprasellar region, 96 CT for imaging, 254 germinona, 95 differential diagnosis, 258–259 histological examination, cell types, 96 differential gene expression in, 270–271 magnetic resonance imaging of, 96 LIM domain-interacting transcripts, 270 locations, mainly midline, 95 reelin signaling cascade, factors modification, and non-germinoma, histological examination, 95 270 choriocarcinoma, and teratomas, 96 epileptogenicity, 263 yolk-sac tumors and embryonal carcinoma, 96 expression of specific glutamate receptors (GluR) SEER-17 registry data for study, 97 subtypes, 263 See also Central nervous system (CNS) gene expression analysis, approaches, 272 GFAP (Glial fibrillary acidic protein), 75, 82–83, aRNA amplification method, 269 85–87 glass microscope slide DNA arrays, 268–269 Giannini, C., 200 microarray systems, limitations, 269 Glial tumors, malignancy grades, 16 oligonucleotide arrays, 268–269 Glioblastoma multiforme (GBM), 187, 214 in situ-RT and immunolaser microdissection, develop de novo, 36 268–269 doppel expression, 16 histopathological features, and hallmark of, epigenetic alterations in, 9 257–258, 268–269 genetic changes associated, 37 IHC characterization of, 258 GPNMB gene role, 153 imaging, 254 gross total surgical resection (GTR) in, 233 incidence and age/sex distribution, 254 nanotechnology-based delivery of therapeutics, intraoperative diagnosis, 256 features, 188–189 Index 281

primary and secondary, chromosomal aberrations Wnt genes associated with, 37, 39–40 in, 36 Wnt inhibitory factor-1 (WIF-1), antagonist, 39 TP53 mutation, 37 Wnt proteins, 39–40 Glioblastomas, 36, 135–136, 161 Wnt receptor complex, 37 CA IX expression in, 69–70 in women, 146 cell types, 37 Glioneuronal lesions, 253, 261 EGFRvIII mutation, 112 Glioneuronal tumors, see Gangliogliomas (GG) GBM, see Glioblastoma multiforme (GBM) GLI transcript, 112–113 p16/INKa4 protein, relation with p53, 27–28 Glutamate decarboxylase (GAD), 169 poor prognosis, 58 Glycogen synthase kinase 3 (GSK 3), 41 Gliomas, 57, 135, 161 Glycosylphosphatidyl-inositol (GPI), 14–15, 18 animal model systems, for preclinical trials, 188 Gonzalez-Aguero, G., 60–61 astrocytomas, 35–36, 57 Goodwin, T., 97 cell culture studies, limitation, 188 Gottfried, O.N., 207 diagnosis, in vivo measurements Gotze, S., 39 fluorescence signature of diffuse astrocytoma, GPI, see Glycosylphosphatidyl-inositol (GPI) 170 GPNMB (glycoprotein nmb), 49 spectroscopic parameters analysis, 170 Grasbon-Frodl, E.M., 91 TR-LIFS characteristics, 170 Groucho (Grg/TLE) family, transcriptional ependymomas, 35–36 co-repressors, 42 of grades III-IV, 187 GTPase-activating protein, 47 histological characteristics for grading, 35 Guba, M., 49 IAPs activation in, 31–32 Guerra-Araiza, C., 59 malignancy grades, and survival rates, 57–58 Gunny, R.S., 146 malignant, 187–188 Guo, G., 41 mixed oligoastrocytomas, 35 nuclear polymorphism, 36 H oligodendrogliomas, 35–36 Haapasalo, H., 201 progress, microvascular hyperplasia, 135 Harada, H., 130 spectroscopic classification, 164 Harringtonine, 146 surgical resection of, 161–162 Health-related quality of life (HRQOL) assessment, survivin and cell cycle progression, 32–33 223 Wnt/β-catenin/Tcf signaling pathway components Helin, K., 58 in, 35, 38 Hemangioblastomas, 233, 239–240, 242, 245, 250 Axin and APC proteins, 38 associated with von Hippel-Lindau syndrome, 233 Axin-APC-GSK3β, 41 conventional radiotherapy for, 