",isbn:"978-1-83969-561-2",printIsbn:"978-1-83969-560-5",pdfIsbn:"978-1-83969-562-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"65f2a1fef9c804c29b18ef3ac4a35066",bookSignature:"Dr. Luis Loures",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10756.jpg",keywords:"Urban Processes, Urban Patterns, Redevelopment Strategies, Landscape, Land Transformation, Urban Models, Urban Evolution, Urban Organisation, Legislation, Sustainable Development, Green Infrastructure, Regional Planning",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 23rd 2021",dateEndSecondStepPublish:"March 22nd 2021",dateEndThirdStepPublish:"May 21st 2021",dateEndFourthStepPublish:"August 9th 2021",dateEndFifthStepPublish:"October 8th 2021",remainingDaysToSecondStep:"21 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Loures has worked on pioneering research on circular planning applied to post-industrial landscape redevelopment. Since he graduated he has published several peer-reviewed papers at the national and international levels and he has been a guest researcher and lecturer both at Michigan State University (USA) and at the University of Toronto (Canada) where he has developed part of his Ph.D. research with the Financial support from the Portuguese Foundation for Science and Technology (Ph.D. grant).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"108118",title:"Dr.",name:"Luis",middleName:null,surname:"Loures",slug:"luis-loures",fullName:"Luis Loures",profilePictureURL:"https://mts.intechopen.com/storage/users/108118/images/system/108118.png",biography:"Luís Loures is a Landscape Architect and Agronomic Engineer, Vice-President of the Polytechnic Institute of Portalegre, who holds a Ph.D. in Planning and a Post-Doc in Agronomy. Since he graduated, he has published several peer reviewed papers at the national and international levels and he has been a guest researcher and lecturer both at Michigan State University (USA), and at University of Toronto (Canada) where he has developed part of his Ph.D. research with the Financial support from the Portuguese Foundation for Science and Technology (Ph.D. grant).\nDuring his academic career he had taught in several courses in different Universities around the world, mainly regarding the fields of landscape architecture, urban and environmental planning and sustainability. Currently, he is a researcher both at VALORIZA - Research Centre for Endogenous Resource Valorization – Polytechnic Institute of Portalegre, and the CinTurs - Research Centre for Tourism, Sustainability and Well-being, University of Algarve where he is a researcher on several financed research projects focusing several different investigation domains such as urban planning, landscape reclamation and urban redevelopment, and the use of urban planning as a tool for achieving sustainable development.",institutionString:"Polytechnic Institute of Portalegre",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Polytechnic Institute of Portalegre",institutionURL:null,country:{name:"Portugal"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"10",title:"Earth and Planetary Sciences",slug:"earth-and-planetary-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"205697",firstName:"Kristina",lastName:"Kardum Cvitan",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/205697/images/5186_n.jpg",email:"kristina.k@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"7476",title:"Land Use",subtitle:"Assessing the Past, Envisioning the Future",isOpenForSubmission:!1,hash:"5b0c406adac8447ffeb089e29eac8ea9",slug:"land-use-assessing-the-past-envisioning-the-future",bookSignature:"Luís Carlos Loures",coverURL:"https://cdn.intechopen.com/books/images_new/7476.jpg",editedByType:"Edited by",editors:[{id:"108118",title:"Dr.",name:"Luis",surname:"Loures",slug:"luis-loures",fullName:"Luis Loures"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8295",title:"Landscape Reclamation",subtitle:"Rising From What's Left",isOpenForSubmission:!1,hash:"1fb7d9e280708a190a90c3b352c93d45",slug:"landscape-reclamation-rising-from-what-s-left",bookSignature:"Luis Loures",coverURL:"https://cdn.intechopen.com/books/images_new/8295.jpg",editedByType:"Edited by",editors:[{id:"108118",title:"Dr.",name:"Luis",surname:"Loures",slug:"luis-loures",fullName:"Luis Loures"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5962",title:"Estuary",subtitle:null,isOpenForSubmission:!1,hash:"43058846a64b270e9167d478e966161a",slug:"estuary",bookSignature:"William Froneman",coverURL:"https://cdn.intechopen.com/books/images_new/5962.jpg",editedByType:"Edited by",editors:[{id:"109336",title:"Prof.",name:"William",surname:"Froneman",slug:"william-froneman",fullName:"William Froneman"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"18143",title:"Chemotherapy of Medulloblastoma in Children",doi:"10.5772/20259",slug:"chemotherapy-of-medulloblastoma-in-children",body:'\n\t\t
\n\t\t\t
1. Introduction
\n\t\t\t
Medulloblastoma is one of the most common childhood tumour of the central nervous system. During the past years several researchers dealt with its aetiology, pathology and therapy: surgical-, radio- and chemotherapy. The objective of the present chapter is to review the chemotherapy and we shall present our results and the few clinical data about the targeted therapy.
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2. Incidence
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Tumours of the central nervous system (CNS) are the second most common childhood malignant diseases after hematological malignancies. The incidence is similar in the different developed countries: in Europe is 29.9/million (1978-1997), in USA 30.7/million (1992-2006). However, the highest incidence is registered in Hungary and the Scandinavian countries. In Hungary the incidence was 37.41/million between 1999 and 2008 and 43.9/million in 2009. The cause of this high incidence in Hungary is unknown (Gupta & Banerjee et al, 2004; Hauser et al., 2003; Kaderali et al., 2009; Mc Neil et al., 2002; Peris-Bonet et al., 2006; Pizzo & Poplack, 2011). Astrocytomas and medulloblastoma are the most frequent among childhood CNS tumours.
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3. Prognostic factors
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The prognostic factors are especially important in risk group assignment of brain tumours, because the increased intensity of treatment in high risk cases has much more side effects, than the therapy of the average risk patients.
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The most frequently used prognostic factors in the past were: the size of the tumour, the metastases including the tumour cells in the spinal fluid 2 weeks after the surgery (Chang (T1-4; M0-3) (Laurent et al., 1985) and the extent of the surgical intervention (Albright et al., 1996). Later the age and the histology of tumour were also introduced (Ellison, 2010; Giangaspero et al., 2006; Packer et al., 1994). According to several publications residual tumour mass greater than 1.5 cm2 after the surgical intervention, the presence of metastases, age younger than 3 years are unfavourable prognostic factors (Albright et al., 1996; Chang et al., 1969; Eberhart et al., 2002; Jenkin et al., 2000; Klesse & Bowers, 2010) The histology of the tumours (desmoplastic/nodular, classic, large cell/anaplastic) is an important, independent prognostic factor too, which was proved by Rutkowski et al. in a study of 260 young children (\n\t\t\t\t\tRutkowski et al, 2010\n\t\t\t\t).
\n\t\t\t
Several biological factors have prognostic value (ERBB2, TP53, PDGFRA, TRKC, CDK6, α and β-catenin). The prognostic role of the aberrantly expressed miRNAs is yet under investigation (Birks et al., 2011). However, the most reliable and independent prognostic factor is microarray gene expression profile (Aihara et al., 2010; Fernandez-T et al., 2004; Pizzo & Poplack, 2010; \n\t\t\t\t\tRutkowski et al., 2010\n\t\t\t\t; Tabori et al., 2010). Four distinct groups were established by Northcott (Northcott et al., 2010): Wnt, Shh, C and D. Wnt and Shh was previously described as the wingless type and sonic hedgehoge pathway involvement in the tumorproliferation (Wechsler-Reya & Scott, 2001). In Group C and D a clear molecular pathway involvement could not be clearly identified. The new classification does not follow the classical pathological classification (as classic, desmoplastic, large cell/anaplastic subtypes) and it shows some association with age and metastatis production. The separation of these groups by immunohistochemical analysis only was a great step toward the everyday practice in using this classification as prognostic factor. Group Wnt, Shh, C, D are characterized by the presence of CTNNB1, GLI1, NPR3 and KCNA1 proteins. Wnt and Shh groups seem to need less intensive therapy with outstanding survival and less side effects.
The therapy of the malignant tumours is surgical, radio- and chemotherapy, similarly to other childhood tumours. In brain tumours the most important is the surgical therapy and is curative if it is radical ablation and no metastases are found. However, the surgical therapy is hindered by the localisation of the tumour and the difficulty in differentiating the tumour from the normal tissues.
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The radiotherapy of medulloblastoma is an important and effective part of therapy. However its use is limited by the irreversible damage caused in children, which is specially serious in young children and infants causing serious neurocognitive damage (Fouladi et al., 2005; Mulhern et al., 2004). Hence it should be avoided in children less than 3 years old in spite of their lower survival rate (Johnston et al., 2009). It is remarkable, that the increased intensity of the chemotherapy enabled the decrease of the craniospinal radiation dose in the average risk cases without the worsening the survival to 23.4Gy along an unchanged focus-dose (55.8Gy) which decreased significantly the late side-effects (Mulhern et al., 1998; Packer et al., 1999, 2006).
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4.1. Chemotherapy
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It is difficult to compare the different studies to select the optimal treatment protocol due to the non-uniform prognostic factors, the lack of reliable – centrally checked – patho-histological and molecular diagnostics and the often low number of patients and duration of observation. Hoff (von Hoff et al., 2009) and collaborators published the results of a 10 years long follow up. In their patient-group 12% of relapse occurred five years or more after the end of therapy.
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An important obstacle of the chemotherapy is the blood-brain barrier despite the fact that the tumour breaks through the barrier when growing. There were several trials for increasing the possibility of passing the barrier but without any provable result. (Kobrinsky et al., 1999; Prados et al., 2003)
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The additive curative effect of chemotherapy after surgery and radiotherapy was proved by a prospective, multicentric, randomised trial in 1990 (Evans et al., 1990; Tait et al., 1990). In the beginning vincristine and the nitrosoureas were applied, which are still used in several protocols for the treatment of medulloblastoma. However, the usefulness of vincristine was recently challenged because vincristine could not be detected in the spinal fluid in measurable concentration after 1,5 mg/m2 i.v. bolus injection. Later more and more chemotherapeutic drug combinations have been used. The key agents are the nitrosoureas (lomustine, carmustine), cyclophosphamide, vincristine and the later used cisplatin, carboplatin, and etoposide (Mueller & Chang, 2009). Some protocols apply ifosfamide alternating with cyclophosphamide (Park et al., 2010). The application of methotrexate is limited not only because of its potential side effects, but also because it can be used only before radiotherapy, however, some protocols described rather good results in cases when no irradiation was done (Bleyer, 1981; Chi et al., 2004; Fossati-Bellani et al., 1990; Rutkowski et al., 2005). The alkylating oral drug dibromdulcitol was an excellent substance for the treatment of medulloblastomas because its favourable pharmacokinetic properties in the spinal fluid and its tolerable toxicity (Paál et al., 1994; Schuler et al., 1988, 1992). Later in spite of the good clinical results the drug became unavailable. However, this may be partially substituted by temozolomide, but there is no study yet, which proves its efficacy in medulloblastoma.
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The increased arsenal of the chemotherapeutics and the higher intensity of the treatment resulted in improved survival. In cases with favourable prognosis the survival rate is already over 80%, and around 70% in cases with unfavourable prognosis (Gottardo & Gajjar, 2008). However, the toxicity of the treatment increased, too. Therefore, besides improving survival rates reducing early and late toxicity are also important. In the future a less toxic treatment is expected thanks to the development of the targeted molecular therapy based on tumour-biological knowledge.
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The most important criteria are:
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the optimal timing of the chemotherapy
the most effective combination of cytostatics
sufficient intensity and length of the chemotherapy
a tolerable toxicity of the drugs used in the protocol.
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Some trials proved that the chemotherapy given before and after the irradiation (sandwich therapy) is disadvantageous; the survival is shorter if the radiotherapy is longer than 50 days (von Hoff et al., 2009; Taylor et al., 2003). Hence the radiotherapy should be given as early after the surgery as it is possible (Bailey et al., 1995; Kortmann et al., 2000). During the radiotherapy several protocols contain the administration of vincristine (von Hoff et al., 2009; Packer et al., 1994, 1999) or in one protocol carboplatin (Jakacki et al., 2007). A preoperative chemotherapy is applied in several paediatric tumours, because it decreases the size of the tumour and facilitate the tumour removal. Hence it would be reasonable to introduce it in huge chemosensitive brain tumours, too (Schuler et al., 1993). The preoperative chemotherapy is feasible and safe in children with high risk medulloblastoma according to some pilot trials (Di Rocco et al., 1995; Grill et al., 2005; Schuler et al., 1993). However, it is not applied in the practice up to now.
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In most protocols a combination of vincristine, a nitrosourea (lomustine or camustine) and a platinum compound (cisplatin or carboplatin) is used. In several protocols cyclophosphamide is used instead of nitrosourea because of the good antitumour effect and shorter bone marrow toxicity of cyclophosphamide, (von Hoff et al., 2009; Mueller & Chang, 2009; Packer et al., 1994) and in some treatment protocols etoposide is also added to this combination (Chi et al., 2004; Dhall et al., 2008; Hauser et al., 2009).
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Our protocol for average risk cases begins with three intrathecal triplet (methotrexate, ara-C, prednisolone) and VECp-block (vincristine, cyclophosphamide, etoposide) after the surgery. This is followed by radiotherapy (5th - 11th week). During the radiotherapy the patients get weekly vincristine. 2 weeks after the radiotherapy chemotherapy is continued by vincristine ― etoposide ― cyclophosphamide/ carboplatin; vincristine ― cisplatin ― etoposide / BCNU blocks until the 73nd postoperative week.
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In high risk cases autologous stem cell transplantation is made after the 40th postoperative week instead of maintenance therapy. If a residual tumour is present it is removed by a “second look” surgery before the transplantation.
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In children less than 3 years old the therapy is similar to that in high risk cases, except that no radiotherapy is given and the stem cell transplantation is made as soon as no tumour is seen by MRI. Radiotherapy is given only, if the tumour is still present after the age of three years.
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The toxicity of our protocol was tolerable; and there was no therapy related mortality. After 31 months the overall survival was 79% in the average risk patients and 63% in high risk patients.
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The best therapeutic results in average risk cases were achieved by the multicentre trial HIT’91 (von Hoff et al., 2009). The overall survival in patients without metastasis was 91% after 10 years. After the removal of tumour a combination of radiotherapy and vincristine was applied, which was followed 6 weeks later by 8 cycles with lomustine (CCNU), vincristine and cisplatin. Packer et al., described a 86% survival after 3 years follow up by a similar regime (Packer et al., 1999). A 93% survival was published by Strother et al. (2001) (Strother et al., 2001) with a more aggressive therapy. They administered 4 cycles of high dose chemotherapy after surgery and radiotherapy (cyclophosphamide, cisplatin, and vincristine) followed by auto-transplantation after each cycle.
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The results in high risk cases are more consistent ranging from 34 to 40% across studies (Mueller & Chang, 2009). However, Chi et al. achieved 60% overall survival after 3 years by 5 cycles of vincristine, cisplatin, etoposide, cyclophosphamide and methotrexate given after surgery followed by myeloablative chemotherapy with autologous stem cell rescue (Chi et al., 2004). The results of Gajjar et al. (Gajjar et al., 2006) was similar: 83% event free survival in average risk patients and 70% in high risk cases after 5 years.
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Good survival was achieved by the COG99701 study (Jakacki et al., 2007). They administered vincristine and carboplatin during the radiotherapy in patients with metastatic medulloblastoma. 6 weeks later the patients received 6 courses of monthly cyclophosphamide and vincristine. The overall survival after 4 years was 81%.
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The increased intensity of therapy resulting a longer survival has more late side effect. Hence the stratification of the tumours according to prognostic factors into average or high risk group is important.
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In cases of medulloblastomas of children less than 3 years old radiotherapy should avoid. The most favourable approach after surgery is the myeloablative consolidation chemotherapy after conventional induction therapy which may result 60% overall survival after 3 years (Chi et al., 2004). The result of the intensive chemotherapy depends both on the histologic type and the presence of the residual tumour (Dhall et al., 2008). Those trials which combine the systematic and intraventricular chemotherapy had better results only among children without metastases and residual tumour (Zeltzer et al., 1999)
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The survival of relapsed patients is very poor, especially in patients who had already received radiotherapy and/or auto-transplantation (Butturini et al., 2009). However, there are several trials by intensive chemotherapy and transplantations. (Park et al., 2010). The prolongation of the survival with metronomic therapy was possible in some studies. The metronomic therapy is referred to as low-dose chemotherapy or antiangiogenic chemotherapy (Kieran et al., 2005; Privitera et al., 2009; Sterba et al., 2010). Recently, the combination of the alkylating agent temozolomide with etoposide, which is a topoisomerase II inhibitor was found to be efficacious in prologing the survival in relapsed medulloblastoma. (Wang CH et al., 2009; Ruggiero A et al., 2010). However, the study of the application of the metronomic therapy for a longer time after the about 6 months long intensive and maintenance therapy in the primordial therapy of high risk cases may be justified too due to the occurrence of late relapses.
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The toxicity of the previously described chemotherapeutic modalities depends on their intensity independent from the well known side effects of the radiotherapy. The most common and most serious ones are the acut myelotoxic effect and infections. Some authors describe yet anorexia, nausea, diarrhoea, pain and hypokalemia.
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Better comparability of the different therapeutic modalities, improvement of results and the decrease of side effects are expected from the application of the molecular biologic procedures in the stratification and tailored therapy.
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4.2. Targeted treatment
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There is still not any new, successful, widely accepted therapeutic approach which can substitute or at least complement the standard treatment of medulloblastoma.
