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1.
Int J Cancer ; 146(3): 819-828, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30980681

RESUMO

Large, comprehensive studies of the risk for neurologic disorders among long-term survivors of noncentral nervous system (CNS) childhood cancers are lacking. Thus, the aim of our study was to assess the lifetime risk of Nordic non-CNS childhood cancer survivors for neurologic disorders. We identified 15,967 5-year survivors of non-CNS childhood cancer diagnosed in Denmark, Iceland, Finland and Sweden in 1943-2008, and 151,118 matched population comparison subjects. In-patient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). A neurologic disorder was diagnosed in 755 of the survivors while 370 were expected, yielding a RR of 2.0 (95% confidence interval (CI) 1.9-2.2). The highest risks were found among survivors of neuroblastoma (4.1; 95% CI 3.2-5.3) and leukemia (2.8; 95% CI 2.4-3.2). The AER decreased from 331 (278-383) excess neurologic disorders per 100,000 person-years 5-9 years after diagnosis to 82 (46-118) ≥ 20 years after diagnosis. Epilepsy was the most common diagnosis (n = 229, 1.4% of all survivors), and significantly increased risks were seen among survivors of eight out of 12 types of childhood cancer. Survivors of neuroblastoma had remarkably high risks (RR ≥ 10) for hospitalization for paralytic syndromes and hydrocephalus, while survivors of leukemia had additional high risks for dementia and encephalopathy. In conclusion, survivors of non-CNS childhood cancer are at high risk for neurologic disorders, especially within the first decade after diagnosis. Therefore, intensive follow-up to identify those who require close management is needed.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Doenças do Sistema Nervoso/epidemiologia , Neoplasias do Sistema Nervoso/complicações , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/terapia , Neoplasias do Sistema Nervoso/mortalidade , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Países Escandinavos e Nórdicos/epidemiologia , Adulto Jovem
2.
Cancer Imaging ; 19(1): 57, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426862

RESUMO

Technical advances in imaging are well demonstrated by MRI (Magnetic Resonance Imaging) and PET (Positron Emission Tomography). Excellent anatomical detail and a lack of ionising radiation make MRI the standard of care for most neuroimaging indications, and advanced sequences are providing an ever-growing ability for lesion characterisation. PET utilising the tracer fluorine-18 fluorodeoxyglucose is widely used in oncology, while newer PET tracers are able to target a growing number of metabolic pathways and cell membrane receptors. The sequential use of these modalities harnesses the strengths of both, providing complementary diagnostic and therapeutic information.Here we outline the ways in which we use MRI and PET in a complementary manner to improve lesion characterisation in neuro-oncology. Most commonly, an abnormality is detected on either PET or MRI, and the addition of the other modality allows a more confident diagnosis and/or demonstrates additional lesions, guiding treatment decisions and, in some cases, obviating the need for biopsy. These modalities may also be combined to guide the treatment of intracranial masses for which the diagnosis is known, such as neuro-endocrine tumour metastases or meningiomas refractory to conventional therapies.


Assuntos
Imagem por Ressonância Magnética/métodos , Neoplasias do Sistema Nervoso/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Fluordesoxiglucose F18 , Humanos , Compostos Radiofarmacêuticos
3.
Artigo em Inglês | MEDLINE | ID: mdl-31370357

RESUMO

Mortality-to-incidence ratios (MIRs) are alternative parameters used to evaluate the prognosis of a disease. In addition, MIRs are associated with the ranking of health care systems and expenditures for certain types of cancer. However, a lack of association between MIRs and pancreatic cancer has been noted. Given the poor prognosis of brain and nervous system cancers, similar to pancreatic cancer, the relation of MIRs and health care disparities is worth investigating. We used the Spearman's rank correlation coefficient (CC) to analyze the correlation between the MIRs in brain and nervous system cancers and inter-country disparities, including expenditures on health and human development index. Interestingly, the MIRs in brain and nervous system cancers are associated with the human development index score (N = 157, CC = -0.394, p < 0.001), current health expenditure (CHE) per capita (N = 157, CC = -0.438, p < 0.001), and CHE as percentage of gross domestic product (N = 157, CC = -0.245, p = 0.002). In conclusion, the MIRs in the brain and nervous system cancer are significantly associated with health expenditures and human development index. However, their role as an indicator of health disparity warrants further investigation.


