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[PMID]:28792659
[Au] Autor:Porkholm M; Raunio A; Vainionpää R; Salonen T; Hernesniemi J; Valanne L; Satopää J; Karppinen A; Oinas M; Tynninen O; Pentikäinen V; Kivivuori SM
[Ad] Endereço:Department of Children and Adolescents, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
[Ti] Título:Molecular alterations in pediatric brainstem gliomas.
[So] Source:Pediatr Blood Cancer;65(1), 2018 Jan.
[Is] ISSN:1545-5017
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis. Previously, diagnosis was based on a typical clinical presentation and magnetic resonance imaging findings. After the start of the era of biopsies, DIPGs bearing H3 K27 mutations have been reclassified into a novel entity, diffuse midline glioma, based on the presence of this molecular alteration. However, it is not well established how clinically diagnosed DIPG overlap with H3 K27-mutated diffuse midline gliomas, and whether rare long-term survivors also belong to this group. METHODS: We studied tumor samples obtained at diagnosis or upon autopsy from 23 children, including two long-term survivors. Based on clinical, radiological, and histological findings, all tumors were previously diagnosed as DIPGs. All samples were analyzed for genetic alterations by next-generation sequencing (NGS) and for protein expression by immunohistochemistry (IHC). RESULTS: H3 K27 was mutated in NGS or IHC in 20 patients, excluding both long-term survivors. One of these long-term survivors harbored a mutation in IDH1, formerly considered to be an alteration absent in pediatric diffuse brainstem gliomas. Other altered genes in NGS included TP53 (10 patients), MET and PDGFRA (3 patients each), VEGFR and SMARCA4 (2 patients each), and PPARγ, PTEN and EGFR in 1 patient, respectively. IHC revealed cMYC expression in 15 of 24 (63%) of all samples, exclusively in the biopsies. CONCLUSIONS: Eighty-seven percent of the tumors formerly diagnosed as DIPGs could be reclassified as H3 K27-mutated diffuse midline gliomas. Both long-term survivors lacked this alteration. Contrary to former conceptions, IDH1 mutations may occur also in pediatric brainstem gliomas.
[Mh] Termos MeSH primário: Regulação Neoplásica da Expressão Gênica
Glioma
Sequenciamento de Nucleotídeos em Larga Escala
Proteínas de Neoplasias
Proteínas do Tecido Nervoso
[Mh] Termos MeSH secundário: Adolescente
Biópsia
Neoplasias do Tronco Encefálico/genética
Neoplasias do Tronco Encefálico/metabolismo
Neoplasias do Tronco Encefálico/patologia
Criança
Pré-Escolar
Feminino
Glioma/genética
Glioma/metabolismo
Glioma/patologia
Seres Humanos
Masculino
Proteínas de Neoplasias/biossíntese
Proteínas de Neoplasias/genética
Proteínas do Tecido Nervoso/biossíntese
Proteínas do Tecido Nervoso/genética
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neoplasm Proteins); 0 (Nerve Tissue Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171129
[Lr] Data última revisão:
171129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE
[do] DOI:10.1002/pbc.26751


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Stavale, Joäo N
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[PMID]:28966033
[Au] Autor:Mackay A; Burford A; Carvalho D; Izquierdo E; Fazal-Salom J; Taylor KR; Bjerke L; Clarke M; Vinci M; Nandhabalan M; Temelso S; Popov S; Molinari V; Raman P; Waanders AJ; Han HJ; Gupta S; Marshall L; Zacharoulis S; Vaidya S; Mandeville HC; Bridges LR; Martin AJ; Al-Sarraj S; Chandler C; Ng HK; Li X; Mu K; Trabelsi S; Brahim DH; Kisljakov AN; Konovalov DM; Moore AS; Carcaboso AM; Sunol M; de Torres C; Cruz O; Mora J; Shats LI; Stavale JN; Bidinotto LT; Reis RM; Entz-Werle N; Farrell M; Cryan J; Crimmins D; Caird J; Pears J; Monje M; Debily MA
[Ad] Endereço:Division of Molecular Pathology, The Institute of Cancer Research, London, UK; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.