246 β-catenin, central player, 38, 41–42 cysts, formation mechanisms in Dishevelled (Dvl), 40 aquaporin-1 (AQP1) role, 240 DKK family, 39–40 histologic appearance of, 246 FRAT1, 40 intraoperative ICG videography use in, 233–235 Frizzled family, 37–38 resection of intracranial and spinal, 235–237 frizzled receptors, 40 photodynamic diagnosis (PDD), with 5-ALA, Lef/Tcf family transcription factors, 42 239–240 LRP5 and LRP6, 37, 39 radiosurgery for neural stem cells regulation, 38 contraindications, 246 overview, 37 current indications, 246 pygopus 2, 43 radiosurgical complications, 249–250 sFRPs and Dickkopf family, extracellular rationale for use, 246 inhibitors, 39 stereotactic, 246–249 282 Index

Hemangioblastomas (cont.) I radiosurgical treatment of, key studies, 247–249 ICG, see Indocyanine green (ICG) rare vascular tumors, 233 Ichikawa, T., 48 recurrence rate, 239, 245 Ichimura, K., 58 residual tumors detection, by ALA-derived PpIX IHC markers, 90 fluorescence method, 241–242 ([123I]iodobenzoyl)norbiotinamide (123I-IBB), 129 treatment modalities, 250 123I-IPOS, probe, 129 types, as per MRI studies, 240 Immunohistochemistry, 131 Heme Indirubin, 147 pathway regulation, ALAS feedback inhibition Indocyanine green (ICG), 234 role, 240–241 intracranial practical applications, 234–235 synthesis steps, 240 intraoperative use, in hemangioblastomas, 233–237 Hengstschlaeger, M., 50 resection of intracranial and spinal, 235 Henske, E.P., 48 Inhibitor of apoptosis (IAP) proteins family Hernandez-Hernandez, T., 60 activation in gliomas, 31–32 HIF-1-active tumors imaging, using 123I-IPOS classification, 30–31 based on pretargeting approach, concept, eight human members, 30 131–132 survivin, and cell cycle progression, 32–33 hypoxia imaging concept, 130–131 Inoki, K., 49 size-exclusion analysis, 131 Inorganic nanoparticles, 189 High mobility group (HMG), 42 Integrated genomic analysis, 115–116 High-resolution magic angle spinning (HRMAS) 1H Intermediate filament (IF) proteins MRS, 121–122 functions, 81–82 lipid peaks, 126 GFAP (Glial fibrillary acidic protein), 75, 82–83, of non-necrotic (top spectrum) and necrotic 85–87 (middle spectrum) biopsy, 123, 125 nestin, 81–82, 85–87 taurine concentrations, 126 prospects for astrocytoma therapy, 86–87 Higuchi, N., 178 synemin, 81–83 Hilvo, M., 68 vimentin, 81, 83, 85–87 Hirai, T., 218 See also Astrocytoma(s) , of LITT-induced lesions, see Laser Interstitial hyperthermia concept, 173–174 interstitial thermotherapy (LITT) Intracranial germ cell tumors, malignant, 95 Histone modifications, 3 Intracranial xenografts, 191 HMG, see High mobility group (HMG) Intraoperative ICG videography, applications, 234 Homoharringtonine, 146 in identifying regions of tumor, 235 Horbinski, C., 199 in the resection of 100 craniotomies of mixed Howng, S.L., 40 pathology, 235 HRMAS; 1H MRS, see High-resolution magic angle in the resection of hemangioblastoma, 235 spinning (HRMAS) in resection of spinal hemangioblastomas, 235–236 Hulleman, E., 58 to stain glioma margins in animal models, 234–235 Human angiogenesis array, 137–138 in vascular neurosurgery, 234 Human ICF syndrome, 5 Intratumoral, 240–241 Humphrey, P.A., 112 accumulation, 191 Hydrocephalus, 149–150 administration, 191 Hydroxycamptothecin, 146 cysts, 240–242 Hyperplasia, 135 hemorrhages, 150 Hyperthermia, 177 infusion, 192 Hypoxia-inducible factors (HIFs), 47, 67 necrosis, 240 Hypoxic regions, 129 Isbert, C., 177 Index 283