Assuntos
Saúde Global/economia , Gastos em Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/economia , Neoplasias do Sistema Nervoso/economia , Neoplasias do Sistema Nervoso/epidemiologia , Neoplasias Encefálicas/economia , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/mortalidade , Estudos Transversais , Bases de Dados Factuais , Saúde Global/estatística & dados numéricos , Produto Interno Bruto , Desenvolvimento Humano , Humanos , Incidência , Neoplasias do Sistema Nervoso/mortalidade , Prognóstico
4.
PLoS One ; 14(6): e0218269, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31188873

RESUMO

Although the administration of retinoids represents an important part of treatment for children suffering from high-risk neuroblastomas, approximately 50% of these patients do not respond to this therapy or develop resistance to retinoids during treatment. Our study focused on the comparative analysis of the expression of five genes and corresponding proteins (DDX39A, HMGA1, HMGA2, HOXC9 and PBX1) that have recently been discussed as possible predictive biomarkers of clinical response to retinoid differentiation therapy. Expression of these five candidate biomarkers was evaluated at both the mRNA and protein level in the same subset of 8 neuroblastoma cell lines after treatment with natural or synthetic retinoids. We found that the cell lines that were HMGA2-positive and/or HOXC9-negative have a reduced sensitivity to retinoids. Furthermore, the experiments revealed that the retinoid-sensitive cell lines showed a uniform pattern of change after treatment with both natural and sensitive retinoids: increased DDX39A and decreased PBX1 protein levels. Our results showed that in NBL cells, these putative protein biomarkers are associated with sensitivity or resistance to retinoids, and their endogenous or induced expression can distinguish between these two phenotypes.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores Farmacológicos/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Isotretinoína/farmacologia , Neuroblastoma/genética , Tretinoína/análogos & derivados , Tretinoína/farmacologia , Adolescente , Bexaroteno/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Criança , Pré-Escolar , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Fenretinida/farmacologia , Proteína HMGA1a/genética , Proteína HMGA1a/metabolismo , Proteína HMGA2/genética , Proteína HMGA2/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias do Sistema Nervoso/genética , Neoplasias do Sistema Nervoso/metabolismo , Neoplasias do Sistema Nervoso/patologia , Neoplasias do Sistema Nervoso/cirurgia , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Neuroblastoma/cirurgia , Inclusão em Parafina , Fator de Transcrição 1 de Leucemia de Células Pré-B/genética , Fator de Transcrição 1 de Leucemia de Células Pré-B/metabolismo , Fixação de Tecidos , Adulto Jovem
5.
Cell Mol Life Sci ; 76(11): 2231-2243, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30770954

RESUMO

Current therapies for most non-infectious diseases are directed at or affect functionality of the human translated genome, barely 2% of all genetic information. By contrast, the therapeutic potential of targeting the transcriptome, ~ 70% of the genome, remains largely unexplored. RNA therapeutics is an emerging field that widens the range of druggable targets and includes elements such as microRNA. Here, we sought to screen for microRNA with tumor-suppressive functions in neuroblastoma, an aggressive pediatric tumor of the sympathetic nervous system that requires the development of new therapies. We found miR-323a-5p and miR-342-5p to be capable of reducing cell proliferation in multiple neuroblastoma cell lines in vitro and in vivo, thereby providing a proof of concept for miRNA-based therapies for neuroblastoma. Furthermore, the combined inhibition of the direct identified targets such as CCND1, CHAF1A, INCENP and BCL-XL could reveal new vulnerabilities of high-risk neuroblastoma.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias do Sistema Nervoso/genética , Neuroblastoma/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Criança , Fator 1 de Modelagem da Cromatina/genética , Fator 1 de Modelagem da Cromatina/metabolismo , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Feminino , Células HEK293 , Ensaios de Triagem em Larga Escala , Humanos , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Neoplasias do Sistema Nervoso/mortalidade , Neoplasias do Sistema Nervoso/patologia , Neoplasias do Sistema Nervoso/terapia , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Neuroblastoma/terapia , Neurônios/metabolismo , Neurônios/patologia , Ligação Proteica , Transdução de Sinais , Análise de Sobrevida , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína bcl-X/genética , Proteína bcl-X/metabolismo
6.
Vet Pathol ; 56(3): 342-349, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30663521