[Ti] Título:Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.
[So] Source:Cancer Cell;32(4):520-537.e5, 2017 Oct 09.
[Is] ISSN:1878-3686
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.
[Mh] Termos MeSH primário: Neoplasias do Tronco Encefálico/genética
Glioma/genética
Histonas/genética
Mutação
[Mh] Termos MeSH secundário: Adolescente
Neoplasias do Tronco Encefálico/patologia
Proteínas de Ciclo Celular/genética
Criança
Pré-Escolar
DNA Topoisomerases Tipo I/genética
Exoma
Proteínas F-Box/genética
Proteína 7 com Repetições F-Box-WD
Feminino
Dosagem de Genes
Glioma/patologia
Seres Humanos
Lactente
Recém-Nascido
Masculino
Proteínas Proto-Oncogênicas/genética
Proteínas Repressoras/genética
Ubiquitina-Proteína Ligases/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (BCOR protein, human); 0 (Cell Cycle Proteins); 0 (F-Box Proteins); 0 (F-Box-WD Repeat-Containing Protein 7); 0 (FBXW7 protein, human); 0 (Histones); 0 (Proto-Oncogene Proteins); 0 (Repressor Proteins); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 5.99.1.2 (DNA Topoisomerases, Type I); EC 5.99.1.2 (DNA topoisomerase III)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171003
[St] Status:MEDLINE


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[PMID]:28947132
[Au] Autor:Meel MH; Sewing ACP; Waranecki P; Metselaar DS; Wedekind LE; Koster J; van Vuurden DG; Kaspers GJL; Hulleman E
[Ad] Endereço:Departments of Pediatric Oncology / Hematology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. Electronic address: m.meel@vumc.nl.
[Ti] Título:Culture methods of diffuse intrinsic pontine glioma cells determine response to targeted therapies.
[So] Source:Exp Cell Res;360(2):397-403, 2017 Nov 15.
[Is] ISSN:1090-2422
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Diffuse intrinsic pontine glioma (DIPG) is an aggressive type of brainstem cancer occurring mainly in children, for which there currently is no effective therapy. Current efforts to develop novel therapeutics for this tumor make use of primary cultures of DIPG cells, maintained either as adherent monolayer in serum containing medium, or as neurospheres in serum-free medium. In this manuscript, we demonstrate that the response of DIPG cells to targeted therapies in vitro is mainly determined by the culture conditions. We show that particular culture conditions induce the activation of different receptor tyrosine kinases and signal transduction pathways, as well as major changes in gene expression profiles of DIPG cells in culture. These differences correlate strongly with the observed discrepancies in response to targeted therapies of DIPG cells cultured as either adherent monolayers or neurospheres. With this research, we provide an argument for the concurrent use of both culture conditions to avoid false positive and false negative results due to the chosen method.
[Mh] Termos MeSH primário: Neoplasias do Tronco Encefálico/patologia
Ensaios de Seleção de Medicamentos Antitumorais/métodos
Ensaios de Seleção de Medicamentos Antitumorais/normas
Glioma/patologia
Terapia de Alvo Molecular
Cultura Primária de Células/métodos
[Mh] Termos MeSH secundário: Adolescente
Neoplasias do Tronco Encefálico/tratamento farmacológico
Linhagem Celular Tumoral
Glioma/tratamento farmacológico
Seres Humanos
Masculino
Receptores Proteína Tirosina Quinases/farmacologia
Receptores Proteína Tirosina Quinases/uso terapêutico
Esferoides Celulares/efeitos dos fármacos
Esferoides Celulares/patologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170927
[St] Status:MEDLINE


  4 / 1259 MEDLINE  
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[PMID]:28871999
[Au] Autor:Calmon R; Puget S; Varlet P; Beccaria K; Blauwblomme T; Grevent D; Sainte-Rose C; Castel D; Dufour C; Dhermain F; Bolle S; Saitovitch A; Zilbovicius M; Brunelle F; Grill J; Boddaert N
[Ad] Endereço:Pediatric Radiology Department, Hôpital Necker Enfants Malades, Paris, France; Institut National de la Santé et de la Recherche Médicale, Unité 1000, Paris, France; Imagine-Institut des Maladies Génétiques, UMR 1163, Paris, France; Université Paris Descartes, ComUE Sorbonne Paris Cité, Paris, France
[Ti] Título:Multimodal Magnetic Resonance Imaging of Treatment-Induced Changes to Diffuse Infiltrating Pontine Gliomas in Children and Correlation to Patient Progression-Free Survival.