Ischemic tumour necrosis, 145 Laser-induced fluorescence spectroscopy (LIFS), 162 36-isoLD1, expression of, 109 Laser interstitial thermotherapy (LITT), 173 Ivanov, S., 69 applied to brain tumors, clinical studies Ivarsson, K., 177 CT-guided stereotactic procedures, 182 devices, manufactured for, 184–185 J Gd-DTPA-enhancing rim, 183 Jagannathan, J., 242 heating process and temperature elevation, 183 Jawahar, A., 248 histological analysis, 183 Johnson, M.W., 48 hyperthermia treatment with Nd-YAG laser, 182 Jolesz, F.A., 179 real-time magnetic resonance-guided LITT Jó´zwiak, S., 48, 51–52 system, 183 for deepseated tumors, 174 K limitations, 175 Kageji, T., 207 MRI imaging and, 179 Kahn, T., 178, 180–181, 183 brain thermal lesions on MRI, evolution, Kangasniemi, M., 176, 178, 181–182 181–182 Kano, H., 247 MRI thermal imaging sequences, 179–180 Karabagli, H., 247, 249 real time computation, 180–181 Karayan-Tapon, L., 92 procedures on patients, with brain metastases, 174 Karnofsky performance score, 204 with real-time MRI, 174 Karyotypic analysis, 111 treatments consist of, 173 Kastner, P., 58–59 Laser (Light Amplification by Stimulated Emission of Kazuno, M., 140 Radiation), 173–174 Keene, D., 97 control delivery software Kerr, J.F., 23 with real time with MRI thermometry analysis, Khalid, H., 60 181 KIAA1549 protein, 101 emission in active medium, 175 Kickhefel, A., 180 functioning principles, 175–176 Klein, R., 200 history, 174–175 Knudson’s two-hit model, tumor development, 48 interactions with biological tissues, mechanisms, Kohler, G., 108 177 Komakula, S.T., 207 histology of LITT-induced lesions in brain Komotar, R.J., 207 tissue, 178–179 Kondo, I., 111 immediate and secondary, 177–178 Korkolopoulou, P., 69 thermal dosimetry, 179 Korur, S., 41 main elements, 175 Kou, L., 176 physics, 175 Kraus, W.L., 59 produce high energy light, properties, 175 Krueger, D.A., 52 technology, fundamental principles, 175 Kudo, T., 130 transmission of beam, 176 Kuratsu, J., 97 used in LITT, 176–177 use in neurosurgery, 173 L Law, M., 218 Lam, C., 45, 52 LDL receptors (LDLR), 191 LAMP-1 and 2 (Lysosomal membrane proteins), Lee, N., 52 74–78 Lef/Tcf family transcription factors, 42 Lange, C.A., 58–59 Leonhardt, S.A., 58 Large-scale array analysis, 113 Leon, S.P., 139 Laser fibers, 176 Lev, M.H., 218 284 Index

Libermann, T.A., 111–112 Matsunaga, S., 248 LIM-domain-binding 2 (LDB2) gene, 261 Maxwell, J.A., 91 LINAC-based radiosurgery, 247 McCowage, G., 207 Lipid NPs, categories, 190 McKenna, N.J., 58 Liposomes, 190 Menovsky, T., 179 LITT, see Laser interstitial thermotherapy (LITT) Mental retardation, 150 Liu, X., 42 Methylation, importance in clinic, 10–11 Liu, Z.J., 60 Methylation-specific PCR (MSP) method, 7–8 Lockshin, R.A., 23 O6-Methylguanine-DNA methyltransferase (MGMT), Loncaster, J.A., 67 9, 89 LTF (lactotransferrin), 49 IHC expression in diffuse gilomas, see Diffuse Lycobetaine, 147 astrocytoma(s) Lysosomal protease, 73–74 immunohistochemistry Lysosomes, 73–74 with clone MT3.1 and MT23.3, 92 double, 91–92 M expression, 9, 89–90 Magnetic resonance imaging (MRI), 145, 254 marker of patient outcome, 93 astrocytomas characterization, imaging method, and non-neoplastic cells, 91–92 214 technical considerations, 90–91 brain, case report, 204–206 tumors identification with loss of MGMT contrast T1 MRI follow-up after LITT treatment, expression, 92–93 