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1.
J Oncol Pharm Pract ; 26(1): 228-231, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30885040

RESUMO

BACKGROUND: Hypersensitivity reactions to etoposide have been reported and patients have been safely transitioned to etoposide phosphate for continued therapy. However, the safety and efficacy of substituting etoposide phosphate for etoposide has not been well established in pediatric orthopedic malignancies. The aim of this study is to determine whether etoposide phosphate can be substituted for etoposide in pediatric orthopedic malignancies. METHODS: A chart review of pediatric patients who developed hypersensitivity reactions to etoposide while being treated for orthopedic malignancies was performed at a large academic medical center. Three patients were identified, two with Ewing sarcoma and one with an osteosarcoma. All three patients experienced hypersensitivity reactions to their first doses of etoposide and were switched to etoposide phosphate for further therapy. RESULTS: After premedication, all three patients tolerated full doses of etoposide phosphate without a graded dose challenge or desensitization. Two of the patients were premedicated with diphenhydramine alone, while the third received diphenhydramine and dexamethasone. CONCLUSIONS: Etoposide phosphate is a potentially safe alternative for pediatric patients with orthopedic malignancies who experience etoposide hypersensitivity. However, caution is needed as there are cases of etoposide phosphate hypersensitivity.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Hipersensibilidade a Drogas/etiologia , Etoposídeo/análogos & derivados , Etoposídeo/efeitos adversos , Compostos Organofosforados/uso terapêutico , Osteossarcoma/tratamento farmacológico , Sarcoma de Ewing/tratamento farmacológico , Adolescente , Etoposídeo/uso terapêutico , Humanos , Masculino
3.
Pathol Res Pract ; 215(10): 152613, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31471105

RESUMO

BACKGROUND: In Ewing sarcomas (ES), histological response to polychemotherapy is the main prognostic factor. We aimed at evaluating the histological response separately for the extraosseous and intraosseous tumor compartment as well as its prognostic influence. METHODS: Thirty-one patients with ES and marked soft tissue expansion, treated at our department between January 2006 and December 2015, were retrospectively included. Data was taken from medical records. Original histologic specimens of the resected tumors were re-evaluated separately for intra- and extraosseous tumor regression according to Salzer-Kuntschik regression grading. Multivariate survival analysis with stepwise backward variable selection was calculated to determine the impact of extraosseous and intraosseous regression on prognosis. RESULTS: All patients had received chemotherapy, 15 (48.4%) had been administered preoperative radiotherapy. Extraosseous tumor regression was significantly worse than intraosseous regression (Wilcoxon signed-rank test, p = 0.018). While neither intraosseous nor extraosseous tumor regression had an impact on overall survival, extraosseous complete remission had a beneficial impact on event-free-survival in the multivariate analysis (Cox-regression; hazard ratio: 0.148, 95% confidence interval 0.031-0.707, p = 0.017). CONCLUSIONS: On average, regression of ES seems to be worse in the extraosseous tumor compartment following preoperative chemotherapy. Moreover, extraosseous tumor regression may have a stronger prognostic influence on event-free survival than intraosseous regression.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Sarcoma de Ewing/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adolescente , Adulto , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sarcoma de Ewing/patologia , Neoplasias de Tecidos Moles/patologia , Resultado do Tratamento , Adulto Jovem
4.
Int J Mol Sci ; 20(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370265