RESUMO

In routine diagnostic activity, pathologists may be confronted with nervous system tumors. The lack of clinical information, economic restrictions for additional testing, and the lack of expertise in neuropathology may render the diagnosis challenging. The goals of this study were to assess the agreement in diagnosing nervous system tumors in domestic carnivores among 4 board-certified surgical pathologists without particular expertise in neuropathology and a neuropathologist expert, and to investigate the utility of special stains frequently used in routine diagnostic laboratories. Forty-six tumors (7 cats, 38 dogs, and 1 unknown carnivore) were retrieved and 1 hematoxylin and eosin-stained slide per tumor was selected. Diagnoses (tumor type and subtype) were formulated based on histological features and available clinical information. Confidence in the diagnosis was also scored. Subsequently, a panel of histochemical and immunohistochemical stains (Gordon Sweet silver stain and immunohistochemistry for AE1/AE3, vimentin, glial fibrillary acid protein, S100, neuron-specific enolase and neurofilament) was evaluated by the pathologists, who either confirmed or changed their original diagnoses. Intraobserver and interobserver agreement and confidence in relation to diagnosis before and after analysis of special stains were assessed. The use of special stains increased the complete agreement among surgical pathologists, with regard to tumor type, from 63% to 74%. Cases with a high confidence score had a higher interobserver agreement than cases with a low confidence score. These results suggest that pathologists without expertise in neuropathology agree in the diagnosis of most nervous system tumors, and special stains available in most laboratories only slightly increase this agreement.


Assuntos
Doenças do Gato/diagnóstico , Doenças do Cão/diagnóstico , Neoplasias do Sistema Nervoso/veterinária , Animais , Doenças do Gato/patologia , Gatos , Corantes , Doenças do Cão/patologia , Cães , Feminino , Masculino , Sistema Nervoso/patologia , Neoplasias do Sistema Nervoso/diagnóstico , Neoplasias do Sistema Nervoso/patologia , Variações Dependentes do Observador
7.
Eur J Radiol ; 110: 112-120, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30599846

RESUMO

PURPOSE: This study is aimed at evaluating the potential role of quantitative magnetic resonance diffusion tensor imaging (DTI) and tractography parameters in the detection and characterization of peripheral zone prostate cancer with a particular attention for fiber tract density. MATERIALS AND METHODS: DTI was acquired from eleven high risk, transrectal ultrasound (TRUS)-guided biopsy proven prostate cancers with perineural invasion (histological Gleason score ≥ 7) on a 3 T magnet. Twenty parameters derived from DTI were quantified in cancer and healthy regions of the prostate. In addition, fiber tract density in normal versus cancer tissues was also calculated using DTI tractography. Support vector machine with a radial basis function kernel and area under receiver operator characteristic (ROC) were used to describe and compare the diagnostic performance of combined fractional anisotropy (FA) and mean diffusivity (MD) and other statistically significant DTI parameters. Spearman correlation analysis between DTI parameters and Gleason scores was conducted. RESULTS: Eighteen DTI parameters yielded statistically significant differences between cancer and healthy regions (p-value < 0.05). The ROC curve of all statistically significant DTI parameters between cancer and healthy regions was higher than the area under ROC curve using FA + MD alone (95% confidence interval = 0.988, range = 0.975-1.00) vs (95% confidence interval = 0.935, range = 0.898-0.999), respectively (p-value < 0.05). Fiber tract density was also found to be higher in cancer than in healthy tissues (+38.22%, p-value = 0.010) and may be related to the increase in nerve and vascular density reported in prostate cancer. The linear and relative anisotropy were highly correlated with Gleason score (Spearman correlation factor r = 0.655, p-value = 0.001 and r = 0.667, p-value < 0.001, respectively). CONCLUSIONS: DTI has the potential to provide imaging biomarkers in the detection and characterization of prostate cancer. Novel quantitative parameters derived from DTI and DTI tractography, including fiber tract density, support the use of DTI in the assessment of high grade prostate cancer.