182 promoter methylation assays coronal MRI images, 255 application and limitations of, 91 diffusion-weighted, 214 MGMT, see O6-Methylguanine-DNA DSC-MRI, 214–215 methyltransferase for evaluating intracranial, neoplastic disease, 196 MGMT methylation, 9–11 with gadolinium enhancement at T1/T2/FLAIR MIB-1 labeling index, 200 weighting, 246 Microarray expression profiling, 8 of gangliogliomas (GG), 253 Microdissection approach, 267, 269–270 imaging and LITT, 179 Microvascular hyperplasia, 135 perfusion-weighted, 214 Microvessel density (MVD) for pilocytic astrocytomas, 197 astrocytoma evaluation, 136 thermal imaging sequences, 179–180 degree of vascularization, 136 tumor determined by, 183 function estimatimation, of p53 mutation status, T2-weighted (FLAIR) MR image, 218 137 to visualize spinal hemangioblastomas, 236 IHC detected P53 protein, 138 Mahaley, S.M., 108 Milstein, C., 108 MALDI-TOF mass spectrometry, 8 Mineura, K., 91 Male fertility, and doppel, 15, 21 Mi, R., 51 Mamelak, A.N., 207 Missense mutant p53 proteins, 139 Mammal development, and DNA methylation role, Mitogen activated protein kinase (MAPK) pathway 4–5 activation via BRAF fusion gene, in PAs, 103 MAPK, see Mitogen activated protein kinase (MAPK) alternative activation mechanisms, 103–104 pathway targeted therapy against Maser (Microwaves Amplification by Stimulated AZD6244, 103 Emission of Radiation), 174 PLX4032 inhibitor, 103 Massimino, M.L., 19 Sorafenib, target, 103 Mast cells, 245 Mizobuchi, Y., 40 Matrix metalloproteinase-9 (MMP-9), 140 Momparler, R.L., 60 Index 285

Monoclonal antibodies (MAbs), 108–110 inorganic, 189 Monocrotaline, 147 lipid, 190 Moore R.C., 15 liposomes, 190 Mordon, S., 177 polymeric, 189 Moss, J.M., 247, 249 polymeric micelles, 190 Motor deficit, 224 xenograft systems models, tumor biology, 188 MRI imaging, 145 Natural remedies and herbs, anti-cancer effects, See also Magnetic resonance imaging (MRI) 146–147 MRI thermal imaging sequences, 179–180 Necrosis prediction, 180 MSP derived methods, 8 Necrotic biopsies, analysis of, 122–126 mTOR (mammalian Target Of Rapamycin) pathway, Neodimium(Nd)-YAG lasers, 173–177, 179–180, 46 182–183 inhibitors, anti-angiogenic effects Neovascularization, 135–136, 139 effects on cell cultures and animal models of Nestin, 81–82, 85–87 TSC, 51–52 Neural stem cells-gliomas, 39 everolimus (RAD001), selective nature, 52 Neurooncology, 107 rapamycin action process, 49–50 Neurosurgery sirolimus, mechanism involved, 51 interstitial hyperthermia in, 174 temsirolimus (CCI-779), action mode, 49–51 ultrasound-based monitoring techniques not in Subependymal Giant Cell Astrocytoma, 48 feasible for, 179 genes regulating activity, 48 use of intraoperative ICG, 234 targeting, 52–53 use of lasers in, 173 in Tuberous Sclerosis Complex, 46–47 NF1 (Neurofibromatosis 1) gene, 100, 102 autophagy inhibition, 47 Niemela, M., 249 genes regulated by HIFs, 46 Nikuseva Martic, T., 41 inactivating mutations TSC1/TSC2 gene, 46 NPTX1 (neuronal pentraxin I), 49 Ras-homoloque-enriched in brain (Rheb) target, Nuclear factor-κB, 25 46 Nuclear medicine imaging, 130 mTOR protein, 46 Nuclear polymorphism, in tumor cells, 36 Mulac-Jericevic, B., 59, 61 Muller, W., 40 O Murai, Y., 235 Oligodendroglioma, 259 Oligonucleotide arrays, 268–269 N Olson, J.J., 60 Nakasu, S., 93 Oridonin, 147 Nanooncology, 187 Oxygen-dependent degradation domain (ODD) fusion Nanotechnology, 187–189 proteins, 