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[PMID]:29465563
[Au] Autor:Marginean CO; Melit LE; Horvath E; Gozar H; Chincesan MI
[Ad] Endereço:Department of Pediatrics I.
[Ti] Título:Non-Hodgkin lymphoma, diagnostic, and prognostic particularities in children - a series of case reports and a review of the literature (CARE compliant).
[So] Source:Medicine (Baltimore);97(8):e9802, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Non-Hodgkin lymphoma remains an unpredictable condition in pediatric patients. PATIENT CONCERNS: Our first case describes an 8-year-old boy with a history of iron deficiency anemia, admitted in our clinic for recurrent abdominal pain, weight loss, loss of appetite, diarrheic stools, and fever. The second case also describes an 8-year-old boy admitted for abdominal pain and vomiting. The 3rd case refers to a 4 years and 10 months old boy admitted in our clinic with abdominal pain and loss of appetite, who was initially admitted in the Pediatrics Surgery Clinic with the suspicion of appendicitis. Our 4th patient was a 5-year-old boy admitted in our clinic for abdominal pain and intermittent diarrheic stools. DIAGNOSES: In the first case, the laboratory tests showed anemia, thrombocytosis, elevated inflammatory biomarkers, a low level of iron, and hypoproteinemia. The abdominal ultrasound and CT exam revealed an abdominal mass, and the histopathological exam established the diagnosis of diffuse large B-cell lymphoma of the bowel. In the second case, the laboratory tests pointed out anemia, elevated ESR and lactate dehydrogenase level, while both abdominal ultrasound and CT exams showed an abdominal mass. The histopathological exam confirmed the diagnosis of Burkitt lymphoma. Regarding our 3rd case, the laboratory findings revealed leukocytosis, anemia, thrombocytosis, increased inflammatory biomarkers, elevated LDH, and a low level of iron. The abdominal ultrasound and the CT scan revealed an abdominal mass which, according to the histopathological exam, was a Burkitt lymphoma. Due to the cranial CT findings the patient was diagnosed with IV stage Burkitt lymphoma with central nervous system metastases. In our 4th patients we found leukocytosis, anemia, mildly increased inflammatory biomarkers, a high level of LDH, hypoproteinemia, and a low level of serum Ir. Both ultrasound and abdominal CT exams were negative, but the exploratory laparotomy identified an abdominal mass, and according to the histopathological exam the patient was diagnosed with Burkitt lymphoma. INTERVENTIONS: All the patients followed chemotherapy (B-NHL BFM 04 protocol) and supportive treatment. OUTCOMES: The first patient died approximately 4 months after the completion of chemotherapy due to tumor relapse, the second patient died after the first cure of chemotherapy and the fourth patient died at approximately 2 years after the diagnosis. The third patient is recurrence-free after 2 years. LESSONS: Despite the advances in the management, NHL remains a fatal condition in pediatrics.
[Mh] Termos MeSH primário: Linfoma não Hodgkin/diagnóstico
[Mh] Termos MeSH secundário: Dor Abdominal/etiologia
Anemia Ferropriva/etiologia
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Asparaginase/uso terapêutico
Criança
Pré-Escolar
Daunorrubicina/uso terapêutico
Diarreia/etiologia
Evolução Fatal
Seres Humanos
Linfoma não Hodgkin/complicações
Linfoma não Hodgkin/tratamento farmacológico
Masculino
Prednisona/uso terapêutico
Prognóstico
Resultado do Tratamento
Vincristina/uso terapêutico
Vômito/etiologia
Perda de Peso
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
5J49Q6B70F (Vincristine); EC 3.5.1.1 (Asparaginase); VB0R961HZT (Prednisone); ZS7284E0ZP (Daunorubicin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180222
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009802


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[PMID]:29381943
[Au] Autor:Xu X; Liang G; Duan M; Zhang L
[Ad] Endereço:Department of Anesthesiology.
[Ti] Título:Acute myeloid leukemia presenting as erythema nodosum: A case report.
