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[PMID]:29332262
[Au] Autor:Karpinsky G; Krawczyk MA; Izycka-Swieszewska E; Fatyga A; Budka A; Balwierz W; Sobol G; Zalewska-Szewczyk B; Rychlowska-Pruszynska M; Klepacka T; Dembowska-Baginska B; Kazanowska B; Gabrych A; Bien E
[Ad] Endereço:Children's Hospital of Michigan, 3901 Beaubien St, Detroit, MI, USA.
[Ti] Título:Tumor expression of survivin, p53, cyclin D1, osteopontin and fibronectin in predicting the response to neo-adjuvant chemotherapy in children with advanced malignant peripheral nerve sheath tumor.
[So] Source:J Cancer Res Clin Oncol;144(3):519-529, 2018 Mar.
[Is] ISSN:1432-1335
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Selected cell-cycle regulators and extracellular matrix proteins were found to play roles in malignant peripheral nerve sheath tumor (MPNST) biology. We aimed to analyze whether initial tumor tissue expressions of survivin, p53, cyclin D1, osteopontin (OPN) and fibronectin (FN) correlate with the response to neo-adjuvant CHT (naCHT) in children with advanced inoperable MPNST. METHODS: The study included 26 children with MPNST (M/F 14/12, median age 130 months) treated in Polish centers of pediatric oncology between 1992 and 2013. Tissue expression of markers was studied immunohistochemically in the manually performed tissue microarrays and assessed semi-quantitatively as low and high, based on the rate of positive cells and staining intensity. RESULTS: Good response to naCHT was noted in 47.6%, while poor-in 52.4% of patients. The response to naCHT was influenced negatively by the presence of neurofibromatosis NF1 and high initial tumor tissue expression of OPN, survivin, p53 and cyclin D1. Patients with high tumor expression of either OPN, survivin or p53 and those with simultaneous high expression of ≥ 3 of the markers, responded significantly worse to naCHT, than patients, in whom expression of ≤ 2 markers were detected at diagnosis. Nearly, 85% of patients expressing ≥ 3 markers, responded poor to CHT; while 87.5% of children, expressing ≤ 2 markers, were good responders. CONCLUSION: The initial tumor tissue expression of OPN, survivin, p53 and cyclin D1 may serve as markers to predict response to naCHT in pediatric advanced MPNST. Future studies in more numerous group of patients are needed to confirm these preliminary results.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Biomarcadores Tumorais/metabolismo
Ciclina D1/metabolismo
Citocinas/metabolismo
Proteínas Inibidoras de Apoptose/metabolismo
Neoplasias da Bainha Neural/diagnóstico
Neoplasias da Bainha Neural/tratamento farmacológico
Osteopontina/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Biomarcadores Farmacológicos/metabolismo
Criança
Pré-Escolar
Progressão da Doença
Feminino
Seres Humanos
Lactente
Masculino
Terapia Neoadjuvante
Neoplasias da Bainha Neural/metabolismo
Neoplasias da Bainha Neural/patologia
Neurilemoma/tratamento farmacológico
Neurilemoma/metabolismo
Neurilemoma/patologia
Prognóstico
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BIRC5 protein, human); 0 (Biomarkers, Pharmacological); 0 (Biomarkers, Tumor); 0 (CCND1 protein, human); 0 (Cytokines); 0 (Inhibitor of Apoptosis Proteins); 0 (SPP1 protein, human); 0 (migration stimulating factor, human); 106441-73-0 (Osteopontin); 136601-57-5 (Cyclin D1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180115
[St] Status:MEDLINE
[do] DOI:10.1007/s00432-018-2580-1


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[PMID]:29304038
[Au] Autor:Madhankumar AB; Mrowczynski OD; Slagle-Webb B; Ravi V; Bourcier AJ; Payne R; Harbaugh KS; Rizk E; Connor JR
[Ad] Endereço:Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, PA, United States of America.
[Ti] Título:Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors.