130 based delivery of therapeutics to GBM, 188 for brain cancer, 189 P nanomaterials delivery, 190 PAI-1 gene, 140 convection-enhanced delivery (CED), Paixão Becker, A., 199 192–193 Paralogue compensation process, 18 methods to increase targeting specificity, Park, Y.S., 248 191–192 Parsons, D.W., 115 strategies to overcome BBB, 192 Pastorek, J., 65 systemic delivery, 190–191 Pastoreková, S., 68 nanoparticles (NPs), 188 Patient-reported outcomes (PROs), 224–225 designed to delivery, 188–189 commonly used PRO instruments, 229 formulations, 189 computer-based, 226–228 286 Index

Patient-reported outcomes (PROs) (cont.) MAPK activation via RAF fusion genes, 99–101 tele-monitoring, 227–228 BRAF:KIAA1549 fusion genes, 100–101 See also electronic Patient-Reported Outcome BRAF V600E mutation, 103 Monitoring (ePROM) fusion variants, 100–101 Pecina-Slaus, N., 41 mutation of KRAS and BRAF, 101–102 Pediatric gliomas, 195 NF1 gene mutation, 102 high grade, and for MGMT IHC, 93 targeted therapy against MAPK pathway, See also Pilocytic astrocytomas (PAs) 102–103 Petronio, J., 207 MIB-1 labeling indices of, 200–201 P53 gene molecular genetic changes in, 100 expression, 140 oligodendroglioma-like features, 199 immunohistochemistry, 137 of optic pathways, 195 -mediated regulation on angiogenesis, in low grade role of EGBs in cyst development in, 73, 75–77 astrocytomas, 135, 139–140 slow-growing tumors, 76 mutations, 138 treatment strategies, 196 in astrocytomas, 135, 137–138 tumorigenesis, importance of MAPK signaling, characterization of, 137 99–100 protein expressions, 138–139 variants, 99, 197–198 tumor suppressor, 136 See also Eosinophilic granular bodies (EGBs) P-glycoprotein (P-gp), 263 Pilomyxoid astrocytoma (PMA), 198, 203 Phosphatidylethanolamine (PE), 190 case reports, 204–206 Phospholipid, 190–191 chemotherapeutic regimens, 207–208 Photoablative effect, 177 clinical characteristics, 203 Photochemical effect, 177 different features from PA, 203, 206 Photodynamic diagnosis (PDD), for residual tumors, drug combination 240 cisplatin (CDDP)/carboplatin (CBDCA) and Photomechanical effect, 177 etoposide, 203 Photosensitizing agent, 177 higher rate of recurrence, 203, 207 Photothermal effect, 177 management of, 203 PI3K-mTOR pathway, 261 MIB-1 labeling index, 204 Pilocytic astrocytomas (PAs), 36, 73–74, 195–196, with monomorphous pilomyxoid features, 206 203, 259 patients with CSF dissemination, 204 biphasic tumors, 76, 99 temozolomide as first line adjuvant chemotherapy, cerebellum, most frequent site, 99 207–208 classic form, Rosenthal fibers presence, therapeutic strategies for PMA patients, 207 196–198 WHO classification, 207 common pediatric tumors of CNS, 73, 99 See also Pilocytic astrocytomas (PAs) EGBs presence in microcysts, 76–77 Pinski, J., 60 histological analyses, 198–199 Piroli, G., 60 histopathology, 73 Plasminogen activator (PA), 140 imaging characteristics, 196–197 Pleomorphic xanthoastrocytoma, 259 immunohistochemical analyses, 199–201 P53, nuclear phosphoprotein and increased intracranial pressure in, activity regulation, 26 76, 78 cell cycle progression, control mechanism, 26–27 LAMP-1, LAMP-2, and cathepsin D involvement as genome guardian, 26 in EGBs formation, 76 p16/INKa4 protein, relation with, 27–28 leptomeningeal infiltration in, 199 relationship between PTEN and, 28–29 lysosomal proteinases, in EGBs role, 76–77 Pollack, I.F., 93, 195 management complexity, 196 Polymeric micelles, 190 Index 287