[So] Source:Medicine (Baltimore);96(47):e8666, 2017 Nov.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Erythema nodosum (EN), a type of septal panniculitis, could be a rare nonspecific cutaneous presentation of acute myeloid leukemia (AML). PATIENT CONCERNS: A 58-year-old Chinese female was admitted for a 4-week history of painful cutaneous lesions, accompanied by a sternal pain and fever. The lesions once resolved spontaneously but then recurred. Physical examination revealed warm, tender, indurated, rounded, erythematous to violaceous nodules in bilateral lower extremities, ranging in diameter from 1 to 6 cm. Blood marrow examination was compatible with AML-M2. DIAGNOSES: AML-M2 presenting as EN. INTERVENTIONS: Daunorubicin and cytarabine were used in induction chemotherapy. The patient achieved complete remission and her skin lesions disappeared simultaneously. Six courses of consolidation chemotherapy were conducted in the following 6 months. OUTCOMES: The patient died due to AML relapse. LESSONS: The case strengthens the awareness of cutaneous involvement of AML and raises oncological vigilance in patients with EN.
[Mh] Termos MeSH primário: Citarabina/administração & dosagem
Daunorrubicina/administração & dosagem
Eritema Nodoso
Leucemia Mieloide Aguda
[Mh] Termos MeSH secundário: Antineoplásicos/administração & dosagem
Exame de Medula Óssea/métodos
Eritema Nodoso/diagnóstico
Eritema Nodoso/etiologia
Evolução Fatal
Feminino
Seres Humanos
Quimioterapia de Indução/métodos
Leucemia Mieloide Aguda/complicações
Leucemia Mieloide Aguda/diagnóstico
Leucemia Mieloide Aguda/fisiopatologia
Meia-Idade
Recidiva
Indução de Remissão/métodos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 04079A1RDZ (Cytarabine); ZS7284E0ZP (Daunorubicin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008666


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[PMID]:29037126
[Au] Autor:Zhu K; Jiang B; Yang Y; Hu R; Liu Z
[Ad] Endereço:1 Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, China.
[Ti] Título:DACT1 overexpression inhibits proliferation, enhances apoptosis, and increases daunorubicin chemosensitivity in KG-1α cells.
[So] Source:Tumour Biol;39(10):1010428317711089, 2017 Oct.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:DACT1 has been shown to participate in the development of many types of tumors; however, its role and precise molecular mechanisms in leukemia are unclear. In this study, we investigated the effect of DACT1 on KG-1α leukemia cells to further understand the mechanisms of DACT1-mediated tumor suppression. We transfected a DACT1 expression plasmid to upregulate DACT1 in KG-1α cells and analyzed the resulting phenotypic changes. The results demonstrated that DACT1 overexpression inhibited KG-1α proliferation, increased apoptosis, and arrested cells in the G0/G1 phase. Mechanistically, DACT1 overexpression inhibited Wnt/ß-catenin signaling by reducing nuclear ß-catenin levels in KG-1α cells. Furthermore, the viability of KG-1α cells transfected with DACT1 was significantly reduced when treated with daunorubicin. We also found that DACT1 reduced P-glycoprotein expression in KG-1α cells. These findings revealed an inhibitory role for DACT1 in leukemogenesis and provided evidence that DACT1 is an attractive target for the development of novel anti-leukemia therapies.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/genética
Apoptose/genética
Proliferação Celular/genética
Daunorrubicina/farmacologia
Regulação Leucêmica da Expressão Gênica/genética
Leucemia/tratamento farmacológico
Leucemia/genética
Proteínas Nucleares/genética
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética
Carcinogênese/genética
Linhagem Celular Tumoral
Fase G1/genética
Seres Humanos
Fase de Repouso do Ciclo Celular/genética
Transfecção/métodos
Regulação para Cima/genética
Via de Sinalização Wnt/genética
beta Catenina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Adaptor Proteins, Signal Transducing); 0 (DACT1 protein, human); 0 (Nuclear Proteins); 0 (beta Catenin); ZS7284E0ZP (Daunorubicin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171018
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317711089


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[PMID]:28843934
[Au] Autor:Saljooqi A; Shamspur T; Mostafavi A
[Ad] Endereço:Department of Chemistry, Shahid Bahonar University of Kerman, Kerman, PO Box 76169-133, Iran; Young Research Society, Shahid Bahonar University of Kerman, Kerman, PO Box 76169-133, Iran.
