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1.
Dev Cell ; 58(2): 81-93, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36693322

RESUMO

Similar to their pivotal roles in nervous system development, neurons have emerged as critical regulators of cancer initiation, maintenance, and progression. Focusing on nervous system tumors, we describe the normal relationships between neurons and other cell types relevant to normal nerve function, and discuss how disruptions of these interactions promote tumor evolution, focusing on electrical (gap junctions) and chemical (synaptic) coupling, as well as the establishment of new paracrine relationships. We also review how neuron-tumor communication contributes to some of the complications of cancer, including neuropathy, chemobrain, seizures, and pain. Finally, we consider the implications of cancer neuroscience in establishing risk for tumor penetrance and in the design of future anti-tumoral treatments.


Assuntos
Neoplasias do Sistema Nervoso , Neurônios , Humanos , Neurônios/metabolismo , Junções Comunicantes/metabolismo , Neoplasias do Sistema Nervoso/metabolismo
2.
Int J Mol Sci ; 23(15)2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35955830

RESUMO

This Special Issue focused on the current understanding of signaling pathways as well as genetic and epigenetic features involved in the pathogenesis of brain tumors and other nervous system tumors, with emphasis on the development of novel therapeutic approaches aimed at improving the current standard of care [...].


Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso , Neoplasias Encefálicas/patologia , Epigenômica , Humanos , Transdução de Sinais/genética
3.
Curr Oncol Rep ; 24(1): 99-103, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35059995

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to describe the current state of telemedicine within neuro-oncology. This article will address the development of tele-neuro-oncology over time with a focus on current use and applications of telemedicine within the field. Current modalities and practical considerations for tele-neuro-oncology visits and opportunities for growth will be highlighted. RECENT FINDINGS: The use of telemedicine has expanded significantly during the COVID-19 pandemic, particularly within neuro-oncology. The use of telemedicine is widely accepted by neuro-oncologic patients and providers and continues to expand in utilization and scope. The use of tele-neuro-oncology is expected to develop further with opportunities for multidisciplinary and integrated care, clinical trials, research, and education. Telemedicine provides a unique, patient-centered approach to neuro-oncologic care. Telehealth will remain a valuable tool, and its use and role are expected to expand within neuro-oncology.


Assuntos
COVID-19/prevenção & controle , Oncologia/métodos , Neoplasias do Sistema Nervoso , Telemedicina/tendências , Humanos , Neoplasias do Sistema Nervoso/diagnóstico , Neoplasias do Sistema Nervoso/terapia , Assistência Centrada no Paciente , SARS-CoV-2 , Telemedicina/normas
4.
J Neurooncol ; 156(1): 49-59, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34661791

RESUMO

INTRODUCTION: Despite manifold advances in oncology, cancers of the central nervous system remain among the most lethal. Unique features of the brain, including distinct cellular composition, immunological privilege, and physical barriers to therapeutic delivery, likely contribute to the poor prognosis of patients with neuro-oncological disease. Focused ultrasound is an emerging technology that allows transcranial delivery of ultrasound energy to focal brain targets with great precision. METHODS: A review of the clinical and preclinical focused ultrasound literature was performed to obtain data regarding the current state of the focused ultrasound in context of neuro-oncology. A narrative review was then constructed to provide an overview of current and future applications of this technology. RESULTS: Focused ultrasound can facilitate direct control of tumors by thermal or mechanical ablation, as well as enhance delivery of diverse therapeutics by disruption of the blood-brain barrier without local tissue damage. Indeed, ultrasound-sensitive drug formulations or sonosensitizers may be combined with ultrasound blood-brain barrier disruption to achieve high local drug concentration while limiting systemic exposure to therapeutics. Furthermore, focused ultrasound can induce radiosensitization, immunomodulation, and neuromodulation. Here we review applications of focused ultrasound with a focus on approaches currently under clinical investigation for the treatment of neuro-oncological disease, such as blood-brain barrier disruption for drug delivery and thermal ablation. We also discuss design of clinical trials, selection of patient cohorts, and emerging approaches to improve the efficacy of transcranial ultrasound, such as histotripsy, as well as combinatorial strategies to exploit synergistic biological effects of existing cancer therapies and ultrasound. CONCLUSIONS: Focused ultrasound is a promising and actively expanding therapeutic modality for diverse neuro-oncological diseases.


