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1.
Medicine (Baltimore) ; 99(23): e20639, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502048

RESUMO

Retroperitoneal neuroblastoma is a rare subtype of neuroblastoma and the role of age in its clinical prognosis is still unknown.To describe the age distribution and investigate the association between age and survival outcomes in patients diagnosed with retroperitoneal neuroblastoma.We retrospectively analyzed patients registered for retroperitoneal neuroblastoma in the Surveillance, Epidemiology, and End Results (SEER) national database from 1973 to 2015. Age distribution was described and Cox proportional hazard regression was used to evaluate the measured effect of age on overall survival and disease-specific survival.A total of 399 retroperitoneal neuroblastoma patients with a median follow-up of 53.0 (interquartile range 17.0-133.5) months were included. We found a unimodal distribution of age with a median age of diagnosis to be 1.0 (interquartile range 0.0-4.0) years. Univariate analysis suggested that transformed age was associated with an increased risk of total death and disease-specific death (OR = 4.2, 95% CI 3.0-5.9; OR = 4.7, 95% CI 3.2-6.8). Adjusted smoothed plots showed a nonlinear correlation between age and disease-specific death. The risk of disease-specific death did not increase sharply as the age increased until reaching the inflection point (age < 3 years, OR = 0.4, 95% CI 0.2-1.0; age ≥ 3 years, OR = 1.2, 95% CI 0.9-1.5). There was, however, a linear relationship between age and total deaths (OR = 1.0, 95% CI 0.7-1.2). Adjusted multivariate Cox regression analysis showed that ages ≥ 3 years were associated with a significant increased risks of disease-specific death and total death (OR = 2.5, 95% CI 1.7-3.8; OR = 2.3, 95% CI 1.6-3.3, respectively).There was a unimodal age distribution of retroperitoneal neuroblastoma usually presented in infants or younger child. Older age was associated with a lower chance of overall survival and the risk of disease-specific death increased sharply after 3 years of age.


Assuntos
Neuroblastoma/mortalidade , Neoplasias Retroperitoneais/mortalidade , Distribuição por Idade , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Neuroblastoma/terapia , Modelos de Riscos Proporcionais , Neoplasias Retroperitoneais/terapia , Estudos Retrospectivos , Programa de SEER/estatística & dados numéricos
2.
Medicine (Baltimore) ; 99(26): e20896, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590800

RESUMO

INTRODUCTION: Metastatic neuroblastoma (NB) is an aggressive malignancy with a poor prognosis. Many patients present with relapsed high-risk NB after undergoing first-line treatment, and there is no standard therapy available in this setting. PATIENT CONCERNS: The present study aimed to present the cases of 2 patients with recurrent high-risk NB. DIAGNOSIS: Two children with International Neuroblastoma Stage System stage 4 high-risk NB chemotherapy. The disease recurrent after finishing the treatment. INTERVENTIONS: Both patients (34 months old and 41 months old) experienced recurrence, received second-line treatment, and then received maintenance treatment using apatinib plus retinoic acid. The apatinib (10 mg/kg per day) and retinoic acid (160 mg/m per day) were administered on alternating 2-week cycles, which was continued for 1 year. OUTCOMES: The 2 patients had achieved complete response by the 1-year follow-up after starting apatinib plus retinoic acid, and did not experience any adverse drug reactions. CONCLUSION: The outcomes from these cases suggest that apatinib plus isotretinoin might be an option for maintenance therapy in patients with recurrent high-risk NB.


Assuntos
Neuroblastoma/complicações , Neuroblastoma/tratamento farmacológico , Piridinas/uso terapêutico , Tretinoína/uso terapêutico , Dor Abdominal/etiologia , Antineoplásicos/uso terapêutico , Pré-Escolar , Tratamento Farmacológico/métodos , Tratamento Farmacológico/normas , Humanos , Masculino , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/fisiopatologia , Neuroblastoma/fisiopatologia , Recidiva
4.
Medicine (Baltimore) ; 99(25): e20853, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569234