[So] Source:PLoS One;13(1):e0181529, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peripheral nerve sheath tumors are benign tumors that have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs). Interleukin-13 receptor alpha 2 (IL13Rα2) is a cancer associated receptor expressed in glioblastoma and other invasive cancers. We analyzed IL13Rα2 expression in several MPNST cell lines including the STS26T cell line, as well as in several peripheral nerve sheath tumors to utilize the IL13Rα2 receptor as a target for therapy. In our studies, we demonstrated the selective expression of IL13Rα2 in several peripheral nerve sheath tumors by immunohistochemistry (IHC) and immunoblots. We established a sciatic nerve MPNST mouse model in NIH III nude mice using a luciferase transfected STS26T MPNST cell line. Similarly, analysis of the mouse sciatic nerves after tumor induction revealed significant expression of IL13Rα2 by IHC when compared to a normal sciatic nerve. IL13 conjugated liposomal doxorubicin was formulated and shown to bind and internalized in the MPNST cell culture model demonstrating cytotoxic effect. Our subsequent in vivo investigation in the STS26T MPNST sciatic nerve tumor model indicated that IL13 conjugated liposomal doxorubicin (IL13LIPDXR) was more effective in inhibiting tumor progression compared to unconjugated liposomal doxorubicin (LIPDXR). This further supports that IL13 receptor targeted nanoliposomes is a potential approach for treating MPNSTs.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/administração & dosagem
Doxorrubicina/análogos & derivados
Neoplasias da Bainha Neural/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antibióticos Antineoplásicos/farmacocinética
Linhagem Celular Tumoral
Doxorrubicina/administração & dosagem
Doxorrubicina/farmacocinética
Sistemas de Liberação de Medicamentos
Seres Humanos
Imuno-Histoquímica
Interleucina-13/administração & dosagem
Subunidade alfa2 de Receptor de Interleucina-13/metabolismo
Antígeno Ki-67/metabolismo
Camundongos
Camundongos Nus
Neoplasias da Bainha Neural/imunologia
Neoplasias da Bainha Neural/metabolismo
Polietilenoglicóis/administração & dosagem
Polietilenoglicóis/farmacocinética
Proteínas S100/metabolismo
Neuropatia Ciática/tratamento farmacológico
Neuropatia Ciática/imunologia
Neuropatia Ciática/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Interleukin-13); 0 (Interleukin-13 Receptor alpha2 Subunit); 0 (Ki-67 Antigen); 0 (Mki67 protein, mouse); 0 (S100 Proteins); 0 (liposomal doxorubicin); 30IQX730WE (Polyethylene Glycols); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181529


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[PMID]:29245354
[Au] Autor:Li J; Zeng H; Li Z; Wang J
[Ad] Endereço:Department of Anesthesiology, Peking University Third Hospital, Beijing, P.R. China.
[Ti] Título:Anesthesia for a parturient with intraneural perineurioma: A case report.
[So] Source:Medicine (Baltimore);96(49):e9135, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Intraneural perineurioma is an extremely rare form of peripheral nerve sheath tumor; and the anesthetic management of a parturient with intraneural perineurioma, especially affecting spinal roots and nerves of extremities, is very rare. PATIENT CONCERNS: A 28-year-old woman was referred to the hospital at 37+5 weeks' gestation, presenting with a 10-year history of paroxysmal acroanesthesia and aching with distal limbs. DIAGNOSES: Based on the biopsy results, including immunohistochemical and electron microscopic findings, and molecular studies, her condition was diagnosed as intraneural perineurioma. INTERVENTIONS: The size of pelvic nervous masses gradually increased with pregnancy. A scheduled elective cesarean section under general anesthesia was concluded for the patient under preoperative multidisciplinary consultation with anesthesiologist, neonatologist, and neurologist. OUTCOMES: The patient and the neonate were discharged smoothly on the fourth postoperative day. During a 6-month follow-up period, no new neurologic complication was observed. LESSONS: To our knowledge, this is the first case report that documented the anesthetic management for a parturient with intraneural perineuroma. Careful preconception care and multidisciplinary assessment are essential to achieve optimal reproductive outcomes.