Assuntos
Próstata/patologia , Neoplasias da Próstata/patologia , Adulto , Algoritmos , Anisotropia , Imagem de Tensor de Difusão/métodos , Detecção Precoce de Câncer/métodos , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Neoplasias do Sistema Nervoso/patologia , Estudos Prospectivos , Curva ROC
9.
Curr Med Chem ; 26(30): 5649-5663, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30182849

RESUMO

Long non-coding RNAs (lncRNAs) constitute one of the most broad and diverse classes of cellular transcripts, playing key roles as regulatory molecules in many biological processes. Although the biology of lncRNAs is a new and emerging field of research, several studies have already shown that alterations in the expression of lncRNAs are associated with the development and progression of cancer in different organs and tissues, including central and peripheral nervous system. In this review, we summarize the oncogenic and tumor suppressive roles of lncRNAs in malignant tumors of the nervous system, such as glioma and neuroblastoma, focusing on their functional interactions with DNA, other RNA and protein molecules. We further discuss the potential use of lncRNAs as biomarkers for diagnosis, prognosis and tumor treatment. Gaining insight into the functional association between nervous system malignancies and lncRNAs could offer new perspectives to the development of promising therapeutic tools against cancer.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Neoplasias do Sistema Nervoso/diagnóstico , Neoplasias do Sistema Nervoso/tratamento farmacológico , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , Animais , Antineoplásicos/química , Humanos , Neoplasias do Sistema Nervoso/genética
10.
Sci Data ; 5: 180240, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30375995

RESUMO

Neuroblastoma, a pediatric tumor of the sympathetic nervous system, is predominantly driven by copy number aberrations, which predict survival outcome in global neuroblastoma cohorts and in low-risk cases. For high-risk patients there is still a need for better prognostic biomarkers. Via an international collaboration, we collected copy number profiles of 556 high-risk neuroblastomas generated on different array platforms. This manuscript describes the composition of the dataset, the methods used to process the data, including segmentation and aberration calling, and data validation. t-SNE analysis shows that samples cluster according to MYCN status, and shows a difference between array platforms. 97.3% of samples are characterized by the presence of segmental aberrations, in regions frequently affected in neuroblastoma. Focal aberrations affect genes known to be involved in neuroblastoma, such as ALK and LIN28B. To conclude, we compiled a unique large copy number dataset of high-risk neuroblastoma tumors, available via R2 and a Shiny web application. The availability of patient survival data allows to further investigate the prognostic value of copy number aberrations.


Assuntos
Variações do Número de Cópias de DNA , Neoplasias do Sistema Nervoso/genética , Neuroblastoma/genética , Biomarcadores Tumorais/genética , Criança , Pré-Escolar , DNA de Neoplasias/genética , Humanos
12.
Zhonghua Liu Xing Bing Xue Za Zhi ; 39(7): 988-992, 2018 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-30060317

RESUMO

Objective: To investigate the influence of postoperative infection on average hospitalization days and medical costs in patients with nervous system tumor. Methods: The tumor patients treated in neurosurgery ward from July 1, 2015 to June 30, 2017 were included in the study. The patients with and without postoperative infections were divided into a case group and a control group, respectively (1 ∶ 1 ratio), matched by admission time (±3 months), age (±5 years) and surgical site. Average hospitalization days and medical costs between the two groups were analyzed. Results: The incidence of postoperative infection was 5.66%, the surgical site infection and lower respiratory tract infection accounted for 54.72% and 31.32% of the total, respectively. The median of hospitalization days in the case group was 20.5, 8.5 days longer than that in the control group (Z=-10.618, P<0.001). The median of total medical costs in the case group was 91 573.42 yuan, higher than that of the control group by 30 518.17 yuan (Z=-9.988, P<0.001). The average costs of surgical and lower respiratory tract infection were 84 888.50 yuan and 110 442.64 yuan, respectively. Among them, surgical site infection or lower respiratory tract infection caused the extra cost of 23 627.49 yuan (Z=-6.627, P<0.001) and 43 631.36 yuan (Z=-4.954, P<0.001), respectively. Conclusions: Postoperative infection greatly increased the patient's financial burden, prolonged the hospitalization duration and resulted in unnecessary use of health resources. It is necessary to pay close attention to postoperative infection.