Polymeric nanoparticles, 189 Q POS and 123I-IBB method Qin, K., 19 for imaging HIF-1 active regions in tumors, QOL-instrument, 225 130–131 in vivo molecular imaging, 130 R pretargeting approach, 131–133 Radionuclides, 132 oxygen-dependent degradable probe, development, Radiosurgery, 173, 182, 245–246 130 contraindications, 246 P response elements (PRE), 58 current indications, 246 Pretargeting approach, 129, 131–133 frame-based linear accelerator, 249 advantages, 132 indications, 246 defined, 129, 131 key studies, 247–249 for imaging of HIF-1-active tumors, principle, radiosurgical complications, 250 132–133 rationale for use, 246 Preusser, M., 92 stereotactic, 245–249 Prion diseases, see transmissible spongiform See also Hemangioblastomas encephalopathies (TSEs) Radiotherapy, 145 Prion–doppel interaction, 13, 19–20 Rapamycin, 45, 49–50 Prion-like protein, see Doppel protein rCBV, see Relative cerebral blood volume (rCBV) PR isoforms, 57 Real time computation, 180–181 expression, regulation of, 59–60, 62 Real time MRI thermal imaging, 180 estrogens effects, and interaction with ERs, 59 Reelin, 270 PR-B and PR-A, 57 Relative cerebral blood volume (rCBV), 213, 215–218 regulation and function in astrocytomas, 57, 60–61 Relaxivity, 214–215 PR-A transfection effects, on U373 human Reoxygenation, 131 astrocytomas growth, 61 Restriction landmark genomic scanning (RLGS) regulation by phosphorylation, 58–59, 62 method, 8–9 transcriptional activity of, 58–59 disadvantages, 9 U373 and D54 cell lines, expressed in, 57 Reticuloendothelial system (RES), 190 up-regulation by E, 59 Rett’s syndrome, 5 See also Progesterone (P) Richardson, E.P. Jr, 143 Probe, 129–132 Richer, J.K., 58–59, 61 Proescholdt, M.A., 70 RND3 (Rho family GTPase 3), 49 Progesterone (P), 57 Rodriguez, F.J., 197 genomic mechanism of action, PR interaction with, Roggendorf, W., 200 58–59 Roninson, I.B., 113 induced cell proliferation, in cell lines, 60 Rosenfeld, M.G., 58 interaction with intracellular receptor (PR), 57 Rosenthal fibers, 203, 206 and PR isoforms role in astrocytomas cell growth, Rosner, M., 50 57, 60 Roth, W., 39 Programmed cell death, see Apoptosis Rousseau, A., 57 Proliferating cell nuclear antigen (PCNA), 27 Roux, F.X., 176–177, 179, 182 Proptosis, 195 Ruby-based laser, 174–176 Proton-resonance frequency (PRF), 175 Rüegg, S., 49 Protoporphyrin IX (PpIX), 239 PTEN, tumor suppressor gene, 28–29 S P53, tumor suppressor gene, 136 Saarnio, J., 66 Pu, P., 40–41 Sager, G., 60 Pygopus 2, 42 Sandlund, J., 67 288 Index

Sapareto, S.A., 179 gene regulation, by mTOR kinase at transcriptional Saraswathy, S., 218 level, 155–156 Sarcomas, 145 genes with highest up-or down-regulation scores Sasai, K., 91 in, 152–153 S100A11 (S100 calcium binding protein a11), 49 mixed-lineage phenotype, 155 Sathornsumetee, S., 69 mTOR effector genes in, 49 Saunders, D.E., 145 mTOR pathway in, 48, 150–151 Schatz, S.W., 178 genes regulating activity, 49 Schlosser, S., 93 targeting, everolimus and rapamycin treatment, Schober, R., 178 52–53 Schubert, G.A., 236 TSC1/TSC2 disruption, 48 Schulze, C.P., 178–180 restricted ability to differentiate into glial cells or Schulze, P.C., 183 neurons, 154 Schwabe, B., 181, 183 with Tuberous sclerosis complex (TSC), 45, Secondary glioblastomas, 139 149–150 Seizures, 150 dual neuronal and glial origin, 48 Serpin E1, 138, 140 epilepsy, symptom, 