RESUMO

Osteosarcoma and Ewing sarcoma are the most common malignant primary bone tumors mainly occurring in children, adolescents and young adults. Current standard therapy includes multidrug chemotherapy and/or radiation specifically for Ewing sarcoma, associated with tumor resection. However, patient survival has not evolved for the past decade and remains closely related to the response of tumor cells to chemotherapy, reaching around 75% at 5 years for patients with localized forms of osteosarcoma or Ewing sarcoma but less than 30% in metastatic diseases and patients resistant to initial chemotherapy. Despite Ewing sarcoma being characterized by specific EWSR1-ETS gene fusions resulting in oncogenic transcription factors, currently, no targeted therapy could be implemented. It seems even more difficult to develop a targeted therapeutic strategy in osteosarcoma which is characterized by high complexity and heterogeneity in genomic alterations. Nevertheless, the common point between these different bone tumors is their ability to deregulate bone homeostasis and remodeling and divert them to their benefit. Therefore, targeting different actors of the bone tumor microenvironment has been hypothesized to develop new therapeutic strategies. In this context, it is well known that the Wnt/ß-catenin signaling pathway plays a key role in cancer development, including osteosarcoma and Ewing sarcoma as well as in bone remodeling. Moreover, recent studies highlight the implication of the Wnt/ß-catenin pathway in angiogenesis and immuno-surveillance, two key mechanisms involved in metastatic dissemination. This review focuses on the role played by this signaling pathway in the development of primary bone tumors and the modulation of their specific microenvironment.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica , Osteossarcoma/tratamento farmacológico , Sarcoma de Ewing/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Adolescente , Neoplasias Ósseas/genética , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/mortalidade , Osso e Ossos , Criança , Humanos , Metástase Linfática , Terapia de Alvo Molecular/métodos , Neovascularização Patológica/genética , Neovascularização Patológica/imunologia , Neovascularização Patológica/mortalidade , Neovascularização Patológica/prevenção & controle , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/imunologia , Osteossarcoma/genética , Osteossarcoma/imunologia , Osteossarcoma/mortalidade , Proteínas Proto-Oncogênicas c-ets/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Proto-Oncogênicas c-ets/imunologia , Proteína EWS de Ligação a RNA/antagonistas & inibidores , Proteína EWS de Ligação a RNA/genética , Proteína EWS de Ligação a RNA/imunologia , Sarcoma de Ewing/genética , Sarcoma de Ewing/imunologia , Sarcoma de Ewing/mortalidade , Análise de Sobrevida , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Via de Sinalização Wnt/efeitos dos fármacos , Adulto Jovem , beta Catenina/antagonistas & inibidores , beta Catenina/genética , beta Catenina/imunologia
5.
Anticancer Res ; 39(8): 4463-4465, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366545

RESUMO

This case report describes a patient with a rare occurrence of primary spinal intramedullary Ewing's sarcoma (ES) in the cervical and thoracic spine. The older age of disease occurrence, uncommon location in the cervical and thoracic spine, and EWSR1 gene fusion as the basis of diagnosis are unique features of this case. There is no clear protocol for treatment of primary extraskeletal ES of the spine, with controversy between evidence for pursuing surgery versus a combination of radiation and chemotherapy. Our patient was treated with temozolomide chemotherapy for recurrent metastatic disease of primary ES of the spine.


Assuntos
Tumores Neuroectodérmicos Primitivos/tratamento farmacológico , Proteína EWS de Ligação a RNA/genética , Sarcoma de Ewing/tratamento farmacológico , Temozolomida/administração & dosagem , Adulto , Idoso , Humanos , Masculino , Pescoço/patologia , Tumores Neuroectodérmicos Primitivos/genética , Tumores Neuroectodérmicos Primitivos/patologia , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia , Coluna Vertebral/efeitos dos fármacos , Coluna Vertebral/patologia , Parede Torácica/efeitos dos fármacos , Parede Torácica/patologia
6.
Pediatr Blood Cancer ; 66(11): e27938, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31347793

RESUMO

The therapies used to treat Ewing sarcoma are associated with a risk of second malignant neoplasm (SMN). We conducted a systematic review to pool available evidence on the risks, types, and outcomes after SMN. We obtained 52 articles that met inclusion criteria. Cumulative incidence rates of SMN ranged from 0.9 to 8.4% and 10.1 to 20.5% at 5 and 30 years after initial diagnosis. Of the 327 reported SMNs, 63.6% were solid tumors, although acute myeloid leukemia /myelodysplastic syndrome was the single most commonly diagnosed SMN, with generally poor outcomes. Patients treated for Ewing sarcoma are at substantial risk of SMN, with a broad range of reported secondary cancers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Radioterapia/efeitos adversos , Sarcoma de Ewing , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/cirurgia , Carcinoma/epidemiologia , Carcinoma/etiologia , Carcinoma/terapia , Humanos , Incidência , Leucemia Mieloide/epidemiologia , Leucemia Mieloide/etiologia , Leucemia Mieloide/terapia , Linfoma/epidemiologia , Linfoma/etiologia , Linfoma/terapia , Melanoma/epidemiologia , Melanoma/etiologia , Melanoma/terapia , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/terapia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/terapia , Risco , Sarcoma/epidemiologia , Sarcoma/etiologia , Sarcoma/terapia , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/radioterapia , Sarcoma de Ewing/cirurgia , Fatores de Tempo , Resultado do Tratamento
7.
Gulf J Oncolog ; 1(30): 22-28, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31242978