[Ti] Título:Ag-4-ATP-MWCNT electrode modified with dsDNA as label-free electrochemical sensor for the detection of daunorubicin anticancer drug.
[So] Source:Bioelectrochemistry;118:161-167, 2017 Dec.
[Is] ISSN:1878-562X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:This paper describes the synthesis of Ag-4-ATP-MWCNT nanocomposite and its use as a modifier of working electrode. The surface of the electrochemical Ag-4-ATP-MWCNT electrode was modified with a double-stranded DNA (dsDNA) to detect daunorubicin-DNA interactions. Differential pulse voltammetry was applied to develop an electroanalytical procedure for the determination of daunorubicin and evaluate its interaction with dsDNA immobilized on the electrode surface. After the optimization of operational parameters, the linear dependence of the peak current on the daunorubicin concentration was observed in the range of 0.10×10 to 1.00×10 molL , with the detection and quantification limits of 3.00×10 and 1.00×10 molL , respectively. The proposed biosensor was successfully applied to validate its capability for the determination of daunorubicin in human serum and urine samples.
[Mh] Termos MeSH primário: Trifosfato de Adenosina/química
Técnicas Biossensoriais/instrumentação
DNA/química
Daunorrubicina/análise
Nanocompostos/química
Nanotecnologia/instrumentação
Nanotubos de Carbono/química
[Mh] Termos MeSH secundário: Antineoplásicos/análise
Antineoplásicos/sangue
Antineoplásicos/química
Antineoplásicos/urina
Daunorrubicina/sangue
Daunorrubicina/química
Daunorrubicina/urina
Eletroquímica
Eletrodos
Seres Humanos
Concentração de Íons de Hidrogênio
Limite de Detecção
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Nanotubes, Carbon); 8L70Q75FXE (Adenosine Triphosphate); 9007-49-2 (DNA); ZS7284E0ZP (Daunorubicin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170828
[St] Status:MEDLINE


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[PMID]:28787435
[Au] Autor:Piatopoulou D; Avgeris M; Marmarinos A; Xagorari M; Baka M; Doganis D; Kossiva L; Scorilas A; Gourgiotis D
[Ad] Endereço:Laboratory of Clinical Biochemistry-Molecular Diagnostics, 2nd Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, 'P &A Kyriakou' Children's Hospital, Levadias 13 Street, Athens 11527, Greece.
[Ti] Título:miR-125b predicts childhood acute lymphoblastic leukaemia poor response to BFM chemotherapy treatment.