[So] Source:Int J Radiat Oncol Biol Phys;99(2):476-485, 2017 Oct 01.
[Is] ISSN:1879-355X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To use multimodal magnetic resonance imaging (MRI) to quantify treatment-induced changes in the whole volume of diffuse infiltrating pontine gliomas and correlate them with progression-free survival (PFS). METHODS AND MATERIALS: This prospective study included 22 children aged 3.3 to 14.7 years (median, 5.9 years). Multimodal MRI was performed at 3 distinct time points: before treatment, the first week following radiation therapy (RT), and 2 months after RT. The imaging protocol included morphologic, multi b-value diffusion; arterial spin labeling; and dynamic susceptibility contrast-enhanced perfusion. Morphologic and multimodal data-lesion volume, diffusion coefficients, relative cerebral blood flow, and relative cerebral blood volume (rCBV)-were recorded at the 3 aforementioned time points. The Wilcoxon test was used to compare each individual parameter variation between time points, and its correlation with PFS was assessed by the Spearman test. RESULTS: Following RT, the tumors' solid component volume decreased by 40% (P<.001). Their median diffusion coefficients decreased by 20% to 40% (P<.001), while median relative cerebral blood flow increased by 60% to 80% (P<.001) and median rCBV increased by 70% (P<.001). PFS was positively correlated with rCBV measured immediately after RT (P=.003), and in patients whose rCBV was above the cutoff value of 2.46, the median PFS was 4.6 months longer (P=.001). These indexes tended to return to baseline 2 months after RT. Lesion volume before or after RT was not correlated with survival. CONCLUSIONS: Multimodal MRI provides useful information about diffuse infiltrating pontine gliomas' response to treatment; rCBV increases following RT, and higher values are correlated with better PFS. High rCBV values following RT should not be mistaken for progression and could be an indicator of response to therapy.
[Mh] Termos MeSH primário: Neoplasias do Tronco Encefálico/diagnóstico por imagem
Neoplasias do Tronco Encefálico/radioterapia
Encéfalo/irrigação sanguínea
Glioma/diagnóstico por imagem
Glioma/radioterapia
[Mh] Termos MeSH secundário: Adolescente
Antineoplásicos/uso terapêutico
Encéfalo/efeitos da radiação
Neoplasias do Tronco Encefálico/irrigação sanguínea
Neoplasias do Tronco Encefálico/patologia
Quimioterapia Adjuvante
Criança
Pré-Escolar
Meios de Contraste
Progressão da Doença
Intervalo Livre de Doença
Cloridrato de Erlotinib/administração & dosagem
Feminino
Glioma/irrigação sanguínea
Glioma/patologia
Seres Humanos
Imagem por Ressonância Magnética/métodos
Masculino
Estudos Prospectivos
Sirolimo/administração & dosagem
Estatísticas não Paramétricas
Análise de Sobrevida
Fatores de Tempo
Carga Tumoral/efeitos da radiação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Contrast Media); DA87705X9K (Erlotinib Hydrochloride); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170906
[St] Status:MEDLINE


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[PMID]:28753090
[Au] Autor:Weaver KJ; Crawford LM; Bennett JA; Rivera-Zengotita ML; Pincus DW
[Ad] Endereço:Departments of 1 Neurosurgery.
[Ti] Título:Brainstem angiocentric glioma: report of 2 cases.
[So] Source:J Neurosurg Pediatr;20(4):347-351, 2017 Oct.