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Presently, targeted treatment exists only in SHH group among the four groups described by Northcott et al. (2010). In this group tumor proliferation is attributed to the lack of inhibition of SMO protein by loss of function of inhibitory Patched protein (Ptch1) or activating mutation of SMO. SMO inhibitors, as cyclopamin, IPI-926 and the orally available GDC-0449 inhibit hedgehoge pathway. The latter went through a Phase 1 study, resulting in a 3-month long transient well-defined remission achieved in one 26-year old patient with proven Ptch1 mutation (Rudin et al., 2009).
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Before the establishment of the new subgroups of medulloblastoma, there were also other molecularly targeted treatments. In some cases they were administered to some individual patients. Common feature of these treatments was the transient success, which finally turned into progression. The background of the progression could be the mutation of the targeted receptor or other involved proteins.
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One of these targets were somatostatin receptors (SSTR), which were recognized in medulloblastoma cell surface in late nineties of the last century (Fruhwald et al., 2004; Guyotat et al., 2001;). Several attempts were to bind radioactive isotope to its agonist octreotide or its derivates, providing localized, targeted radiotherapy, which did not show extra survival advantage above conventional irradiation, (Beutler et al., 2005). Somatostatin analogues themselves through SSTR receptors may inhibit cell proliferation. Medulloblastoma express high amount of SSTR based on Octreoscan examination (Muller et al., 1998). Only one patient was described who received only octreotide without radioactive isotope, and was a long term survivor (Glas et al., 2008).
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Receptor tirozin kinases another possible target group. There are several drugs targeting these receptors which are also expressed in a certain part of medulloblastoma (ErbB2, PDGFR). Their increased expression usually results in worse survival and increased metastatic ability (Gilbertson et al., 1995; Gilbertson & Clifford, 2003). The most experience is reported with imatinib, which proved to be effective in vitro, however, in vivo successful human experiences are still missing (Abouantoun & MacDonald, 2009). This may be partially caused by their hindered penetration through blood brain barrier.
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Another possible therapeutic approach is the inhibition of histon deacetylases (HDAC). Acetylation of histones’ amino terminal tails by histon acetyltransferase relaxes the chromatin for transcription, and removal of acetyl groups by HDAC repress transcription (Roth et al., 2001; de Ruijter et al., 2003). Histon hypoacetylation and inappropriate transcriptional repression are hypothesized to be a key contributor to the development of human cancers (Marks et al, 2001; Marks & Dokmanovic, 2005). HDAC inhibitors have been shown to cause pleiotropic effect on human cancer cells, including apoptosis, cell cycle arrest and differentiation (Su et al., 2011). Valproic acid (VPA), an anticonvulsive drug is one of the recently discovered HDAC inhibitors. There is one published Phase 1 study in pediatric CNS tumors, 2 patients with medulloblastoma were included (Su et al., 2011). The treatment was well-tolerated, however response was not observed among this little cohort of patients with medulloblastoma.
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Another promising area in the treatment of medulloblastoma could be the administration of retinoic acid (RA). RA has been shown to have anticancer efficacy in a variety of cancers. Retinoic acid is commonly used in the treatment of certain childhood cancers. It is a drug with protean effects including cytodifferentiation, apoptosis, and inhibition of angiogenesis to name a few (Miller, 1998). RA has been shown in preclinical models to cause apoptotic cell death in medulloblastoma by promoting BMP-2 transcription (Hallahan et al., 2003). This results in production of soluble BMP-2 protein that induces p38 MAP kinase phosphorylation and ultimately apoptosis (Spiller et al., 2008). Recently a phase 3 trial has been opened to treat medulloblastoma with RA.
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There are several different approaches to try to kill medulloblastoma cells by means of immunotherapy. Only some of them were introduced in small series of pediatric patients with limited success. In the last decades of the twentieth century application of lymphokine actived killer (LAK) cells directly administered intrathecally with co-administration of human recombinant IL-2 for patients with recurrent disseminated medulloblastoma was published. Some of the limited number of patients showed long term survival (Okamoto et al., 1988; Silvani et al., 1994).
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Another method is the adoptive transfer of tumor-specific cytolytic T cells to the tumor bed and cerebrospinal fluid. This is an attractive strategy, but limited in its clinical application owing the paucity of defined antigens consistently expressed by medulloblastoma. So far only two in vitro animal medulloblastoma xenograft models have been published. One is targeting IL13Receptor-alpha2 by genetically modified CD8+ citotoxic T-cells expressing an IL13-zetakine chimeric immunoreceptor (Stastny et al., 2007). The other model is targeting HER2 expression, which is a feature of the malignant phenotype of medulloblastoma (Gilbertson et al., 1995). Recruiting the cellular arm of the immune response to HER2 positive tumor cells, genetically engineered HER2-specific T-cell with antigen binding property and lytic capacity were created. Adoptive transferred HER2-specific T-cells were administered in SCID mouse orthotopic medulloblastoma xenograft, which resulted in sustained regression of HER2 positive medulloblastoma, which might have resulted in a promising immunotherapeutic approach (Ahmed et al., 2007). Phase 1 study of adoptive transfer of tumor-specific cytolytic T cells exists in patients with recurrent glioblastoma multiforme and neuroblastoma.
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Another immunotherapeutic method which is already investigated in human patients with recurrent medulloblastoma is based on dendritic cell-based tumor vaccination. Dendritic cells are the antigen presenting cells, which are present in central nervous system exclusively. Autologous mature dendritic cells loaded with tumor lysates derived from autologous, resected medulloblastomas were injected subcutaneously in 5 patients with medulloblastoma. Although the treatment was safe, no response was observed in any patient (Ardon et al., 2010).
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Natural killer (NK) cells display the highest cytolytic activity against tumor cells, and are considered suitable candidates for adoptive immunotherapy to treat cancer patients. Castriconi et al showed that in vitro medulloblastoma cell lines express ligands for activating NK-receptors, which makes medulloblastoma highly susceptible to NK-mediated cytolysis (Castriconi et al., 2007). However, human studies using NK-cells in medulloblastoma are lacking at this moment.
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5. Conclusions
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The therapy of medulloblastoma has changed during the last few decades which resulted in the improvement of the long-term survival up to almost 80%. This is due to the complex chemotherapy beyond the improved surgical and radiotherapeutical techniques. After cyclophosphamide, nitrosoureas and methotrexate more effective drugs would be applied in the treatment of medulloblastoma: carboplatin, cisplatin, etoposide and ifosfamide. In resistant or relapsed cases several other drugs are used, too, as Temozolomide. The preoperative therapy in spite of the encouraging pilot studies could not become a general practice. The high dose chemotherapy with autologous stem cell rescue seems to be effective to eradicate the remained tumour cells in high risk cases. The prolongation of the chemotherapy with cytostatic drugs in low doses and/or antiproliferative agents (retinoic acid, valproic acid, antiangiogenic agents) seems to be effective to prolong the remission in incurable cases. The chemotherapy is especially important in very young children (less than 3 years old) because of the serious late side effects of radiotherapy. The targeted molecular therapy is promising, however, in spite of the several clinical studies the effectivity of molecular therapy is not proved yet in phase III. studies.
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\n\t\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/18143.pdf",chapterXML:"https://mts.intechopen.com/source/xml/18143.xml",downloadPdfUrl:"/chapter/pdf-download/18143",previewPdfUrl:"/chapter/pdf-preview/18143",totalDownloads:4088,totalViews:178,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,dateSubmitted:"November 8th 2010",dateReviewed:"May 4th 2011",datePrePublished:null,datePublished:"August 23rd 2011",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/18143",risUrl:"/chapter/ris/18143",book:{slug:"brain-tumors-current-and-emerging-therapeutic-strategies"},signatures:"Dezső Schuler, Péter Hauser and Miklós Garami",authors:[{id:"34821",title:"Dr.",name:"Miklos",middleName:null,surname:"Garami",fullName:"Miklos Garami",slug:"miklos-garami",email:"miklos.garami@gmail.com",position:null,institution:{name:"Semmelweis University",institutionURL:null,country:{name:"Hungary"}}},{id:"38127",title:"Prof.",name:"Dezső",middleName:null,surname:"Schuler",fullName:"Dezső Schuler",slug:"dezso-schuler",email:"schdez@gyer2.sote.hu",position:null,institution:{name:"Semmelweis University",institutionURL:null,country:{name:"Hungary"}}},{id:"48801",title:"Dr.",name:"Péter",middleName:null,surname:"Hauser",fullName:"Péter Hauser",slug:"peter-hauser",email:"haupet@gyer2.sote.hu",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Incidence",level:"1"},{id:"sec_3",title:"3. Prognostic factors",level:"1"},{id:"sec_4",title:"4. Therapy",level:"1"},{id:"sec_4_2",title:"4.1. Chemotherapy",level:"2"},{id:"sec_5_2",title:"4.2. Targeted treatment",level:"2"},{id:"sec_7",title:"5. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAbouantoun\n\t\t\t\t\t\t\tT. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMac\n\t\t\t\t\t\t\tDonald. T. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Imatinib blocks migration and invasion of medulloblastoma cells by concurrently inhibiting activation of platelet-derived growth factor receptor and transactivation of epidermal growth factor receptor. Mol Cancer Ther, 8, 5, (May 2009), 1137 EOF\n\t\t\t\t\t1147 EOF\n\t\t\t\t\n\t\t\t'},{id:"B2",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAhmed\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRatnayake\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSavoldo\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPerlaky\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDotti\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWels\n\t\t\t\t\t\t\tW. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBhattacharjee\n\t\t\t\t\t\t\tM. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGilbertson\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShine\n\t\t\t\t\t\t\tH. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWeiss\n\t\t\t\t\t\t\tH. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRooney\n\t\t\t\t\t\t\tC. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHeslop\n\t\t\t\t\t\t\tH. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGottschalk\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007Regression of experimental medulloblastoma following transfer of HER2specific T cells. Cancer Res, 67, 12, (Jun 2007), 5957-64.\n\t\t\t'},{id:"B3",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAihara\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTsuruta\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKawamata\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKanno\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMaebayashi\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSakauchi\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWada\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOsawa\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFujii\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKubo\n\t\t\t\t\t\t\tO.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHori\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Double high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation for primary disseminated medulloblastoma: a report of 3 cases. J Pediatr Hematol Oncol, 32, 2, (Mar 2010), e70\n\t\t\t\t\t4\n\t\t\t\t\n\t\t\t'},{id:"B4",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlbright\n\t\t\t\t\t\t\tA. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWisoff\n\t\t\t\t\t\t\tJ. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZeltzer\n\t\t\t\t\t\t\tP. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoyett\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRorke\n\t\t\t\t\t\t\tL. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStanley\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1996Effects of medulloblastoma resections on outcome in children: a report from the Children’s Cancer Group. Neurosurgery, 38, 2, (Feb 1996), 265 EOF\n\t\t\t\t\t271 EOF\n\t\t\t\t\n\t\t\t'},{id:"B5",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tArdon\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDe Vleeschouwer\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVan Calenbergh\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tClaes\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKramm\n\t\t\t\t\t\t\tC. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRutkowski\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWolff\n\t\t\t\t\t\t\tJ. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVan Gool\n\t\t\t\t\t\t\tS. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Adjuvant dendritic cell-based tumour vaccination for children with malignant brain tumours. Pediatr Blood Cancer, 54, 4, (Apr 2010). 519\n\t\t\t\t\t25\n\t\t\t\t\n\t\t\t'},{id:"B6",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBailey\n\t\t\t\t\t\t\tC. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGnekow\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWellek\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJones\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRound\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrown\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPhillips\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNeidhardt\n\t\t\t\t\t\t\tM. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1995Prospective randomised trial of chemotherapy given before radiotherapy in childhood medulloblastoma. International Society of Paediatric Oncology (SIOP) and the (German) Society of Paediatric Oncology (GPO): SIOP II. Med Pediatr Oncol, 25, 3, (Sep 1995), 166 EOF\n\t\t\t\t\t78 EOF\n\t\t\t\t\n\t\t\t'},{id:"B7",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBeutler\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAvoledo\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tReubi\n\t\t\t\t\t\t\tJ. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMacke\n\t\t\t\t\t\t\tH. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMuller-Brand\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMerlo\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKühne\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005Three-year recurrence-free survival in a patient with recurrent medulloblastoma after resection, high-dose chemotherapy, and intrathecal Yttrium-90labeled DOTA0-D-Phe1-Tyr3-octreotide radiopeptide brachytherapy. Cancer, 103, 4, (Feb 2005), 869-73.\n\t\t\t'},{id:"B8",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBirks\n\t\t\t\t\t\t\tD. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBarton\n\t\t\t\t\t\t\tV. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDonson\n\t\t\t\t\t\t\tA. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHandler\n\t\t\t\t\t\t\tM. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVibhakar\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tForeman\n\t\t\t\t\t\t\tN. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011Survey of MicroRNA expression in pediatric brain tumors. Pediatr Blood Cancer, 56, 2, (2011), 211 EOF\n\t\t\t\t\t6 EOF\n\t\t\t\t\n\t\t\t'},{id:"B9",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBleyer\n\t\t\t\t\t\t\tW. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1981Neurologic sequelae of methotrexate and ionizing radiation: a new classification. Cancer Treat Rep, 65 Suppl 1, (1981), 89 EOF\n\t\t\t\t\t98 EOF\n\t\t\t\t\n\t\t\t'},{id:"B10",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tButturini\n\t\t\t\t\t\t\tA. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJacob\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAguajo\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVander-Walde\n\t\t\t\t\t\t\tN. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVillablanca\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJubran\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tErdreich-Epstein\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMarachelian\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDhall\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFinlay\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009High-dose chemotherapy and autologous hematopoietic progenitor cell rescue in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors: the impact of prior radiotherapy on outcome. Cancer, 115, 13, (Jul 2009), 2956 EOF\n\t\t\t\t\t2963 EOF\n\t\t\t\t\n\t\t\t'},{id:"B11",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCastriconi\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDondero\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNegri\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBellora\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNozza\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCarnemolla\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRaso\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoretta\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoretta\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBottino\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007Both CD133+ and CD133medulloblastoma cell lines express ligands for triggering NK receptors and are susceptible to NK-mediated cytotoxicity. Eur J Immunol, 37, 11, (Nov 2007), 3190-6.\n\t\t\t'},{id:"B12",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChang\n\t\t\t\t\t\t\tC. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHousepian\n\t\t\t\t\t\t\tE. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHerbert\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJr \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1969An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology, 93, 6, (Dec 1969), 1351 EOF\n\t\t\t\t\t9 EOF\n\t\t\t\t\n\t\t\t'},{id:"B13",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChi\n\t\t\t\t\t\t\tS. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGardner\n\t\t\t\t\t\t\tS. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAS\n\t\t\t\t\t\t\tLevy\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKnopp\n\t\t\t\t\t\t\tE. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiller\n\t\t\t\t\t\t\tD. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWisoff\n\t\t\t\t\t\t\tJ. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWeiner\n\t\t\t\t\t\t\tH. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFinlay\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma. J Clin Oncol, 22, 24, (Dec 2004), 4881 EOF\n\t\t\t\t\t7 EOF\n\t\t\t\t\n\t\t\t'},{id:"B14",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDhall\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrodman\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJi\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSands\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGardner\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDunkel\n\t\t\t\t\t\t\tI. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Cowage\n\t\t\t\t\t\t\tG. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDiez\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAllen\n\t\t\t\t\t\t\tJ. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGopalan\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAS\n\t\t\t\t\t\t\tCornelius\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTermuhlen\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAbromowitch\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSposto\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFinlay\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the "Head Start" I and II protocols. Pediatr Blood Cancer, 50, 6, (Jun 2008), 1169 EOF\n\t\t\t\t\t1175 EOF\n\t\t\t\t\n\t\t\t'},{id:"B15",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEberhart\n\t\t\t\t\t\t\tC. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKepner\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoldthwaite\n\t\t\t\t\t\t\tP. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKun\n\t\t\t\t\t\t\tL. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDuffner\n\t\t\t\t\t\t\tP. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFriedman\n\t\t\t\t\t\t\tH. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStrother\n\t\t\t\t\t\t\tD. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBurger\n\t\t\t\t\t\t\tP. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002Histopathologic grading of medulloblastomas: a Pediatric Oncology Group study. Cancer, 94, 2, (Jan 2002), 552 EOF\n\t\t\t\t\t60 EOF\n\t\t\t\t\n\t\t\t'},{id:"B16",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEllison\n\t\t\t\t\t\t\tD. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Childhood medulloblastoma: novel approaches to the classification of a heterogeneous disease. Acta Neuropathol, 120, 3, (2010), 305 EOF\n\t\t\t\t\t316 EOF\n\t\t\t\t\n\t\t\t'},{id:"B17",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEvans\n\t\t\t\t\t\t\tA. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJenkin\n\t\t\t\t\t\t\tR. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSposto\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOrtega\n\t\t\t\t\t\t\tJ. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilson\n\t\t\t\t\t\t\tC. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWara\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tErtel\n\t\t\t\t\t\t\tI. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKramer\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChang\n\t\t\t\t\t\t\tC. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLeikin\n\t\t\t\t\t\t\tS. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHammond\n\t\t\t\t\t\t\tG. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1990The treatment of medulloblastoma. Results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone. J Neurosurg, 72, 4, (Apr 1990), 572 EOF\n\t\t\t\t\t582 EOF\n\t\t\t\t\n\t\t\t'},{id:"B18",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFernandez-Teijeiro\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBetensky\n\t\t\t\t\t\t\tR. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSturla\n\t\t\t\t\t\t\tL. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tJ. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTamayo\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPomeroy\n\t\t\t\t\t\t\tS. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004Combining gene expression profiles and clinical parameters for risk stratification in medulloblastomas. J Clin Oncol, 22, 6, (Mar 2004), 994 EOF\n\t\t\t\t\t8 EOF\n\t\t\t\t\n\t\t\t'},{id:"B19",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFouladi\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGilger\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKocak\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWallace\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBuchanan\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tReeves\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRobbins\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMerchant\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKun\n\t\t\t\t\t\t\tL. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKhan\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGajjar\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMulhern\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005Intellectual and functional outcome of children 3 years old or younger who have CNS malignancies. J Clin Oncol, 23, 28, (Oct 2005), 7152 EOF\n\t\t\t\t\t60 EOF\n\t\t\t\t\n\t\t\t'},{id:"B20",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFruhwald\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRickert\n\t\t\t\t\t\t\tC. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMS\n\t\t\t\t\t\t\tO’Dorisio\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMadsen\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWarmuth-Metz\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKhanna\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPaulus\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKühl\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJürgens\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchneider\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMüller\n\t\t\t\t\t\t\tH. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004Somatostatin receptor subtype 2 is expressed by supratentorial primitive neuroectodermal tumors of childhood and can be targeted for somatostatin receptor imaging. Clin Cancer Res, 10, 9, (May 2004), 2997 EOF\n\t\t\t\t\t3006 EOF\n\t\t\t\t\n\t\t\t'},{id:"B21",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGajjar\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChintagumpala\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAshley\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKellie\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKun\n\t\t\t\t\t\t\tL. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMerchant\n\t\t\t\t\t\t\tT. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWoo\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWheeler\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAhern\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMJ\n\t\t\t\t\t\t\tKrasin\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFouladi\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBroniscer\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKrance\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHale\n\t\t\t\t\t\t\tG. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStewart\n\t\t\t\t\t\t\tC. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDauser\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSanford\n\t\t\t\t\t\t\tR. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFuller\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLau\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoyett\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWallace\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGilbertson\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol, 7, 10, (Oct 2006), 813 EOF\n\t\t\t\t\t820 EOF\n\t\t\t\t\n\t\t\t'},{id:"B22",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGiangaspero\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWellek\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMasuoka\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGessi\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKleihues\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOhgaki\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006Stratification of medulloblastoma on the basis of histopathological grading. Acta Neuropathol, 112, 1, (Jul 2006), 5 EOF\n\t\t\t\t\t12 EOF\n\t\t\t\t\n\t\t\t'},{id:"B23",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGilbertson\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPearson\n\t\t\t\t\t\t\tA. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPerry\n\t\t\t\t\t\t\tR. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJaros\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKelly\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1995Prognostic significance of the c-erbB-2 oncogene product in childhood medulloblastoma. Br J Cancer, 71, 3, (Mar 1995), 473 EOF\n\t\t\t\t\t7 EOF\n\t\t\t\t\n\t\t\t'},{id:"B24",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGilbertson\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tClifford\n\t\t\t\t\t\t\tS. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003PDGFRB is overexpressed in metastatic medulloblastoma. Nat Genet, 35, 3, (Nov 2003), 197 EOF\n\t\t\t\t\t8 EOF\n\t\t\t\t\n\t\t\t'},{id:"B25",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGlas\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHennemann\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHirschmann\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMarienhagen\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchmidt-Wolf\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHerrlinger\n\t\t\t\t\t\t\tU.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBogdahn\n\t\t\t\t\t\t\tU.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHau\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008Complete response after treatment with a somatostatin analogue in an adult patient with recurrent medulloblastoma. Acta Oncol, 47, 3, (2008), 479 EOF\n\t\t\t\t\t480 EOF\n\t\t\t\t\n\t\t\t'},{id:"B26",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGottardo\n\t\t\t\t\t\t\tN. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGajjar\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008Chemotherapy for malignant brain tumors of childhood. J Child Neurol, 23, 10, (Oct 2008), 1149 EOF\n\t\t\t\t\t1159 EOF\n\t\t\t\t\n\t\t\t'},{id:"B27",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrill\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLellouch-Tubiana\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tElouahdani\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPierre-Kahn\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZerah\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRenier\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tValteau-Couanet\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHartmann\n\t\t\t\t\t\t\tO.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKalifa\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSainte-Rose\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005Preoperative chemotherapy in children with high-risk medulloblastomas: a feasibility study. J Neurosurg, 103, 4 Suppl, (Oct 2005), 312 EOF\n\t\t\t\t\t8 EOF\n\t\t\t\t\n\t\t\t'},{id:"B28",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGupta\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBanerjee\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHaas-Kogan\n\t\t\t\t\t\t\tD. (.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMarch\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004\n\t\t\t\t\tPediatric CNS Tumors. (Fisrt ed.), Springer, 3-54000-294-4Heidelberg, New York, Hong Kong, London, Milan, Paris, Tokyo\n\t\t\t'},{id:"B29",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuyotat\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChampier\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPierre\n\t\t\t\t\t\t\tG. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJouvet\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBret\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrisson\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBelin\n\t\t\t\t\t\t\tM. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSignorelli\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMontange\n\t\t\t\t\t\t\tM. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001Differential expression of somatostatin receptors in medulloblastoma. J Neurooncol, 51, 2, (Jan 2001), 93 EOF\n\t\t\t\t\t103 EOF\n\t\t\t\t\n\t\t\t'},{id:"B30",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHallahan\n\t\t\t\t\t\t\tA. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPritchard\n\t\t\t\t\t\t\tJ. I.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChandraratna\n\t\t\t\t\t\t\tR. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEllenbogen\n\t\t\t\t\t\t\tR. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGeyer\n\t\t\t\t\t\t\tJ. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOverland\n\t\t\t\t\t\t\tR. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStrand\n\t\t\t\t\t\t\tA. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTapscott\n\t\t\t\t\t\t\tS. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOlson\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect. Nat Med, 9, (Aug 2003), 1033 EOF\n\t\t\t\t\t8 EOF\n\t\t\t\t\n\t\t\t'},{id:"B31",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHauser\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJakab\n\t\t\t\t\t\t\tZs.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLáng\n\t\t\t\t\t\t\tO.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKondás\n\t\t\t\t\t\t\tO.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTörök\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGarami\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBognár\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchuler\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003High incidence of brain tumors of childhood in Hungary between 1989 and 2001. Med Pediatr Oncol, 41, 6, (2003), 590 EOF\n\t\t\t\t\t1 EOF\n\t\t\t\t\n\t\t\t'},{id:"B32",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHauser\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJakab\n\t\t\t\t\t\t\tZs.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKiss\n\t\t\t\t\t\t\tCs.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSzegedi\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBárdi\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBartyik\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOttóffy\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKajtár\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSzűcs\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNagy\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCservenák\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMasát\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBálint\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKordás\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBognár\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKocsis\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVízkeleti\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKriván\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKállay\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBenyó\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchuler\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGarami\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Előzetes eredmények a medulloblastoma/PNET kezelésében a magyar MBL2004 kezelési sémával. Magy Belorv Arch, 62, (2009), 196-201.\n\t\t\t'},{id:"B33",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tvon\n\t\t\t\t\t\t\tHoff. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHinkes\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGerber\n\t\t\t\t\t\t\tN. U.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDeinlein\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMittler\n\t\t\t\t\t\t\tU.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tUrban\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBenesch\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWarmuth-Metz\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSoerensen\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZwiener\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoette\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchlegel\n\t\t\t\t\t\t\tP. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPietsch\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKortmann\n\t\t\t\t\t\t\tR. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKuehl\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRutkowski\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Long-term outcome and clinical prognostic factors in children with medulloblastoma treated in the prospective randomised multicentre trial HIT’91. Eur J Cancer, 45, 7, (2009), 1209 EOF\n\t\t\t\t\t1217 EOF\n\t\t\t\t\n\t\t\t'},{id:"B34",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJakacki\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBurger\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhou\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHolmes\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPacker\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoldwein\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMehta\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPollack\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007Outcome for metastatic (M+) medulloblastoma (MB) treated with carboplatin during craniospinal radiotherapy (CSRT) followed by cyclophosphamide (CPM) and vincristine (VCR): Preliminary results of COG 99701. J Clin Oncol, 25, 18S, (Jun 2007), 2017.\n\t\t\t'},{id:"B35",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJenkin\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMA\n\t\t\t\t\t\t\tShabanah\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShail\n\t\t\t\t\t\t\tE. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGray\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHassounah\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKhafaga\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKofide\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMustafa\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchultz\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000Prognostic factors for medulloblastoma. Int J Radiat Oncol Biol Phys,47, 3, (Jun 2000), 573 EOF\n\t\t\t\t\t84 EOF\n\t\t\t\t\n\t\t\t'},{id:"B36",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJohnston\n\t\t\t\t\t\t\tD. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeene\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBartels\n\t\t\t\t\t\t\tU.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAS\n\t\t\t\t\t\t\tCarret\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCrooks\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEisenstat\n\t\t\t\t\t\t\tD. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFryer\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLafay-Cousin\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLarouche\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoghrabi\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilson\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZelcer\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSilva\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrossard\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBouffet\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Medulloblastoma in children under the age of three years: a retrospective Canadian review. J Neurooncol, 94, 1, (Aug 2009), 51 EOF\n\t\t\t\t\t56 EOF\n\t\t\t\t\n\t\t\t'},{id:"B37",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKaderali\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLamberti-Pasculli\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRutka\n\t\t\t\t\t\t\tJ. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009The changing epidemiology of paediatric brain tumours: a review from the Hospital for Sick Children. Childs Nerv Syst, 25, 7, (Jul 2009), 787 EOF\n\t\t\t\t\t793 EOF\n\t\t\t\t\n\t\t\t'},{id:"B38",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKieran\n\t\t\t\t\t\t\tM. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTurner\n\t\t\t\t\t\t\tC. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRubin\n\t\t\t\t\t\t\tJ. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChi\n\t\t\t\t\t\t\tS. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMA\n\t\t\t\t\t\t\tZimmerman\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChordas\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKlement\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLaforme\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGordon\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tThomas\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNeuberg\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrowder\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFolkman\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005A feasibility trial of antiangiogenic (metronomic) chemotherapy in pediatric patients with recurrent or progressive cancer. J Pediatr Hematol Oncol. 27, 11, (Nov 2005), 573 EOF\n\t\t\t\t\t81 EOF\n\t\t\t\t\n\t\t\t'},{id:"B39",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKlesse\n\t\t\t\t\t\t\tL. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBowers\n\t\t\t\t\t\t\tD. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Childhood medulloblastoma: current status of biology and treatment. CNS Drugs, 24, 4, (2010), 285 EOF\n\t\t\t\t\t301 EOF\n\t\t\t\t\n\t\t\t'},{id:"B40",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKobrinsky\n\t\t\t\t\t\t\tN. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPacker\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoyett\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStanley\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShiminski-Maher\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAllen\n\t\t\t\t\t\t\tJ. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGarvin\n\t\t\t\t\t\t\tJ. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStewart\n\t\t\t\t\t\t\tD. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFinlay\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999Etoposide with or without mannitol for the treatment of recurrent or primarily unresponsive brain tumors: a Children’s Cancer Group Study, CCG-9881. J Neurooncol, 45, 1, (1999), 47 EOF\n\t\t\t\t\t54 EOF\n\t\t\t\t\n\t\t\t'},{id:"B41",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKortmann\n\t\t\t\t\t\t\tR. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKühl\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTimmermann\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMittler\n\t\t\t\t\t\t\tU.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tUrban\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBudach\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRichter\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWillich\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFlentje\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBerthold\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSlavc\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWolff\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMeisner\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWiestler\n\t\t\t\t\t\t\tO.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSörensen\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWarmuth-Metz\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBamberg\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT ‘91. Int J Radiat Oncol Biol Phys, 46, 2, (Jan 2000), 269 EOF\n\t\t\t\t\t79 EOF\n\t\t\t\t\n\t\t\t'},{id:"B42",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLaurent\n\t\t\t\t\t\t\tJ. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChang\n\t\t\t\t\t\t\tC. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tME\n\t\t\t\t\t\t\tCohen\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1985A classification system for primitive neuroectodermal tumors (medulloblastoma) of the posterior fossa. Cancer, 1, 56, (Oct 1985), 1807 EOF\n\t\t\t\t\t9 EOF\n\t\t\t\t\n\t\t\t'},{id:"B43",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMarks\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRifkind\n\t\t\t\t\t\t\tR. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRichon\n\t\t\t\t\t\t\tV. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBreslow\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiller\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKelly\n\t\t\t\t\t\t\tW. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer, 1, (Dec 2001), 194 EOF\n\t\t\t\t\t202 EOF\n\t\t\t\t\n\t\t\t'},{id:"B44",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMarks\n\t\t\t\t\t\t\tP. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDokmanovic\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005Histone deacetylase inhibitors: discovery and development as anticancer agents. Expert Opin Investig Drugs, 14, (Dec 2005), 1497 EOF\n\t\t\t\t\t511 EOF\n\t\t\t\t\n\t\t\t'},{id:"B45",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Neil\n\t\t\t\t\t\t\tD. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCoté\n\t\t\t\t\t\t\tT. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tClegg\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRorke\n\t\t\t\t\t\t\tL. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002Incidence and trends in pediatric malignancies medulloblastoma/primitive neuroectodermal tumor: a SEER update. Surveillance Epidemiology and End Results. Med Pediatr Oncol, 39, 3, (Sep 2002), 190 EOF\n\t\t\t\t\t4 EOF\n\t\t\t\t\n\t\t\t'},{id:"B46",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiller\n\t\t\t\t\t\t\tW. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1998The emerging role of retinoids and retinoic acid metabolism blocking agents in the treatment of cancer. Cancer, 83, (Oct 1998), 1471 EOF\n\t\t\t\t\t82 EOF\n\t\t\t\t\n\t\t\t'},{id:"B47",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMueller\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChang\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Pediatric brain tumors: current treatment strategies and future therapeutic approaches. Neurotherapeutics, 6, 3, (Jul 2009), 570 EOF\n\t\t\t\t\t586 EOF\n\t\t\t\t\n\t\t\t'},{id:"B48",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMulhern\n\t\t\t\t\t\t\tR. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKepner\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tThomas\n\t\t\t\t\t\t\tP. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tArmstrong\n\t\t\t\t\t\t\tF. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFriedman\n\t\t\t\t\t\t\tH. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKun\n\t\t\t\t\t\t\tL. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1998Neuropsychologic functioning of survivors of childhood medulloblastoma randomized to receive conventional or reduced-dose craniospinal irradiation: a Pediatric Oncology Group study. J Clin Oncol, 16, 5, (May 1998), 1723 EOF\n\t\t\t\t\t1728 EOF\n\t\t\t\t\n\t\t\t'},{id:"B49",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMulhern\n\t\t\t\t\t\t\tR. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMerchant\n\t\t\t\t\t\t\tT. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGajjar\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tReddick\n\t\t\t\t\t\t\tW. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKun\n\t\t\t\t\t\t\tL. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004Late neurocognitive sequelae in survivors of brain tumours in childhood. Lancet Oncol, 5, 7, ( Jul 2004), 399 EOF\n\t\t\t\t\t408 EOF\n\t\t\t\t\n\t\t\t'},{id:"B50",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMuller\n\t\t\t\t\t\t\tH. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFruhwald\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tScheubeck\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRendl\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWarmuth-Metz\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSörensen\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKühl\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tReubi\n\t\t\t\t\t\t\tJ. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t19 EOF\n\t\t\t\t\t26 EOF\n\t\t\t\t\t1998A possible role for somatostatin receptor scintigraphy in the diagnosis and follow-up of children with medulloblastoma. J Neurooncol, 38, 1, (May 1998), 27-40.\n\t\t\t'},{id:"B51",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNorthcott\n\t\t\t\t\t\t\tP. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKorshunov\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWitt\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHielscher\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEberhart\n\t\t\t\t\t\t\tC. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMack\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBouffet\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tClifford\n\t\t\t\t\t\t\tS. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCE\n\t\t\t\t\t\t\tHawkins\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFrench\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRutka\n\t\t\t\t\t\t\tJ. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPfister\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMD\n\t\t\t\t\t\t\tTaylor\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Medulloblastoma Comprises Four Distinct Molecular Variants. J Clin Oncol. 2010 Dec 6. [Epub ahead of print]\n\t\t\t'},{id:"B52",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOkamoto\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShimizu\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTamura\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiyao\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamada\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMatsui\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTsuda\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakimoto\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHayakawa\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMogami\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1988An adoptive immunotherapy of patients with medulloblastoma by lymphokine-activated killer cells (LAK). Acta Neurochir (Wien), 94, 1-2, (1988), 47 EOF\n\t\t\t\t\t52 EOF\n\t\t\t\t\n\t\t\t'},{id:"B53",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPaál\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tErdélyi-Tóth\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPap\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCsáki\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFerencz\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchuler\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJD\n\t\t\t\t\t\t\tBorsi\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1994Pharmacokinetic studies on Elobromol in children with brain tumors. Anticancer Drugs, 5, 5, (Oct 1994), 539 EOF\n\t\t\t\t\t47 EOF\n\t\t\t\t\n\t\t\t'},{id:"B54",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPacker\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSutton\n\t\t\t\t\t\t\tL. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tElterman\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLange\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoldwein\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNicholson\n\t\t\t\t\t\t\tH. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMulne\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoyett\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tD’Angio\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWechsler-Jentzsch\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tReaman\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCohen\n\t\t\t\t\t\t\tB. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBruce\n\t\t\t\t\t\t\tD. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRorke\n\t\t\t\t\t\t\tL. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMolloy\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRyan\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLa Fond\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEvans\n\t\t\t\t\t\t\tA. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchut\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1994Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy. J Neurosurg, 81, 5, (Nov 1994), 690 EOF\n\t\t\t\t\t8 EOF\n\t\t\t\t\n\t\t\t'},{id:"B55",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPacker\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoldwein\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNicholson\n\t\t\t\t\t\t\tH. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVezina\n\t\t\t\t\t\t\tL. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAllen\n\t\t\t\t\t\t\tJ. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMD\n\t\t\t\t\t\t\tRis\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMuraszko\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRorke\n\t\t\t\t\t\t\tL. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWara\n\t\t\t\t\t\t\tW. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCohen\n\t\t\t\t\t\t\tB. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoyett\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999Treatment of children with medulloblastomas with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: A Children’s Cancer Group Study. J Clin Oncol, 17, 7, (Jul 1999), 2127 EOF\n\t\t\t\t\t36 EOF\n\t\t\t\t\n\t\t\t'},{id:"B56",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPacker\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGajjar\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVezina\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRorke-Adams\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBurger\n\t\t\t\t\t\t\tP. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRobertson\n\t\t\t\t\t\t\tP. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBayer\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLa Fond\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDonahue\n\t\t\t\t\t\t\tB. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMarymont\n\t\t\t\t\t\t\tM. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMuraszko\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLangston\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSposto\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol, 24, 25, (Sep 2006), 4202 EOF\n\t\t\t\t\t8 EOF\n\t\t\t\t\n\t\t\t'},{id:"B57",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPark\n\t\t\t\t\t\t\tJ. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKang\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYoo\n\t\t\t\t\t\t\tK. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSung\n\t\t\t\t\t\t\tK. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKoo\n\t\t\t\t\t\t\tH. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tdo\n\t\t\t\t\t\t\tLim\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShin\n\t\t\t\t\t\t\tH. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKang\n\t\t\t\t\t\t\tH. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPark\n\t\t\t\t\t\t\tK. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShin\n\t\t\t\t\t\t\tH. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tI. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCho\n\t\t\t\t\t\t\tB. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIm\n\t\t\t\t\t\t\tH. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSeo\n\t\t\t\t\t\t\tJ. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPark\n\t\t\t\t\t\t\tH. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPark\n\t\t\t\t\t\t\tB. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAhn\n\t\t\t\t\t\t\tH. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Efficacy of high-dose chemotherapy and autologous stem cell transplantation in patients with relapsed medulloblastoma: a report on the Korean Society for Pediatric Neuro-Oncology (KSPNO)-S-053 study. J Korean Med Sci, 25, 8, (2010), 1160-6.\n\t\t\t'},{id:"B58",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPeris-Bonet\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMartinez-Garcia\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLacour\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPetrovich\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGiner-Ripoll\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNavajas\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSteliarov-Foucher\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006Childhood central nervous system tumours--incidence and survival in Europe (1978-1997): report from Automated Childhood Cancer Information System project. European Journal of Cancer, 42, 13, (Sept 2006), 1064-80.\n\t\t\t'},{id:"B59",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPizzo\n\t\t\t\t\t\t\tP. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPoplack\n\t\t\t\t\t\t\tD. G. (.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOctober\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010\n\t\t\t\t\tPrinciples and Practice of Pediatric Oncology (Sixth ed.), 2011 Lippincott Williams & Wilkins, 978-1-60547-682-7Philadelphia, Baltimore, New York, London, Buenos Aires, Hong Kong, Sydney, Tokyo\n\t\t\t'},{id:"B60",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMD\n\t\t\t\t\t\t\tPrados\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchold\n\t\t\t\t\t\t\tS. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJr Fine\n\t\t\t\t\t\t\tH. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJaeckle\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHochberg\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMechtler\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFetell\n\t\t\t\t\t\t\tM. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPhuphanich\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFeun\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJanus\n\t\t\t\t\t\t\tT. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFord\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGraney\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma. Neuro Oncol, 5, 2, (Apr 2003), 96-103.\n\t\t\t'},{id:"B61",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPrivitera\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAcquaviva\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEttorre\n\t\t\t\t\t\t\tG. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSpatola\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Antiangiogenic therapy in the treatment of recurrent medulloblastoma in the adult: case report and review of the literature. J Oncol, 2009, (Epub Dec 2009), 247873 EOF\n\t\t\t\t\t4 EOF\n\t\t\t\t\n\t\t\t'},{id:"B62",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDi Rocco\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIannelli\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLa Marca\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTornesello\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMastrangelo\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRiccardi\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1995Preoperative chemotherapy with carboplatin alone in high risk medulloblastoma. Childs Nerv Syst,11, 10, (Oct 1995), 574 EOF\n\t\t\t\t\t8 EOF\n\t\t\t\t\n\t\t\t'},{id:"B63",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRoth\n\t\t\t\t\t\t\tS. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDenu\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAllis\n\t\t\t\t\t\t\tC. D. .\n\t\t\t\t\t\t\n\t\t\t\t\tHistone acetyltransferases. Annu Rev Biochem, 70, (2001\n\t\t\t\t\t81 EOF\n\t\t\t\t\t120 EOF\n\t\t\t\t\n\t\t\t'},{id:"B64",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRudin\n\t\t\t\t\t\t\tC. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHann\n\t\t\t\t\t\t\tC. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLaterra\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYauch\n\t\t\t\t\t\t\tR. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCA\n\t\t\t\t\t\t\tCallahan\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFu\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHolcomb\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStinson\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGould\n\t\t\t\t\t\t\tS. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tColeman\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLo\n\t\t\t\t\t\t\tRusso. P. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVon\n\t\t\t\t\t\t\tHoff. D. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tde Sauvage\n\t\t\t\t\t\t\tF. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLow\n\t\t\t\t\t\t\tJ. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med, 361, 12, (Sep 2009), 1173 EOF\n\t\t\t\t\t1178 EOF\n\t\t\t\t\n\t\t\t'},{id:"B65",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRuggiero\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRizzo\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAttinà\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLazzareschi\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMastrangelo\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMaurizi\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMigliorati\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBertolini\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPastore\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tColosimo\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRiccardi\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Phase I study of temozolomide combined with oral etoposide in children with recurrent or progressive medulloblastoma. Eur J Cancer, 46, 16, (Nov 2010), 2943 EOF\n\t\t\t\t\t2949 EOF\n\t\t\t\t\n\t\t\t'},{id:"B66",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tde Ruijter\n\t\t\t\t\t\t\tA. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tvan Gennip\n\t\t\t\t\t\t\tA. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCaron\n\t\t\t\t\t\t\tH. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKemp\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tvan Kuilenburg\n\t\t\t\t\t\t\tA. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J,;370, Pt 3, (Mar 2003), 737 EOF\n\t\t\t\t\t49 EOF\n\t\t\t\t\n\t\t\t'},{id:"B67",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRutkowski\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBode\n\t\t\t\t\t\t\tU.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDeinlein\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOttensmeier\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWarmuth-Metz\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSoerensen\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGraf\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEmser\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPietsch\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWolff\n\t\t\t\t\t\t\tJ. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKortmann\n\t\t\t\t\t\t\tR. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKuehl\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med, 352, 10, (Mar 2005), 978 EOF\n\t\t\t\t\t86 EOF\n\t\t\t\t\n\t\t\t'},{id:"B68",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRutkowski\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCohen\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFinlay\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLuksch\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRidola\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tValteau-Couanet\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHara\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGarre\n\t\t\t\t\t\t\tM. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrill\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Medulloblastoma in young children. Pediatr Blood Cancer, 54, 4, (Apr 2010), 635 EOF\n\t\t\t\t\t637 EOF\n\t\t\t\t\n\t\t\t'},{id:"B69",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRutkowski\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tvon\n\t\t\t\t\t\t\tHoff. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEmser\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZwiener\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPietsch\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFigarella-Branger\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGiangaspero\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEllison\n\t\t\t\t\t\t\tD. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGarre\n\t\t\t\t\t\t\tM. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBiassoni\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrundy\n\t\t\t\t\t\t\tR. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFinlay\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDhall\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMA\n\t\t\t\t\t\t\tRaquin\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrill\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Survival and prognostic factors of early childhood medulloblastoma: an international meta-analysis. J Clin Oncol, 28, 33, (Nov 2010), 4961 EOF\n\t\t\t\t\t4968 EOF\n\t\t\t\t\n\t\t\t'},{id:"B70",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchuler\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSomló\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBorsi\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParaicz\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRévész\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKardos\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKoós\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\tNew drug combination for the treatment of relapsed brain tumors in children. Pediatr Hematol Oncol, 5, 2, (1988\n\t\t\t\t\t153 EOF\n\t\t\t\t\t6 EOF\n\t\t\t\t\n\t\t\t'},{id:"B71",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchuler\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSomló\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKoós\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKálmánchey\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParaicz\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1992Treatment of malignant scala posterior brain tumors in children: the chemotherapy of relapsed medulloblastoma with a dibromdulcitol containing drug regime and pharmacokinetic studies of dibromdulcitol in children. Med Pediatr Oncol, 20, 4, (1992), 312 EOF\n\t\t\t\t\t4 EOF\n\t\t\t\t\n\t\t\t'},{id:"B72",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchuler\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSomló\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKoós\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKálmánchey\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParaicz\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1993The treatment of malignant scala posterior tumors in children: II. Preliminary result of the pre- and postoperative adjuvant chemotherapy of scala posterior tumors. Med Pediatr Oncol, 21, 4, (1993), 274 EOF\n\t\t\t\t\t9 EOF\n\t\t\t\t\n\t\t\t'},{id:"B73",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSilvani\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSalmaggi\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParmiani\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoiardi\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1994Successful adoptive immunotherapy with lymphokine-activated killer cells in the treatment of medulloblastoma disseminated via cerebrospinal fluid: case report. Neurosurgery, 34, 6, (Jun 1994), 1078 EOF\n\t\t\t\t\t80%3B EOF\n\t\t\t\t\n\t\t\t'},{id:"B74",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSpiller\n\t\t\t\t\t\t\tS. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDitzler\n\t\t\t\t\t\t\tS. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPullar\n\t\t\t\t\t\t\tB. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOlson\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008Response of preclinical medulloblastoma models to combination therapy with 13cis retinoic acid and suberoylanilide hydroxamic acid (SAHA). J Neurooncol, 87, 2, (Apr 2008), 133-41.\n\t\t\t'},{id:"B75",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMJ\n\t\t\t\t\t\t\tStastny\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCE\n\t\t\t\t\t\t\tBrown\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRuel\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJensen\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007Medulloblastomas expressing IL13Ralpha2 are targets for IL13zetakine+ cytolytic T cells. J Pediatr Hematol Oncol, 29, 10, (Oct 2007), 669-77.\n\t\t\t'},{id:"B76",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSterba\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPavelka\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAndre\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVentruba\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSkotakova\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBajciova\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBronisova\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDubska\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tValik\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Second complete remission of relapsed medulloblastoma induced by metronomic chemotherapy. Pediatr Blood Cancer, 54, 4, (Apr 2010), 616 EOF\n\t\t\t\t\t617 EOF\n\t\t\t\t\n\t\t\t'},{id:"B77",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStrother\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAshley\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKellie\n\t\t\t\t\t\t\tS. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPatel\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJones-Wallace\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tThompson\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHeideman\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBenaim\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKrance\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBowman\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGajjar\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001Feasibility of four consecutive high-dose chemotherapy cycles with stem-cell rescue for patients with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor after craniospinal radiotherapy: results of a collaborative study. J Clin Oncol, 19, 10, (May 2001), 2696 EOF\n\t\t\t\t\t704 EOF\n\t\t\t\t\n\t\t\t'},{id:"B78",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSu\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tX. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tThompson\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOu\n\t\t\t\t\t\t\tC. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIngle\n\t\t\t\t\t\t\tA. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRussell\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLau\n\t\t\t\t\t\t\tC. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAdamson\n\t\t\t\t\t\t\tP. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBlaney\n\t\t\t\t\t\t\tS. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011Phase 1 study of valproic acid in pediatric patients with refractory solid or CNS tumors: a children’s oncology group report. Clin Cancer Res, 17, 3, (Feb 2011), 589 EOF\n\t\t\t\t\t597 EOF\n\t\t\t\t\n\t\t\t'},{id:"B79",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTabori\n\t\t\t\t\t\t\tU.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBaskin\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShago\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlon\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMD\n\t\t\t\t\t\t\tTaylor\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRay\n\t\t\t\t\t\t\tP. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBouffet\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMalkin\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHawkins\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010Universal poor survival in children with medulloblastoma harboring somatic TP53 mutations. J Clin Oncol, 28, 8, (Mar 2010), 1345 EOF\n\t\t\t\t\t1350 EOF\n\t\t\t\t\n\t\t\t'},{id:"B80",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTait\n\t\t\t\t\t\t\tD. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tThornton-Jones\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBloom\n\t\t\t\t\t\t\tH. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLemerle\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorris-Jones\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1990Adjuvant chemotherapy for medulloblastoma: the first multi-centre control trial of the International Society of Paediatric Oncology (SIOP I). Eur J Cancer, 26, 4, (Apr 1990), 464 EOF\n\t\t\t\t\t9 EOF\n\t\t\t\t\n\t\t\t'},{id:"B81",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakei\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNguyen\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMehta\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChintagumpala\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDauser\n\t\t\t\t\t\t\tR. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAdesina\n\t\t\t\t\t\t\tA. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Low-level copy gain versus amplification of myc oncogenes in medulloblastoma: utility in predicting prognosis and survival. Laboratory investigation. J Neurosurg Pediatr, 3, 1, (Jan 2009), 61 EOF\n\t\t\t\t\t65 EOF\n\t\t\t\t\n\t\t\t'},{id:"B82",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTaylor\n\t\t\t\t\t\t\tR. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBailey\n\t\t\t\t\t\t\tC. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRobinson\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWeston\n\t\t\t\t\t\t\tC. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEllison\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIronside\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLucraft\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGilbertson\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTait\n\t\t\t\t\t\t\tD. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWalker\n\t\t\t\t\t\t\tD. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPizer\n\t\t\t\t\t\t\tB. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tImeson\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLashford\n\t\t\t\t\t\t\tL. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInternational\n\t\t\t\t\t\t\tSociety.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tof\n\t\t\t\t\t\t\tPaediatric.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOncology\n\t\t\t\t\t\t\tUnited.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKingdom\n\t\t\t\t\t\t\tChildren’s.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCancer\n\t\t\t\t\t\t\tStudy.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGroup\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: The International Society of Paediatric Oncology/United Kingdom Children’s Cancer Study Group PNET-3 Study. J Clin Oncol, 21, 8, (Apr 2003), 1581-91.\n\t\t\t'},{id:"B83",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tC. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHsu\n\t\t\t\t\t\t\tT. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWong\n\t\t\t\t\t\t\tT. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChang\n\t\t\t\t\t\t\tK. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009Efficacy of temozolomide for recurrent embryonal brain tumors in children. Childs Nerv Syst, 25, 5, (May 2009), 535 EOF\n\t\t\t\t\t541 EOF\n\t\t\t\t\n\t\t\t'},{id:"B84",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWechsler-Reya\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tScott\n\t\t\t\t\t\t\tM. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001The developmental biology of brain tumors. Annu Rev Neurosci, 24, (2001), 385 EOF\n\t\t\t\t\t428 EOF\n\t\t\t\t\n\t\t\t'},{id:"B85",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZeltzer\n\t\t\t\t\t\t\tP. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoyett\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFinlay\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlbright\n\t\t\t\t\t\t\tA. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRorke\n\t\t\t\t\t\t\tL. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMilstein\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAllen\n\t\t\t\t\t\t\tJ. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStevens\n\t\t\t\t\t\t\tK. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStanley\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWisoff\n\t\t\t\t\t\t\tJ. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGeyer\n\t\t\t\t\t\t\tJ. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Guire-Cullen\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStehbens\n\t\t\t\t\t\t\tJ. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShurin\n\t\t\t\t\t\t\tS. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPacker\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children’s Cancer Group 921 randomized phase III study. J Clin Oncol, 17, 3, (Mar 1999), 832 EOF\n\t\t\t\t\t45 EOF\n\t\t\t\t\n\t\t\t'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Dezső Schuler",address:"",affiliation:'
2ndDepartment of Paediatrics, Faculty of MedicineSemmelweis University, Budapest, Hungary
2ndDepartment of Paediatrics, Faculty of MedicineSemmelweis University, Budapest, Hungary
'}],corrections:null},book:{id:"537",title:"Brain Tumors",subtitle:"Current and Emerging Therapeutic Strategies",fullTitle:"Brain Tumors - Current and Emerging Therapeutic Strategies",slug:"brain-tumors-current-and-emerging-therapeutic-strategies",publishedDate:"August 23rd 2011",bookSignature:"Ana L. 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1. Introduction
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Aging is an extensively studied process, identifying a growing interest in how and why cognitive processes are affected from a neurobiological approach [1]. Aging is a multifactorial biological process, characterized by deterioration of physiological and cellular functions including brain function [2], where age is the main risk factor for the development of pathologies such as cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases [3]. Cognitive deterioration occurs during aging, where reasoning, attention, and memory, among other processes, decrease gradually with the age [4]. Cellular senescence and alterations to mitochondria and in proteolytic systems are considered hallmarks of aging [3], where one of the most studied is the mitochondria [5]. In fact, mitochondrial dysfunction has been directly associated with the aging phenotype and the majority of diseases that lead to cognitive damage.