[Mh] Termos MeSH primário: Neoplasias da Bainha Neural/patologia
Neoplasias da Bainha Neural/cirurgia
[Mh] Termos MeSH secundário: Adulto
Axônios/patologia
Feminino
Seres Humanos
Gravidez
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009135


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[PMID]:29206885
[Au] Autor:Berzaczy D; Mayerhoefer ME; Azizi AA; Haug AR; Senn D; Beitzke D; Weber M; Traub-Weidinger T
[Ad] Endereço:Department of Biomedical Imaging and Image-guided Therapy, Division of General and Pediatric Radiology, Medical University of Vienna, Waehringer Guertel, Vienna, Austria, E.U.
[Ti] Título:Does elevated glucose metabolism correlate with higher cell density in Neurofibromatosis type 1 associated peripheral nerve sheath tumors?
[So] Source:PLoS One;12(12):e0189093, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To investigate whether elevated glucose metabolism in neurofibroma, determined by [F18]-FDG-PET, is correlated with cell density in MRI, as expressed through the apparent diffusion coefficient. MATERIALS AND METHODS: Patients diagnosed with neurofibromatosis type 1 and peripheral nerve sheath tumors (PNST) were enrolled in this prospective, IRB-approved study. After a single [F18]-FDG injection, patients consecutively underwent [F18]-FDG-PET/CT and [F18]-FDG-PET/MRI on the same day. Maximum and mean standardized uptake values (SUVmax, SUVmean) on [F18]-FDG-PET/CT and [F18]-FDG-PET/MRI were compared, and correlated with minimum and mean apparent diffusion coefficients (ADCmean, ADCmin). RESULTS: A total of 12 (6 male/6 female, mean age was 16.2 ± 5.2 years) patients were prospectively included and analyzed on a per-lesion (n = 39) basis. The SUVmean of examined PNST showed a moderate negative correlation with the ADCmean (r = -.441) and ADCmin (r = -.477), which proved to be statistically significant (p = .005 and p = .002). The SUVmax of the respective lesions, however, showed a weaker negative correlation for ADCmean (r: -.311) and ADCmin (r: -.300) and did not reach statistical significance (p = .054 and p = .057). Lesion-based correlation between [F18]-FDG-PET/MRI and [F18]-FDG-PET/CT showed a moderate correlation for SUVmax (r = .353; p = .027) and a strong one for SUVmean (r = .879; p = .001)). Patient-based liver uptake (SUVmax and mean) of [F18]-FDG-PET/MRI and [F18]-FDG-PET/CT were strongly positively correlated (r = .827; p < .001 and r = .721; p < .001) but differed significantly (p < .001). CONCLUSIONS: We found a statistically significant, negative correlation between glucose metabolism and cell density in PNST. Thus, ADCmean and ADCmin could possibly add complimentary information to the SUVmax and SUVmean and may serve as a potential determinant of malignant transformation of PNST.
[Mh] Termos MeSH primário: Neoplasias da Bainha Neural/patologia
Neurofibromatose 1/patologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Feminino
Seres Humanos
Imagem por Ressonância Magnética
Masculino
Neoplasias da Bainha Neural/complicações
Neoplasias da Bainha Neural/metabolismo
Neurofibromatose 1/complicações
Neurofibromatose 1/metabolismo
Tomografia por Emissão de Pósitrons
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189093


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[PMID]:29187472
[Au] Autor:Friedrich RE; Schüller U; Hagel C
[Ad] Endereço:Oral and Craniomaxillofacial Surgery, Eppendorf University Hospital, University of Hamburg, Hamburg, Germany rfriedrich@uke.de.
[Ti] Título:Pilomatrixoma of the Neck/Shoulder Region Mimicking a Rapidly Growing Neoplasm of Peripheral Nerve Sheath Origin in Neurofibromatosis Type 1.
[So] Source:Anticancer Res;37(12):6907-6910, 2017 12.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disorder. Neurofibroma is the most common neoplasm of this disease. This lesion is characterized by circumscribed soft or knotty skin tumors derived from peripheral nerve sheath cells. Numerous other neoplasms have been described for this tumor predisposition syndrome. This case report adds the diagnostic and therapeutic procedures in the case of an NF1 patient in whom the rapidly growing, nodular, subcutaneous tumor initially led to the suspicion of a malignant neoplasm. The tumor proved to be pilomatrixoma, which closely adhered to a neurofibroma.