Assuntos
Custos e Análise de Custo , Hospitalização/economia , Neoplasias do Sistema Nervoso/cirurgia , Infecção da Ferida Cirúrgica/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Neoplasias do Sistema Nervoso/economia , Infecção da Ferida Cirúrgica/terapia
13.
Sci Total Environ ; 642: 1406-1414, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30045521

RESUMO

BACKGROUND AND OBJECTIVE: Previous epidemiological studies suggested association between parental occupational exposure to extremely low frequency magnetic fields (ELF-MF) and risk of childhood nervous system tumors, but the results were inconsistent. We conducted a meta-analysis of case-control and cohort studies to re-evaluate this association. METHODS: Relevant studies were identified by searching PubMed and Web of Science databases as well as by manual searching. Summary odds ratio (OR) with 95% confidence interval (CI) were pooled with a fixed-effects or random-effects model. RESULTS: A total of 22 eligible articles (21 case-control studies and 1 cohort study) were included for the quantitative analysis. The results showed that parental occupational ELF-MF exposure was significantly associated with an increased risk of childhood nervous system tumors (OR = 1.11, 95% CI = 1.02-1.21), and this association remained in studies on central nervous system (CNS) tumors (OR = 1.13, 95% CI = 1.02-1.27) but not neuroblastoma (OR = 1.02, 95% CI = 0.92-1.14). Furthermore, maternal (OR = 1.14, 95% CI = 1.05-1.23) but not paternal (OR = 1.05, 95% CI = 0.98-1.13) occupational ELF-MF exposure significantly increased risk of childhood nervous system tumors. Increased risk of childhood CNS tumors was significant associated with maternal (OR = 1.16, 95% CI = 1.06-1.26) but not paternal (OR = 1.15, 95% CI = 0.98-1.34) occupational ELF-MF exposure. CONCLUSION: In conclusion, our results provide limited evidence for the association between maternal occupational exposure to ELF-MF and increased risk of childhood CNS tumors, which should be explained with cautions. Future studies are needed to further evaluate the association of paternal occupational ELF-MF exposure with risk of childhood CNS tumors.


Assuntos
Campos Magnéticos , Neoplasias do Sistema Nervoso/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Criança , Estudos de Coortes , Campos Eletromagnéticos , Feminino , Humanos , Risco
14.
Artigo em Inglês | MEDLINE | ID: mdl-29866879

RESUMO

Pneumocystis jirovecii pneumonia is a life-threatening opportunistic infection in children receiving immunosuppressive chemotherapy. Without prophylaxis, up to 25% of pediatric oncology patients receiving chemotherapy will develop Pneumocystis jirovecii pneumonia. Trimethoprim-sulfamethoxazole is the preferred agent for prophylaxis against Pneumocystis jirovecii pneumonia. Pentamidine may be an acceptable alternative for pediatric patients unable to tolerate trimethoprim-sulfamethoxazole. A retrospective review was conducted of pediatric oncology patients who received ≥1 dose of pentamidine for Pneumocystis jirovecii pneumonia prophylaxis between January 2007 and August 2014. Electronic medical records were reviewed to determine the incidence of breakthrough Pneumocystis jirovecii pneumonia or discontinuation of pentamidine associated with adverse events. A total of 754 patients received pentamidine prophylaxis during the period. There were no cases of probable or proven Pneumocystis pneumonia, and 4 cases (0.5%) of possible Pneumocystis pneumonia. The incidence of possible breakthrough Pneumocystis pneumonia was not significantly different between subgroups based on age (<12 months [1.7%] versus ≥12 months [0.4%], P = 0.3), route of administration (aerosolized [0%] versus intravenous [1.0%], P = 0.2), or hematopoietic stem cell transplant status (transplant [0.4%] versus no transplant [0.8%], P = 0.6). Pentamidine was discontinued due to an adverse drug event in 23 children (3.1%), more frequently for aerosolized than for intravenous administration (7.6% versus 2.2%, respectively, P = 0.004). Intravenous or inhaled pentamidine may be a safe and effective second-line alternative for prophylaxis against Pneumocystis jirovecii pneumonia in children with cancer receiving immunosuppressive chemotherapy or hematopoietic stem cell transplantation.