Assuntos
Neoplasias do Sistema Nervoso , Terapia por Ultrassom , Humanos , Oncologia , Neoplasias do Sistema Nervoso/terapia , Neurologia
5.
Pediatr Blood Cancer ; 69(1): e29316, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34546642

RESUMO

BACKGROUND: There is a paucity of knowledge regarding pediatric biomarkers, including the relevance of ErbB pathway aberrations in pediatric tumors. We investigated the occurrence of ErbB receptor aberrations across different pediatric malignancies, to identify patterns of ErbB dysregulation and define biomarkers suitable for patient enrichment in clinical studies. PROCEDURE: Tissue samples from 297 patients with nervous system tumors and rhabdomyosarcoma were analyzed for immunohistochemical expression or gene amplification of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Exploratory analyses of HER3/HER4 expression, and mRNA expression of ErbB receptors/ligands (NanoString) were performed. Assay validation followed general procedures, with additional validation to address Clinical Laboratory Improvement Amendments (CLIA) requirements. RESULTS: In most tumor types, samples with high ErbB receptor expression were found with heterogeneous distribution. We considered increased/aberrant ErbB pathway activation when greater than or equal to two EGFR/HER2 markers were simultaneously upregulated. ErbB pathway dysregulation was identified in ∼20%-30% of samples for most tumor types (medulloblastoma/primitive neuroectodermal tumors 31.1%, high-grade glioma 27.1%, neuroblastoma 22.7%, rhabdomyosarcoma 23.1%, ependymoma 18.8%), 4.2% of diffuse intrinsic pontine gliomas, and no recurrent or refractory low-grade astrocytomas. In medulloblastoma/primitive neuroectodermal tumors and neuroblastoma, this was attributed mainly to high EGFR polysomy/HER2 amplification, whereas EGFR gene amplification was observed in some high-grade glioma samples. EGFR/HER2 overexpression was most prevalent in ependymoma. CONCLUSIONS: Overexpression and/or amplification of EGFR/HER2 were identified as potential enrichment biomarkers for clinical trials of ErbB-targeted drugs.


Assuntos
Neoplasias do Sistema Nervoso , Rabdomiossarcoma , Criança , Receptores ErbB , Humanos
6.
BMJ ; 375: n2305, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34666981

RESUMO

OBJECTIVE: To examine the risk of urogenital, colorectal, and neurological cancers after a first diagnosis of acute urinary retention. DESIGN: Nationwide population based cohort study. SETTING: All hospitals in Denmark. PARTICIPANTS: 75 983 patients aged 50 years or older with a first hospital admission for acute urinary retention during 1995-2017. MAIN OUTCOME MEASURES: Absolute risk of urogenital, colorectal, and neurological cancer and excess risk of these cancers among patients with acute urinary retention compared with the general population. RESULTS: The absolute risk of prostate cancer after a first diagnosis of acute urinary retention was 5.1% (n=3198) at three months, 6.7% (n=4233) at one year, and 8.5% (n=5217) at five years. Within three months of follow-up, 218 excess cases of prostate cancer per 1000 person years were detected. An additional 21 excess cases per 1000 person years were detected during three to less than 12 months of follow-up, but beyond 12 months the excess risk was negligible. Within three months of follow-up the excess risk for urinary tract cancer was 56 per 1000 person years, for genital cancer in women was 24 per 1000 person years, for colorectal cancer was 12 per 1000 person years, and for neurological cancer was 2 per 1000 person years. For most of the studied cancers, the excess risk was confined to within three months of follow-up, but the risk of prostate and urinary tract cancer remained increased during three to less than 12 months of follow-up. In women, an excess risk of invasive bladder cancer persisted for several years. CONCLUSIONS: Acute urinary retention might be a clinical marker for occult urogenital, colorectal, and neurological cancers. Occult cancer should possibly be considered in patients aged 50 years or older presenting with acute urinary retention and no obvious underlying cause.