[Is] ISSN:1933-0715
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Angiocentric glioma is a rare tumor that was recognized by the WHO Classification of Tumours of the Central Nervous System as a distinct clinicopathological entity in 2007. Since this initial description, the vast majority of cases of angiocentric glioma reported in the literature have involved tumors of the cerebral hemispheres. To date, only 1 case of angiocentric glioma arising from the posterior midbrain has been reported. The authors present the cases of 2 pediatric patients who were found to have brainstem angiocentric gliomas. The clinical course, radiological and pathological features, treatment, and follow-up are described. The first case is one of a 5-year-old girl who presented with double vision, headache, and nausea and was found to have a midbrain lesion with pathological features consistent with angiocentric glioma. She was treated with resection and endoscopic third ventriculostomy (ETV), followed by close observation and serial neuroimaging. The second case is one of a 6-year-old boy who presented with progressive mouth drooping and problems with balance. He was found to have a pontine lesion with pathological features consistent with angiocentric glioma. This patient was treated with ETV, followed by close observation and serial neuroimaging. This report includes 6 and 1.5 years of follow-up of the patients, respectively. While there are limited data regarding the prognosis or long-term management of patients with brainstem angiocentric gliomas, the cases described in this report suggest an indolent course for this tumor, similar to the course of angiocentric gliomas located in the cerebral hemispheres.
[Mh] Termos MeSH primário: Neoplasias do Tronco Encefálico/cirurgia
Glioma/cirurgia
Ventriculostomia/métodos
[Mh] Termos MeSH secundário: Antígenos CD19/metabolismo
Tronco Encefálico/metabolismo
Tronco Encefálico/patologia
Neoplasias do Tronco Encefálico/diagnóstico por imagem
Criança
Pré-Escolar
Feminino
Proteína Glial Fibrilar Ácida/metabolismo
Glioma/complicações
Glioma/diagnóstico por imagem
Seres Humanos
Imagem por Ressonância Magnética
Masculino
Mucina-1/metabolismo
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD19); 0 (Glial Fibrillary Acidic Protein); 0 (Mucin-1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170729
[St] Status:MEDLINE
[do] DOI:10.3171/2017.5.PEDS16402


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[PMID]:28727518
[Au] Autor:Lassaletta A; Zapotocky M; Mistry M; Ramaswamy V; Honnorat M; Krishnatry R; Guerreiro Stucklin A; Zhukova N; Arnoldo A; Ryall S; Ling C; McKeown T; Loukides J; Cruz O; de Torres C; Ho CY; Packer RJ; Tatevossian R; Qaddoumi I; Harreld JH; Dalton JD; Mulcahy-Levy J; Foreman N; Karajannis MA; Wang S; Snuderl M; Nageswara Rao A; Giannini C; Kieran M; Ligon KL; Garre ML; Nozza P; Mascelli S; Raso A; Mueller S; Nicolaides T; Silva K; Perbet R; Vasiljevic A; Faure Conter C; Frappaz D; Leary S; Crane C; Chan A; Ng HK; Shi ZF; Mao Y; Finch E; Eisenstat D; Wilson B
[Ad] Endereço:Alvaro Lassaletta, Michal Zapotocky, Matthew Mistry, Vijay Ramaswamy, Marion Honnorat, Rahul Krishnatry, Ana Guerreiro Stucklin, Nataliya Zhukova, Anthony Arnoldo, Scott Ryall, Catriona Ling, Tara McKeown, Jim Loukides, James T. Rutka, Peter Dirks, Michael D. Taylor, Shiyi Chen, Ute Bartels, Annie H
[Ti] Título:Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas.
[So] Source:J Clin Oncol;35(25):2934-2941, 2017 Sep 01.