RESUMO

INTRODUCTION: Paediatric soft tissue sarcoma treatments and outcomes have improved significantly in the last few decades. However, a significant number of patients still succumb to the disease. In low-middle income countries there are dual problems of advanced disease at presentation and financial burden leading to poor compliance to therapy. Hence, we designed a low-cost oral metronomic chemotherapy protocol for these patients and studied the responses and toxicities to therapy in a tertiary referral hospital. PATIENTS AND METHODS: This is retrospective, single institutional, observational study. We retrospectively reviewed data of patients with relapsed, refractory or metastatic soft tissue sarcoma (STS) [ Ewing Sarcoma (ES); Rhabdomyosarcoma (RMS) or other STS] who were treated with the metronomic protocol of oral Tamoxifen, Etoposide and Cyclophosphamide (TEC) during the period April 1998 to September 2013, at the Tata Memorial Hospital, Parel, Mumbai. Patients with ES and RMS were primarily treated on our Institutional protocols. The patients included in the analysis were those who had relapsed after the primary protocols and then treated with metronomic TEC protocol; or those with primary refractory or metastatic disease (RMS, ES) and received metronomic TEC therapy. RESULTS: 49 patients were enrolled. Among the 49 patients, 32 were diagnosed ES, 13 RMS and 4 other STS. For the whole cohort response rates (RR) were 59% and clinical benefit rate (CBR) was 79%. Patients in the study were grouped into the following subgroups. Systemic recurrent/relapsed disease (N=24), metastatic disease at presentation (N=15) and local disease (refractory/recurrent) (N=10). None of the patients required blood or platelet support or admission for supportive care. The PFS for the above groups were 16.8 months, 12.5 months and 126.68 months respectively. This compares favorably with other historical cohorts in a similar setting. CONCLUSIONS: This study provides a preliminary evidence efficacy and tolerability of metronomic chemotherapy in poor risk ES and RMS. It also demonstrates that with this low-cost low risk treatment few patients could go into long term remissions despite high disease burden.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia/mortalidade , Rabdomiossarcoma/mortalidade , Terapia de Salvação , Sarcoma de Ewing/mortalidade , Sarcoma/mortalidade , Administração Metronômica , Adolescente , Adulto , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/secundário , Sarcoma/tratamento farmacológico , Sarcoma/secundário , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/secundário , Taxa de Sobrevida , Tamoxifeno/administração & dosagem , Adulto Jovem
8.
Pediatr Blood Cancer ; 66(9): e27888, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31207107

RESUMO

BACKGROUND: Ewing sarcoma and desmoplastic small round cell tumors (DSRCT) are rare and clinically aggressive sarcomas usually characterized by oncogenic fusion proteins involving EWS. Emerging studies of Ewing sarcoma have demonstrated EWS-FLI1-driven chromatin remodeling as a key aspect of tumorigenicity. In particular, the lysine-specific demethylase KDM1A/LSD1 is linked to transcriptional regulation of target genes orchestrated by the EWS portion of the fusion protein interacting with repressive chromatin-remodeling complexes. Consistent with this model, depletion of KDM1A supports it is a molecular therapeutic target in Ewing sarcoma cells, but effective drugs need to be identified. PROCEDURE: A comprehensive phenotypic analysis of the effects of catalytic KDM1A inhibitors ORY-1001 and GSK2879552, including clinically relevant doses, was carried out in 2D and 3D spheroid models of Ewing sarcoma and DSRCT. RESULTS: Catalytic inhibition of KDM1A did not affect cell viability in 2D and 3D assays and had no impact on invasion in a 3D assay. CONCLUSIONS: Overall, evidence presented here does not support inhibition of KDM1A catalytic demethylase activity as an effective therapeutic strategy for Ewing sarcoma or DSRCT. However, roles of KDM1A beyond its demethylase activity should be considered for these sarcomas.