Assuntos
Neoplasias Colorretais , Neoplasias do Sistema Nervoso , Medição de Risco , Retenção Urinária , Neoplasias Urogenitais , Assistência ao Convalescente/estatística & dados numéricos , Idoso , Causalidade , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Dinamarca/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Neoplasias do Sistema Nervoso/epidemiologia , Neoplasias do Sistema Nervoso/patologia , Neoplasias da Próstata/epidemiologia , Sistema de Registros/estatística & dados numéricos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Retenção Urinária/diagnóstico , Retenção Urinária/epidemiologia , Neoplasias Urogenitais/epidemiologia , Neoplasias Urogenitais/patologia
7.
Biomolecules ; 11(8)2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34439779

RESUMO

Telomere maintenance plays important roles in genome stability and cell proliferation. Tumor cells acquire replicative immortality by activating a telomere-maintenance mechanism (TMM), either telomerase, a reverse transcriptase, or the alternative lengthening of telomeres (ALT) mechanism. Recent advances in the genetic and molecular characterization of TMM revealed that telomerase activation and ALT define distinct neuroblastoma (NB) subgroups with adverse outcomes, and represent promising therapeutic targets in high-risk neuroblastoma (HRNB), an aggressive childhood solid tumor that accounts for 15% of all pediatric-cancer deaths. Patients with HRNB frequently present with widely metastatic disease, with tumors harboring recurrent genetic aberrations (MYCN amplification, TERT rearrangements, and ATRX mutations), which are mutually exclusive and capable of promoting TMM. This review provides recent insights into our understanding of TMM in NB tumors, and highlights emerging therapeutic strategies as potential treatments for telomerase- and ALT-positive tumors.


Assuntos
Genoma Humano , Proteína Proto-Oncogênica N-Myc/genética , Neoplasias do Sistema Nervoso/genética , Neuroblastoma/genética , Telomerase/genética , Telômero/química , Proteína Nuclear Ligada ao X/genética , Antineoplásicos/uso terapêutico , Criança , Regulação Neoplásica da Expressão Gênica , Instabilidade Genômica , Humanos , Mutação , Proteína Proto-Oncogênica N-Myc/metabolismo , Metástase Neoplásica , Neoplasias do Sistema Nervoso/tratamento farmacológico , Neoplasias do Sistema Nervoso/mortalidade , Neoplasias do Sistema Nervoso/patologia , Neuroblastoma/tratamento farmacológico , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Fatores de Risco , Transdução de Sinais , Análise de Sobrevida , Telomerase/metabolismo , Telômero/efeitos dos fármacos , Telômero/patologia , Homeostase do Telômero , Proteína Nuclear Ligada ao X/metabolismo
8.
Biomolecules ; 11(8)2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34439783

RESUMO

Neuroblastoma is a pediatric cancer, onset with localized as well as metastatic disease. Localized tumors usually show a high content of aneuploid cells. It is suggested that aneuploid cells with numerical copy number variation (CNV) are generated by chromosome instability (CIN). Patients with a localized tumor respond well to the therapy and show a good outcome. On the contrary, patients with a metastatic tumor have worse outcomes and the cells with structural CNV show high levels of CIN. It is proposed that a favorable outcome in patients with localized disease is associated to the grade of CIN.


Assuntos
Aneuploidia , Genoma Humano , Neoplasias do Sistema Nervoso/genética , Neuroblastoma/genética , Fatores de Proteção , Antineoplásicos/uso terapêutico , Instabilidade Cromossômica , Variações do Número de Cópias de DNA , Humanos , Lactente , Metástase Neoplásica , Neoplasias do Sistema Nervoso/tratamento farmacológico , Neoplasias do Sistema Nervoso/mortalidade , Neoplasias do Sistema Nervoso/patologia , Crista Neural/metabolismo , Crista Neural/patologia , Neuroblastoma/tratamento farmacológico , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Análise de Sobrevida , Resultado do Tratamento
9.
Cell Rep Med ; 2(6): 100297, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34195677