Assuntos
Antifúngicos/administração & dosagem , Neoplasias Hematológicas/imunologia , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Neoplasias do Sistema Nervoso/imunologia , Pentamidina/administração & dosagem , Pneumonia por Pneumocystis/prevenção & controle , Administração Intravenosa , Aerossóis , Antifúngicos/efeitos adversos , Pré-Escolar , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/patologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunossupressores/administração & dosagem , Lactente , Recém-Nascido , Masculino , Neoplasias do Sistema Nervoso/tratamento farmacológico , Neoplasias do Sistema Nervoso/patologia , Pentamidina/efeitos adversos , Pneumocystis carinii/efeitos dos fármacos , Pneumocystis carinii/crescimento & desenvolvimento , Pneumonia por Pneumocystis/microbiologia , Estudos Retrospectivos , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem
15.
J Neurooncol ; 139(3): 679-688, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29846895

RESUMO

INTRODUCTION: Stereotactic radiation technique is widely reported as an effective treatment for various types of benign intracranial tumors. However, single fraction radiosurgery (SRS) is not recommended for tumors located close to the optic apparatus due to the restricted radiation tolerance dose of the optic pathway. Recent advances in radiotherapy include advanced frameless radiosurgery using hypofractionated stereotactic radiotherapy (HSRT), and this has become an attractive treatment option for perioptic tumors within 2-3 mm of the optic pathway. Accordingly, the aim of this study was to investigate the clinical outcomes of perioptic tumors treated with HSRT using CyberKnife® (CK) robotic radiosurgery system relative to tumor control, vision preservation and toxicity. METHODS: This retrospective analysis of prospectively collected data included consecutive 100 patients that were diagnosed with and treated for perioptic tumor at the Radiosurgery center, Ramathibodi Hospital during the January 2009 to December 2012 study period. RESULTS: The median tumor volume was 6.81 cm3 (range 0.37-51.6), and the median prescribed dose was 25 Gy (range 20-35) in 5 fractions (range 3-5). After the median follow-up time of 37.5 months (range 21-103), two patients developed tumor progression at 6 and 34 months post-HSRT. The 5-year overall survival was 97%, and the 5-year local control was 97.5%. At the last follow-up, no vision deterioration or newly developed hypopituitarism was detected in our study. CONCLUSIONS: Although a longer follow-up is needed, HSRT yields a high level of local control and vision preservation, and should be considered a treatment of choice for perioptic tumor located close to the optic apparatus.


Assuntos
Neoplasias Meníngeas/radioterapia , Neoplasias de Tecido Vascular/radioterapia , Neoplasias do Sistema Nervoso/radioterapia , Neoplasias Hipofisárias/radioterapia , Radiocirurgia , Adolescente , Adulto , Idoso , Olho , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Meníngeas/mortalidade , Pessoa de Meia-Idade , Neoplasias de Tecido Vascular/mortalidade , Neoplasias do Sistema Nervoso/mortalidade , Neoplasias Hipofisárias/mortalidade , Estudos Prospectivos , Hipofracionamento da Dose de Radiação , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
16.
Semin Neurol ; 38(1): 1-2, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29548044
18.
Semin Neurol ; 38(1): 73-85, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29548054

RESUMO

Neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis are a group of related classically inherited but often times sporadic tumor suppressor syndromes. Neuro-oncologists should recognize these syndromes, initiate necessary tests in patients with a clinical suspicion, and support genetic counseling of patients and families. In this review, clinical presentation, diagnostic criteria, day-to-day management including supportive care as well as updates on genetics, and experimental treatment strategies are discussed.


Assuntos
Neoplasias do Sistema Nervoso , Neurilemoma , Neurofibromatoses , Neoplasias Cutâneas , Humanos , Neoplasias do Sistema Nervoso/genética , Neoplasias do Sistema Nervoso/patologia , Neoplasias do Sistema Nervoso/terapia , Neurilemoma/genética , Neurilemoma/patologia , Neurilemoma/terapia , Neurofibromatoses/genética , Neurofibromatoses/patologia , Neurofibromatoses/terapia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia
19.
J Int Med Res ; 46(3): 1209-1220, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29322842

