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[PMID]: 29330228 [Au] Autor: McCormack A; Dekkers OM; Petersenn S; Popovic V; Trouillas J; Raverot G; Burman P; ESE survey collaborators [Ad] Endereço: St Vincent's Hospital and Garvan Institute of Medical ResearchSydney, Australia. [Ti] Título: Treatment of aggressive pituitary tumours and carcinomas: results of a European Society of Endocrinology (ESE) survey 2016. [So] Source: Eur J Endocrinol;178(3):265-276, 2018 03. [Is] ISSN: 1479-683X [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: OBJECTIVE: To collect outcome data in a large cohort of patients with aggressive pituitary tumours (APT)/carcinomas (PC) and specifically report effects of temozolomide (TMZ) treatment. DESIGN: Electronic survey to ESE members Dec 2015-Nov 2016. RESULTS: Reports on 166 patients (40 PC, 125 APT, 1 unclassified) were obtained. Median age at diagnosis was 43 (range 4-79) years. 69% of the tumours were clinically functioning, and the most frequent immunohistochemical subtype were corticotroph tumours (45%). Ki-67 index did not distinguish APT from PC, median 7% and 10% respectively. TMZ was first-line chemotherapy in 157 patients. At the end of the treatment (median 9 cycles), radiological evaluation showed complete response (CR) in 6%, partial response (PR) in 31%, stable disease (SD) in 33% and progressive disease in 30%. Response was more frequent in patients receiving concomitant radiotherapy and TMZ. CR was seen only in patients with low MGMT expression. Clinically functioning tumours were more likely to respond than non-functioning tumours, independent of MGMT status. Of patients with CR, PR and SD, 25, 40 and 48% respectively progressed after a median of 12-month follow-up. Other oncological drugs given as primary treatment and to TMZ failures resulted in PR in 20%. CONCLUSION: This survey confirms that TMZ is established as first-line chemotherapeutic treatment of APT/PC. Clinically functioning tumours, low MGMT and concurrent radiotherapy were associated with a better response. The limited long-term effect of TMZ and the poor efficacy of other drugs highlight the need to identify additional effective therapies. [Mh] Termos MeSH primário: Adenoma/terapia Antineoplásicos Alquilantes/uso terapêutico Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico Carcinoma/terapia Irradiação Craniana Dacarbazina/análogos & derivados Procedimentos Neurocirúrgicos Neoplasias Hipofisárias/terapia [Mh] Termos MeSH secundário: Adenoma/metabolismo Adenoma/patologia Adolescente Adulto Idoso Bevacizumab/administração & dosagem Capecitabina/administração & dosagem Carcinoma/metabolismo Carcinoma/patologia Carmustina/administração & dosagem Criança Pré-Escolar Metilases de Modificação do DNA/metabolismo Enzimas Reparadoras do DNA/metabolismo Dacarbazina/administração & dosagem Dacarbazina/uso terapêutico Endocrinologia Europa (Continente) Feminino Seres Humanos Antígeno Ki-67/metabolismo Masculino Meia-Idade Invasividade Neoplásica Neoplasias Hipofisárias/metabolismo Neoplasias Hipofisárias/patologia Sociedades Médicas Inquéritos e Questionários Talidomida/administração & dosagem Proteínas Supressoras de Tumor/metabolismo Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antineoplastic Agents, Alkylating); 0 (Ki-67 Antigen); 0 (Tumor Suppressor Proteins); 2S9ZZM9Q9V (Bevacizumab); 4Z8R6ORS6L (Thalidomide); 6804DJ8Z9U (Capecitabine); 7GR28W0FJI (Dacarbazine); EC 2.1.1.- (DNA Modification Methylases); EC 2.1.1.63 (MGMT protein, human); EC 6.5.1.- (DNA Repair Enzymes); U68WG3173Y (Carmustine); YF1K15M17Y (temozolomide) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180309 [Lr] Data última revisão: 180309 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180114 [St] Status: MEDLINE [do] DOI: 10.1530/EJE-17-0933

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[PMID]: 29157615 [Au] Autor: Jaccard A [Ad] Endereço: Department of Clinical Hematology, Reference Center for AL Amyloidosis, CHU, 2 Avenue ML King, Limoges 87000, France. Electronic address: arnaud.jaccard@chu-limoges.fr. [Ti] Título: POEMS Syndrome: Therapeutic Options. [So] Source: Hematol Oncol Clin North Am;32(1):141-151, 2018 02. [Is] ISSN: 1558-1977 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Treatment of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome should be directed at the underlying plasma cell clone with risk-adapted therapy based on the extent of the plasma cell disorder. Radiation therapy is effective for patients with a