RESUMO

Targeting solid tumors must overcome several major obstacles, in particular, the identification of elusive tumor-specific antigens. Here, we devise a strategy to help identify tumor-specific epitopes. Glypican 2 (GPC2) is overexpressed in neuroblastoma. Using RNA sequencing (RNA-seq) analysis, we show that exon 3 and exons 7-10 of GPC2 are expressed in cancer but are minimally expressed in normal tissues. Accordingly, we discover a monoclonal antibody (CT3) that binds exons 3 and 10 and visualize the complex structure of CT3 and GPC2 by electron microscopy. The potential of this approach is exemplified by designing CT3-derived chimeric antigen receptor (CAR) T cells that regress neuroblastoma in mice. Genomic sequencing of T cells recovered from mice reveals the CAR integration sites that may contribute to CAR T cell proliferation and persistence. These studies demonstrate how RNA-seq data can be exploited to help identify tumor-associated exons that can be targeted by CAR T cell therapies.


Assuntos
Anticorpos Monoclonais/farmacologia , Glipicanas/genética , Neoplasias do Sistema Nervoso/terapia , Neuroblastoma/terapia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Éxons , Feminino , Expressão Gênica , Glipicanas/antagonistas & inibidores , Glipicanas/química , Glipicanas/imunologia , Humanos , Imunoterapia Adotiva/métodos , Camundongos , Camundongos Nus , Modelos Moleculares , Neoplasias do Sistema Nervoso/genética , Neoplasias do Sistema Nervoso/mortalidade , Neoplasias do Sistema Nervoso/patologia , Neuroblastoma/genética , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Ligação Proteica , Conformação Proteica , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos Quiméricos/imunologia , Análise de Sequência de RNA , Análise de Sobrevida , Linfócitos T/imunologia , Linfócitos T/metabolismo , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Curr Treat Options Oncol ; 22(9): 78, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34213625

RESUMO

OPINION STATEMENT: Clinical trials play a critical role in discovering new treatments, but the path to regulatory approval can be cumbersome and time consuming. Efforts to increase the efficiency and interpretability of clinical trials within the neuro-oncology community have focused on standardization of response assessment, development of consensus guidelines for clinical trial conduct, decentralization of clinical trials, removal of barriers to clinical trial accrual, and re-examination of patient eligibility criteria.


Assuntos
Ensaios Clínicos como Assunto , Oncologia , Neoplasias do Sistema Nervoso/diagnóstico , Neoplasias do Sistema Nervoso/terapia , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Humanos , Oncologia/métodos , Oncologia/normas , Avaliação de Resultados em Cuidados de Saúde , Guias de Prática Clínica como Assunto , Projetos de Pesquisa
12.
Cells ; 10(3)2021 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800887

RESUMO

For nearly a decade, researchers in the field of pediatric oncology have been using zebrafish as a model for understanding the contributions of genetic alternations to the pathogenesis of neuroblastoma (NB), and exploring the molecular and cellular mechanisms that underlie neuroblastoma initiation and metastasis. In this review, we will enumerate and illustrate the key advantages of using the zebrafish model in NB research, which allows researchers to: monitor tumor development in real-time; robustly manipulate gene expression (either transiently or stably); rapidly evaluate the cooperative interactions of multiple genetic alterations to disease pathogenesis; and provide a highly efficient and low-cost methodology to screen for effective pharmaceutical interventions (both alone and in combination with one another). This review will then list some of the common challenges of using the zebrafish model and provide strategies for overcoming these difficulties. We have also included visual diagram and figures to illustrate the workflow of cancer model development in zebrafish and provide a summary comparison of commonly used animal models in cancer research, as well as key findings of cooperative contributions between MYCN and diverse singling pathways in NB pathogenesis.