Assuntos
Antineoplásicos , Neoplasias Ósseas , Inibidores Enzimáticos , Histona Desmetilases/antagonistas & inibidores , Sarcoma de Ewing , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/enzimologia , Linhagem Celular Tumoral , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Histona Desmetilases/metabolismo , Humanos , Proteínas de Fusão Oncogênica/metabolismo , Proteína Proto-Oncogênica c-fli-1/metabolismo , Proteína EWS de Ligação a RNA/metabolismo , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/enzimologia
9.
Mol Med Rep ; 20(1): 135-140, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115517

RESUMO

Toosendanin, a triterpenoid extracted from the root bark of Melia toosendan, has its origin from traditional Chinese medicine and has been used as a non­polluting and pesticide­free plant insecticide in China for fruit and vegetable production. In recent years, toosendanin has been found to inhibit tumor cell proliferation and promote tumor cell apoptosis. Ewing's sarcoma (ES) is the second most common primary malignant bone and soft tissue tumor in children and adolescents. Although the overall prognosis of ES has improved, the 5­year survival rate has not significantly increased. To analyze the role of toosendanin on ES progression, CCK­8 viability assay, flow cytometry, Hoechst 33258 staining and western blotting were performed. The present results suggested that toosendanin suppressed cell viability and induced apoptosis in human SK­ES­1 cells compared with DMSO treatment. In addition, in the present study, toosendanin was found to upregulate the expression of Bax and downregulate the expression of Bcl­2, altering the Bax/Bcl­2 ratio. Additionally, toosendanin promoted the release of cytochrome c, resulting in the activation of the mitochondrial apoptotic pathway, thus inducing the activation of caspase­9 and caspase­3, and the cleavage of PARP. Our results demonstrated that toosendanin inhibited the growth of ES cells in a dose­dependent manner and triggered mitochondrial apoptotic pathway to induce apoptosis. Therefore, toosendanin can potentially be utilized as an anticancer botanical drug for the treatment of ES.


Assuntos
Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Mitocôndrias/efeitos dos fármacos , Sarcoma de Ewing/tratamento farmacológico , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 9/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mitocôndrias/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/genética
10.
Dev Period Med ; 23(1): 39-44, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30954980

RESUMO

OBJECTIVE: Background: Patients with Ewing sarcoma have a dismal outcome. Maintenance treatment with trofosfamide has been proposed as an effective regimen for some paediatric malignancies. Aim: We sought to evaluate the schedule of trofosfamide for patients with high-risk primary bone Ewing sarcoma. PATIENTS AND METHODS: Materials and methods: Fifteen patients with primary bone Ewing sarcoma received treatment with trofosfamide (150 mg/m2 p.o. days 1-10) every 28 days. All patients had standard tumour imaging and laboratory evaluation. All toxicities were documented. RESULTS: Results: A total of 90 cycles (median 5 cycles/patient) were administered. A complete response was maintained in nine patients, while six patients had disease progression during treatment. Median time to progression was 1.9 months (range 1.8 to 4.6). Eleven patients (73.3%) are alive including nine with no evidence of disease with a median follow-up of 3.9 years (range 1.4 to 7.6). All patients with active disease at the start of the trofosfamide treatment died. There were no significant toxicities. CONCLUSION: Conclusions: Treatment with trofosfamide is well-tolerated and could have a role to maintain response in patients with primary bone Ewing sarcoma. Further studies are needed to better define the use of this regimen in the upfront management of those patients.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Ciclofosfamida/análogos & derivados , Sarcoma de Ewing/tratamento farmacológico , Adolescente , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/diagnóstico por imagem , Criança , Pré-Escolar , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Masculino , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/diagnóstico por imagem , Resultado do Tratamento , Adulto Jovem
11.
Molecules ; 24(6)2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30893786