RESUMO

Objectives Neuroblastoma (NB) is the most common pediatric solid tumor derived from the sympathetic nervous system. MYCN is amplified in nearly half of patients with NB, and its association with rapid disease progression and poor outcome is controversial. Characterization of cancer stem cells (CSCs) in NBs has been rarely studied. This study was performed to determine whether MYCN and CD133+ CSCs are associated with chemotherapy resistance and the survival time of patients with NB. Methods Fifty patients with an unequivocal pathological diagnosis of NB were recruited. MYCN expression levels were measured before therapy. CSCs were derived and their multipotency tested by directed differentiation. The patients' responses to chemotherapy and average survival time were compared among the groups as follows: CD133+, CD133-, MYCN amplification ≥5 times (i.e. MYCN≥5), MYCN<5, CD133+ plus MYCN≥5, and CD133- plus MYCN<5. Results CD133+ CSCs differentiated into neuron-like cells. CD133+ patients had a significantly poorer response to chemotherapy than did CD133- patients. CD133+ plus MYCN≥5 patients had a significantly shorter average survival time than did CD133- plus MYCN<5 patients. Conclusions CD133+ CSCs are chemoresistance. CD133 expression and MYCN amplification can be used together as a prognostic indicator of disease outcome.


Assuntos
Antígeno AC133/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Proteína Proto-Oncogênica N-Myc/genética , Neoplasias do Sistema Nervoso/genética , Neuroblastoma/genética , Antineoplásicos/uso terapêutico , Diferenciação Celular , Criança , Pré-Escolar , Resistencia a Medicamentos Antineoplásicos , Feminino , Dosagem de Genes , Humanos , Lactente , Masculino , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias do Sistema Nervoso/diagnóstico , Neoplasias do Sistema Nervoso/tratamento farmacológico , Neoplasias do Sistema Nervoso/mortalidade , Neuroblastoma/diagnóstico , Neuroblastoma/tratamento farmacológico , Neuroblastoma/mortalidade , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Prognóstico , Análise de Sobrevida , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/patologia
20.
Biochem J ; 475(2): 531-545, 2018 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-29295892

RESUMO

The eukaryotic initiation factor 5A (eIF5A), which contributes to several crucial processes during protein translation, is the only protein that requires activation by a unique post-translational hypusine modification. eIF5A hypusination controls cell proliferation and has been linked to cancer. eIF5A hypusination requires the enzymes deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase and uniquely depends on the polyamine (PA) spermidine as the sole substrate. Ornithine decarboxylase (ODC) is the rate-limiting enzyme in PA biosynthesis. Both ODC and PAs control cell proliferation and are frequently dysregulated in cancer. Since only spermidine can activate eIF5A, we chose the hypusine-PA nexus as a rational target to identify new drug combinations with synergistic antiproliferative effects. We show that elevated mRNA levels of the two target enzymes DHPS and ODC correlate with poor prognosis in a large cohort of neuroblastoma (NB) tumors. The DHPS inhibitor GC7 (N1-guanyl-1,7-diaminoheptane) and the ODC inhibitor α-difluoromethylornithine (DFMO) are target-specific and in combination induced synergistic effects in NB at concentrations that were not individually cytotoxic. Strikingly, while each drug alone at higher concentrations is known to induce p21/Rb- or p27/Rb-mediated G1 cell cycle arrest, we found that the drug combination induced caspase 3/7/9, but not caspase 8-mediated apoptosis, in NB cells. Hypusinated eIF5A levels and intracellular spermidine levels correlated directly with drug treatments, signifying specific drug targeting effects. This two-pronged GC7/DFMO combination approach specifically inhibits both spermidine biosynthesis and post-translational, spermidine-dependent hypusine-eIF5A activation, offering an exciting clue for improved NB drug therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Eflornitina/farmacologia , Regulação Neoplásica da Expressão Gênica , Guanina/análogos & derivados , Neoplasias do Sistema Nervoso/genética , Neuroblastoma/genética , Fatores de Iniciação de Peptídeos/genética , Proteínas de Ligação a RNA/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Sinergismo Farmacológico , Guanina/farmacologia , Humanos , Lisina/análogos & derivados , Lisina/metabolismo , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Neoplasias do Sistema Nervoso/metabolismo , Neoplasias do Sistema Nervoso/mortalidade , Neoplasias do Sistema Nervoso/patologia , Neuroblastoma/metabolismo , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Ornitina Descarboxilase/genética , Ornitina Descarboxilase/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Fatores de Iniciação de Peptídeos/antagonistas & inibidores , Fatores de Iniciação de Peptídeos/metabolismo , Prognóstico , Processamento de Proteína Pós-Traducional , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/metabolismo , Proteína do Retinoblastoma/genética , Proteína do Retinoblastoma/metabolismo , Transdução de Sinais , Espermidina/metabolismo
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