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Over the last decades, a great interest has arisen regarding mitochondrial structure and function due to its relation with the aging brain [5]. Mitochondria are organelles essential for energy production, whose size is usually 0.5–1 μm, composed by two membranes, forming the intermembranous space and the mitochondrial matrix [6]. The outer membrane contains many copies of the transport protein porin (or voltage-dependent anion-selective channels (VDAC)), which allows the passage of molecules with a maximum weight of 5 KDalton (KDa), and the inner membrane forms numerous invaginations, tubular structures, called cristae [6]. Mitochondria are capable of remodeling their architecture through fission and fusion processes, allowing morphological adaptation to different situations [6]. Fission is essential for mitochondrial duplication and is necessary for mitophagy, allowing dysfunctional mitochondrial sections to be recycled. Fusion allows mitochondria to interconnect, allowing damaged mitochondria to maintain their function. However, fission-fusion processes are interrupted during aging, generating damaged mitochondria [7].
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Mitochondria have a small circular genome called mtDNA, which encodes 22 tRNAs, 2 mitochondrial rRNAs, and 13 subunits of the electron transport chain (ETC) [8]. mtDNA can be damaged by exposure to reactive oxygen species (ROS), chemical carcinogens, and ionizing radiation affecting the mitochondrial function; changes are also observed during aging [9]. The internal mitochondrial membrane contains the ETC, responsible for generating ATP. ETC is formed by five protein complexes; complex I (NADH dehydrogenase) receives electrons of NADH which pass through the ETC via oxidation-reduction reactions forming an electrochemical gradient that allows the formation of ATP. In addition, FADH2 donates its electrons to complex II (succinate dehydrogenase) performing the same action for ATP generation but at lower production levels [10]. As a secondary product, the ETC forms ROS, specifically by complexes I and III, but its production is controlled by antioxidant enzymes [11]. Therefore, in normal conditions ROS production is moderate, providing certain physiological roles [11]; however, during aging ROS accumulation causes biological damage known as “oxidative stress” [12].
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In the past, mitochondria have always been highlighted for its role in ATP production; however, another key function is to maintain intracellular calcium homeostasis [13]. The outer mitochondrial membrane is permeable to ions and ~5 KDa metabolites because its lipid bilayer has transmembrane proteins that form the mitochondrial permeability transition pore (mPTP). mPTP opening and closing dynamics regulates the concentration of calcium [13]. However, in conditions of high calcium concentrations, permanent mPTP opening generates massive transport of ions and small molecules <1.5 KDa through the membrane, causing increased ROS production, inhibition of the ETC, and mitochondrial swelling, which finally results in the release of pro-apoptotic factors and cell death [14].
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In this chapter we will discuss the mitochondrial alterations observed in the brain during aging, focusing on mitochondrial functions including redox balance, bioenergetics, and calcium homeostasis, and its implications in the aging process. In addition, we will discuss the contribution of mitochondrial dysfunction to synaptic failure and cognitive impairment. Finally, we will summarize potential treatments that have been proposed to prevent or attenuate the loss of mitochondrial function that could be used as potential antiaging treatment.
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2. Oxidative stress: the main characteristic of normal aging
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Aging is a complex process that involves both intrinsic and extrinsic factors [3]. Several researches showed that the reduction of synaptic function during aging could be related to increased oxidative stress and mitochondrial dysfunction [15, 16]. The latter involves decreased production of energy and redox balance, activation of nitric oxide synthase, and an abundant generation of free radicals; meanwhile increased ROS production impairs neuronal function at advanced ages [17].
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Mitochondria have a pivotal role in ROS production; they are the main organelle producer of species such as hydrogen peroxide (H2O2), superoxide anion (O2−), and hydroxyl radicals (OH−) [18]. ROS comprise all molecules derived from oxygen, can exist independently, and contain one or more unpaired electrons in their orbitals [19]. Normally, mitochondria generate ROS as a result of adequate function of the ETC by complexes I and III in OXPHOS to produce ATP. Likewise, electrons that escape mitochondrial ETC can reduce oxygen to form O2− [20]. Additionally, H2O2 is more stable than O2− and can diffuse freely through the membranes to the cytosol or nucleus, causing oxidative damage to many cellular compartments [21].
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The mitochondrial ROS produced in normal conditions have important physiological roles in maintaining cell homeostasis, participate as signaling molecules, and are also related to the regulation of cell survival [22]. In contrast, excessive ROS production promotes cellular damage [23]. For example, recent evidence suggests that higher mitochondrion-derived ROS result in enhanced formation of Aβ, an effect that is prevented with the use of antioxidants that rescue mitochondrial function in cellular and animal models of Alzheimer’s disease (AD) [24]. This suggests that higher ROS generation mediated by mitochondria is involved in early stages of age-associated diseases and during aging [25].
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Cells maintain a balance between free radicals by the action of antioxidants molecules, which neutralize or remove them [22]. Cells are equipped with a variety of defense mechanisms to remove ROS, including antioxidant enzymes that facilitate antioxidant reactions and decompose ROS [26]. Among the antioxidant enzymes are glutathione reductase (GR), glutathione peroxidase (GPx), and catalase (CAT). In addition, superoxide dismutases (SODs), such as copper-zinc-superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD), help the dismutation of superoxide radicals to generate H2O2, which is further removed by CAT and GPx enzymes [26]. Altogether, these antioxidant defenses regulate the amount of ROS, preventing accumulation and oxidative stress [27].
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Oxidative stress occurs when the antioxidant defense mechanisms are unable to neutralize free radicals in the cell. This imbalance between the production of oxidative molecules and the antioxidant defense leads to an accumulation of ROS, which oxidize and produce damage to lipids, proteins, and DNA molecules. Similarly, ROS could alter many cell compartments, for example, promoting peroxidation of lipid membranes and inactivation of enzymes by oxidation [28].
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In oxidative stress conditions, the concentration of ROS increases transiently or chronically, altering the cellular metabolism and its regulation [23]. Interestingly, these elements are implicated in the aging process, the mitochondrial free radical theory of aging (MFRTA) being the most accepted theory to explain the age-associated degeneration [29]. This theory exposed by Harman proposes that mitochondria play a central role in aging and indicates that aging is the product of accumulated damage caused by mitochondrial ROS in the cells and tissues of organisms [30, 31]. Nevertheless, this theory has also been questioned, since aging is a multifactorial biological process and not just the consequence of a unique factor [32]. Thus, the mitochondrial theory of aging is relevant since these organelles are energy sources for cells and coordinate important processes such as apoptosis. During aging, accumulation of mtDNA mutations is increased, the mitochondrial genes related to energy production become progressively less active, and the mitochondria are observed as fragmented, producing less energy [33]. The brain is particularly susceptible to oxidative damage being the most aerobically active organ in the body due to its high metabolism [34]. The brain is generally in a redox balance; however, the high production and accumulation of ROS accompanied by a reduction in the antioxidant defense system plays a key role in aging, causing damaging effects due to the large number of potential harmful intermediates that cause neuronal dysfunction [3, 35]. In turn, increased oxygen radical-induced oxidative damage during aging leads to significant changes in brain mitochondrial function [29]. Therefore, oxidative stress is implicated in aging and a wide range of age-related pathologies, such as AD and Parkinson’s disease (PD), among others [3, 16, 36].
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In the aged brain, a reduction in normal antioxidant defense machineries is observed, which increases the brain’s susceptibility to the harmful effects of oxidative molecules [27, 37]. In addition to this, mitochondrial dysfunction contributes to ROS overproduction. It is important to emphasize that a decrease in the activity of oxidative enzymes accompanied by excessive production of oxidant molecules during aging is the main toxic mechanism that explains the neurodegeneration observed at an advanced age [27, 37]. Since mitochondria are the main source of ROS production, they are in turn more exposed to oxidative damage at a faster and stronger rate than other organelles and cell compartments [16]. Moreover, the mitochondrial antioxidant system is less active than the antioxidant systems of other organelles, a feature that increases with age [5]. These mitochondrial “defects” can greatly affect several cellular processes that contribute to the aging phenotype [38]. Therefore, age is an important risk factor that increases the susceptibility of mitochondria, making them more vulnerable to oxidative stress, resulting in a vicious cycle of mitochondrial dysfunction and more oxidative damage [5, 33]. Mitochondria should be considered as a key factor in the development of age-related neurodegeneration, and therefore therapeutic strategies such as mitochondrial protectors or antioxidants that improve mitochondrial function could be used to prevent or delay aging.
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3. Bioenergetic failure during aging
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One of the main functions of mitochondria is energy production in the form of ATP through OXPHOS [39]. The main substrate of neurons is glucose. Through the glycolytic pathway, the cell generates only two ATP molecules per glucose molecule; however in this pathway two pyruvate molecules are produced. These molecules then enter the mitochondria to be oxidized in the tricarboxylic acid (TCA) cycle producing NADH and FADH2, which in turn enter the ETC to produce high amounts of ATP by OXPHOS [40]. Electrons from NADH and FADH2 are transferred through four complexes to molecular oxygen, pumping protons to the intermembrane space, which form a proton gradient that generates the mitochondrial membrane potential (Δψm). This Δψm is fundamental for adequate mitochondrial function, mainly for ATP synthesis by the ATPase complex [39].
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Due to the importance of mitochondrial energy production, failures in mitochondrial bioenergetics are related to several neurological diseases such as amyotrophic lateral sclerosis (ALS) [41] and several age-associated neurodegenerative disorders such as AD [42]. A mitochondrial failure can be caused by either a dysfunction in the OXPHOS complexes or by mutations in the mtDNA, which encodes for 13 proteins that makes the different subunits of the ETC complexes. Interestingly, mtDNA mutations produce a group of pathologies known as primary mitochondrial disorders, characterized by neurological alterations. Thus, neurodegeneration is often related to mitochondrial dysfunction as a primary or secondary target, mediating the pathogenic events [43]. Since the main energy source in brain cells is glucose oxidation, the energy obtained from the mitochondrial OXPHOS system is vital to fulfilling their high basal energy requirement, including maintenance of the membrane potential for the propagation of electric signals, reestablishment of the ion balance after the action potential (Na+/K+ ATPase activity), vesicle recycling, and neurotransmitter release [44].
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Therefore, a deficit in ATP production can lead to neuronal damage and finally cell death, producing diverse defects in brain functions as occurs during normal aging, considered an important risk to the development of neurodegenerative disease [45]. An example of this is the glutamate-glutamine cycle, an essential process for the release of glutamate from the presynaptic terminal. Glutamate uptake occurs in astrocytes, where it is converted to glutamine and then transferred back to glutamatergic neurons. For these processes to occur, the neuron requires ATP [46], as well as for the accumulation of glutamate in synaptic vesicles [47]. Therefore lower ATP levels will result in reduced glutamate release leading to decreased excitatory synapsis and consequently decreased synaptic plasticity as a result of altered long-term potentiation (LTP) and long-term depression (LTD) [48].
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In addition, AD is a neurodegenerative pathology where mitochondrial deficiency is observed in oxidative phosphorylation, with defective OXPHOS enzymes [49]. Several studies showed decreased cytochrome c oxidase activity but an increase in mitochondrial mRNA for complex IV, which may be a compensatory response for the reduced cytochrome c oxidase activity [50, 51]. Also, there is a decrease in NADH dehydrogenase expression and an increase in complex III mRNA in AD patients [51]. These defects in the OXPHOS complex impede correct ATP production and increase ROS production [52], which could generate damage to mitochondrial proteins, activate the mPTP, and mutagenize the mtDNA, leading to defective OXPHOS. All these mitochondrial defects can ultimately contribute to the characteristic synapse loss in the neocortex and hippocampus of AD patients [53], which correlates with cognitive impairment and memory loss. Similarly, critical mitochondrial dysfunction has been associated with PD. Several mutations in proteins that can directly or indirectly regulate mitochondrial activity and morphology have been described. Examples of this are PTEN-induced kinase 1 (PINK1) which induced mitochondrial autophagy during stress [54] and protein deglycase (DJ-1) which is a multifunctional protein that reacts against anti-oxidative stress [55]. These two proteins are localized in the mitochondria, while parkin, another protein that degrades dysfunctional mitochondria, translocates to damaged mitochondria [54]. The first evidence that mitochondria could be related to PD was published by Langston et al. in 1983 where they showed that the mitochondrial complex I inhibitor, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can cause acute and irreversible parkinsonian symptoms in humans [56]. Later, other mitochondrial toxins such as rotenone, which induces similar symptoms to MPTP, were described, leading to the development of a rotenone rodent model of Parkinson’s disease [57]. Other studies of postmortem tissue from PD patients showed defects in complex I, NADH dehydrogenase in the substantia nigra [58].
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Interestingly, similar bioenergetic deficits present in neurodegenerative disease are also seen in normal aging. In this natural process, it is well known that a large number of mutations accumulate in the mtDNA in different tissues, such as the brain and the muscle, the tissues with most accumulation of mutations, possibly due to the higher energetic demand [59]. For example, in a study performed with humans between 49 and 92 years old, they showed an increase by 25% in the muscle fibers that exhibit abnormalities in mitochondrial ETC in 92-year-old individuals compared to 49 year olds [60]. Another study showed that a mouse with a deficiency for mitochondrial DNA polymerase γ (POLG) had an impaired proofreading ability, accumulated mtDNA mutations, and presented a premature-aged phenotype (hair loss, graying, kyphosis, reduced survival percentage, loss of bone mass, etc.) at the age of 9 months [61]. These mutations can lead to mitochondrial dysfunction associated with a deficient respiratory chain and a decrease in ATP production [62]. There is evidence that the brain of aged mice (26 months old) contains mutations in protein-coding regions that result in significant changes in the complex I subunit ND5 and complex III subunit CytB [62]. These mutations may limit correct assembly of these complexes, which correlates with their decreased activity during aging [62]. Other studies also showed downregulation of several genes coding for mitochondrial proteins in heart tissue, which correlated with a significant decrease in the respiratory capacity of mitochondria to oxidize substrates [63]. In liver tissue, there is a decrease in the respiratory control ratio and in ADP/oxygen (an index of ATP synthesis efficiency) in senescence-accelerated mice (SAMP8) mitochondria [64], suggesting that at 18 months of age, there is insufficient ATP for normal cell metabolism, which may be due to a dysfunctional energy transfer mechanism.
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In the brain, it is widely known that with aging there is a decrease in the electron transfer activity accompanied by a decrease mainly in complexes I and IV [65, 66]. Several studies showed that complex IV activity is decreased in substantia nigra, hippocampal dentate gyrus, frontal cortex, and cerebellum during aging [67, 68]. A study performed with aged CD1 Swiss mice showed that NADH-cytochrome c reductase (complexes I and III) activity is the most affected during aging, decreasing by 48% in old mice (18 months), while succinate-cytochrome c reductase activity (complexes II and III) remain unmodified with age, indicating selective impairment of NADH dehydrogenase activity (complex I) during normal aging [69]. Likewise, cytochrome oxidase (complex IV) activity is decreased by 13% in old animals [69]. Additionally, there is evidence of increased expression of mitochondrial genes for complexes I, III, IV, and V in 18-month-old mice in the hippocampus, medial prefrontal cortex, and striatum [70], suggesting a compensatory mechanism that could induce overproduction of ETC proteins. However, this increased mRNA expression is not sustained over time, since 24-month-old mice have decreased expression of ETC complexes [70].
\n
Another parameter that is altered during aging is the Δψm due to increased H+ permeability of the inner mitochondrial membrane and a consequent failure in maintaining the H+ electrochemical gradient [71]. There is evidence that there is a decrease in the membrane potential in the cortical and striatal mitochondria of 33-month-old rats [72]. In the same way, a study in primary cultures of glial cells from the brain of young (4–6 months) and old (26–29 months) mice shows a decay in the Δψm in astrocytes [73].
\n
Thus, mitochondrial bioenergetic failure is a hallmark of different diseases including neurodegenerative disorders. Interestingly, these same patterns of decreased ATP production, OXPHOS failure, and depolarization of the mitochondrial membrane are seen during aging, a natural process of everybody’s life. This makes the mitochondria an important player in all neurological degeneration related with aging, such as synaptic failure and cognitive impairment.
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4. Age-associated calcium dysregulation
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Calcium (Ca+2) is an ion that participates in a wide variety of functions in the cells of organisms, being an intracellular regulator of many physiological processes [74]. Intracellular calcium signals participate in the regulation of a large number of processes, which include gene expression, cell cycle stages, control of muscle contraction, autophagy, and cell death, among other functions, being a second intracellular messenger [74, 75].
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In the central nervous system (CNS), Ca+2 plays a very important role in the neuronal synapse, mainly promoting exocytosis of the synaptic vesicles in the presynaptic region, meanwhile in the postsynaptic site is important for regulating the morphology of dendritic spines and spinogenesis [76, 77]. Calcium homeostasis is fundamental for correct cellular function, and the mitochondria are structures important for maintaining the intracellular calcium concentrations [78]. They participate in the local regulation of cellular Ca+2 homeostasis, since it captures Ca+2 from the cytosol in response to ion fluxes through channels in both the inner and outer plasma membranes or by release of Ca+2 from the endoplasmic reticulum (ER) [79]. Thus, when the cytosolic concentration of calcium increases, mitochondria capture and accumulate large amounts of the ion in order to control intracellular concentrations. Therefore, for appropriate neuronal functioning, adequate parameters of intracellular calcium concentrations must be maintained [80]. Interestingly, aged brain neurons are incapable of regulating intracellular calcium, mainly due to dysfunctional mitochondria and increased oxidative stress [78, 81].