RESUMO

BACKGROUND: Improved outcome prediction is vital for the delivery of risk-adjusted, appropriate and effective care to paediatric patients with Ewing sarcoma-the second most common paediatric malignant bone tumour. Fourier transform infrared (FTIR) spectroscopy of tissues allows the bulk biochemical content of a biological sample to be probed and makes possible the study and diagnosis of disease. METHODS: In this retrospective study, FTIR spectra of sections of biopsy-obtained bone tissue were recorded. Twenty-seven patients (between 5 and 20 years of age) with newly diagnosed Ewing sarcoma of bone were included in this study. The prognostic value of FTIR spectra obtained from Ewing sarcoma (ES) tumours before and after neoadjuvant chemotherapy were analysed in combination with various data-reduction and machine learning approaches. RESULTS: Random forest and linear discriminant analysis supervised learning models were able to correctly predict patient mortality in 92% of cases using leave-one-out cross-validation. The best performing model for predicting patient relapse was a linear Support Vector Machine trained on the observed spectral changes as a result of chemotherapy treatment, which achieved 92% accuracy. CONCLUSION: FTIR spectra of tumour biopsy samples may predict treatment outcome in paediatric Ewing sarcoma patients with greater than 92% accuracy.


Assuntos
Aprendizado de Máquina , Espectrofotometria Infravermelho , Adolescente , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Criança , Pré-Escolar , Humanos , Terapia Neoadjuvante , Prognóstico , Estudos Retrospectivos , Sarcoma de Ewing/diagnóstico por imagem , Sarcoma de Ewing/tratamento farmacológico , Espectroscopia de Infravermelho com Transformada de Fourier , Resultado do Tratamento , Adulto Jovem
12.
Cell Death Dis ; 10(2): 116, 2019 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-30741933

RESUMO

Ewing sarcoma (EwS) is an aggressive cancer characterized by chromosomal translocations generating fusions of the EWSR1 gene with ETS transcription factors (in 85% FLI1). EWSR1-FLI1 induces gene expression via binding to enhancer-like GGAA-microsatellites, whose activity correlates with the number of consecutive GGAA-repeats. Herein we investigate the role of the secretory neuropeptide CALCB (calcitonin-related polypeptide ß) in EwS, which signals via the CGRP (calcitonin gene-related peptide) receptor complex, containing RAMP1 (receptor activity modifying protein 1) as crucial part for receptor specificity. Analysis of 2678 gene expression microarrays comprising 50 tumor entities and 71 normal tissue types revealed that CALCB is specifically and highly overexpressed in EwS. Time-course knockdown experiments showed that CALCB expression is tightly linked to that of EWSR1-FLI1. Consistently, gene set enrichment analyses of genes whose expression in primary EwS is correlated to that of CALCB indicated that it is co-expressed with other EWSR1-FLI1 target genes and associated with signatures involved in stemness and proliferation. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) data for FLI1 and histone marks from EwS cell lines demonstrated that EWSR1-FLI1 binds to a GGAA-microsatellite close to CALCB, which exhibits characteristics of an active enhancer. Reporter assays confirmed the strong EWSR1-FLI1- and length-dependent enhancer activity of this GGAA-microsatellite. Mass spectrometric analyses of EwS cell culture supernatants demonstrated that CALCB is secreted by EwS cells. While short-term RNA interference-mediated CALCB knockdown had no effect on proliferation and clonogenic growth of EwS cells in vitro, its long-term knockdown decreased EwS growth in vitro and in vivo. Similarly, knockdown of RAMP1 reduced clonogenic/spheroidal growth and tumorigenicity, and small-molecule inhibitors directed against the RAMP1-comprising CGRP receptor reduced growth of EwS. Collectively, our findings suggest that CALCB is a direct EWSR1-FLI1 target and that targeting the CALCB/RAMP1 axis may offer a new therapeutic strategy for inhibition of EwS growth.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Proteína 1 Modificadora da Atividade de Receptores/metabolismo , Sarcoma de Ewing/patologia , Animais , Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Peptídeo Relacionado com Gene de Calcitonina/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos NOD , Repetições de Microssatélites/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/uso terapêutico , Proteína 1 Modificadora da Atividade de Receptores/antagonistas & inibidores , Proteína 1 Modificadora da Atividade de Receptores/genética , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Transplante Heterólogo
13.
Clin Transl Oncol ; 21(10): 1374-1382, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30798513