[Mh] Termos MeSH primário: Neoplasias da Bainha Neural/diagnóstico
Neurofibromatose 1/complicações
Pilomatrixoma/diagnóstico
[Mh] Termos MeSH secundário: Diagnóstico Diferencial
Feminino
Seres Humanos
Pescoço
Neoplasias da Bainha Neural/etiologia
Pilomatrixoma/etiologia
Pilomatrixoma/cirurgia
Ombro
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171211
[Lr] Data última revisão:
171211
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE


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[PMID]:28813519
[Au] Autor:Amirnasr A; Verdijk RM; van Kuijk PF; Taal W; Sleijfer S; Wiemer EAC
[Ad] Endereço:Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
[Ti] Título:Expression and inhibition of BRD4, EZH2 and TOP2A in neurofibromas and malignant peripheral nerve sheath tumors.
[So] Source:PLoS One;12(8):e0183155, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Malignant peripheral nerve sheath tumors (MPNST) are rare, highly aggressive sarcomas that can occur spontaneously or from pre-existing plexiform neurofibromas in neurofibromatosis type1 (NF1) patients. MPNSTs have high local recurrence rates, metastasize easily, are generally resistant to therapeutic intervention and frequently fatal for the patient. Novel targeted therapeutic strategies are urgently needed. Standard treatment for patients presenting with advanced disease is doxorubicin based chemotherapy which inhibits the actions of the enzyme topoisomerase IIα (TOP2A). Recent molecular studies using murine models and cell lines identified the bromodomain containing protein 4 (BRD4) and enhancer of zeste homolog 2 (EZH2) as novel targets for MPNST treatment. We investigated the expression and potential use of BRD4, EZH2 and TOP2A as therapeutic targets in human NF1-derived MPNSTs. The transcript levels of BRD4, EZH2 and TOP2A were determined in paired formalin-fixed paraffin-embedded (FFPE) neurofibroma/MPNST samples derived from the same NF1 patient and in a set of plexiform neurofibromas, atypical neurofibromas and MPNST. We further examined the effect on cell viability of genetic or pharmacological inhibition of BRD4, EZH2 and TOP2A in an MPNST cell line panel. Our results indicated that in MPNST samples BRD4 mRNA levels were not upregulated and that MPNST cell lines were relatively insensitive to the bromodomain inhibitor JQ1. We corroborated that EZH2 mRNA expression is increased in MPNST but failed to confirm its reported pivotal role in MPNST pathogenesis as EZH2 knockdown by siRNA did not interfere with cellular proliferation and viability. Finally, the relation between TOP2A levels and sensitivity for doxorubicin was examined, confirming reports that TOP2A mRNA levels were overexpressed in MPNST and showing that MPNST cell lines exhibited relatively high TOP2A protein levels and sensitivity to doxorubicin. We tentatively conclude that the potential for effective therapeutic intervention in MPNST by targeting BRD4, EZH2 and TOP2A individually, may be limited. Clinical studies are necessary to ultimately prove the relevance of BRD4 and EZH2 inhibition as novel therapeutic strategies for MPNST.
[Mh] Termos MeSH primário: Antígenos de Neoplasias/genética
DNA Topoisomerases Tipo II/genética
Proteínas de Ligação a DNA/genética
Proteína Potenciadora do Homólogo 2 de Zeste/genética
Regulação Neoplásica da Expressão Gênica
Neoplasias da Bainha Neural/fisiopatologia
Neurofibroma/fisiopatologia
Proteínas Nucleares/metabolismo
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Antibióticos Antineoplásicos/farmacologia
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Criança
Pré-Escolar
Proteínas de Ligação a DNA/antagonistas & inibidores
Doxorrubicina/farmacologia
Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores
Feminino
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Técnicas In Vitro
Masculino
Meia-Idade
Neoplasias da Bainha Neural/genética
Neurofibroma/genética
Proteínas Nucleares/antagonistas & inibidores
Proteínas de Ligação a Poli-ADP-Ribose
Fatores de Transcrição/antagonistas & inibidores
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Antigens, Neoplasm); 0 (BRD4 protein, human); 0 (DNA-Binding Proteins); 0 (Nuclear Proteins); 0 (Poly-ADP-Ribose Binding Proteins); 0 (Transcription Factors); 80168379AG (Doxorubicin); EC 2.1.1.43 (EZH2 protein, human); EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein); EC 5.99.1.3 (DNA Topoisomerases, Type II); EC 5.99.1.3 (TOP2A protein, human)
[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:170817
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183155


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[PMID]:28672720
[Au] Autor:Kerezoudis P; Bydon M; Spinner RJ
[Ad] Endereço:Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota, USA.