[So] Source:Br J Cancer;117(6):801-812, 2017 Sep 05.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Despite the favourable survival rates of childhood acute lymphoblastic leukaemia (ALL), a significant number of patients present resistance to antileukaemic agents and dismal prognosis. In this study, we analysed miR-125b expression in childhood ALL and evaluated its clinical utility for patients treated with Berlin-Frankfurt-Münster (BFM) protocol. METHODS: The study included 272 bone marrow specimens obtained on diagnosis and on BFM day 33 from 125 patients and 64 healthy children. Following extraction, RNA was polyadenylated and reverse transcribed. miR-125b levels were quantified by quantitative PCR. Cytogenetics, immunohistotype and MRD were analysed according to international guidelines. RESULTS: Downregulated miR-125b levels were detected in childhood ALL patients and correlated with adverse prognosis. Following BFM induction, miR-125b levels were significantly increased, however, elevated day 33/diagnosis miR-125b ratio was associated with unfavourable disease features. Loss of miR-125b during diagnosis and higher day 33/diagnosis ratio were correlated with stronger risk for disease short-term relapse and patients' worse survival. Moreover, multivariate regression models highlighted the independent prognostic value of miR-125b for childhood ALL. Finally, the combination of miR-125b with clinically used disease markers clearly enhanced the prediction of patients' resistance to BFM chemotherapy. CONCLUSIONS: miR-125b significantly improves the prognosis of childhood ALL patients' outcome under BFM treatment.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
MicroRNAs/metabolismo
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo
[Mh] Termos MeSH secundário: Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Asparaginase/administração & dosagem
Biomarcadores Tumorais/análise
Biomarcadores Tumorais/metabolismo
Medula Óssea/patologia
Criança
Pré-Escolar
DNA Complementar
Daunorrubicina/administração & dosagem
Progressão da Doença
Regulação para Baixo
Resistência a Medicamentos Antineoplásicos
Feminino
Seres Humanos
Lactente
Estimativa de Kaplan-Meier
Masculino
MicroRNAs/análise
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade
Prednisona/administração & dosagem
Prognóstico
Reação em Cadeia da Polimerase em Tempo Real
Análise de Regressão
Resultado do Tratamento
Vincristina/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (DNA, Complementary); 0 (MIRN125 microRNA, human); 0 (MicroRNAs); 5J49Q6B70F (Vincristine); EC 3.5.1.1 (Asparaginase); VB0R961HZT (Prednisone); ZS7284E0ZP (Daunorubicin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2017.256


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[PMID]:28644114
[Au] Autor:Stone RM; Mandrekar SJ; Sanford BL; Laumann K; Geyer S; Bloomfield CD; Thiede C; Prior TW; Döhner K; Marcucci G; Lo-Coco F; Klisovic RB; Wei A; Sierra J; Sanz MA; Brandwein JM; de Witte T; Niederwieser D; Appelbaum FR; Medeiros BC; Tallman MS; Krauter J; Schlenk RF; Ganser A; Serve H; Ehninger G; Amadori S; Larson RA; Döhner H
[Ad] Endereço:From the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston (R.M.S.); the Division of Biomedical Statistics and Informatics (S.J.M., K.L.) and the Alliance Statistics and Data Center (S.J.M., K.L., S.G.), Mayo Clinic, Rochester, MN; the Alliance Statistics and Data Center, Duke Uni
[Ti] Título:Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation.
[So] Source:N Engl J Med;377(5):454-464, 2017 08 03.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Patients with acute myeloid leukemia (AML) and a FLT3 mutation have poor outcomes. We conducted a phase 3 trial to determine whether the addition of midostaurin - an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation - to standard chemotherapy would prolong overall survival in this population. METHODS: We screened 3277 patients, 18 to 59 years of age, who had newly diagnosed AML for FLT3 mutations. Patients were randomly assigned to receive standard chemotherapy (induction therapy with daunorubicin and cytarabine and consolidation therapy with high-dose cytarabine) plus either midostaurin or placebo; those who were in remission after consolidation therapy entered a maintenance phase in which they received either midostaurin or placebo. Randomization was stratified according to subtype of FLT3 mutation: point mutation in the tyrosine kinase domain (TKD) or internal tandem duplication (ITD) mutation with either a high ratio (>0.7) or a low ratio (0.05 to 0.7) of mutant to wild-type alleles (ITD [high] and ITD [low], respectively). Allogeneic transplantation was allowed. The primary end point was overall survival. RESULTS: A total of 717 patients underwent randomization; 360 were assigned to the midostaurin group, and 357 to the placebo group. The FLT3 subtype was ITD (high) in 214 patients, ITD (low) in 341 patients, and TKD in 162 patients. The treatment groups were well balanced with respect to age, race, FLT3 subtype, cytogenetic risk, and blood counts but not with respect to sex (51.7% in the midostaurin group vs. 59.4% in the placebo group were women, P=0.04). Overall survival was significantly longer in the midostaurin group than in the placebo group (hazard ratio for death, 0.78; one-sided P=0.009), as was event-free survival (hazard ratio for event or death, 0.78; one-sided P=0.002). In both the primary analysis and an analysis in which data for patients who underwent transplantation were censored, the benefit of midostaurin was consistent across all FLT3 subtypes. The rate of severe adverse events was similar in the two groups. CONCLUSIONS: The addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy significantly prolonged overall and event-free survival among patients with AML and a FLT3 mutation. (Funded by the National Cancer Institute and Novartis; ClinicalTrials.gov number, NCT00651261 .).