RESUMO

INTRODUCTION: Neuroblastoma (NB) with MYCN amplification has a poor prognosis and high mortality. The potential molecular biological relationship between clinical features and MYCN amplification should be explored. METHODS: NB patients were examined by fluorescence in situ hybridization (FISH) for MYCN amplification in the tumor mass or bone marrow samples to determine whether MYCN was amplified. A series of eleven MYCN-amplified NB patients were included. The age, primary site, tumor size, specific biomarkers, and invaded organs were analyzed. All patients accepted standardized treatment of surgery, chemotherapy, and radiotherapy. Progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: The median age at diagnosis was 24 months. Nine patients (81.8%) were in stage IV, with high serum neuron-specific enolase (NSE) expression, normal urine vanillylmandelic acid (VMA) level and extensive metastases. All patients accepted a chemotherapy protocol with 8 to 10 cycles, and 9 patients (81.8%) were sensitive to the initial chemotherapy protocol. At the end of follow-up, four patients (36.3%) died with a median OS of 15 months. Five patients (45%) survived with a median PFS of 13 months. Two patients were still receiving chemotherapy. CONCLUSION: Given the effect of MYCN amplification on poor outcome in NB, novel treatments targeting MYCN should be developed for patients with NB.


Assuntos
Proteína Proto-Oncogênica N-Myc/metabolismo , Neuroblastoma/patologia , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Neuroblastoma/metabolismo , Neuroblastoma/mortalidade , Neuroblastoma/terapia , Análise de Sobrevida
5.
Medicine (Baltimore) ; 99(25): e20905, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569238

RESUMO

RATIONALE: Chronic radiation enteritis, a disease secondary to radiation exposure, has been widely reported in adults. However, few studies have described chronic radiation enteritis in children. Early diagnosis is essential, and nutrition management plays an important role in pediatric chronic radiation enteritis management. PATIENT CONCERNS: A Chinese 3-year-10-month-old boy was admitted with vomiting, weight loss (1-2 kg) after radiotherapy for a neuroblastoma. DIAGNOSES: The patient was diagnosed as neuroblastoma (primary site: left adrenal grand; site of metastasis: multiple bone metastasis, bone marrow invasion, intraperitoneal lymph node metastasis) in 2015. Five months after radiotherapy, he showed vomiting and weight loss with stricture in intestine and thickening intestinal wall in imaging finding. His daily intake was not sufficient and extra supplements were needed by intravenous infusion. He had a weight-for-age z score of -5.04, a weight-for-height z score of -6.19, a height-for-age z score of -2.22, and a body mass index-for-age z score of -5.87. The highest level of alanine aminotransferase was 1433 U/L. Those findings established a diagnosis of chronic radiation enteritis with intestinal failure, intestinal stenosis, severe malnutrition, and hepatic dysfunction. INTERVENTIONS: This patient was treated by parenteral nutrition with minimal enteral feeding. Other treatments were aiming at complications during hospitalization. OUTCOMES: The patient weaned off parenteral nutrition finally with nutrition status and quality of life improved. There were no signs of tumor recurrence during the 4-year follow-up. LESSONS: Pediatric radiation enteritis is rare. Our study highlights the characteristics of pediatric chronic radiation enteritis. Nutrition therapy is an important part of the whole therapy strategy in pediatric chronic radiation enteritis.


Assuntos
Enterite/etiologia , Exposição à Radiação/efeitos adversos , Neoplasias das Glândulas Suprarrenais/radioterapia , Pré-Escolar , Nutrição Enteral , Enterite/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Neuroblastoma/radioterapia , Radiografia
6.
Chem Biol Interact ; 326: 109134, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32464120