localized presentation, without bone marrow involvement, and 1 to 3 bone lesions. Patients with disseminated disease should receive, preferably, high-dose chemotherapy with peripheral blood transplantation. Low-dose melphalan and dexamethasone or new agents used in myeloma are also effective. The most promising agent is lenalidomide, which could be given before high-dose therapy or radiation to get rapid neurologic responses. [Mh] Termos MeSH primário: Síndrome POEMS/terapia Transplante de Células-Tronco de Sangue Periférico Talidomida/análogos & derivados [Mh] Termos MeSH secundário: Aloenxertos Seres Humanos Síndrome POEMS/diagnóstico Síndrome POEMS/patologia Radioterapia Talidomida/uso terapêutico [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 4Z8R6ORS6L (Thalidomide); F0P408N6V4 (lenalidomide) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180307 [Lr] Data última revisão: 180307 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171122 [St] Status: MEDLINE

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[PMID]: 28460478 [Au] Autor: Vo MC; Nguyen-Pham TN; Lee HJ; Jaya Lakshmi T; Yang S; Jung SH; Kim HJ; Lee JJ [Ad] Endereço: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea. [Ti] Título: Combination therapy with dendritic cells and lenalidomide is an effective approach to enhance antitumor immunity in a mouse colon cancer model. [So] Source: Oncotarget;8(16):27252-27262, 2017 Apr 18. [Is] ISSN: 1949-2553 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: In this study, we investigated efficacy of lenalidomide in combination with tumor antigen-loaded dendritic cells (DCs) in murine colon cancer model. MC-38 cell lines were injected subcutaneously to establish colon cancer-bearing mice. After tumor growth, lenalidomide (50 mg/kg/day) was injected intraperitoneally on 3 consecutive days in combination with tumor antigen-loaded DC vaccination on days 8, 12, 16, and 20. The tumor antigen-loaded DCs plus lenalidomide combination treatment exhibited a significant inhibition of tumor growth compared with the other groups. These effects were associated with a reduction in immune suppressor cells, such as myeloid-derived suppressor cells and regulatory T cells, with the induction of immune effector cells, such as natural killer cells, CD4+ T cells and CD8+ T cells in spleen, and with the activation of cytotoxic T lymphocytes and NK cells. This study suggests that a combination of tumor antigen-loaded DC vaccination and lenalidomide synergistically enhanced antitumor immune response in the murine colon cancer model, by inhibiting the generation of immune suppressive cells and recovery of effector cells, and demonstrated superior polarization of Th1/Th2 balance in favor of Th1 immune response. This combination approach with DCs and lenalidomide may provide a new therapeutic option to improve the treatment of colon cancer. [Mh] Termos MeSH primário: Neoplasias do Colo/imunologia Neoplasias do Colo/patologia Células Dendríticas/imunologia Imunidade Talidomida/análogos & derivados [Mh] Termos MeSH secundário: Animais Antígenos de Neoplasias/imunologia Vacinas Anticâncer/administração & dosagem Vacinas Anticâncer/imunologia Linhagem Celular Tumoral Sobrevivência Celular/efeitos dos fármacos Neoplasias do Colo/genética Neoplasias do Colo/terapia Terapia Combinada Citocinas/biossíntese Células Dendríticas/metabolismo Modelos Animais de Doenças Feminino Expressão Gênica Imunidade/efeitos dos fármacos Imunoterapia Células Matadoras Naturais/imunologia Células Matadoras Naturais/metabolismo Camundongos Linfócitos T Citotóxicos/efeitos dos fármacos Linfócitos T Citotóxicos/imunologia Linfócitos T Citotóxicos/metabolismo Linfócitos T Reguladores/efeitos dos fármacos Linfócitos T Reguladores/imunologia Linfócitos T Reguladores/metabolismo Talidomida/farmacologia Vacinação [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antigens, Neoplasm); 0 (Cancer Vaccines); 0 (Cytokines); 4Z8R6ORS6L (Thalidomide); F0P408N6V4 (lenalidomide) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180305 [Lr] Data última revisão: 180305 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170503 [St] Status: MEDLINE [do] DOI: 10.18632/oncotarget.15917