RESUMO

PURPOSE: Survival in Ewing's sarcoma (ES) has increased with the use of chemotherapy. Surgical techniques such as limb salvage (LS) have been developed. Survival and adverse events have been widely studied in general series of ES, but there are few specific series of ES cases treated by LS, despite this being the most commonly used (surgical) approach. The aim of this study was to determine survival and prognostic factors in ES patients undergoing LS. PATIENTS AND METHODS: We analysed all ES patients treated between January 1984 and May 2008 and selected all those treated by systemic multimodal therapy and LS. We assessed the influence of patient characteristics, tumour parameters and therapeutic results in event-free survival (EFS). RESULTS: Ninety patients were included. Fifty of them were treated by systemic multimodal therapy and locally by LS. ean age was 20 years. Overall survival (OS) was 68.8% and EFS was 60.6% at years. In the univariate analysis, pelvic location, age and response to chemotherapy were associated with poor prognosis. After multivariate analysis, poor response to treatment, pelvis location and age between 12 and 17 years were found to be independent prognostic factors. Dissemination at diagnosis was not a prognostic factor. CONCLUSIONS: OS and EFS in ES treated by LS were similar to findings in previous ES studies. factors are no different, except for the presence of metastasis at diagnosis.


Assuntos
Neoplasias Ósseas/cirurgia , Salvamento de Membro , Sarcoma de Ewing/cirurgia , Adolescente , Adulto , Análise de Variância , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Salvamento de Membro/efeitos adversos , Salvamento de Membro/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/mortalidade , Adulto Jovem
14.
Cancer Chemother Pharmacol ; 83(5): 809-815, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30758647

RESUMO

PURPOSE: Ewing's sarcoma (ES) is a rare and recalcitrant disease which is in need of a development of a novel effective therapy. The aim of this study was to investigate the efficacy of regorafenib on an ES tumor in a patient-derived orthotopic xenograft (PDOX) model. METHODS: The ES PDOX models were established orthotopically in the right chest wall of nude mice to match the site of the tumor in the donor patient. The ES PDOX models were randomized into three groups (G) when the tumor volume reached 75 mm3: G1: untreated control; G2: doxorubicin (DOX) (i.p., 3 mg/kg, weekly, 2 weeks); G3: regorafenib (REG) (p.o., 30 mg/kg, daily, 2 weeks). Tumor volume and body weight were measured twice a week. All mice were sacrificed on day 15. RESULTS: DOX was ineffective compared to the control group (P = 0.229). REG regressed the tumor size (P < 0.001 and P < 0.001, relative to control and DOX, respectively). CONCLUSIONS: Our findings suggest that REG has clinical potential for ES patients whose tumors respond to REG in a PDOX model.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Sarcoma de Ewing/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Peso Corporal/efeitos dos fármacos , Neoplasias Ósseas/patologia , Feminino , Humanos , Camundongos Nus , Compostos de Fenilureia/administração & dosagem , Piridinas/administração & dosagem , Sarcoma de Ewing/patologia , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Intern Med ; 58(9): 1335-1339, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30626819