[Ti] Título:Peripheral Nerve Sheath Tumors: The "Orphan Disease" of National Databases.
[So] Source:World Neurosurg;103:948-949, 2017 07.
[Is] ISSN:1878-8769
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Bases de Dados Factuais
Neoplasias da Bainha Neural/cirurgia
Neurilemoma/cirurgia
Neurofibroma/cirurgia
Procedimentos Neurocirúrgicos
Sarcoma/cirurgia
[Mh] Termos MeSH secundário: Seres Humanos
Doenças Raras
[Pt] Tipo de publicação:LETTER
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE


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[PMID]:28658406
[Au] Autor:Vasconcelos RAT; Coscarelli PG; Alvarenga RP; Acioly MA
[Ad] Endereço:Instituto Nacional do Câncer, Departamento de Oncologia Cirúrgica, Divisão de Osso e Tecido Conjuntivo, Rio de Janeiro RJ, Brasil.
[Ti] Título:Malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1.
[So] Source:Arq Neuropsiquiatr;75(6):366-371, 2017 Jun.
[Is] ISSN:1678-4227
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Objective: In this study, we review the institution's experience in treating malignant peripheral nerve sheath tumors (MPNSTs). A secondary aim was to compare outcomes between MPNSTs with and without neurofibromatosis type 1 (NF1). Methods: Ninety-two patients with MPNSTs, over a period of 20 years, were reviewed. A retrospective chart review was performed. The median age was 43.5 years (range, 3-84 years) and 55.4% were female; 41 patients (44.6%) had NF1-associated tumors. Results: Mean tumor sizes were 15.8 ± 8.2 cm and 10.8 ± 6.3 cm for patients with and without NF1, respectively. Combined two- and five-year overall survival was 48.5% and 29%. Multivariate analysis confirmed the association of tumor size greater than 10 cm (hazard ratio (HR) 2.99; 95% confidence interval (CI) 1.14-7.85; p = 0.0258) and presence of NF1 (HR 3.41; 95%CI 1.88-6.19; p < 0.001) with a decreased overall survival. Conclusion: Tumor size and NF1 status were the most important predictors of overall survival in our population.
[Mh] Termos MeSH primário: Neoplasias da Bainha Neural/mortalidade
Neoplasias da Bainha Neural/terapia
Neurofibromatose 1
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Criança
Pré-Escolar
Feminino
Seres Humanos
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Estadiamento de Neoplasias
Neoplasias da Bainha Neural/patologia
Neurofibromatose 1/mortalidade
Neurofibromatose 1/terapia
Prognóstico
Estudos Retrospectivos
Carga Tumoral
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170726
[Lr] Data última revisão:
170726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170629
[St] Status:MEDLINE


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[PMID]:28646022
[Au] Autor:Dodd RD; Lee CL; Overton T; Huang W; Eward WC; Luo L; Ma Y; Ingram DR; Torres KE; Cardona DM; Lazar AJ; Kirsch DG
[Ad] Endereço:Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina.
[Ti] Título:NF1 Hematopoietic Cells Accelerate Malignant Peripheral Nerve Sheath Tumor Development without Altering Chemotherapy Response.