RESUMO

Montelukast is a cysteinyl leukotriene (CysLT) receptor antagonist with efficacy against a variety of diseases, including asthma and inflammation-related conditions. However, various neuropsychiatric events (NEs) suspected to be related to montelukast have been reported recently, with limited understanding on their association and underlying mechanisms. This study aimed to investigate whether montelukast can induce neuroinflammation and neurotoxicity in microglial HAPI cells and neural SH-SY5Y cells. The present study also compared the effects of montelukast with a 5-lipoxygenase inhibitor (zileuton) and a cyclooxygenase-2 inhibitor (celecoxib) to better understand modulation of related pathways. HAPI or SH-SY5Y cells were treated with the indicated drugs (3.125 µM-100 µM) for 24 h to investigate drug-induced neuroinflammation and neurotoxicity. Montelukast induced cytotoxicity in HAPI cells (50-100 µM), accompanied with caspase-3/7 activation, prostaglandin E2 (PGE2) release, and reactive oxygen species (ROS) production. Whilst both montelukast and zileuton down-regulated CysLT release in HAPI cells, zileuton did not significantly affect cell viability or inflammatory and oxidative factors. Celecoxib decreased HAPI cell viability (6.25-100 µM), accompanied with increasing caspase-3/7 activation and ROS production, but in contrast to montelukast increased CysLT release and decreased PGE2 production. Similar to observations in HAPI cells, both montelukast and celecoxib (50-100 µM) but not zileuton produced toxicity in SH-SY5Y neuroblastoma cells. Similarly, CM from HAPI cells treated with either montelukast or zileuton produced toxicity in SH-SY5Y cells. The results of the current study show the capability of montelukast to directly induce toxicity and inflammation in HAPI cells, possibly through the involvement of PGE2 and ROS, and toxicity in undifferentiated SH-SY5Y neuroblastoma cells. The current study highlights the importance of consideration between benefit and risk of montelukast usage and provides references for future investigation on decreasing montelukast-related NEs.


Assuntos
Acetatos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Quinolinas/farmacologia , Animais , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Dinoprostona/metabolismo , Humanos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo
7.
PLoS Comput Biol ; 16(4): e1007753, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32275708

RESUMO

Precision oncology has primarily relied on coding mutations as biomarkers of response to therapies. While transcriptome analysis can provide valuable information, incorporation into workflows has been difficult. For example, the relative rather than absolute gene expression level needs to be considered, requiring differential expression analysis across samples. However, expression programs related to the cell-of-origin and tumor microenvironment effects confound the search for cancer-specific expression changes. To address these challenges, we developed an unsupervised clustering approach for discovering differential pathway expression within cancer cohorts using gene expression measurements. The hydra approach uses a Dirichlet process mixture model to automatically detect multimodally distributed genes and expression signatures without the need for matched normal tissue. We demonstrate that the hydra approach is more sensitive than widely-used gene set enrichment approaches for detecting multimodal expression signatures. Application of the hydra analysis framework to small blue round cell tumors (including rhabdomyosarcoma, synovial sarcoma, neuroblastoma, Ewing sarcoma, and osteosarcoma) identified expression signatures associated with changes in the tumor microenvironment. The hydra approach also identified an association between ATRX deletions and elevated immune marker expression in high-risk neuroblastoma. Notably, hydra analysis of all small blue round cell tumors revealed similar subtypes, characterized by changes to infiltrating immune and stromal expression signatures.


Assuntos
Perfilação da Expressão Gênica/métodos , Neoplasias/genética , Transcriptoma/genética , Biomarcadores Tumorais , Criança , Análise por Conglomerados , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Modelos Estatísticos , Neuroblastoma/genética , Medicina de Precisão/métodos , Microambiente Tumoral/genética
8.
J Korean Med Sci ; 35(14): e82, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32281311

RESUMO

BACKGROUND: This study aimed to investigate the incidence and clinical significance of segmental chromosomal aberrations (SCAs) in Korean patients with neuroblastoma. METHODS: Patients diagnosed with neuroblastoma from 2012 to 2018 were included for retrospective review. Fluorescence in situ hybridization (FISH) was used to analyze four SCAs (MYCN amplification, 1p deletion, 11q deletion, and 17q gain). Clinical characteristics at diagnosis, early tumor response (reduction in primary tumor volume and neuron-specific enolase level after the first three cycles of chemotherapy), and survival rates were compared according to SCAs. RESULTS: Among 173 patients with FISH results, 92 (53.2%) had at least one of the four SCAs, while 25 (14.5%) had two co-aberrations, and eight (4.6%) had three co-aberrations. SCAs detected in our study were MYCN amplification (n = 17, 9.8%), 1p deletion (n = 26, 15.2%), 11q deletion (n = 44, 25.6%), and 17q gain (n = 46, 27.1%). Patients with MYCN amplification showed a better early response but a worse survival than those without (5-year overall survival: 46.2% ± 13.1% vs. 88.6% ± 3.4%). Furthermore, 1p deletion was associated with a better early response but a worse survival; however, it was not an independent factor for survival. We could not find any prognostic significance associated with 11q deletion or 17q gain. CONCLUSION: This is the first study investigating SCAs in Korean neuroblastoma patients. Prognostic significance of SCAs other than MYCN amplification was different from those reported in western countries. Further study with a larger cohort and longer follow-up is needed to confirm our findings.