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Mitochondrial dysfunction substantially contributes to biological aging [78]. In aging, oxidative stress affects mitochondrial function and, therefore, its role in Ca+2 homeostasis [78, 82]. When calcium homeostasis is altered, it has a detrimental role on the aging brain and is also associated with the development of neurodegenerative diseases [83]. Several studies showed that an increase of the Ca+2 affects synaptic communication, neurotransmitter release, and signal transduction, all this generating excitotoxicity and neuronal loss [84]. In addition, these alterations could also contribute to memory impairment [16, 84].
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In this way, since the aging is associated with a marked cognitive decline, the calcium imbalance hypothesis proposed by Khachaturian turns out to be well accepted [85, 86]. This hypothesis proposes that changes in calcium regulation gradually modulate normal brain aging and, at the same time, increase their vulnerability to neurodegenerative diseases such as AD [87]. Calcium signaling depends of the transient elevation of its intracellular concentration. In brain cells, reduced regulation of calcium homeostasis is an early event during aging, altering multiple signaling pathways and affecting various molecular and cellular functions [88].
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Due to their high buffering capacity, mitochondria are an essential component for maintaining calcium homeostasis, due to their involvement in the regulation of intracellular calcium signaling [89]. Also, other mitochondrial characteristics that facilitate its role in the regulation of calcium signaling is its structural plasticity produced by fusion and fission processes in the mitochondrial network, as well as its distribution within the neuron [90]. Aging affects mitochondrial dynamics leading to mitochondrial fragmentation and alterations to these functions [90]. Studies in mitochondria isolated from the cortex of aged animals exhibited more ROS production and mitochondrial swelling after increased Ca+2 loading than that of young animals [78]. Therefore, these findings suggest that the aging increased the sensitivity of the mitochondria to calcium overload, generating mitochondrial swelling [81]. Mitochondrial swelling results in the opening of the mPTP [91], and in aged animals, mPTP opening occurs prematurely, indicating reduced Ca+2 buffering during aging [78, 81].
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The mPTP is a large nonselective channel located in the inner mitochondrial membrane and communicates the mitochondrial matrix directly with the cytoplasm [81]. Their opening is activated by Ca+2, phosphate, ROS, increased pH, and magnesium (Mg+2) [92]. Transitory opening of mPTP allows the release of excessive calcium ions that accumulate in the mitochondria, but prolonged opening leads to the movement of ions and small molecules generating depolarization of the mitochondrial membrane and in turn releasing pro-apoptotic factors, which results in a reduction of ATP and finally causes cell death [81, 91].
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The structure of mPTP is not completely clear. Experimental approaches have distinguished several protein components such as VDAC, the adenine nucleotide translocase protein (ANT), and the mitochondrial matrix protein cyclophilin D (Cyp-D) [91]. Recent research incorporates the F1FO subunits of ATP synthase, a key enzyme of the OXPHOS complex, which participates in ATP production and maintenance of the membrane potential [91]. Interestingly, deregulation of this enzyme associated with aging has been reported, showing decreased expression of OSCP and in F1FO ATP synthase activity [81, 91]. These changes have also been observed in imaged brains that present age-related neurodegenerative pathologies [81, 91]. Cyp-D is a specific mitochondrial protein and generally considered to be a critical component of mPTP formation [91]. Several studies indicate that Cyp-D is the most important component facilitating mPTP formation, thus leading to decreased ATP production, increasing ROS generation, and eventually causing cell death [81, 91], although it is not yet completely clear how Cyp-D triggers mPTP formation [92]. The opening of mPTP dissipates Δψm, uncoupling the mitochondria and causing swelling [91]. The expression of Cyp-D increases with age and is related to several age-associated neurological diseases such as AD [91, 93]. For example, Gauba et al. have reported that Cyp-D promotes the dysfunction of ATP synthase F1FO, in the mitochondria of aged brains, observing a significant increase in the expression of this protein with age [91]. In contrast, it has been observed that deletion of Cyp-D improves cognitive and mitochondrial functions in both aging and in neurodegenerative diseases [91, 93].
\n
The increased life expectancy and the high incidence of neurodegenerative diseases require a better understanding of the aging processes and the mechanisms associated with it. Thus, comprehension of the interactions between calcium homeostasis and calcium-dependent processes during aging can help in the design of more effective therapeutic strategies. Maintaining calcium homeostasis and controlling the opening of mPTP are important factors that can be considered as a potential therapeutic objective to maintain the quality of life during aging and prevent mitochondrial damage and progressive cognitive deterioration associated with age that contribute to the development of neurodegenerative diseases.
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\nFigure 1 is a schematic representation of the main mitochondrial functions affected during normal aging. It shows increased oxidative stress as a result of a REDOX imbalance due to decreased activity of antioxidant enzymes and increased reactive oxygen species. It also shows the characteristic bioenergetics failure, as a consequence of diminished OXPHOS functioning, specifically by decreased activity of complexes I and IV of the ETC, which lead to reduced ATP production and, finally, calcium dysregulation, which leads to mitochondrial swelling due to a permanent opening of the mitochondrial permeability transition pore.
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Figure 1.
The mitochondrial functions are impaired during aging.
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Figure 2.
A synaptic failure leads to cognitive impairment in aging.
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5. Mitochondrial dysfunction and cognitive impairment
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Synaptic plasticity in the adult nervous system is a response to changes in the environment and synaptic activity, involving dendritic spine growth or retraction and synaptogenesis, which are believed to be responsible for learning and memory [94]. In the hippocampus, one form of synapse plasticity is LTP, which produces a stronger transmission for consolidation of long-term memory [95]. For this process, neurons need to synthesize proteins de novo at the dendritic spines where different neurotrophic factors play a key role [96]. An impairment in this process leads to neurodegeneration, as a result of the initial loss of synaptic structure and function and finally cell death [96].
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The previously described mitochondrial dysfunction could be an important factor in synapse loss associated with cognitive decline observed during aging and in neurodegenerative disease [97]. Since mitochondria are present in axonal terminals and dendrite spines playing a critical role in calcium flux, ROS homeostasis, and ATP production in the synapses, this organelle is a key element for neuronal plasticity [94]. In addition, mitochondrial transport to the synaptic regions is essential for the correct function of this neuronal network [98].
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Multiple pathological conditions present cognitive impairment related with a mitochondrial dysfunction. For example, chronic kidney disease (CKD) patients with cognitive damage have increased oxidative stress and decreased antioxidant enzymes (SOD, CAT, GPx, and GSH levels in plasma) compared to CKD patients without cognitive impairment [99]. Also, patients with hypoxia, ischemia induced by a traumatic brain injury (TBI), and diabetes showed cognitive decline and different signs of mitochondrial impairment such as glutamate excitotoxicity, calcium overload, opening of mPTP (which dissipates the mitochondrial electrochemical gradient leading to cell death), and increased ROS levels [100, 101, 102]. Interestingly, pyramidal neurons in the cerebral cortex and hippocampus are more susceptible to this type of injury [103], suggesting that these cellular defects may affect mainly synaptic plasticity, learning, and memory.
\n
In the context of neurodegenerative disease, mitochondrial impairment and oxidative stress are the target of Aβ neurotoxicity, promoting cognitive impairment in AD [104]. The degree of cognitive impairment in AD has been related to the amount of Aβ accumulated in mitochondria [105], resulting in a loss of the Δψm in synaptic regions and ultimately leading to the characteristic synaptic loss observed in AD [106]. It has been suggest that Cyp-D can interact with Aβ contributing to synaptic perturbations. A Cyp-D deficiency can notably improve synaptic function and therefore improve learning and memory in an AD mouse model [107]. It was recently proposed that tau protein can regulate synaptic activity, affecting mitochondrial function and axonal transport [108], and post-transductionally modified tau can induce mitochondrial damage, leading to synaptic dysfunction [109]. In fact, hyper-phosphorylated tau impairs mitochondrial respiratory chain function, increases ROS levels, decreases the activity of detoxifying enzymes, and produces Δψm dissipation [108]. Thus, the accumulation of tau can lead to synaptic deficits and cognitive impairment [110].
\n
Interestingly, cognitive decline is not only characteristic of disease and injury, since cognitive impairment is also observed during aging. During normal aging, it is well established that there is a reduction in the surface area and cortical thickness, resulting in a volume loss in the whole brain, being the non-cortical regions, such as the hippocampus and striatum, more vulnerable to this age-related atrophy [111]. In this context, a study performed with Sprague-Dawley rats of 14, 18, 23, and 27 months of age showed changes in the volume of different brain parts using magnetic resonance imaging (MRI) [112]. In that study they showed enlargement of lateral ventricles and a decrease in the volume of the medial prefrontal cortex, hippocampus, and striatum in 27-month-old rats, which correlates with cognitive deficiency. Twenty-three- and twenty-seven-month-old rats have decreased recognition memory and decreased spatial learning and memory [112]. Another common symptom of aging is cognitive fatigue (CF) characterized by an increase in the facility of becoming tired, lack of energy, and failure to sustain attention when performing cognitively demanding tasks with a high mental effort [113]. There is evidence of a correlation between the decreased connectivity strength of the neuronal network established between the cortical and the striatum areas and a higher CF at an advanced age, suggesting that the cortical-striatal network plays a crucial role in the CF phenomenon [114].
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In humans, similar cognitive decline is observed during aging, present as a deficit in episodic or declarative memory, spatial learning, working memory, and attention [115]. These processes are mainly dependent on an adequate function of the hippocampus. Structural and functional changes in the hippocampus are related to the severity and development of neurodegenerative disorders associated with cognitive decline. In fact, many of the cognitive deficits seen with aging can be replicated in animal models with bilateral hippocampal damage [116]. The connection between dentate gyrus (DG) and the CA3 area of the hippocampus is responsible for the formation of new memories, and this is naturally decreased in the aged brain [117], with different biochemical modifications that affect its ability to generate and consolidate LTP [117]. Diverse studies have shown that during aging, the auto-associative network of CA3 is strengthened, and the processing of new information coming in from the entorhinal cortex is weaker [118]. Thus, the stored information becomes dominant in contrast to the ability to encode new information [118]. Also, there is a decrease in gray matter volume, where age-related changes in the temporal lobe involve mainly changes in the hippocampus [4].
\n
Also, different studies show high levels of tau in cerebrospinal fluid (CSF) during aging [119, 120]. For example, the characteristic hearing loss (HL) present in aging influences neurodegeneration by promoting tau pathology in CSF [120], which produces cognitive impairment via synapsis dysfunction and neuronal loss [110]. Other studies evidence the age-related impairment of executive functions, verbal and nonverbal cognitive switching (independent of gender, education, and IQ), and the ability to focus attention and/or multitask [121, 122]. Studies have shown that during aging, there is a reduction in inhibitory mechanisms in the CA3, where short-term plasticity and LTP are compromised [123]. Interestingly, mitochondria play a central role in LTP, enhancing mitochondrial gene expression [124], satisfying the ATP demand by producing changes in mitochondrial energy production, and regulating calcium homeostasis by increasing calcium pump activity [125]. Also, there is evidence that mitochondrial dysfunction can lead to failure in connectivity of brain cortex producing cognitive impairment [126]. Thus, mitochondrial dysfunction during aging can be related with degeneration of synapses, triggering cell death.
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In this mitochondrial context of aging, it is interesting that in brain regions highly associated with cognitive function, such as the hippocampus and cortex, there is a high amount of impaired mitochondria, with dysfunctional respiration, excessive ROS production, loss of Δψm, and decreased cytochrome c oxidase activity. Meanwhile mitochondria are less affected in areas of the brain that are less involved in cognitive abilities [105]. Therefore, mitochondrial function is a key component in cognition. It allows proper information processing through the brain network, being an important player in synaptic transmission. Mitochondrial dysfunction generates deficits in synapsis that trigger cognitive impairment in neurodegenerative disease but also in natural aging. Thus, the understanding of these processes may be critical in these times where the aged population is increasing; therefore, improving their quality of life is a priority.
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\nFigure 2 above shows the synaptic effects of mitochondrial failure. In the presynaptic region, decreased mitochondrial activity diminishes ATP content, altering the exocytosis of synaptic vesicles. Also, increased ROS production induces lipid peroxidation, affecting glutamate and glucose transport. In the postsynaptic region, decreased mitochondrial activity disrupts calcium homeostasis, altering postsynaptic signaling. Besides, the increased ROS production and consequent lipid peroxidation impaired ion-motive ATPases. Figure 2 below schematizes that mitochondrial dysfunction at the CA1 of the hippocampus impaired synaptic transmission resulting in cognitive impairment.
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6. Mitochondrial therapies as an antiaging treatment
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Since mitochondrial dysfunction is a key event promoting aging, interventions that focus on maintaining or restoring the correct functioning of the mitochondria seem fundamental. For this purpose, two different experimental strategies could be used [127], physiological approaches or pharmacological approximations, which will be briefly summarized in this section.
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From the physiological point of view, maintaining a lifestyle that includes recurrent physical exercise preserves mitochondrial function [127]. During aging a loss of age-associated muscle mass is directly related with decreased mitochondria-dependent metabolic capacity, as well as with reduced mitochondrial biogenesis [128]. Biogenesis of new mitochondria is regulated by the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), which also regulates redox balance and energetic function [129]. Interestingly, PGC-1α expression is decreased in aging reducing its signaling pathway and gene target [129], an effect that could be counteracted by exercise, demonstrating that exercise also increases mtDNA content in the muscle of aged rats [130]. In addition, exercise increases the expression of the CAT enzyme, reducing ROS levels [131]. Similarly, exercise promotes both fission and fusion events as indicated by upregulated levels of Fis1 and Mfn1 protein in the muscle tissue of old animals and by increased Mfn2 and Drp1 mRNA in the skeletal muscle of older women [132]. Finally, exercise could contribute to restoration of mitochondrial Ca+2 homeostasis, increasing the protein levels of mitochondrial Ca+2 uniporter (MCU) [132]. Thus, exercise during aging could promote the genesis of new mitochondria or could attenuate the mitochondrial dysfunction observed at an advanced age.
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A second physiological approximation important for simulating mitochondrial function is caloric restriction, which has been demonstrated in different models that are able to reduce the age-related phenotype and to increase lifespan [133]. The beneficial effects of caloric restriction are directly associated with the bioenergetic defects observed in aging, activating ATP production through fatty acid metabolism [134]. Mechanistically, caloric restriction increases the activity of complexes I, III, and IV of the ETC, as well as MnSOD, which results in increased ATP and reduced ROS levels [135]. Likewise, caloric restriction enhances Ca+2 mitochondrial buffering, decreasing Cyp-D levels [135]. Therefore, regulating caloric ingestion is possible for maintaining mitochondrial activity during aging.
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Mitochondrial function can also be regulated pharmacologically, for example, through the administration of polyphenols such as resveratrol, green tea, and red wine [127, 136]. Specifically, they act by promoting mitochondrial OXPHOS and activating cellular antioxidant mechanisms [137]. Another possibility is the use of antioxidant compounds such as MitoQ , an electron scavenger that prevents the formation of mitochondrial free radicals [138]. Similarly, α-tocopherol (MitoVitE), α-phenyl-tert-butylnitrone (MitoPBN), the piperidine nitroxide MitoTEMPOL, the antioxidant SkQ1, and elamipretide (SS-31) enter and accumulate in the mitochondria preventing oxidative stress and preserving mitochondrial function [139, 140]. The numerous studies probing the clinical efficacy of these compounds validate the importance of mitochondria in aging [139]. To promote the natural antioxidant effect in the cell, treatment with N-acetylcysteine, vitamin, C and other physiological antioxidant molecules have also been shown to be effective as palliative treatment of senescence [141, 142].
\n
It is also important to highlight the positive effects induced by the direct administration of fatty acids including omega-3 fatty acid α-linolenic acid, due to studies in vivo that have shown its capacity to extend lifespan [143]. This could be a consequence of increased β-oxidation, which results in higher mitochondrial energy production, by increasing mitochondrial biogenesis or by reducing oxidative stress [144]. Finally, we will mention the effects of Metformin, a drug commonly used for the treatment of type 2 diabetes. Metformin has a hypoglycemic effect in the plasma and promotes increased insulin sensibility by a mechanism that remains unclear [145]. However, favorable effects have been observed, where DNA damage and inflammation are prevented, impeding cellular damage by reducing ROS production [146].
\n
Therefore, these approaches highlight the key role that mitochondrial function play during aging, where correct mitochondrial activity could extend lifespan, whereas metabolic alterations could compromise mitochondrial function, accelerating the aging phenotype.
\n
\n
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7. Future directions: importance of synaptic mitochondrial dysfunction in aging
\n
It is now known that the mitochondria have a fundamental role during the aging process. In neurons, the mitochondria are classified into two groups according to their localization, such as synaptic and non-synaptic mitochondria. Non-synaptic mitochondria are distributed throughout the cell body and in the neural prolongations, meanwhile synaptic mitochondria are exclusively found in synapses, both at the pre- and postsynaptic level [147]. Thus, it is not surprising that synaptic mitochondria, which have a higher energy requirement in order to sustain synaptic activity, present functional differences compared to non-synaptic mitochondria. For example, synaptic mitochondria have higher peroxide production than non-synaptic ones [148]. During aging, it seems that these differences are accentuated between these two mitochondrial populations. Aged cortical synaptic mitochondria present decreased oxidative capacity and higher susceptibility to calcium overload, in contrast to non-synaptic mitochondria that preserve their respiratory capacity [16]. Similarly, we observed that hippocampal synaptic mitochondria fail previous to non-synaptic mitochondria during aging and suffer premature mitochondrial swelling with age, contributing hippocampus-dependent memory loss (manuscript in preparation). Thus, maintaining adequate function of synaptic mitochondria seems to be the new challenge in order to attenuate the aging phenotype, reducing the synaptic and cognitive failure characteristics of older individuals.