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[PMID]: 29390339 [Au] Autor: Chen Y; Shen Y; Ma HF; Cai JF; Hua YQ; Zou J; Guan JL [Ad] Endereço: Rheumatology and Immunology Department. [Ti] Título: Infliximab associated with life-threatening lung infection in a patient with Behcet disease with intestinal and hematopoietic system involvement: A case report. [So] Source: Medicine (Baltimore);96(50):e9202, 2017 Dec. [Is] ISSN: 1536-5964 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: RATIONALE: Tumor necrosis factor (TNF-α) participates in the pathophysiology of Behcet's disease (BD) and myelodysplastic syndrome (MDS). Infliximab is recommaned for the most severe type of BD, however, there is little evidence for its effectiveness in BD associated MDS. PATIENT CONCERNS: A 46-year-old female, initially diagnosed with intestinal BD and leukopenia was later diagnosed as MDS. Treatement with infliximab and other immunoregulators lead to life-threatening pneumonia. DIAGNOSIS: Intestinal BD associated with MDS involving trisomy 8. INTERVENTIONS: The patient initially treated with methylprednisolone, thalidomide, cyclosporine A, and infliximab, which lead to severe lung infection. Therefore, the patient was transferred to Intensive Care Unit for life supportive, anti-infection and immune improving therapy. OUTCOMES: The patient survived from the lung infection. With combination of methylprednisolone, thalidomide and cyclosporine A, the patient recovered from her intestinal ulceration and MDS manifestations. LESSONS: Infliximab treatment may not benefit a patient with BD associated with MDS but place the patient at risk of infection. [Mh] Termos MeSH primário: Antirreumáticos/efeitos adversos Antirreumáticos/uso terapêutico Síndrome de Behçet/complicações Síndrome de Behçet/tratamento farmacológico Infliximab/efeitos adversos Infliximab/uso terapêutico Síndromes Mielodisplásicas/tratamento farmacológico Síndromes Mielodisplásicas/etiologia Pneumonia/induzido quimicamente [Mh] Termos MeSH secundário: Ciclosporina/uso terapêutico Feminino Glucocorticoides/uso terapêutico Seres Humanos Imunossupressores/uso terapêutico Metilprednisolona/uso terapêutico Meia-Idade Talidomida/uso terapêutico [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antirheumatic Agents); 0 (Glucocorticoids); 0 (Immunosuppressive Agents); 4Z8R6ORS6L (Thalidomide); 83HN0GTJ6D (Cyclosporine); B72HH48FLU (Infliximab); X4W7ZR7023 (Methylprednisolone) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180301 [Lr] Data última revisão: 180301 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 180203 [St] Status: MEDLINE [do] DOI: 10.1097/MD.0000000000009202

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[PMID]: 29193019 [Au] Autor: Arcaini L; Lamy T; Walewski J; Belada D; Mayer J; Radford J; Jurczak W; Morschhauser F; Alexeeva J; Rule S; Cabeçadas J; Campo E; Pileri SA; Biyukov T; Patturajan M; Casadebaig Bravo ML; Trnený M; SPRINT Trial Investigators [Ad] Endereço: Department of Molecular Medicine, University of Pavia, Pavia, Italy. [Ti] Título: Prospective subgroup analyses of the randomized MCL-002 (SPRINT) study: lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma. [So] Source: Br J Haematol;180(2):224-235, 2018 01. [Is] ISSN: 1365-2141 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: In the mantle cell lymphoma (MCL)-002 study, lenalidomide demonstrated significantly improved median progression-free survival (PFS) compared with investigator's choice (IC) in patients with relapsed/refractory MCL. Here we present the long-term follow-up data and results of preplanned subgroup exploratory analyses from MCL-002 to evaluate the potential impact of demographic factors, baseline clinical characteristics and prior therapies on PFS. In MCL-002, patients with relapsed/refractory MCL were randomized 2:1 to receive lenalidomide (25 mg/day orally on days 1-21; 28-day cycles) or single-agent IC therapy (rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine). The intent-to-treat population comprised 254 patients (lenalidomide, n = 170; IC, n = 84). Subgroup analyses of PFS favoured lenalidomide over IC across most characteristics, including risk factors, such as high MCL International Prognostic Index score, age ≥65 years, high lactate dehydrogenase (LDH), stage III/IV disease, high tumour burden, and refractoriness to last prior therapy. By multivariate Cox regression analysis, factors associated with significantly longer PFS (other than lenalidomide treatment) included normal LDH levels (P < 0·001), nonbulky disease (P = 0·045), <3 prior antilymphoma treatments (P = 0·005), and ≥6 months since last prior treatment (P = 0·032). Overall, lenalidomide improved PFS versus single-agent IC therapy in patients with relapsed/refractory MCL, irrespective of many demographic