[So] Source:Cancer Res;77(16):4486-4497, 2017 Aug 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Haploinsufficiency in the tumor suppressor NF1 contributes to the pathobiology of neurofibromatosis type 1, but a related role has not been established in malignant peripheral nerve sheath tumors (MPNST) where NF1 mutations also occur. Patients with NF1-associated MPNST appear to have worse outcomes than patients with sporadic MPNST, but the mechanism underlying this correlation is not understood. To define the impact of stromal genetics on the biology of this malignancy, we developed unique mouse models that reflect the genetics of patient-associated MPNST. Specifically, we used adenovirus-Cre injections to generate MPNST in Nf1 ; Ink4a/Arf and Nf1 ; Ink4a/Arf paired littermate mice to model tumors from NF1-wild-type and NF1-associated patients, respectively. In these models, Nf1 haploinsufficiency in hematopoietic cells accelerated tumor onset and increased levels of tumor-infiltrating immune cells comprised of CD11b cells, monocytes, and mast cells. We observed that mast cells were also enriched in human NF1-associated MPNST. In a coclinical trial to examine how the tumor microenvironment influences the response to multiagent chemotherapy, we found that stromal Nf1 status had no effect. Taken together, our results clarify the role of the NF1-haploinsufficient tumor microenvironment in MPNST. .
[Mh] Termos MeSH primário: Células-Tronco Hematopoéticas/patologia
Neoplasias da Bainha Neural/tratamento farmacológico
Neoplasias da Bainha Neural/patologia
Neurofibromatose 1/tratamento farmacológico
Neurofibromatose 1/patologia
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Células-Tronco Hematopoéticas/metabolismo
Seres Humanos
Camundongos
Neoplasias da Bainha Neural/genética
Neurofibromatose 1/genética
Neurofibromatose 1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171121
[Lr] Data última revisão:
171121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170625
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-16-2643


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[PMID]:28635234
[Au] Autor:Yuan ZN; Xu LB; Zhao ZG; Xu SF; Zhang XX; Liu T; Zhang SG; Yu SJ
[Ad] Endereço:Department of Orthopaedics, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
[Ti] Título:[Clinicopathological features and prognosis of malignant peripheral nerve sheath tumor: a retrospective study of 140 cases].
[So] Source:Zhonghua Zhong Liu Za Zhi;39(6):439-444, 2017 Jun 23.
[Is] ISSN:0253-3766
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To investigate the clinicopathological features and prognosis of malignant peripheral nerve sheath tumors (MPNST). We retrospectively reviewed the clinical data of MPNST patients who were treated at Cancer Institute & Hospital, Chinese Academy of Medical Science from January 1999 to January 2016. A total of 140 patients with 66 male and 74 female with MPNST were enrolled in the study. The median age was 40 at the time of diagnosis. Survival analysis were estimated by Kaplan-Meier method and Log rank test. Multivariate analysis were estimated by Cox proportional hazards regression model. The median follow-up time was 43.0 months. The 3- and 5-year overall survival (OS) rates were 56.4% and 48.6%, respectively. The 3-year local recurrence (LR) rate and distant metastasis (DM) rates were 42.9% and 49.3%, respectively. Univariate analysis showed that the tumor location, AJCC stage, S-100, radiotherapy and margin status affected 5-year OS rate (all <0.05). The tumor location, AJCC stage, S-100, Ki-67 staining, margin status, radiotherapy and chemotherapy affected 3-year LR rate (all <0.05). The tumor location, AJCC stage, S-100, Ki-67 staining and margin status affected 3-year DM rate (all <0.05). Multivariate analysis showed that the tumor location, AJCC stage, S-100 were independent factors for 5-year OS rate (all <0.05). The tumor location, Ki-67 staining and chemotherapy were independent factors for LR (all <0.05) while the AJCC stage, margin status and Ki-67 staining were independent factors for DM (all <0.05). MPSNT is an aggressive tumor with poor prognosis. Multiple factors were identified in this study. Patients with the tumor located at head and neck, advanced AJCC stage and negative S-100 usually have a low 5-year overall survival rate. Patients with the tumor located at head and neck, Ki-67 staining ≥ 20% and without chemotherapy had a higher tendency of local recurrence. Poor prognosis factors for DM were advanced AJCC stage, positive margin and Ki-67 staining ≥ 20%.
[Mh] Termos MeSH primário: Neoplasias da Bainha Neural/mortalidade
Neoplasias da Bainha Neural/patologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Feminino
Seguimentos
Seres Humanos
Masculino
Meia-Idade
Análise Multivariada
Prognóstico
Modelos de Riscos Proporcionais
Estudos Retrospectivos
Análise de Sobrevida
Taxa de Sobrevida
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170901
[Lr] Data última revisão:
170901
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170622
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0253-3766.2017.06.008



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