Assuntos
Aberrações Cromossômicas , Neuroblastoma/genética , Adolescente , Criança , Pré-Escolar , Cromossomos Humanos , Feminino , Amplificação de Genes , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Masculino , República da Coreia , Estudos Retrospectivos , Adulto Jovem
9.
Life Sci ; 252: 117657, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32289431

RESUMO

AIMS: The lncRNA distal-less homeobox 6 antisense 1 (DLX6-AS1) has been reported to be an oncogenic lncRNA in diverse malignant cancers; however, whether it has oncogenic role in neuroblastoma(NB) remain largely unknown. This study explored the expression status, function and potential mechanism of DLX6-AS1 in NB. MAIN METHOD: In the current study, a total of 70 human NB tissues and matched adjacent non-tumor tissues were collected. Quantitative PCR (qPCR) was performed to study the expression differences of DLX6-AS1 in tissues and NB cell lines. Proliferation, migration, invasion and EMT status of transfected NB cells were evaluated by WST-1 assay, colony formation unit assay, Transwell assay and qPCR, respectively. The interaction between DLX6-AS1 and its potential targets was confirmed by luciferase reporter assay. Xenograft models were established to evaluate tumor proliferation in vivo. KEY FINDING: We found that the expression of DLX6-AS1 was significantly increased in both NB tissues and cell lines, and elevated DLX6AS1 expression was positively correlated with advanced stage and poor survival. Proliferation rate, migration and invasion ability, as well as EMT process of NB cells was inhibited after DLX6-AS1 knockdown, meanwhile, the tumor growth in vivo was impaired after DLX6-AS1 inhibition. Further analysis showed that DLX6-AS1 regulates the expression of YAP1 by sponging miR-497-5p. DLX6-AS1 directly interacts with miR-497-5p and reduces the binding of miR-497-5p to YAP1 3'UTR, thus inhibiting the degradation of YAP1 by miR-497-5p. SIGNIFICANCE: This work demonstrates that DLX6-AS1 partially enhances the proliferation, migration and invasion abilities of NB cells through the miR-497-5p/YAP1 pathway, DLX6-AS1 might act as a promising therapeutic target for NB.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Homeodomínio/genética , MicroRNAs/genética , Neuroblastoma/genética , RNA Longo não Codificante/genética , Fatores de Transcrição/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Criança , Pré-Escolar , Progressão da Doença , Feminino , Técnicas de Silenciamento de Genes , Humanos , Lactente , Masculino , Invasividade Neoplásica/genética , Neuroblastoma/patologia
10.
Surgery ; 167(6): 969-977, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32122657

RESUMO

BACKGROUND: Neuroblastoma is the most common pediatric extracranial solid malignancy with limited effective treatment. We have shown that sustained-release, single drugs delivered locally through a silk-based biomaterial are effective in decreasing orthotopic neuroblastoma xenograft growth. We further optimized this approach and hypothesized that increasing doses of local chemotherapy or delivering 2 chemotherapeutic agents simultaneously inhibit additional tumor growth. METHODS: MYCN-amplified and non-MYCN-amplified neuroblastoma cells were treated with combinations of cisplatin, vincristine, doxorubicin, and etoposide to determine cytotoxicity and synergy. Drug-loaded silk material was created, and the amounts of drug released from the material over time were recorded. Murine orthotopic neuroblastoma xenografts were generated; tumors were implanted with single- or dual-agent chemotherapy-loaded silk. Ultrasound was used to monitor tumor growth, and tumor histology was evaluated. RESULTS: In vitro, vincristine/cisplatin combination was synergistic and significantly decreased cell viability relative to other combinations. Both drugs loaded into silk could be released effectively for over 2 weeks. Locally implanted vincristine/cisplatin silk induced increased tumor growth suppression compared with either agent alone in MYCN-amplified tumors (P < .05). The dose-dependent effect seen in MYCN-amplified tumors treated with combination therapy diminished at higher doses in non-MYCN-amplified tumors, with little benefit with doses >50 µg to 500 µg for vincristine-cisplatin, respectively. Tumor histology demonstrated tumor cell necrosis adjacent to drug-loaded silk material and presence of large cell neuroblastoma. CONCLUSION: Local delivery of sustained release chemotherapy can suppress tumor growth especially at high doses or with 2 synergistic drugs. Locally delivered dual therapy is a promising approach for future clinical testing.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Neuroblastoma/tratamento farmacológico , Vincristina/administração & dosagem , Animais , Preparações de Ação Retardada , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Humanos , Camundongos , Transplante de Neoplasias , Neuroblastoma/patologia , Seda , Células Tumorais Cultivadas
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(3): 262-268, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32204764