factors, disease characteristics and prior treatment history. [Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico Linfoma de Célula do Manto/tratamento farmacológico Linfoma de Célula do Manto/patologia Talidomida/análogos & derivados [Mh] Termos MeSH secundário: Idoso Idoso de 80 Anos ou mais Antineoplásicos/administração & dosagem Antineoplásicos/efeitos adversos Resistência a Medicamentos Antineoplásicos Feminino Seguimentos Seres Humanos Estimativa de Kaplan-Meier Linfoma de Célula do Manto/mortalidade Masculino Meia-Idade Estadiamento de Neoplasias Modelos de Riscos Proporcionais Recidiva Retratamento Talidomida/administração & dosagem Talidomida/efeitos adversos Talidomida/uso terapêutico Resultado do Tratamento [Pt] Tipo de publicação: CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Antineoplastic Agents); 4Z8R6ORS6L (Thalidomide); F0P408N6V4 (lenalidomide) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180228 [Lr] Data última revisão: 180228 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171202 [St] Status: MEDLINE [do] DOI: 10.1111/bjh.15025

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[PMID]: 27779105 [Au] Autor: Oliva S; Gambella M; Gilestro M; Muccio VE; Gay F; Drandi D; Ferrero S; Passera R; Pautasso C; Bernardini A; Genuardi M; Patriarca F; Saraci E; Petrucci MT; Pescosta N; Liberati AM; Caravita T; Conticello C; Rocci A; Musto P; Boccadoro M; Palumbo A; Omedè P [Ad] Endereço: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospeadliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy. [Ti] Título: Minimal residual disease after transplantation or lenalidomide-based consolidation in myeloma patients: a prospective analysis. [So] Source: Oncotarget;8(4):5924-5935, 2017 Jan 24. [Is] ISSN: 1949-2553 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: We analyzed 50 patients who achieved at least a very good partial response in the RV-MM-EMN-441 study. Patients received consolidation with autologous stem-cell transplantation (ASCT) or cyclophosphamide-lenalidomide-dexamethasone (CRD), followed by Lenalidomide-based maintenance. We assessed minimal residual disease (MRD) by multi-parameter flow cytometry (MFC) and allelic-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQ-PCR) after consolidation, after 3 and 6 courses of maintenance, and thereafter every 6 months until progression. By MFC analysis, 19/50 patients achieved complete response (CR) after consolidation, and 7 additional patients during maintenance. A molecular marker was identified in 25/50 patients, 4/25 achieved molecular-CR after consolidation, and 3 additional patients during maintenance. A lower MRD value by MFC was found in ASCT patients compared with CRD patients (p=0.0134). Tumor burden reduction was different in patients with high-risk vs standard-risk cytogenetics (3.4 vs 5.2, ln-MFC; 3 vs 6 ln-PCR, respectively) and in patients who relapsed vs those who did not (4 vs 5, ln-MFC; 4.4 vs 7.8 ln-PCR). MRD progression anticipated clinical relapse by a median of 9 months while biochemical relapse by a median of 4 months. MRD allows the identification of a low-risk group, independently of response, and a better characterization of the activity of treatments. [Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem Biomarcadores Tumorais/genética Mieloma Múltiplo/terapia Talidomida/análogos & derivados Transplante Autólogo/métodos [Mh] Termos MeSH secundário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico Quimioterapia de Consolidação Progressão da Doença Feminino Seres Humanos Quimioterapia de Manutenção Masculino Meia-Idade Mieloma Múltiplo/genética Mieloma Múltiplo/patologia Neoplasia Residual Estudos Prospectivos Talidomida/administração & dosagem Talidomida/uso terapêutico Resultado do Tratamento [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Biomarkers, Tumor); 4Z8R6ORS6L (Thalidomide); F0P408N6V4 (lenalidomide) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180222 [Lr] Data última revisão: 180222 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161026 [St] Status: MEDLINE [do] DOI: 10.18632/oncotarget.12641