[Is] ISSN:1527-7755
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180). Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively ( P < .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG. Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/enzimologia
Glioma/enzimologia
Proteínas Proto-Oncogênicas B-raf/genética
[Mh] Termos MeSH secundário: Adolescente
Neoplasias Encefálicas/genética
Neoplasias Encefálicas/patologia
Neoplasias Encefálicas/terapia
Neoplasias do Tronco Encefálico/enzimologia
Neoplasias do Tronco Encefálico/genética
Neoplasias do Tronco Encefálico/patologia
Neoplasias do Tronco Encefálico/terapia
Criança
Pré-Escolar
Estudos de Coortes
Diencéfalo/enzimologia
Diencéfalo/patologia
Feminino
Glioma/genética
Glioma/patologia
Glioma/terapia
Seres Humanos
Lactente
Masculino
Mutação
Gradação de Tumores
Prognóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.11.1 (BRAF protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1200/JCO.2016.71.8726


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[PMID]:28686124
[Au] Autor:Ivasyk I; Morgenstern PF; Wembacher-Schroeder E; Souweidane MM
[Ad] Endereço:Department of Neurological Surgery, NewYork-Presbyterian Hospital, Weill Cornell Medicine.
[Ti] Título:Influence of an intratumoral cyst on drug distribution by convection-enhanced delivery: case report.
[So] Source:J Neurosurg Pediatr;20(3):256-260, 2017 Sep.
[Is] ISSN:1933-0715
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Convection-enhanced delivery (CED) uses positive pressure to induce convective flow of molecules and maximize drug distribution. Concerns have been raised about the effect of cystic structures on uniform drug distribution with CED. The authors describe the case of a patient with a diffuse intrinsic pontine glioma (DIPG) with a large cyst and examine its effect on drug distribution after CED with a radiolabeled antibody. The patient was treated according to protocol with CED of I-8H9 to the pons for nonprogressive DIPG after radiation therapy as part of a Phase I trial (clinical trial registration no. NCT01502917, clinicaltrials.gov). Care was taken to avoid the cystic cavity in the planned catheter track and target point. Co-infusion with Gd-DTPA was performed to assess drug distribution. Infusate distribution was examined by MRI immediately following infusion and analyzed using iPlan Flow software. Analysis of postinfusion MR images demonstrated convective distribution around the catheter tip and an elongated configuration of drug distribution, consistent with the superoinferior corticospinal fiber orientation in the brainstem. This indicates that the catheter was functioning and a pressure gradient was established. No infusate entry into the cystic region could be identified on T2-weighted FLAIR or T1-weighted images. The effects of ependymal and pial surfaces on drug delivery using CED in brainstem tumors remain controversial. Drug distribution is a critical component of effective application of CED to neurosurgical lesions. This case suggests that cyst cavities may not always behave as fluid "sinks" for drug distribution. The authors observed that infusate was not lost into the cyst cavity, suggesting that lesions with cystic components can be treated by CED without significant alterations to target and infusion planning.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/administração & dosagem
Antineoplásicos/administração & dosagem
Neoplasias do Tronco Encefálico/tratamento farmacológico
Cistos/metabolismo
Glioma/tratamento farmacológico
Ponte/efeitos dos fármacos
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/farmacocinética
Antineoplásicos/farmacocinética
Neoplasias do Tronco Encefálico/diagnóstico por imagem
Neoplasias do Tronco Encefálico/metabolismo
Neoplasias do Tronco Encefálico/radioterapia
Criança
Cistos/diagnóstico por imagem
Sistemas de Liberação de Medicamentos
Feminino
Glioma/diagnóstico por imagem
Glioma/metabolismo
Glioma/radioterapia
Seres Humanos
Ponte/diagnóstico por imagem
Ponte/metabolismo
[Pt] Tipo de publicação:CASE REPORTS; CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (8H9 monoclonal antibody); 0 (Antibodies, Monoclonal); 0 (Antineoplastic Agents)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE
[do] DOI:10.3171/2017.5.PEDS1774


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[PMID]:28621573
[Au] Autor:Hamisch C; Kickingereder P; Fischer M; Simon T; Ruge MI
[Ad] Endereço:Departments of 1 General Neurosurgery.
[Ti] Título:Update on the diagnostic value and safety of stereotactic biopsy for pediatric brainstem tumors: a systematic review and meta-analysis of 735 cases.
[So] Source:J Neurosurg Pediatr;20(3):261-268, 2017 Sep.