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8. Conclusions
\n
Taken together, the evidence presented in this chapter strongly suggests a close relationship between mitochondrial function and a wide range of processes associated with aging. In general, it is possible to propose an age-dependent decline observed in several organs such as the brain correlated with a loss of mitochondrial activity, generating a bioenergetic deficit and redox imbalance that promote oxidative stress. This promotes additional mitochondrial fail, affecting cellular calcium homeostasis, critical for neurons due to its important roles in the synapses. Thus, synaptic defects conduce to cognitive impairment. Finally, we propose that the synaptic mitochondria are a critical mitochondrial pool to preserve synaptic communication despite the passing of the years.
\n
\n
Acknowledgments
\n
This work was supported by FONDECYT N°11170546 and CONICYT PAI N°77170091 to CTR.
\n
\n',keywords:"aging, mitochondria, oxidative stress, synapses, memory",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/68488.pdf",chapterXML:"https://mts.intechopen.com/source/xml/68488.xml",downloadPdfUrl:"/chapter/pdf-download/68488",previewPdfUrl:"/chapter/pdf-preview/68488",totalDownloads:594,totalViews:0,totalCrossrefCites:1,dateSubmitted:"March 21st 2019",dateReviewed:"July 8th 2019",datePrePublished:"August 7th 2019",datePublished:"March 11th 2020",dateFinished:"August 7th 2019",readingETA:"0",abstract:"Mitochondria are important cellular organelles with key regulatory functions in energy production, oxidative balance, and calcium homeostasis. This is especially important in the brain, since neurons require a large number of functional mitochondria to supply their high energy requirement, mainly for synaptic processes. A decrease in the activity and quality of mitochondria in the brain, particularly in the hippocampus, is associated with normal aging and a large number of neurodegenerative diseases compromising memory function. Although synaptic and cognitive dysfunction is multifactorial, growing evidence demonstrates that mitochondria play a key role in these processes and suggests that maintaining mitochondrial function could prevent these age-dependent alterations. In this chapter, we will discuss the hippocampal mitochondrial dysfunction present in aging and how these defects promote age-associated synaptic damage and cognitive impairment. We will summarize evidence that shows how neurodegeneration can be accelerated or attenuated during aging by modulating mitochondrial function.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/68488",risUrl:"/chapter/ris/68488",signatures:"Claudia Jara, Angie K. Torres, Margrethe A. Olesen and Cheril Tapia-Rojas",book:{id:"7850",title:"Mitochondria and Brain Disorders",subtitle:null,fullTitle:"Mitochondria and Brain Disorders",slug:"mitochondria-and-brain-disorders",publishedDate:"March 11th 2020",bookSignature:"Stavros Baloyannis",coverURL:"https://cdn.intechopen.com/books/images_new/7850.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"156098",title:"Emeritus Prof.",name:"Stavros",middleName:"J",surname:"Baloyannis",slug:"stavros-baloyannis",fullName:"Stavros Baloyannis"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"183873",title:"Dr.",name:"Claudia",middleName:null,surname:"Jara",fullName:"Claudia Jara",slug:"claudia-jara",email:"cjcjarao@gmail.com",position:null,institution:null},{id:"299224",title:"Dr.",name:"Cheril",middleName:null,surname:"Tapia-Rojas",fullName:"Cheril Tapia-Rojas",slug:"cheril-tapia-rojas",email:"cheril.tapia@uss.cl",position:null,institution:{name:"San Sebastián University",institutionURL:null,country:{name:"Chile"}}},{id:"299227",title:"Ms.",name:"Angie K.",middleName:null,surname:"Torres",fullName:"Angie K. Torres",slug:"angie-k.-torres",email:"angiekim.torres@gmail.com",position:null,institution:null},{id:"299230",title:"Ms.",name:"Margrethe",middleName:null,surname:"A. Olesen",fullName:"Margrethe A. Olesen",slug:"margrethe-a.-olesen",email:"molesen.2@gmail.com",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Oxidative stress: the main characteristic of normal aging",level:"1"},{id:"sec_3",title:"3. Bioenergetic failure during aging",level:"1"},{id:"sec_4",title:"4. Age-associated calcium dysregulation",level:"1"},{id:"sec_5",title:"5. Mitochondrial dysfunction and cognitive impairment",level:"1"},{id:"sec_6",title:"6. Mitochondrial therapies as an antiaging treatment",level:"1"},{id:"sec_7",title:"7. Future directions: importance of synaptic mitochondrial dysfunction in aging",level:"1"},{id:"sec_8",title:"8. Conclusions",level:"1"},{id:"sec_9",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'\nAnderson ND, Craik FI. 50 years of cognitive aging theory. The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences. 2017;72(1):1-6\n'},{id:"B2",body:'\nLindenberger U et al. Age-related decline in brain resources modulates genetic effects on cognitive functioning. Frontiers in Neuroscience. 2008;2(2):234-244\n'},{id:"B3",body:'\nLopez-Otin C et al. The hallmarks of aging. Cell. 2013;153(6):1194-1217\n'},{id:"B4",body:'\nHarada CN, Natelson Love MC, Triebel KL. Normal cognitive aging. Clinics in Geriatric Medicine. 2013;29(4):737-752\n'},{id:"B5",body:'\nBratic A, Larsson NG. The role of mitochondria in aging. The Journal of Clinical Investigation. 2013;123(3):951-957\n'},{id:"B6",body:'\nLopez-Lluch G et al. Mitochondrial biogenesis and healthy aging. Experimental Gerontology. 2008;43(9):813-819\n'},{id:"B7",body:'\nJendrach M et al. Morpho-dynamic changes of mitochondria during ageing of human endothelial cells. Mechanisms of Ageing and Development. 2005;126(6-7):813-821\n'},{id:"B8",body:'\nFalkenberg M, Larsson NG, Gustafsson CM. DNA replication and transcription in mammalian mitochondria. Annual Review of Biochemistry. 2007;76:679-699\n'},{id:"B9",body:'\nTrifunovic A et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature. 2004;429(6990):417-423\n'},{id:"B10",body:'\nManoj KM. Aerobic respiration: Criticism of the proton-centric explanation involving rotary adenosine triphosphate synthesis, chemiosmosis principle, proton pumps and electron transport chain. Biochemistry Insights. 2018;11:1178626418818442\n'},{id:"B11",body:'\nValko M et al. Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry & Cell Biology. 2007;39(1):44-84\n'},{id:"B12",body:'\nJacinto TA et al. Increased ROS production and DNA damage in monocytes are biomarkers of aging and atherosclerosis. Biological Research. 2018;51(1):33\n'},{id:"B13",body:'\nGunter TE et al. Mitochondrial calcium transport: Mechanisms and functions. Cell Calcium. 2000;28(5-6):285-296\n'},{id:"B14",body:'\nMuller M et al. Mitochondria and calcium regulation as basis of neurodegeneration associated with aging. Frontiers in Neuroscience. 2018;12:470\n'},{id:"B15",body:'\nOliver DMA, Reddy PH. Molecular basis of Alzheimer’s disease: Focus on mitochondria. Journal of Alzheimer’s Disease. Vol. Pre-press. 2019. pp. 1-22\n'},{id:"B16",body:'\nLores-Arnaiz S et al. Brain cortex mitochondrial bioenergetics in synaptosomes and non-synaptic mitochondria during aging. Neurochemical Research. 2016;41(1-2):353-363\n'},{id:"B17",body:'\nCampos PB, Paulsen BS, Rehen SK. Accelerating neuronal aging in in vitro model brain disorders: A focus on reactive oxygen species. Frontiers in Aging Neuroscience. 2014;6:292\n'},{id:"B18",body:'\nMurphy MP. How mitochondria produce reactive oxygen species. The Biochemical Journal. 2009;417(1):1-13\n'},{id:"B19",body:'\nStuart JA et al. A midlife crisis for the mitochondrial free radical theory of aging. Longevity & Healthspan. 2014;3(1):4\n'},{id:"B20",body:'\nLiu Y, Fiskum G, Schubert D. Generation of reactive oxygen species by the mitochondrial electron transport chain. Journal of Neurochemistry. 2002;80(5):780-787\n'},{id:"B21",body:'\nLennicke C et al. Hydrogen peroxide - production, fate and role in redox signaling of tumor cells. Cell Communication and Signaling: CCS. 2015;13:39\n'},{id:"B22",body:'\nSena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Molecular Cell. 2012;48(2):158-167\n'},{id:"B23",body:'\nWang CH et al. Oxidative stress response elicited by mitochondrial dysfunction: Implication in the pathophysiology of aging. Experimental Biology and Medicine (Maywood, N.J.). 2013;238(5):450-460\n'},{id:"B24",body:'\nLeuner K et al. Mitochondrion-derived reactive oxygen species lead to enhanced amyloid beta formation. Antioxidants & Redox Signaling. 2012;16(12):1421-1433\n'},{id:"B25",body:'\nKudryavtseva AV et al. Mitochondrial dysfunction and oxidative stress in aging and cancer. Oncotarget. 2016;7(29):44879-44905\n'},{id:"B26",body:'\nCircu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radical Biology & Medicine. 2010;48(6):749-762\n'},{id:"B27",body:'\nJones DP et al. Redox analysis of human plasma allows separation of pro-oxidant events of aging from decline in antioxidant defenses. Free Radical Biology & Medicine. 2002;33(9):1290-1300\n'},{id:"B28",body:'\nEspinosa-Diez C et al. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biology. 2015;6:183-197\n'},{id:"B29",body:'\nBarja G. Updating the mitochondrial free radical theory of aging: An integrated view, key aspects, and confounding concepts. Antioxidants & Redox Signaling. 2013;19(12):1420-1445\n'},{id:"B30",body:'\nHarman D. The free radical theory of aging: Effect of age on serum copper levels. Journal of Gerontology. 1965;20:151-153\n'},{id:"B31",body:'\nBokov A, Chaudhuri A, Richardson A. The role of oxidative damage and stress in aging. Mechanisms of Ageing and Development. 2004;125(10-11):811-826\n'},{id:"B32",body:'\nPerez VI et al. Is the oxidative stress theory of aging dead? Biochimica et Biophysica Acta. 2009;1790(10):1005-1014\n'},{id:"B33",body:'\nSun N, Youle RJ, Finkel T. The mitochondrial basis of aging. Molecular Cell. 2016;61(5):654-666\n'},{id:"B34",body:'\nBarbagallo M, Marotta F, Dominguez LJ. Oxidative stress in patients with Alzheimer’s disease: Effect of extracts of fermented papaya powder. Mediators of Inflammation. 2015;2015:624801\n'},{id:"B35",body:'\nDeepashree S et al. Oxidative stress resistance as a factor in aging: Evidence from an extended longevity phenotype of Drosophila melanogaster. Biogerontology. 2019;20:497-513\n'},{id:"B36",body:'\nReddy PH, Beal MF. Amyloid beta, mitochondrial dysfunction and synaptic damage: Implications for cognitive decline in aging and Alzheimer’s disease. Trends in Molecular Medicine. 2008;14(2):45-53\n'},{id:"B37",body:'\nRen X et al. Redox Signaling mediated by Thioredoxin and glutathione Systems in the Central Nervous System. Antioxidants & Redox Signaling. 2017;27(13):989-1010\n'},{id:"B38",body:'\nSrivastava S. The mitochondrial basis of aging and age-related disorders. Genes (Basel). 2017;8(12):398\n'},{id:"B39",body:'\nPapa S et al. The oxidative phosphorylation system in mammalian mitochondria. Advances in Experimental Medicine and Biology. 2012;942:3-37\n'},{id:"B40",body:'\nLunt SY, Vander Heiden MG. Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation. Annual Review of Cell and Developmental Biology. 2011;27:441-464\n'},{id:"B41",body:'\nLu H et al. Current therapy of drugs in amyotrophic lateral sclerosis. Current Neuropharmacology. 2016;14(4):314-321\n'},{id:"B42",body:'\nNunomura A et al. Oxidative damage is the earliest event in Alzheimer disease. Journal of Neuropathology and Experimental Neurology. 2001;60(8):759-767\n'},{id:"B43",body:'\nDiMauro S, Schon EA. Mitochondrial disorders in the nervous system. Annual Review of Neuroscience. 2008;31:91-123\n'},{id:"B44",body:'\nRangaraju V, Calloway N, Ryan TA. Activity-driven local ATP synthesis is required for synaptic function. Cell. 2014;156(4):825-835\n'},{id:"B45",body:'\nNavarro A, Boveris A. Rat brain and liver mitochondria develop oxidative stress and lose enzymatic activities on aging. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2004;287(5):R1244-R1249\n'},{id:"B46",body:'\nTakeda K, Ueda T. Effective mechanism for synthesis of neurotransmitter glutamate and its loading into synaptic vesicles. Neurochemical Research. 2017;42(1):64-76\n'},{id:"B47",body:'\nNaito S, Ueda T. Characterization of glutamate uptake into synaptic vesicles. Journal of Neurochemistry. 1985;44(1):99-109\n'},{id:"B48",body:'\nPittenger C, Bloch MH, Williams K. Glutamate abnormalities in obsessive compulsive disorder: Neurobiology, pathophysiology, and treatment. Pharmacology & Therapeutics. 2011;132(3):314-332\n'},{id:"B49",body:'\nYan MH, Wang X, Zhu X. Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease. Free Radical Biology & Medicine. 2013;62:90-101\n'},{id:"B50",body:'\nBriston T, Hicks AR. Mitochondrial dysfunction and neurodegenerative proteinopathies: Mechanisms and prospects for therapeutic intervention. Biochemical Society Transactions. 2018;46(4):829-842\n'},{id:"B51",body:'\nManczak M et al. Differential expression of oxidative phosphorylation genes in patients with Alzheimer’s disease: Implications for early mitochondrial dysfunction and oxidative damage. Neuromolecular Medicine. 2004;5(2):147-162\n'},{id:"B52",body:'\nKawamata H, Manfredi G. Proteinopathies and OXPHOS dysfunction in neurodegenerative diseases. The Journal of Cell Biology. 2017;216(12):3917-3929\n'},{id:"B53",body:'\nTerry RD et al. Physical basis of cognitive alterations in Alzheimer’s disease: Synapse loss is the major correlate of cognitive impairment. Annals of Neurology. 1991;30(4):572-580\n'},{id:"B54",body:'\nBarodia SK, Creed RB, Goldberg MS. Parkin and PINK1 functions in oxidative stress and neurodegeneration. Brain Research Bulletin. 2017;133:51-59\n'},{id:"B55",body:'\nAriga H et al. Neuroprotective function of DJ-1 in Parkinson\'s disease. Oxidative Medicine and Cellular Longevity. 2013;2013:683920\n'},{id:"B56",body:'\nLangston JW et al. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983;219(4587):979-980\n'},{id:"B57",body:'\nCannon JR et al. A highly reproducible rotenone model of Parkinson\'s disease. Neurobiology of Disease. 2009;34(2):279-290\n'},{id:"B58",body:'\nSchapira AH et al. Mitochondrial complex I deficiency in Parkinson\'s disease. Journal of Neurochemistry. 1990;54(3):823-827\n'},{id:"B59",body:'\nCortopassi GA et al. A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proceedings of the National Academy of Sciences of the United States of America. 1992;89(16):7370-7374\n'},{id:"B60",body:'\nBua E et al. Mitochondrial DNA-deletion mutations accumulate intracellularly to detrimental levels in aged human skeletal muscle fibers. American Journal of Human Genetics. 2006;79(3):469-480\n'},{id:"B61",body:'\nKujoth GC et al. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science. 2005;309(5733):481-484\n'},{id:"B62",body:'\nLi H et al. Aging-associated mitochondrial DNA mutations alter oxidative phosphorylation machinery and cause mitochondrial dysfunctions. Biochimica et Biophysica Acta - Molecular Basis of Disease. 2017;1863(9):2266-2273\n'},{id:"B63",body:'\nEmelyanova L et al. Effect of aging on mitochondrial energetics in the human atria. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2018;73(5):608-616\n'},{id:"B64",body:'\nNakahara H et al. Mitochondrial dysfunction in the senescence accelerated mouse (SAM). Free Radical Biology & Medicine. 1998;24(1):85-92\n'},{id:"B65",body:'\nLenaz G et al. Mitochondrial complex I defects in aging. Molecular and Cellular Biochemistry. 1997;174(1-2):329-333\n'},{id:"B66",body:'\nBenzi G et al. The mitochondrial electron transfer alteration as a factor involved in the brain aging. Neurobiology of Aging. 1992;13(3):361-368\n'},{id:"B67",body:'\nItoh K et al. Cytochrome c oxidase defects of the human substantia nigra in normal aging. Neurobiology of Aging. 1996;17(6):843-848\n'},{id:"B68",body:'\nBertoni-Freddari C et al. Cytochrome oxidase activity in hippocampal synaptic mitochondria during aging: A quantitative cytochemical investigation. Annals of the New York Academy of Sciences. 2004;1019:33-36\n'},{id:"B69",body:'\nNavarro A et al. Behavioral dysfunction, brain oxidative stress, and impaired mitochondrial electron transfer in aging mice. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2002;282(4):R985-R992\n'},{id:"B70",body:'\nManczak M et al. Time-course of mitochondrial gene expressions in mice brains: Implications for mitochondrial dysfunction, oxidative damage, and cytochrome c in aging. Journal of Neurochemistry. 2005;92(3):494-504\n'},{id:"B71",body:'\nKlohn PC et al. Early resistance to cell death and to onset of the mitochondrial permeability transition during hepatocarcinogenesis with 2-acetylaminofluorene. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(17):10014-10019\n'},{id:"B72",body:'\nLaFrance R et al. Age-related changes in regional brain mitochondria from Fischer 344 rats. Aging Cell. 2005;4(3):139-145\n'},{id:"B73",body:'\nLin DT et al. Ca2+ signaling, mitochondria and sensitivity to oxidative stress in aging astrocytes. Neurobiology of Aging. 2007;28(1):99-111\n'},{id:"B74",body:'\nFrazier HN et al. Calcium\'s role as nuanced modulator of cellular physiology in the brain. Biochemical and Biophysical Research Communications. 2017;483(4):981-987\n'},{id:"B75",body:'\nRaza M et al. Aging is associated with elevated intracellular calcium levels and altered calcium homeostatic mechanisms in hippocampal neurons. Neuroscience Letters. 