Assuntos
Proteínas de Neoplasias/genética , Neoplasias do Sistema Nervoso/genética , Neuroblastoma/genética , Proteínas Proto-Oncogênicas/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Animais Geneticamente Modificados , Antineoplásicos/farmacologia , Modelos Animais de Doenças , Edição de Genes/métodos , Regulação Neoplásica da Expressão Gênica , Ensaios de Triagem em Larga Escala , Humanos , Mutação , Metástase Neoplásica , Proteínas de Neoplasias/metabolismo , Transplante de Neoplasias/métodos , Neoplasias do Sistema Nervoso/tratamento farmacológico , Neoplasias do Sistema Nervoso/metabolismo , Neoplasias do Sistema Nervoso/patologia , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
13.
J Cutan Pathol ; 48(7): 980-985, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33844324

RESUMO

Cellular neurothekeoma is a cutaneous tumor with a distinctive histopathologic appearance characterized by a dermal-based multinodular proliferation of epithelioid to spindled cells. Although the tumor may show varying amounts of myxoid stroma, extensive myxoid change is uncommon. The tumor typically presents as a solitary nodule with a predilection for the head and neck and upper limbs; examples of multiple cellular neurothekeomas are decidedly rare. The present report describes a unique case of multiple myxoid cellular neurothekeomas arising in a 60-year-old female with systemic lupus erythematosus. Two papular lesions were identified involving the skin inferior to the umbilicus and the left inguinal crease. Both lesions were histopathologically similar, forming a nodular mass composed of epithelioid cells in a prominent myxoid stroma. By immunohistochemistry the lesional cells expressed NKI/C3, microphthalmia transcription factor (MiTF), and CD68, with focal staining for PGP9.5, factor XIIIa, and CD10 also observed. The tumors were negative for S-100, SOX-10, epithelial membrane antigen, desmin, smooth muscle actin, glial fibrillary acid protein, and CD34. The present case confirms that cellular neurothekeoma can present clinically as multiple lesions and can have a predominantly myxoid appearance, potentially mimicking other cutaneous myxoid lesions.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Neoplasias do Sistema Nervoso/patologia , Neurotecoma/diagnóstico , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores Tumorais/metabolismo , Criança , Pré-Escolar , Diagnóstico Diferencial , Células Epitelioides/patologia , Fator XIIIa/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Lactente , Masculino , Fator de Transcrição Associado à Microftalmia/metabolismo , Pessoa de Meia-Idade , Mixoma/patologia , Neprilisina/metabolismo , Neurotecoma/metabolismo , Ubiquitina Tiolesterase/metabolismo
14.
Clin Cancer Res ; 27(14): 3916-3925, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33863808

RESUMO

PURPOSE: The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified RANO (mRANO) criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM). PATIENTS AND METHODS: A total of 47 patients with rGBM were enrolled in a prospective phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and centrally by an independent radiologic faculty, then standard RANO, iRANO, and mRANO criteria were applied. RESULTS: A total of 41 of 47 patients (mean age 56 ± 11.7) were evaluable for response. PFS was significantly shorter using standard RANO compared with iRANO (log-rank, P < 0.0001; HR = 0.3) and mRANO (P < 0.0001; HR = 0.3). In patients who died and had confirmed progression on standard RANO, no correlation was observed between PFS and OS (local, P = 0.47; central, P = 0.34). Using iRANO, a weak association was observed between confirmed PFS and OS via local site measurements (P = 0.017), but not central measurements (P = 0.18). A total of 24 of 41 patients (59%) were censored using iRANO and because they lacked confirmation of progression 3 months after initial progression. A strong correlation was observed between mRANO PFS and OS for both local (R2 = 0.66, P < 0.0001) and centrally determined reads (R2 = 0.57, P = 0.0007). CONCLUSIONS: No correlation between radiographic PFS and OS was observed for standard RANO or iRANO, but a correlation was observed between PFS and OS using the mRANO criteria. Also, the iRANO criteria was difficult to implement due to need to confirm progression 3 months after initial progression, censoring more than half the patients.