RESUMO

Ewing's sarcoma (ES)/primitive neuroectodermal tumors (PNETs) are highly malignant neoplasms that usually affect the bones and soft tissues in children and young adults. ES/PNET of the lung is very rare and is associated with a poor prognosis. We herein report a case of ES/PNET of the left lung in a 45-year-old man. He was treated with neoadjuvant chemotherapy and pneumonectomy, but unfortunately his disease recurred 1.5 months after surgery. He was started on pazopanib, which resulted in a five-month progression-free survival. To our knowledge, this is the first demonstration of pazopanib efficacy in ES/PNET of the lung.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Tumores Neuroectodérmicos Primitivos/tratamento farmacológico , Pirimidinas/uso terapêutico , Sarcoma de Ewing/tratamento farmacológico , Sulfonamidas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Evolução Fatal , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Pneumonectomia/métodos , Intervalo Livre de Progressão , Sarcoma de Ewing/cirurgia , Resultado do Tratamento
16.
BMJ Case Rep ; 12(1)2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30696641

RESUMO

Primary Ewing sarcoma (ES) or primitive neuroectodermal tumour (PNET) is a rare tumour in adults and primary renal involvement is extremely rare. Patients with renal ES or PNET respond to and would benefit from conventional ES treatment according to ES study protocols. Here, we report a case of a young woman, presenting with right flank pain and haematuria. After ultrasound and CT evaluation, a right middle pole renal mass was detected. The patient underwent radical right nephrectomy, and a grade 4 ES with peritoneal involvement was documented. Subsequently, the patient underwent adjuvant chemotherapy for 5 months. Follow-up 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan demonstrated bilateral cervical, hilar, mediastinal and retroperitoneal FDG-avid adenopathies associated with mild right-sided pleural effusion with no metabolic activity, signifying the role of PET/CT scan in tumour restaging.


Assuntos
Neoplasias Renais/diagnóstico por imagem , Sarcoma de Ewing/diagnóstico por imagem , Adulto , Quimioterapia Adjuvante , Diagnóstico Diferencial , Feminino , Fluordesoxiglucose F18 , Humanos , Rim/diagnóstico por imagem , Rim/cirurgia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Nefrectomia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia
17.
Am J Med Sci ; 357(1): 75-80, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30314832

RESUMO

Ewing sarcoma/peripheral primitive neuroectodermal tumors (ES/pPNET), a member of the Ewing sarcoma family of tumors, is a malignant soft tissue tumor with small undifferentiated neuroectodermal cells. Primary trachea-bronchial ES/pPNET is very rare. The most common pulmonary ES is due to a metastasis. We describe a case of ES/pPNET which originated in the left basal trunk bronchus. The patient was a 30-year-old male, presenting with irritable cough and fever for 10 days. A tumor of 60 mm in diameter was found in the left basal trunk bronchus, extending to the left lower lobe. No distant metastases were detected. Histopathological examination revealed a malignancy of ES/pPNET with a diffuse proliferation of round cells, a Flexner-Wintersteiner rosette formation and positive staining for CD99. The patient was successfully treated with a combination of left lower lobectomy and adjuvant chemotherapy and has remained disease-free for approximately 18 months at follow-up. This case highlights that ES/pPNET should be considered as a differential diagnosis in cases of trachea-bronchial tumors.


Assuntos
Brônquios/patologia , Neoplasias Brônquicas/diagnóstico , Tumores Neuroectodérmicos Primitivos Periféricos/diagnóstico , Sarcoma de Ewing/diagnóstico , Adulto , Neoplasias Brônquicas/diagnóstico por imagem , Neoplasias Brônquicas/tratamento farmacológico , Neoplasias Brônquicas/cirurgia , Humanos , Masculino , Tumores Neuroectodérmicos Primitivos Periféricos/diagnóstico por imagem , Tumores Neuroectodérmicos Primitivos Periféricos/tratamento farmacológico , Tumores Neuroectodérmicos Primitivos Periféricos/cirurgia , Sarcoma de Ewing/diagnóstico por imagem , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/cirurgia
18.
Nat Prod Res ; 33(4): 516-526, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29052449

RESUMO

Bone cancer is a malignant primary tumour of the bone with different typing, such as, osteosarcoma, chondrosarcoma, Ewing's sarcoma and fibrosarcoma. Despite the clinical efficacy of conventional therapies of bone cancer, most patients eventually relapse and the disease remains incurable. Therefore, new therapeutic strategies are needed to improve patient outcome. In this review article, we have discussed the role of resveratrol in preventing bone and spinal cancers and therapeutics. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural polyphenol, which has been widely reported as an anticancer molecule. Resveratrol exhibits multiple tumour-suppressing activities in bone cancer by affecting a series of critical events. It has the protective effects against oxidative injury, possesses antiproliferative activity and induces apoptosis in cancer cells. Resveratrol might be a good option for the treatment of different types of bone and spinal cancers.