150 sFRP (secreted Frizzled Related Protein), 39 gene expression profiling, 151 SFRP4 (secreted frizzled-related protein4), 49 mental retardation, 150 Shadoo proteins, 19 mixed cells glial/giant, 47 Shimizu, N., 111 molecular pathophysiology of, 150–151 Shou, J., 40 neurologic dysfunctions, genes down-regulation Silica nanocarriers, 189 association with, 154 Sirolimus, antiangiogenic effects, 49 positive for GFAP, 48 Smith, M., 97 tumorigenesis, genes up-regulation link with, Smoots, D.W., 143, 145 151–154 Sorafenib, 103 Subependymal giant cell tumor (SEGT), 48 Span, P.N., 67 Subependymal nodules (SENs), 149 Spontaneous regression, of tumour, 143–144 Sugiyama, K., 174, 178–179, 182 See also Cerebellar astrocytomas (CA) Surgery Spriggs, A.I., 111 cellular necrosis following vascular damage Stafford, R.J., 176 during, 145 Steady state fluorescence spectroscopy, 162 treatment options for glioma, 161 Stellar, S., 174 treatment possibilities of brain tumours, 223 Stening, K., 60 See also Neurosurgery Stereotactic radiosurgery, 246–249 Survivin, and cell cycle progression, 32–33 Steroid hormones, 146 Sutton, C., 173–174 Steroid receptor coactivator (SRC) family, 58 Synemin, 82–83 Streptavidin, 137 α- and β-synemin, expressed in astrocytoma cells, Strong, J.A., 196 83 Students’t-test, 4 characteristic, 82 Stupp, R., 207 contribution to astrocytoma cells, malignant Subependymal giant cell astrocytomas (SEGAs), behavior 47–49, 51–52 Boyden chamber assays, 83–84 analysis of gene expression profiling in, 151 down-regulation impact, 83–84 defined, 149–150 interaction with α-, 83–84 everolimus impact on, 45 invasion, 83 gene expression profiling analysis present in leading edges and ruffled membranes, Affymetrix microarrays, 151 83, 85 Index 289

RNAi experiments, 83 differentiate clearly LGG from normal tissues, siRNAs and scrape wound assays, 83–84 168–169 exhibit alternative splice variants, 82 fluorescent data collection, 164 intermediate filament (IF) protein, 82–83 goal, 163, 170 positive regulator, of cell motility and proliferative histopathological analysis, of tumors, 164 capacity, 81, 83–84 intra-operative tool, instrumental setup, 163–164 prospects for astrocytoma therapy, 86–87 in vivo measurements, for glioma diagnosis, see regulation in pathologies of CNS, 83 Gliomas U-373 MG human glioblastoma cells NC measurements, 169 staining, 85 parameters selection, 164–165 See also Astrocytoma(s); Intermediate filament statistical analysis, and classification, 168 (IF) proteins time-resolved fluorescence characteristics, Synthetic low-density lipoproteins (LDL), 191 166–168 TNFR associated factor (TRAF) family, 25 T TNF superfamily, 23, 25, 32 Tago, M., 248 TP53 mutation, 138 Takei, H., 201 Tracz, R.A., 175, 178, 180 TAT-ODD-procaspase-3 (TOP3), 130 TRAIL, 24–25, 28–30 Temozolomide, chemotherapy for PMA, Transcriptional regulation, 149 207–208 Transfection, 136 Temporal lobe epilepsy (TLE), 267 Transmissible spongiform encephalopathies Temsirolimus (CCI-779), 49–51 (TSEs), 13 Tenascin, 110 TR-LIFS, see Time-resolved laser induced Teratomas, 95 fluorescence spectroscopy (TR-LIFS) Tetrapyrrole, 240 Trypsin-Giemsa banding technique, 111 Thermal dosimetry, 179 TSC, see Tuberous sclerosis complex (TSC) Thrombospondin-1, 138–139 Tsc1, 150–151, 154 Thrombospondin-2, 140 TSC2-Rheb-mTOR pathway, 47 Tibbetts, K.M., 199, 201 TSP-1 expression, 140 Tihan, T., 198, 203, 206–207 Tuberous