RESUMO

OBJECTIVE: To study the differentially expressed mRNAs between MYCN-amplified neuroblastoma (NB) and non-amplified NB, to screen out the genes which can be used to predict the prognosis of MYCN-amplified NB, and to analyze their value in predicting prognosis. METHODS: NB transcriptome data and the clinical data of children were obtained from the TARGET database. According to the presence or absence of MYCN amplification, the children were divided into two groups: MYCN amplification (n=33) and non-MYCN amplification (n=121). The expression of mRNAs was compared between the two groups to obtain differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis was performed to investigate the main functions of DEGs. The Cox proportional-hazards regression model analysis was used to investigate the genes influencing the prognosis of MYCN-amplified NB. The children were divided into a high-risk group (n=77) and a low-risk group (n=77) based on the median of risk score. A survival analysis was used to compare survival rate between the two groups. The receiver operating characteristic (ROC) curve was used to investigate the value of risk score in predicting the prognosis of children with MYCN-amplified NB. RESULTS: A total of 582 DEGs were screened out, and they were involved in important biological functions such as ribosome composition, expression of cell adhesion molecules, and activity of membrane receptor protein. The multivariate Cox regression model analysis showed that FLVCR2, SCN7A, PRSS12, NTRK1, and XAGE1A genes had a marked influence on the prognosis of the children with NB in the MYCN amplification group (P<0.05). The survival analysis showed that the high-risk group had a significantly lower overall survival rate than the low-risk group (P<0.05). The ROC curve analysis showed that risk score had a certain value in predicting the prognosis of the children with NB in the MYCN amplification group (P<0.05), with an area under the ROC curve of 0.729, an optimal cut-off value of 1.316, a sensitivity of 53.2%, and a specificity of 84.4%. CONCLUSIONS: The mRNA expression of FLVCR2, SCN7A, PRSS12, NTRK1, and XAGE1A genes can be used as biomarkers to predict the prognosis of MYCN-amplified NB, which can help to refine clinical risk stratification.


Assuntos
Neuroblastoma , Criança , Amplificação de Genes , Humanos , Proteínas de Membrana Transportadoras , Proteína Proto-Oncogênica N-Myc , Prognóstico , RNA Mensageiro , Receptores Virais
14.
Am Surg ; 86(2): 127-133, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32167055

RESUMO

Adrenal neuroblastoma (NB) is a relatively common malignancy in children. The Surveillance, Epidemiology, and End Results database was used to present demographic data and a survival analysis with the aim of making tumor management better. The Surveillance, Epidemiology, and End Results database was used to search pediatric patients (age ≤16 years) with NB from 2004 to 2013. The Kaplan-Meier method was used to calculate the overall survival. And, we used Cox regression analysis to determine hazard ratios for prognostic variables. Independent prognostic factors were selected into the nomogram to predict individual's three-, five-, and seven-year overall survival. The study included a total of 1870 pediatric patients with NB in our cohort. Overall, three-, five-, and seven-year survival rates for adrenal NB were 0.777, 0.701, and 0.665, respectively, whereas the rates for nonadrenal NB were 0.891, 0.859, and 0.832, respectively. The multivariate analysis identified age >1 year, no complete resection (CR)/CR, radiation, and regional/distant metastasis as independent predictors of mortality for adrenal NB. Concordance index of the nomogram was 0.665 (95% confidence interval, 0.627-0.703). Pediatric patients with adrenal NB have significantly worse survival than those with nonadrenal NB. Adrenal NB with age <1 year, treated with surgery, no radiation, and localized tumor leads to a better survival. There was no survival difference for patients to receive CR and no CR.