Assuntos
Glioblastoma/terapia , Imunoterapia/métodos , Imunotoxinas/farmacologia , Subunidade alfa de Receptor de Interleucina-4/antagonistas & inibidores , Recidiva Local de Neoplasia/terapia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Glioblastoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Neoplasias do Sistema Nervoso/tratamento farmacológico , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
15.
Mol Cancer ; 20(1): 49, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33673851

RESUMO

Neural tumors can generally be divided into central nervous system tumors and peripheral nervous tumors. Because this type of tumor is located in the nerve, even benign tumors are often difficult to remove by surgery. In addition, the majority of neural tumors are malignant, and it is particular the same for the central nervous system tumors. Even treated with the means such as chemotherapy and radiotherapy, they are also difficult to completely cure. In recent years, an increasingly number of studies have focused on the use of mRNA to treat tumors, representing an emerging gene therapy. The use of mRNA can use the expression of some functional proteins for the treatment of genetic disorders or tissue repair, and it can also be applied to immunotherapy through the expression of antigens, antibodies or receptors. Therefore, although these therapies are not fully-fledged enough, they have a broad research prospect. In addition, there are many ways to treat tumors using mRNA vaccines and exosomes carrying mRNA, which have drawn much attention. In this study, we reviewed the current research on the role of mRNA in the development, diagnosis, treatment and prognosis of neural tumors, and examine the future research prospects of mRNA in neural tumors and the opportunities and challenges that will arise in the future application of clinical treatment.


Assuntos
Biomarcadores Tumorais , Transformação Celular Neoplásica/genética , Neoplasias do Sistema Nervoso/diagnóstico , Neoplasias do Sistema Nervoso/genética , Neoplasias do Sistema Nervoso/terapia , RNA Mensageiro/genética , Animais , Vacinas Anticâncer , Transformação Celular Neoplásica/metabolismo , Terapia Combinada , Diagnóstico Diferencial , Gerenciamento Clínico , Suscetibilidade a Doenças , Epigênese Genética , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas de Diagnóstico Molecular , Neoplasias do Sistema Nervoso/mortalidade , Especificidade de Órgãos/genética , Prognóstico , Transporte de RNA , RNA Mensageiro/imunologia , RNA Mensageiro/metabolismo
16.
J Neurooncol ; 151(3): 341-343, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33611701

RESUMO

The American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Joint Section on Tumors was formed in December of 1984 as the first professional organization devoted to the study and treatment of brain tumors. One year earlier, the Journal of Neuro-Oncology had been established and went on to be sponsored by the Joint Section on Tumors. To celebrate the 35th anniversary of the founding of the Section, we are thrilled to bring you this special issue of Journal of Neuro-Oncology in which current leaders of the Joint Section on Tumors highlight their work and the work of others that have led to significant recent advances in the management of tumors of the central nervous system.


Assuntos
Oncologia/tendências , Neoplasias do Sistema Nervoso/terapia , Neurologia/tendências , Aniversários e Eventos Especiais , Neoplasias Encefálicas/cirurgia , Humanos , Imunoterapia , Neoplasias do Sistema Nervoso/cirurgia , Neurocirurgia , Publicações Periódicas como Assunto , Sociedades Médicas , Estados Unidos
18.
Ann Thorac Surg ; 111(1): e35-e36, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32599041

RESUMO

Posterior mediastinal tumors are not infrequent, and among them neurogenic masses and schwannomas are the most common histologic varieties. These benign, initially asymptomatic tumors later become symptomatic as a result of mass effect. Surgical excision is the preferred therapy, and the approach can be determined according to the dimensions of the lesion. This report describes the case of a giant schwannoma originating from the left vagus nerve in a middle-aged woman whose symptoms were exertion-induced dyspnea and atrial fibrillation.


Assuntos
Fibrilação Atrial/etiologia , Neoplasias do Sistema Nervoso/complicações , Neurilemoma/complicações , Nervo Vago , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Sistema Nervoso/patologia , Neurilemoma/patologia , Carga Tumoral
19.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34561301