2007;418(1):77-81\n'},{id:"B76",body:'\nMattson MP. Calcium and neurodegeneration. Aging Cell. 2007;6(3):337-350\n'},{id:"B77",body:'\nKorkotian E, Segal M. Release of calcium from stores alters the morphology of dendritic spines in cultured hippocampal neurons. Proceedings of the National Academy of Sciences of the United States of America. 1999;96(21):12068-12072\n'},{id:"B78",body:'\nBrown MR, Geddes JW, Sullivan PG. Brain region-specific, age-related, alterations in mitochondrial responses to elevated calcium. Journal of Bioenergetics and Biomembranes. 2004;36(4):401-406\n'},{id:"B79",body:'\nDecuypere JP et al. IP(3) receptors, mitochondria, and Ca Signaling: Implications for aging. Journal of Aging Research. 2011;2011:920178\n'},{id:"B80",body:'\nBagur R, Hajnoczky G. Intracellular Ca(2+) sensing: Its role in calcium homeostasis and Signaling. Molecular Cell. 2017;66(6):780-788\n'},{id:"B81",body:'\nPanel M, Ghaleh B, Morin D. Mitochondria and aging: A role for the mitochondrial transition pore? Aging Cell. 2018;17:e12793\n'},{id:"B82",body:'\nOh MM et al. Altered calcium metabolism in aging CA1 hippocampal pyramidal neurons. The Journal of Neuroscience. 2013;33(18):7905-7911\n'},{id:"B83",body:'\nRadzik T et al. Calcium Dyshomeostasis alters CCL5 Signaling in differentiated PC12 cells. BioMed Research International. 2019;2019:9616248\n'},{id:"B84",body:'\nSupnet C, Bezprozvanny I. The dysregulation of intracellular calcium in Alzheimer disease. Cell Calcium. 2010;47(2):183-189\n'},{id:"B85",body:'\nKhachaturian ZS. Hypothesis on the regulation of cytosol calcium concentration and the aging brain. Neurobiology of Aging. 1987;8(4):345-346\n'},{id:"B86",body:'\nKhachaturian ZS. The role of calcium regulation in brain aging: Reexamination of a hypothesis. Aging (Milano). 1989;1(1):17-34\n'},{id:"B87",body:'\nKhachaturian ZS. Calcium hypothesis of Alzheimer’s disease and brain aging. Annals of the New York Academy of Sciences. 1994;747:1-11\n'},{id:"B88",body:'\nBetzer C, Jensen PH. Reduced cytosolic calcium as an early decisive cellular state in Parkinson’s disease and Synucleinopathies. Frontiers in Neuroscience. 2018;12:819\n'},{id:"B89",body:'\nDu H et al. Early deficits in synaptic mitochondria in an Alzheimer’s disease mouse model. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(43):18670-18675\n'},{id:"B90",body:'\nChauhan A, Vera J, Wolkenhauer O. The systems biology of mitochondrial fission and fusion and implications for disease and aging. Biogerontology. 2014;15(1):1-12\n'},{id:"B91",body:'\nGauba E, Guo L, Du H. Cyclophilin D promotes brain mitochondrial F1FO ATP synthase dysfunction in aging mice. Journal of Alzheimer’s Disease. 2017;55(4):1351-1362\n'},{id:"B92",body:'\nKwong JQ , Molkentin JD. Physiological and pathological roles of the mitochondrial permeability transition pore in the heart. Cell Metabolism. 2015;21(2):206-214\n'},{id:"B93",body:'\nDu H et al. Cyclophilin D deficiency improves mitochondrial function and learning/memory in aging Alzheimer disease mouse model. Neurobiology of Aging. 2011;32(3):398-406\n'},{id:"B94",body:'\nMattson MP. Mitochondrial regulation of neuronal plasticity. Neurochemical Research. 2007;32(4-5):707-715\n'},{id:"B95",body:'\nBliss TV, Collingridge GL. A synaptic model of memory: Long-term potentiation in the hippocampus. Nature. 1993;361(6407):31-39\n'},{id:"B96",body:'\nBatool S et al. Synapse formation: From cellular and molecular mechanisms to neurodevelopmental and neurodegenerative disorders. Journal of Neurophysiology. 2019;121(4):1381-1397\n'},{id:"B97",body:'\nCai Q , Tammineni P. Mitochondrial aspects of synaptic dysfunction in Alzheimer’s disease. Journal of Alzheimer’s Disease. 2017;57(4):1087-1103\n'},{id:"B98",body:'\nMattson MP, Gleichmann M, Cheng A. Mitochondria in neuroplasticity and neurological disorders. Neuron. 2008;60(5):748-766\n'},{id:"B99",body:'\nVinothkumar G et al. Abnormal amyloid beta42 expression and increased oxidative stress in plasma of CKD patients with cognitive dysfunction: A small scale case control study comparison with Alzheimer’s disease. BBA Clinical. 2017;8:20-27\n'},{id:"B100",body:'\nWalker KR, Tesco G. Molecular mechanisms of cognitive dysfunction following traumatic brain injury. Frontiers in Aging Neuroscience. 2013;5:29\n'},{id:"B101",body:'\nFujimoto K et al. Targeting cyclophilin D and the mitochondrial permeability transition enhances beta-cell survival and prevents diabetes in Pdx1 deficiency. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(22):10214-10219\n'},{id:"B102",body:'\nTaddeo EP et al. Opening of the mitochondrial permeability transition pore links mitochondrial dysfunction to insulin resistance in skeletal muscle. Molecular Metabolism. 2014;3(2):124-134\n'},{id:"B103",body:'\nGozal D, Daniel JM, Dohanich GP. Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in the rat. The Journal of Neuroscience. 2001;21(7):2442-2450\n'},{id:"B104",body:'\nButterfield DA. Beta-amyloid-associated free radical oxidative stress and neurotoxicity: Implications for Alzheimer’s disease. Chemical Research in Toxicology. 1997;10(5):495-506\n'},{id:"B105",body:'\nDragicevic N et al. Mitochondrial amyloid-beta levels are associated with the extent of mitochondrial dysfunction in different brain regions and the degree of cognitive impairment in Alzheimer’s transgenic mice. Journal of Alzheimer’s Disease. 2010;20(Suppl 2):S535-S550\n'},{id:"B106",body:'\nMattson MP, Partin J, Begley JG. Amyloid beta-peptide induces apoptosis-related events in synapses and dendrites. Brain Research. 1998;807(1-2):167-176\n'},{id:"B107",body:'\nDu H et al. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer’s disease. Nature Medicine. 2008;14(10):1097-1105\n'},{id:"B108",body:'\nEckert A et al. March separate, strike together-role of phosphorylated TAU in mitochondrial dysfunction in Alzheimer’s disease. Biochimica et Biophysica Acta. 2014;1842(8):1258-1266\n'},{id:"B109",body:'\nCheng Y, Bai F. The Association of tau with Mitochondrial Dysfunction in Alzheimer’s disease. Frontiers in Neuroscience. 2018;12:163\n'},{id:"B110",body:'\nDi J et al. Abnormal tau induces cognitive impairment through two different mechanisms: Synaptic dysfunction and neuronal loss. Scientific Reports. 2016;6:20833\n'},{id:"B111",body:'\nLemaitre H et al. Normal age-related brain morphometric changes: Nonuniformity across cortical thickness, surface area and gray matter volume? Neurobiology of Aging. 2012;33(3):617 e1-617 e9\n'},{id:"B112",body:'\nHamezah HS et al. Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions. Experimental Gerontology. 2017;99:69-79\n'},{id:"B113",body:'\nLeavitt VM, DeLuca J. Central fatigue: Issues related to cognition, mood and behavior, and psychiatric diagnoses. PM & R: The Journal of Injury, Function, and Rehabilitation. 2010;2(5):332-337\n'},{id:"B114",body:'\nRen P et al. Cognitive fatigue and cortical-striatal network in old age. Aging (Albany NY). 2019;11:2312-2326\n'},{id:"B115",body:'\nKausler DH. Learning and Memory in Normal Aging. San Diego, CA, US: Academic Press; 1994\n'},{id:"B116",body:'\nBettio LEB, Rajendran L, Gil-Mohapel J. The effects of aging in the hippocampus and cognitive decline. Neuroscience and Biobehavioral Reviews. 2017;79:66-86\n'},{id:"B117",body:'\nYassa MA et al. Age-related memory deficits linked to circuit-specific disruptions in the hippocampus. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(21):8873-8878\n'},{id:"B118",body:'\nWilson IA et al. Neurocognitive aging: Prior memories hinder new hippocampal encoding. Trends in Neurosciences. 2006;29(12):662-670\n'},{id:"B119",body:'\nBlomberg M et al. Cerebrospinal fluid tau levels increase with age in healthy individuals. Dementia and Geriatric Cognitive Disorders. 2001;12(2):127-132\n'},{id:"B120",body:'\nXu W et al. Age-related hearing loss accelerates cerebrospinal fluid tau levels and brain atrophy: A longitudinal study. Aging (Albany NY). 2019;11:3156-3169\n'},{id:"B121",body:'\nWecker NS et al. Mental flexibility: Age effects on switching. Neuropsychology. 2005;19(3):345-352\n'},{id:"B122",body:'\nDarowski ES et al. Age-related differences in cognition: The role of distraction control. Neuropsychology. 2008;22(5):638-644\n'},{id:"B123",body:'\nVillanueva-Castillo C et al. Aging-related impairments of hippocampal mossy fibers synapses on CA3 pyramidal cells. Neurobiology of Aging. 2017;49:119-137\n'},{id:"B124",body:'\nWilliams JM et al. Synaptic activity-dependent modulation of mitochondrial gene expression in the rat hippocampus. Brain Research. Molecular Brain Research. 1998;60(1):50-56\n'},{id:"B125",body:'\nStanton PK, Schanne FA. Hippocampal long-term potentiation increases mitochondrial calcium pump activity in rat. Brain Research. 1986;382(1):185-188\n'},{id:"B126",body:'\nFernandez A et al. Mitochondrial dysfunction leads to cortical under-connectivity and cognitive impairment. Neuron. 2019;102:1127-1142\n'},{id:"B127",body:'\nMadreiter-Sokolowski CT et al. Targeting mitochondria to counteract age-related cellular dysfunction. Genes (Basel). 2018;9(3):165\n'},{id:"B128",body:'\nJoseph AM, Adhihetty PJ, Leeuwenburgh C. Beneficial effects of exercise on age-related mitochondrial dysfunction and oxidative stress in skeletal muscle. The Journal of Physiology. 2016;594(18):5105-5123\n'},{id:"B129",body:'\nAnderson R, Prolla T. PGC-1alpha in aging and anti-aging interventions. Biochimica et Biophysica Acta. 2009;1790(10):1059-1066\n'},{id:"B130",body:'\nKang C et al. Exercise training attenuates aging-associated mitochondrial dysfunction in rat skeletal muscle: Role of PGC-1alpha. Experimental Gerontology. 2013;48(11):1343-1350\n'},{id:"B131",body:'\nGioscia-Ryan RA et al. Voluntary aerobic exercise increases arterial resilience and mitochondrial health with aging in mice. Aging (Albany NY). 2016;8(11):2897-2914\n'},{id:"B132",body:'\nZampieri S et al. Physical exercise in aging human skeletal muscle increases mitochondrial calcium uniporter expression levels and affects mitochondria dynamics. Physiological Reports. 2016;4(24):e13005\n'},{id:"B133",body:'\nLopez-Lluch G, Navas P. Calorie restriction as an intervention in ageing. The Journal of Physiology. 2016;594(8):2043-2060\n'},{id:"B134",body:'\nBruss MD et al. Calorie restriction increases fatty acid synthesis and whole body fat oxidation rates. American Journal of Physiology. Endocrinology and Metabolism. 2010;298(1):E108-E116\n'},{id:"B135",body:'\nAmigo I et al. Caloric restriction increases brain mitochondrial calcium retention capacity and protects against excitotoxicity. Aging Cell. 2017;16(1):73-81\n'},{id:"B136",body:'\nBaur JA et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444(7117):337-342\n'},{id:"B137",body:'\nSandoval-Acuna C, Ferreira J, Speisky H. Polyphenols and mitochondria: An update on their increasingly emerging ROS-scavenging independent actions. Archives of Biochemistry and Biophysics. 2014;559:75-90\n'},{id:"B138",body:'\nSmith RA, Murphy MP. Animal and human studies with the mitochondria-targeted antioxidant MitoQ. Annals of the New York Academy of Sciences. 2010;1201:96-103\n'},{id:"B139",body:'\nEl-Hattab AW et al. Therapies for mitochondrial diseases and current clinical trials. Molecular Genetics and Metabolism. 2017;122(3):1-9\n'},{id:"B140",body:'\nSmith RA, Murphy MP. Mitochondria-targeted antioxidants as therapies. Discovery Medicine. 2011;11(57):106-114\n'},{id:"B141",body:'\nMonacelli F et al. Vitamin C, aging and Alzheimer’s disease. Nutrients. 2017;9(7):670\n'},{id:"B142",body:'\nBrack C, Bechter-Thuring E, Labuhn M. N-acetylcysteine slows down ageing and increases the life span of Drosophila melanogaster. Cellular and Molecular Life Sciences. 1997;53(11-12):960-966\n'},{id:"B143",body:'\nChampigny CM et al. Omega-3 Monoacylglyceride effects on longevity, mitochondrial metabolism and oxidative stress: Insights from drosophila melanogaster. Marine Drugs. 2018;16(11):453\n'},{id:"B144",body:'\nAfshordel S et al. Omega-3 polyunsaturated fatty acids improve mitochondrial dysfunction in brain aging--impact of Bcl-2 and NPD-1 like metabolites. Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2015;92:23-31\n'},{id:"B145",body:'\nBarzilai N et al. Metformin as a tool to target aging. Cell Metabolism. 2016;23(6):1060-1065\n'},{id:"B146",body:'\nKarnewar S et al. Metformin regulates mitochondrial biogenesis and senescence through AMPK mediated H3K79 methylation: Relevance in age-associated vascular dysfunction. Biochimica et Biophysica Acta—Molecular Basis of Disease. 2018;1864(4 Pt A):1115-1128\n'},{id:"B147",body:'\nLy CV, Verstreken P. Mitochondria at the synapse. The Neuroscientist. 2006;12(4):291-299\n'},{id:"B148",body:'\nBorras C et al. Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radical Biology & Medicine. 2003;34(5):546-552\n'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Claudia Jara",address:null,affiliation:'
Laboratory of Neurobiology of Aging, Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Chile
'},{corresp:null,contributorFullName:"Angie K. Torres",address:null,affiliation:'
Laboratory of Neurobiology of Aging, Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Chile
'},{corresp:null,contributorFullName:"Margrethe A. Olesen",address:null,affiliation:'
Laboratory of Neurobiology of Aging, Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Chile
Laboratory of Neurobiology of Aging, Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Chile
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OASPA
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STM
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COPE
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Creative Commons
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Crossref
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iThenticate
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DHL
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OASPA
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The Open Access Scholarly Publishers Association (OASPA) was established in 2008 to represent the interests of Open Access (OA) publishers globally in all scientific, technical and scholarly disciplines. Its mission is carried out through exchange of information, the setting of standards, advancing models, advocacy, education, and the promotion of innovation.
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STM
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The International Association of Scientific, Technical and Medical Publishers (STM) is the leading global trade association for academic and professional publishers. As a member, IntechOpen has not only made a commitment to STM's Ethical Principles.
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COPE
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Creative Commons
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Crossref
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Crossref is the official Digital Object Identifier (DOI) Registration Agency for scholarly and professional publications with a goal of making scholarly communications more effective. IntechOpen deposits metadata and registers DOIs for all content using the Crossref System. IntechOpen also deposits its references and uses the Crossref Cited-by service that enables researchers to track citation statistics.
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Altmetric and Dimensions from Digital Science
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Digital Science is a technology company serving the needs of scientific and research communities at key points along the full cycle of research. They support innovative businesses and technologies that make all parts of the research process more open, efficient and effective. IntechOpen integrates tools such as Altmetric to enable our researchers to track and measure the activity around their academic research and Dimensions, to ease access to the most relevant information and better understand and analyze the global research landscape.
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CLOCKSS
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CLOCKSS preserves scholarly publications in original formats, ensuring that they always remain available and openly accessible to everyone.
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Counter
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COUNTER provides the Code of Practice that enables publishers and vendors to report usage of their electronic resources in a consistent way. This enables libraries to compare data received from different publishers and vendors.
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DORA
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iThenticate
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Enago
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SPi Global
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Amazon
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Amazon is the world’s largest online retailer and cloud services provider. IntechOpen books have been available on Amazon since 2017, guaranteeing more visibility for our Authors and Academic Editors.
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DHL
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