Assuntos
Neoplasias das Glândulas Suprarrenais/mortalidade , Neuroblastoma/mortalidade , Adolescente , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Neuroblastoma/patologia , Neuroblastoma/cirurgia , Nomogramas , Prognóstico , Análise de Regressão , Programa de SEER/estatística & dados numéricos , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo
15.
Int J Mol Sci ; 21(7)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218156

RESUMO

This study examined the biological activities of copaiba essential oil via measurement of its effects on signaling pathways in the SH-SY5Y neuronal cell line. Nanofluidic proteomic technologies were deployed to measure the phosphorylation of biomarker proteins within the signaling cascades. Interestingly, copaiba essential oil upregulated the pI3K/Akt/mTOR, MAPK, and JAK/STAT signaling pathways in neuronal cells. The effects of copaiba essential oil peaked at 30 min post-treatment, with a half-maximal effective concentration (EC50) of approximately 80 ng/mL. Treatment with cannabinoid receptor 2 (CB2) agonist AM1241 or the inverse agonist BML190 abrogated the regulatory effects of copaiba essential oil on the pI3K/Akt/mTOR signaling pathway. Surprisingly, copaiba essential oil also activated the apoptosis signaling pathway and reduced the viability of SH-SY5Y cells with an EC50 of approximately 400 ng/mL. Furthermore, ß-caryophyllene, a principal constituent of copaiba essential oil, downregulated the pI3K/Akt/mTOR signaling pathway. Taken together, the findings indicated that copaiba essential oil upregulated signaling pathways associated with cell metabolism, growth, immunity, and apoptosis. The biological activities of copaiba essential oil were determined to be fast acting, CB2 mediated, and dependent on multiple chemical constituents of the oil. Nanofluidic proteomics provided a powerful means to assess the biological activities of copaiba essential oil.


Assuntos
Fabaceae/química , Neuroblastoma/metabolismo , Óleos Voláteis/farmacologia , Óleos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Humanos , Neuroblastoma/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo
16.
Mol Biol (Mosk) ; 54(1): 128-136, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32163396

RESUMO

Neuroinflammation plays a key role in the pathogenesis of neurodegenerative diseases. Microglial cells are the main immune cells of the central nervous system. On exposure to lipopolysaccharides (LPS, components of the cell wall of Gram-negative enterobacteria), microglia is activated to produce reactive oxygen species (ROS), cytokines, and inflammatory mediators, which may cause neuron death. Exogenous recombinant human heat shock protein 70 (HSP70) was tested for effect on the activation of human microglial and neuroblastoma cells in response to LPS from Escherichia coli. Experiments included cell cultivation separately and transferring the conditioned medium from A-172 microglial cells to SK-N-SH neuroblastoma cells to simulate the effect of microglia treated with LPS and/or HSP70. The levels of ROS, TNFα, and apoptosis in LPS-treated cells were estimated in the presence or absence of HSP70. HSP70 was found to reduce the LPS-induced ROS generation, TNFα production, apoptosis, and necrosis, in both separate cell cultures and neuroblastoma cells grown in the conditioned medium from microglial cells. Signaling pathways involving protein kinases p38MAPK, JNK, and PI3K were demonstrated to play an important role in HSP70-mediated protection of microglial and neuroblastoma cells from LPS-induced apoptosis and ROS production.