[Is] ISSN:1933-0715
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE Recent studies have shed light on the molecular makeup of diffuse intrinsic pontine gliomas and led to the identification of potential treatment targets for these lesions, which account for the majority of pediatric brainstem tumors (pedBSTs). Therefore, stereotactic biopsy-driven molecular characterization of pedBSTs may become an important prerequisite for the management of these fatal brain tumors. The authors conducted a systemic review and meta-analysis to precisely determine the safety and diagnostic success of stereotactic biopsy of pedBSTs. METHODS A systematic search of PubMed, EMBASE, and the Web of Science yielded 944 potentially eligible abstracts. Meta-analysis was conducted on 18 studies (including the authors' own institutional series), describing a total of 735 biopsy procedures for pedBSTs. The primary outcome measures were diagnostic success and procedure-related complications. Pooled estimates were calculated based on the Freeman-Tukey double-arcsine transformation and DerSimonian-Laird random-effects model. Heterogeneity, sensitivity, and meta-regression analyses were also conducted. RESULTS The weighted average proportions across the analyzed studies were 96.1% (95% CI 93.5%-98.1%) for diagnostic success, 6.7% (95% CI 4.2%-9.6%) for overall morbidity, 0.6% (95% CI 0.2%-1.4%) for permanent morbidity, and 0.6% (95% CI 0.2%-1.3%) for mortality. Subgroup analyses at the study level identified no significant correlation between the outcome measures and the distribution of the chosen biopsy trajectories (transfrontal vs transcerebellar), age, year of publication, or the number of biopsy procedures annually performed in each center. CONCLUSION Stereotactic biopsy of pedBSTs is safe and allows successful tissue sampling as a prerequisite for the molecular characterization and the identification of potentially druggable targets toward more individualized treatment concepts to improve the outcome for children harboring such lesions.
[Mh] Termos MeSH primário: Biópsia
Neoplasias do Tronco Encefálico/diagnóstico
Neoplasias do Tronco Encefálico/patologia
Técnicas Estereotáxicas
[Mh] Termos MeSH secundário: Biópsia/efeitos adversos
Biópsia/métodos
Criança
Seres Humanos
Técnicas Estereotáxicas/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170617
[St] Status:MEDLINE
[do] DOI:10.3171/2017.2.PEDS1665


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[PMID]:28544128
[Au] Autor:Macy ME; Kieran MW; Chi SN; Cohen KJ; MacDonald TJ; Smith AA; Etzl MM; Kuei MC; Donson AM; Gore L; DiRenzo J; Trippett TM; Ostrovnaya I; Narendran A; Foreman NK; Dunkel IJ
[Ad] Endereço:Department of Pediatrics, University of Colorado School of Medicine/Children's Hospital Colorado, Aurora, Colorado.
[Ti] Título:A pediatric trial of radiation/cetuximab followed by irinotecan/cetuximab in newly diagnosed diffuse pontine gliomas and high-grade astrocytomas: A Pediatric Oncology Experimental Therapeutics Investigators' Consortium study.
[So] Source:Pediatr Blood Cancer;64(11), 2017 Nov.