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Leucemia Mieloide Aguda/tratamento farmacológico
Inibidores de Proteínas Quinases/administração & dosagem
Estaurosporina/análogos & derivados
Tirosina Quinase 3 Semelhante a fms/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Citarabina/administração & dosagem
Daunorrubicina/administração & dosagem
Feminino
Seres Humanos
Estimativa de Kaplan-Meier
Leucemia Mieloide Aguda/genética
Leucemia Mieloide Aguda/mortalidade
Masculino
Meia-Idade
Mutação
Inibidores de Proteínas Quinases/efeitos adversos
Estaurosporina/administração & dosagem
Estaurosporina/efeitos adversos
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Protein Kinase Inhibitors); 04079A1RDZ (Cytarabine); EC 2.7.10.1 (FLT3 protein, human); EC 2.7.10.1 (fms-Like Tyrosine Kinase 3); H88EPA0A3N (Staurosporine); ID912S5VON (midostaurin); ZS7284E0ZP (Daunorubicin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171126
[Lr] Data última revisão:
171126
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170624
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1614359


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[PMID]:28632487
[Au] Autor:Lee JH; Kim H; Joo YD; Lee WS; Bae SH; Zang DY; Kwon J; Kim MK; Lee J; Lee GW; Lee JH; Choi Y; Kim DY; Hur EH; Lim SN; Lee SM; Ryoo HM; Kim HJ; Hyun MS; Lee KH; Cooperative Study Group A for Hematology
[Ad] Endereço:Je-Hwan Lee, Jung-Hee Lee, Dae-Young Kim, Eun-Hye Hur, and Kyoo-Hyung Lee, Asan Medical Center, University of Ulsan College of Medicine, Seoul; Hawk Kim and Yunsuk Choi, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan; Young-Don Joo and Sung-Nam Lim, Haeundae Paik Hospital,
[Ti] Título:Prospective Randomized Comparison of Idarubicin and High-Dose Daunorubicin in Induction Chemotherapy for Newly Diagnosed Acute Myeloid Leukemia.
[So] Source:J Clin Oncol;35(24):2754-2763, 2017 Aug 20.