Assuntos
Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/prevenção & controle , Resveratrol/farmacologia , Anticarcinógenos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Humanos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/patologia
19.
Turk Patoloji Derg ; 35(2): 139-143, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-28272685

RESUMO

Ewing's sarcoma (ES) is a small round cell tumor of adolescents or young adults that usually arises in the deep soft tissues of the extremities. The tumor cells have uniform round nuclei, fine powdery chromatin and indistinct nucleoli. CD99 (O13) is a product of the MIC 2 gene that is highly sensitive to ES but not specific. A panel of markers should be used for the differential diagnosis of small round cell tumors because nearly all others, on occasion, show membranous staining for CD99. One of the defining feature of ES is the presence of 22q12 gene rearrangement. The presented case is a 6 year-old boy complaining of swelling on his right leg. The biopsy was compatible with classic ES in terms of histopathological, immunohistochemical and cytogenetic criteria. Wide surgical resection was performed after chemotherapy. The posttreatment specimen was composed of uniformly small round cells mixed with areas of ganglion cells embedded in neurophil-like fibrillary background. Immunohistochemically, neoplastic cells revealed strong CD99 (O13) and NSE staining and the tumor had EWSR1 gene rearrangement. Morphologic alterations due to treatment are commonly seen in pediatric tumors. Single case reports have defined neural differentiation in ES but to the best of our knowledge this is the first report of ES in the literature with all histopathological, immunohistochemical, and cytogenetic criteria evaluated in both pretreatment and posttreatment specimens.


Assuntos
Neoplasias Femorais/patologia , Sarcoma de Ewing/patologia , Biópsia/métodos , Criança , Neoplasias Femorais/diagnóstico por imagem , Neoplasias Femorais/tratamento farmacológico , Neoplasias Femorais/cirurgia , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Imagem por Ressonância Magnética , Masculino , Terapia Neoadjuvante , Proteína EWS de Ligação a RNA/genética , Radiografia , Sarcoma de Ewing/diagnóstico por imagem , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/cirurgia , Resultado do Tratamento
20.
BMC Cancer ; 18(1): 1134, 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30453921

RESUMO

BACKGROUND: Nuclear protein in testis (NUT) carcinoma (NC) is a rare epithelial malignancy characterized by rearrangement of the NUT gene on chromosome 15. If NC is not suspected, it is often diagnosed as other malignancies. We present the case of NC of the nasal cavity that responded to a chemotherapy regimen for Ewing's sarcoma family of tumors (ESFT). CASE PRESENTATION: A 49-year-old male presented with epistaxis and pain in the left eye. The patient had a tumor in the left nasal cavity at initial visit and it was biopsied. Firstly, the man was diagnosed with ESFT based on a histopathological examination. The tumor markedly responded to standard cytotoxic chemotherapy for ESFT with distant metastasis. After the start of therapy, a chromosomal analysis revealed an atypical translocation in ESFT and additional immunostaining was positive for anti-NUT antibody. Ultimately, the patient was definitively diagnosed with NC. He received multidisciplinary therapy and symptoms were temporarily relieved. However, he died 9 months after the diagnosis of NC. CONCLUSIONS: When a pathologically undifferentiated tumor is evident along the midline of the body, NC must be included in the differential diagnosis, and immunohistochemical staining or genetic testing/chromosomal analysis needs to be performed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Cavidade Nasal/efeitos dos fármacos , Sarcoma de Ewing/tratamento farmacológico , Carcinoma/diagnóstico , Carcinoma/genética , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/metabolismo , Cavidade Nasal/patologia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/genética , Translocação Genética
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