Assuntos
Meios de Cultivo Condicionados/química , Proteínas de Choque Térmico HSP70/farmacologia , Lipopolissacarídeos/toxicidade , Neuroblastoma/tratamento farmacológico , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Humanos , Lipopolissacarídeos/imunologia , Microglia/efeitos dos fármacos , Microglia/imunologia , Microglia/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Espécies Reativas de Oxigênio/metabolismo
17.
Medicine (Baltimore) ; 99(10): e19199, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150058

RESUMO

Neuroblastoma is the most prevalent malignancy in infants characterized by heterogeneous prognosis. It is critical to stratify the risks for patients with neuroblastoma. To stratify the risks for neuroblastoma, clinical characteristics of neuroblastoma patients were retrieved from the Therapeutically Applicable Research to Generate Effective Treatment program. All patients were randomly sampled into the development and validation sets. Cox regression was used to construct a prediction nomogram. The discrimination and calibration capacity of the nomogram was assessed. Prognostic index (PI) was calculated and tested to evaluate the performance of the nomogram. This nomogram demonstrated reasonable discrimination and calibration capacity. The nomogram derived PI exhibited acceptable accuracy in predicting the prognosis for neuroblastoma patients. The overall survival rate was significantly different between the PI discriminated high and low-risk patient subgroups. In conclusion, besides traditional staging systems, some newly defined risk factors could be involved in risk stratification for patients with neuroblastoma. Our nomogram may aid the risk stratification for neuroblastoma patients.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neuroblastoma/diagnóstico por imagem , Nomogramas , Área Sob a Curva , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Pré-Escolar , China , Bases de Dados Factuais , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Estadiamento de Neoplasias , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Prognóstico , Reprodutibilidade dos Testes , Risco , Análise de Sobrevida
18.
Crit Rev Oncol Hematol ; 149: 102924, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32172225

RESUMO

Neuroblastoma is the most common extracranial solid tumor, arising from primitive sympathetic ganglion cells, in pediatric patients. The unique features of neuroblastoma include variable clinical behaviors, such as rapid progression to death and maturation to benign ganglioneuroma, followed by regression. Radiation therapy (RT) is usually administered to both the primary tumor bed and persistent metastatic sites after induction chemotherapy for high-risk neuroblastoma. RT to the tumor bed after surgical resection contributes significantly to local disease control and prevention of local relapse, confirming the role of RT. Palliative radiotherapy for metastatic neuroblastoma is also effective and safe and mainly provides symptomatic relief. The late side effects of RT in neuroblastoma patients include growth and developmental failure, hypothyroidism, gastrointestinal dysfunction, neurocognitive defects, pulmonary and cardiac abnormalities, infertility, and secondary cancers. In this article, we reviewed the role and toxicity of RT in neuroblastoma patients.


Assuntos
Quimioterapia de Indução/métodos , Neuroblastoma/radioterapia , Cuidados Paliativos/métodos , Neoplasias de Tecidos Moles/radioterapia , Criança , Irradiação Craniana , Humanos , Lactente , Recidiva Local de Neoplasia , Neuroblastoma/patologia , Neuroblastoma/secundário , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/secundário , Resultado do Tratamento
19.
Ann Oncol ; 31(3): 326-327, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32067674
20.
Nat Commun ; 11(1): 913, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060267

RESUMO

Aggressive cancers often have activating mutations in growth-controlling oncogenes and inactivating mutations in tumor-suppressor genes. In neuroblastoma, amplification of the MYCN oncogene and inactivation of the ATRX tumor-suppressor gene correlate with high-risk disease and poor prognosis. Here we show that ATRX mutations and MYCN amplification are mutually exclusive across all ages and stages in neuroblastoma. Using human cell lines and mouse models, we found that elevated MYCN expression and ATRX mutations are incompatible. Elevated MYCN levels promote metabolic reprogramming, mitochondrial dysfunction, reactive-oxygen species generation, and DNA-replicative stress. The combination of replicative stress caused by defects in the ATRX-histone chaperone complex, and that induced by MYCN-mediated metabolic reprogramming, leads to synthetic lethality. Therefore, ATRX and MYCN represent an unusual example, where inactivation of a tumor-suppressor gene and activation of an oncogene are incompatible. This synthetic lethality may eventually be exploited to improve outcomes for patients with high-risk neuroblastoma.


Assuntos
Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/metabolismo , Proteína Nuclear Ligada ao X/genética , Animais , Pré-Escolar , Estudos de Coortes , Feminino , Amplificação de Genes , Humanos , Lactente , Masculino , Camundongos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mutação , Proteína Proto-Oncogênica N-Myc/metabolismo , Neuroblastoma/genética , Espécies Reativas de Oxigênio/metabolismo , Proteína Nuclear Ligada ao X/metabolismo
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