[Is] ISSN:1545-5017
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) and high-grade astrocytomas (HGA) continue to have dismal prognoses. The combination of cetuximab and irinotecan was demonstrated to be safe and tolerable in a previous pediatric phase 1 combination study. We developed this phase 2 trial to investigate the safety and efficacy of cetuximab given with radiation therapy followed by adjuvant cetuximab and irinotecan. METHODS: Eligible patients of age 3-21 years had newly diagnosed DIPG or HGA. Patients received radiation therapy (5,940 cGy) with concurrent cetuximab. Following radiation, patients received cetuximab weekly and irinotecan daily for 5 days per week for 2 weeks every 21 days for 30 weeks. Correlative studies were performed. The regimen was considered to be promising if the number of patients with 1-year progression-free survival (PFS) for DIPG and HGA was at least six of 25 and 14 of 26, respectively. RESULTS: Forty-five evaluable patients were enrolled (25 DIPG and 20 HGA). Six patients with DIPG and five with HGA were progression free at 1 year from the start of therapy with 1-year PFS of 29.6% and 18%, respectively. Fatigue, gastrointestinal complaints, electrolyte abnormalities, and rash were the most common adverse events and generally of grade 1 and 2. Increased epidermal growth factor receptor copy number but no K-ras mutations were identified in available samples. CONCLUSIONS: The trial did not meet the predetermined endpoint to deem this regimen successful for HGA. While the trial met the predetermined endpoint for DIPG, overall survival was not markedly improved from historical controls, therefore does not merit further study in this population.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Astrocitoma/terapia
Neoplasias do Tronco Encefálico/terapia
Quimiorradioterapia/mortalidade
Glioma/terapia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Astrocitoma/patologia
Neoplasias do Tronco Encefálico/patologia
Camptotecina/administração & dosagem
Camptotecina/análogos & derivados
Cetuximab/administração & dosagem
Criança
Pré-Escolar
Terapia Combinada
Feminino
Seguimentos
Glioma/patologia
Seres Humanos
Masculino
Estadiamento de Neoplasias
Prognóstico
Taxa de Sobrevida
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
7673326042 (irinotecan); PQX0D8J21J (Cetuximab); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1002/pbc.26621


  10 / 1259 MEDLINE  
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[PMID]:28542253
[Au] Autor:Killick-Cole CL; Singleton WGB; Bienemann AS; Asby DJ; Wyatt MJ; Boulter LJ; Barua NU; Gill SS
[Ad] Endereço:Functional Neurosurgery Research Group, School of Clinical Sciences, University of Bristol, Learning & Research Building, Southmead Hospital, Bristol, United Kingdom.
[Ti] Título:Repurposing the anti-epileptic drug sodium valproate as an adjuvant treatment for diffuse intrinsic pontine glioma.
[So] Source:PLoS One;12(5):e0176855, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Targeting epigenetic changes in diffuse intrinsic pontine glioma (DIPG) may provide a novel treatment option for patients. This report demonstrates that sodium valproate, a histone deacetylase inhibitor (HDACi), can increase the cytotoxicity of carboplatin in an additive and synergistic manner in DIPG cells in vitro. Sodium valproate causes a dose-dependent decrease in DIPG cell viability in three independent ex vivo cell lines. Furthermore, sodium valproate caused an increase in acetylation of histone H3. Changes in cell viability were consistent with an induction of apoptosis in DIPG cells in vitro, determined by flow cytometric analysis of Annexin V staining and assessment of apoptotic markers by western blotting. Subsequently, immunofluorescent staining of neuronal and glial markers was used to determine toxicity in normal rat hippocampal cells. Pre-treatment of cells with sodium valproate enhanced the cytotoxic effects of carboplatin, in three DIPG cell lines tested. These results demonstrate that sodium valproate causes increased histone H3 acetylation indicative of HDAC inhibition, which is inversely correlated with a reduction in cell viability. Cell viability is reduced through an induction of apoptosis in DIPG cells. Sodium valproate potentiates carboplatin cytotoxicity and prompts further work to define the mechanism responsible for the synergy between these two drugs and determine in vivo efficacy. These findings support the use of sodium valproate as an adjuvant treatment for DIPG.
[Mh] Termos MeSH primário: Adjuvantes Farmacêuticos/farmacologia
Anticonvulsivantes/farmacologia
Neoplasias do Tronco Encefálico/tratamento farmacológico
Glioma/tratamento farmacológico
Ácido Valproico/farmacologia
[Mh] Termos MeSH secundário: Acetilação/efeitos dos fármacos
Animais
Apoptose/efeitos dos fármacos
Neoplasias do Tronco Encefálico/metabolismo
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Células Cultivadas
Reposicionamento de Medicamentos/métodos
Epigênese Genética/efeitos dos fármacos
Glioma/metabolismo
Hipocampo/efeitos dos fármacos
Hipocampo/metabolismo
Inibidores de Histona Desacetilases/farmacologia
Seres Humanos
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Pharmaceutic); 0 (Anticonvulsants); 0 (Histone Deacetylase Inhibitors); 614OI1Z5WI (Valproic Acid)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0176855



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