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[PMID]: 29377069 [Au] Autor: Scharenberg C; Jansson M; Saft L; Hellström-Lindberg E [Ad] Endereço: Department of Medicine, Centre for Haematology and Regenerative Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden. [Ti] Título: Megakaryocytes harbour the del(5q) abnormality despite complete clinical and cytogenetic remission induced by lenalidomide treatment. [So] Source: Br J Haematol;180(4):526-533, 2018 02. [Is] ISSN: 1365-2141 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: The mechanisms underlying lenalidomide-resistance of del(5q) MDS stem cells remain to be elucidated and may include cell-intrinsic as well as microenvironmental causes. Abnormal hypolobated megakaryocytes constitute one of the hallmarks of del(5q) MDS. We hypothesized that these cells have potential implications for the regulation of haematopoietic stem cells (HSC) similarly to what has recently been described for megakaryocytes in the murine system. Therefore, we conducted a study to determine the response of abnormal hypolobated megakaryocytes to lenalidomide therapy. We studied lenalidomide-treated patients in the MDS-004 trial as well as a cohort seen at our institution. Morphological evaluation at time of complete cytogenetic remission (CCyR) demonstrated the persistence of hypolobated megakaryocytes in all evaluable patients (n = 9). Furthermore, we provide evidence that the abnormal hypolobated morphology is restricted to del(5q) megakaryocytes, both at diagnosis and during CCyR. Using fluorescence in situ hybridisation analysis on flow-sorted stem- and progenitor populations, we observed a similar degree of clonal involvement in megakaryocyte-erythroid-progenitors as in HSC. Taken together, our findings suggest that megakaryocyte morphology might aid in the evaluation of patients where discontinuation of lenalidomide is considered and offers interesting hypotheses for further investigation of lenalidomide resistance. [Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico Deleção Cromossômica Cromossomos Humanos Par 5 Neoplasias Hematológicas/tratamento farmacológico Neoplasias Hematológicas/genética Megacariócitos/metabolismo Talidomida/análogos & derivados [Mh] Termos MeSH secundário: Antineoplásicos/administração & dosagem Antineoplásicos/efeitos adversos Medula Óssea/patologia Evolução Clonal Análise Citogenética Neoplasias Hematológicas/diagnóstico Seres Humanos Imunofenotipagem Hibridização in Situ Fluorescente Células Progenitoras de Megacariócitos e Eritrócitos/metabolismo Células Progenitoras de Megacariócitos e Eritrócitos/patologia Megacariócitos/patologia Indução de Remissão Talidomida/administração & dosagem Talidomida/efeitos adversos Talidomida/uso terapêutico Resultado do Tratamento [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Antineoplastic Agents); 4Z8R6ORS6L (Thalidomide); F0P408N6V4 (lenalidomide) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180221 [Lr] Data última revisão: 180221 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180130 [St] Status: MEDLINE [do] DOI: 10.1111/bjh.15094

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[PMID]: 29390485 [Au] Autor: Li Q; Liu Y; Yu Y [Ad] Endereço: Department of Oncology, Xuzhou Central Hospital Affiliated to Dongnan University, Xuzhou, Jiangsu, China. [Ti] Título: Antiangiogenic therapy for primitive neuroectodermal tumor with thalidomide: A case report and review of literature. [So] Source: Medicine (Baltimore);96(51):e9272, 2017 Dec. [Is] ISSN: 1536-5964 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: RATIONALE: Peripheral primitive neuroectodermal tumor (PNET) is a kind of small round cell tumor derived from primitive neuroectodermal tumor. PATIENT CONCERNS: PNET is a highly malignant tumor that is subordinated to Ewing sarcoma. It occurs predominantly in soft tissue and bone and rarely in the bronchi and lung. Traditional surgery, radiotherapy, and chemotherapy are used for the treatment of PNET, but are usually ineffective. DIAGNOSES: There was a rare case of a 17 year-old man diagnoses with primary pulmonary PNET. INTERVENTIONS: The patient was treated by the remedy treatment with thalidomide after the poor effect of conventional radiotherapy and chemotherapy. OUTCOMES: The patient survived without disease progression for 15 months and was in stable condition. LESSONS: Thalidomide provides a choice for maintenance therapy in PNET. [Mh] Termos MeSH primário: Inibidores da Angiogênese/uso terapêutico Neoplasias Pulmonares/tratamento farmacológico Neoplasias Pulmonares/patologia Tumores Neuroectodérmicos Primitivos Periféricos/tratamento farmacológico Tumores Neuroectodérmicos Primitivos Periféricos/patologia Talidomida/uso terapêutico [Mh] Termos MeSH secundário: Adolescente Biópsia por Agulha Broncoscopia/métodos Seguimentos Seres Humanos Imuno-Histoquímica Neoplasias Pulmonares/diagnóstico por imagem Masculino Invasividade Neoplásica/patologia Estadiamento de Neoplasias Tumores Neuroectodérmicos Primitivos Periféricos/diagnóstico por imagem Medição de Risco Tomografia Computadorizada por Raios X/métodos Resultado do Tratamento [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Angiogenesis Inhibitors); 4Z8R6ORS6L (Thalidomide) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180214 [Lr] Data última revisão: 180214 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 180203 [St] Status: MEDLINE [do] DOI: 10.1097/MD.0000000000009272