RESUMO

Nervous system malignancies are characterized by rapid progression and poor survival rates. These clinical observations underscore the need for novel therapeutic insights and pharmacological targets. To this end, here, we identify the orphan nuclear receptor NR5A2/LRH1 as a negative regulator of cancer cell proliferation and promising pharmacological target for nervous system-related tumors. In particular, clinical data from publicly available databases suggest that high expression levels of NR5A2 are associated with favorable prognosis in patients with glioblastoma and neuroblastoma tumors. Consistently, we experimentally show that NR5A2 is sufficient to strongly suppress proliferation of both human and mouse glioblastoma and neuroblastoma cells without inducing apoptosis. Moreover, short hairpin RNA-mediated knockdown of the basal expression levels of NR5A2 in glioblastoma cells promotes their cell cycle progression. The antiproliferative effect of NR5A2 is mediated by the transcriptional induction of negative regulators of the cell cycle, CDKN1A (encoding for p21cip1), CDKN1B (encoding for p27kip1) and Prox1 Interestingly, two well-established agonists of NR5A2, dilauroyl phosphatidylcholine (DLPC) and diundecanoyl phosphatidylcholine, are able to mimic the antiproliferative action of NR5A2 in human glioblastoma cells via the induction of the same critical genes. Most importantly, treatment with DLPC inhibits glioblastoma tumor growth in vivo in heterotopic and orthotopic xenograft mouse models. These data indicate a tumor suppressor role of NR5A2 in the nervous system and render this nuclear receptor a potential pharmacological target for the treatment of nervous tissue-related tumors.


Assuntos
Glioblastoma/patologia , Neoplasias do Sistema Nervoso/patologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Camundongos SCID , Neoplasias do Sistema Nervoso/tratamento farmacológico , Neoplasias do Sistema Nervoso/metabolismo , Neoplasias do Sistema Nervoso/mortalidade , Células-Tronco Neurais/efeitos dos fármacos , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Fosfatidilcolinas/farmacologia , Receptores Citoplasmáticos e Nucleares/agonistas , Receptores Citoplasmáticos e Nucleares/genética , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Acta Biochim Pol ; 67(4): 595-603, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33326736

RESUMO

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are involved in neuroblastoma (NB) pathogenesis. The aim of this study was to elucidate the roles and underlying mechanism of non-coding RNA activated by DNA damage (NORAD) in childhood NB. Both public data and clinical specimens were used to determine NORAD expression. Colony formation, cell proliferation and wound healing assays were performed to evaluate NORAD effects on proliferation and migration of SH-SY5Y and SK-N-BE(2) cells. Flow cytometry was used to examine the cell cycle changes. The expression of genes and proteins involved in chromosomal instability was determined by qRT-PCR and western blotting, respectively. Our results showed that low NORAD expression correlated with advanced tumor stage, high risk and MYCN amplification in both public data and clinical samples. Kaplan-Meier analysis indicated that patients with low NORAD expression had poor survival outcomes. Functional research showed that NORAD knockdown promoted cell proliferation and migration, and arrested the cell cycle at the G2/M phase. Moreover, the expression of the DNA damage sensor, PARP1, increased after NORAD knockdown, indicating a potential contribution of NORAD to DNA damage repair. NORAD silencing also affected the expression of genes and proteins related to sister chromatid cohesion and segregation, which are involved in chromosomal instability and consequent aneuploidy. These results suggest that NORAD may serve as a tumor suppressor in NB pathogenesis and progression. Thus, NORAD is a potential therapeutic target and a promising prognostic marker for NB patients.


Assuntos
Instabilidade Cromossômica , Proteína Proto-Oncogênica N-Myc/genética , Neoplasias do Sistema Nervoso/genética , Neuroblastoma/genética , Neurônios/metabolismo , RNA Longo não Codificante/genética , Aurora Quinase B/genética , Aurora Quinase B/metabolismo , Proteína Quinase CDC2/genética , Proteína Quinase CDC2/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteína Centromérica A/genética , Proteína Centromérica A/metabolismo , Criança , Proteoglicanas de Sulfatos de Condroitina/genética , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Conjuntos de Dados como Assunto , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína Proto-Oncogênica N-Myc/metabolismo , Estadiamento de Neoplasias , Neoplasias do Sistema Nervoso/diagnóstico , Neoplasias do Sistema Nervoso/mortalidade , Neoplasias do Sistema Nervoso/patologia , Neuroblastoma/diagnóstico , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Neurônios/patologia , Poli(ADP-Ribose) Polimerase-1/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo , Prognóstico , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Troca de Cromátide Irmã , Análise de Sobrevida
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