sclerosis complex (TSC), 45–53, 149–150 Time-resolved fluorescence measurements, 162 Akt activation, 49 Time-resolved laser induced fluorescence -associated lesions, 48 spectroscopy (TR-LIFS) defined, 45 advantages, 170 glial dysfunction and, 150 classification and prediction, fluorescence signal global gene expression profiling, 151 classification algorithm elements, and analysis, 151 165–166 GTPase-activating protein (GAP), 46 linear discriminant function analysis (DFA), loss of heterozygosity (LOH) in, 48 165 molecular pathophysiology, 150–151 method limitation, 169 role of mutations in TSC1 and TSC2, 151 training and test phase, 165–166 mTORC1 functions, 151 TR-fluorescence characteristics, 166–168 mTOR inhibitors, cell cultures and animal models classification results using, 168 studies, 51–52 clinical methods, 163 mTOR pathway in, 46–47 data autophagy inhibition, 47 analysis, 164 genes regulated by HIFs, 46 reduction and statistical analysis, 165 inactivating mutations TSC1/TSC2 gene, 46 delivery catheter, 163–164 Ras-homoloque-enriched in brain (Rheb) target, penetration depth for astrocytoma, 164 46 290 Index

Tuberous sclerosis complex (TSC) (cont.) U SEGAs in, 51 Ubiquitin–proteasome system, 58 dual neuronal and glial origin, 48 Ueda, M., 132 mixed cells glial/giant, 48 Ushio, Y., 97 positive for GFAP, 48 TSC1/TSC2-mTOR signaling pathway, 151, V 155–156 Vaporization, 177 tumorigenesis Ventana Benchmark IHC system, 90 hamatrin-tuberin complex inactivation, 49 Videography, intraoperative ICG, 233–237 Knudson’s two-hit model, 48 Vimentin, 81–83, 85–87 See also Subependymal giant cell astrocytomas Vincristine, 207 (SEGAs) Visual field defects, 224 Tumorigenesis von Hippel-Lindau syndrome, 233, 235 apoptosis relation with, 23 EGFRvIII role in, 112 W genes up-regulated in SEGA, link to, 151, Wang, E.M., 248 153–154 Wang, Z.X., 42 hypomethylation role, 5 Weidner, N., 136 MAPK signaling to PA, 102 Wesseling, P., 139 OTX2 gene, medulloblastoma, 115 Williams, C.M., 23 and survivin overexpression, 32 Wnt antagonists, sFRP and Dickkopf class, 39 in TSC, see Tuberous sclerosis complex (TSC) Wnt genes, 37 Tumorigenesis Wnt signaling pathway, 35, 37–39 apoptosis relation with, 23 Axin-APC-GSK3β, 41–42 EGFRvIII role in, 112 β-catenin role, 40–41 genes up-regulated in SEGA, link to, 151, 153–154 destruction complex, 38 hypomethylation role, 5 Dishevelled (Dvl), and FRAT1 action, 40 MAPK signaling to PA, 102 inhibition by extracellular Wnt antagonists OTX2 gene, medulloblastoma, 115 DKK glycoproteins family, 39 and survivin overexpression, 32 sFRPs and Dickkopf family, 39 in TSC, see Tuberous sclerosis complex (TSC) Wnt inhibitory factor-1 (WIF-1), 39 Tumours Lef-1 and Tcf-4 factors, 42 animal models for preclinical trials, 188 neural stem cells-gliomas, 38 associated with NF1, 143 pygopus 2, 42 autoimmunity to, 145 See also Gliomas of central nervous system, 203 Wong, A.J., 111 hemangioblastoma, see Hemangioblastomas hypoxia, importance, 129–130 X imaging HIF-1 active regions Xenograft models, 188 by 123I-IBB and 123IPOS method, 129, 131–133 in vivo molecular imaging, 130 Y pretargeting approach, 131–133 YAG (Yttrium, Aluminum and Garnet) laser, 176 nuclear medicine imaging, 130 Yang, Z., 39 oxygen-dependent degradable probe, development, Yolk-sac tumors, 96 130 Yu, J.M., 40 regression, 146 slow-growing, 213 Z Tumstatin, 139 Zhang, L.Y., 42 Turner, J.R., 66 Zhang, Z., 40