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[PMID]: 29359320 [Au] Autor: Bill M; Kjeldsen E [Ad] Endereço: Department of Haematology, Aarhus University Hospital, Aarhus, Denmark. [Ti] Título: Refining remission evaluation in MDS with isolated del(5q). [So] Source: Br J Haematol;180(4):469-470, 2018 02. [Is] ISSN: 1365-2141 [Cp] País de publicação: England [La] Idioma: eng [Mh] Termos MeSH primário: Cromossomos Humanos Par 5 Síndromes Mielodisplásicas [Mh] Termos MeSH secundário: Deleção Cromossômica Seres Humanos Talidomida [Pt] Tipo de publicação: EDITORIAL; COMMENT [Nm] Nome de substância: 4Z8R6ORS6L (Thalidomide) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180212 [Lr] Data última revisão: 180212 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180124 [St] Status: MEDLINE [do] DOI: 10.1111/bjh.15093

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[PMID]: 28745489 [Au] Autor: Wani TH; Chakrabarty A; Shibata N; Yamazaki H; Guengerich FP; Chowdhury G [Ad] Endereço: Departments of Chemistry and Life Sciences, SONS, Shiv Nadar University , Greater Noida, Uttar Pradesh 201314, India. [Ti] Título: The Dihydroxy Metabolite of the Teratogen Thalidomide Causes Oxidative DNA Damage. [So] Source: Chem Res Toxicol;30(8):1622-1628, 2017 08 21. [Is] ISSN: 1520-5010 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Thalidomide [α-(N-phthalimido)glutarimide] (1) is a sedative and antiemetic drug originally introduced into the clinic in the 1950s for the treatment of morning sickness. Although marketed as entirely safe, more than 10 000 babies were born with severe birth defects. Thalidomide was banned and subsequently approved for the treatment of multiple myeloma and complications associated with leprosy. Although known for more than 5 decades, the mechanism of teratogenicity remains to be conclusively understood. Various theories have been proposed in the literature including DNA damage and ROS and inhibition of angiogenesis and cereblon. All of the theories have their merits and limitations. Although the recently proposed cereblon theory has gained wide acceptance, it fails to explain the metabolism and low-dose requirement reported by a number of groups. Recently, we have provided convincing structural evidence in support of the presence of arene oxide and the quinone-reactive intermediates. However, the ability of these reactive intermediates to impart toxicity/teratogenicity needs investigation. Herein we report that the oxidative metabolite of thalidomide, dihydroxythalidomide, is responsible for generating ROS and causing DNA damage. We show, using cell lines, the formation of comet (DNA damage) and ROS. Using DNA-cleavage assays, we also show that catalase, radical scavengers, and desferal are capable of inhibiting DNA damage. A mechanism of teratogenicity is proposed that not only explains the DNA-damaging property but also the metabolism, low concentration, and species-specificity requirements of thalidomide. [Mh] Termos MeSH primário: Dano ao DNA/efeitos dos fármacos Talidomida/toxicidade [Mh] Termos MeSH secundário: Catalase/metabolismo Clivagem do DNA Depuradores de Radicais Livres/química Células HEK293 Células Hep G2 Células Endoteliais da Veia Umbilical Humana Seres Humanos Microscopia de Fluorescência Plasmídeos/metabolismo Poli(ADP-Ribose) Polimerases/metabolismo Espécies Reativas de Oxigênio/análise Espécies Reativas de Oxigênio/metabolismo Teratogênios/química Teratogênios/metabolismo Teratogênios/toxicidade Talidomida/química Talidomida/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Free Radical Scavengers); 0 (Reactive Oxygen Species); 0 (Teratogens); 4Z8R6ORS6L (Thalidomide); EC 1.11.1.6 (Catalase); EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 180127 [Lr] Data última revisão: 180127 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170727 [St] Status: MEDLINE [do] DOI: 10.1021/acs.chemrestox.7b00127

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