[Is] ISSN:1527-7755
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose We compared two induction regimens, idarubicin (12 mg/m /d for 3 days) versus high-dose daunorubicin (90 mg/m /d for 3 days), in young adults with newly diagnosed acute myeloid leukemia (AML). Patients and Methods A total of 299 patients (149 randomly assigned to cytarabine plus idarubicin [AI] and 150 assigned to cytarabine plus high-dose daunorubicin [AD]) were analyzed. All patients received cytarabine (200 mg/m /d for 7 days). Results Complete remission (CR) was induced in 232 patients (77.6%), with no difference in CR rates between the AI and AD arms (80.5% v 74.7%, respectively; P = .224). At a median follow-up time of 34.9 months, survival and relapse rates did not differ between the AI and AD arms (4-year overall survival, 51.1% v 54.7%, respectively; P = .756; cumulative incidence of relapse, 35.2% v 25.1%, respectively; P = .194; event-free survival, 45.5% v 50.8%, respectively; P = .772). Toxicity profiles were also similar in the two arms. Interestingly, overall and event-free survival times of patients with FLT3 internal tandem duplication (ITD) mutation were significantly different (AI v AD: median overall survival, 15.5 months v not reached, respectively; P = .030; event-free survival, 11.9 months v not reached, respectively; P = .028). Conclusion This phase III trial comparing idarubicin with high-dose daunorubicin did not find significant differences in CR rates, relapse, and survival. Significant interaction between the treatment arm and the FLT3-ITD mutation was found, and high-dose daunorubicin was more effective than idarubicin in patients with FLT3-ITD mutation.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Leucemia Mieloide Aguda/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Citarabina/administração & dosagem
Daunorrubicina/administração & dosagem
Relação Dose-Resposta a Droga
Feminino
Seres Humanos
Idarubicina/administração & dosagem
Quimioterapia de Indução
Masculino
Meia-Idade
Prognóstico
Estudos Prospectivos
Taxa de Sobrevida
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
04079A1RDZ (Cytarabine); ZRP63D75JW (Idarubicin); ZS7284E0ZP (Daunorubicin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170913
[Lr] Data última revisão:
170913
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170621
[St] Status:MEDLINE
[do] DOI:10.1200/JCO.2017.72.8618


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[PMID]:28575020
[Au] Autor:Enyedi KN; Tóth S; Szakács G; Mezo G
[Ad] Endereço:Eötvös Loránd University, Faculty of Science, Institute of Chemistry, Pázmány P. sétány 1/A, Budapest, Hungary.
[Ti] Título:NGR-peptide-drug conjugates with dual targeting properties.
[So] Source:PLoS One;12(6):e0178632, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peptides containing the asparagine-glycine-arginine (NGR) motif are recognized by CD13/aminopeptidase N (APN) receptor isoforms that are selectively overexpressed in tumor neovasculature. Spontaneous decomposition of NGR peptides can result in isoAsp derivatives, which are recognized by RGD-binding integrins that are essential for tumor metastasis. Peptides binding to CD13 and RGD-binding integrins provide tumor-homing, which can be exploited for dual targeted delivery of anticancer drugs. We synthesized small cyclic NGR peptide-daunomycin conjugates using NGR peptides of varying stability (c[KNGRE]-NH2, Ac-c[CNGRC]-NH2 and the thioether bond containing c[CH2-CO-NGRC]-NH2, c[CH2-CO-KNGRC]-NH2). The cytotoxic effect of the novel cyclic NGR peptide-Dau conjugates were examined in vitro on CD13 positive HT-1080 (human fibrosarcoma) and CD13 negative HT-29 (human colon adenocarcinoma) cell lines. Our results confirm the influence of structure on the antitumor activity and dual acting properties of the conjugates. Attachment of the drug through an enzyme-labile spacer to the C-terminus of cyclic NGR peptide resulted in higher antitumor activity on both CD13 positive and negative cells as compared to the branching versions.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/química
Daunorrubicina/química
Oligopeptídeos/química
[Mh] Termos MeSH secundário: Antibióticos Antineoplásicos/farmacologia
Linhagem Celular Tumoral
Cromatografia Líquida de Alta Pressão
Cromatografia de Fase Reversa
Ciclização
Daunorrubicina/farmacologia
Seres Humanos
Oligopeptídeos/farmacologia
Espectrometria de Massas por Ionização por Electrospray
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (NGR peptide); 0 (Oligopeptides); ZS7284E0ZP (Daunorubicin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178632


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[PMID]:28556917
[Au] Autor:Alexander TB; Wang L; Inaba H; Triplett BM; Pounds S; Ribeiro RC; Pui CH; Rubnitz JE
[Ad] Endereço:Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
[Ti] Título:Decreased relapsed rate and treatment-related mortality contribute to improved outcomes for pediatric acute myeloid leukemia in successive clinical trials.
[So] Source:Cancer;123(19):3791-3798, 2017 Oct 01.
[Is] ISSN:1097-0142
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Outcomes for children with acute myeloid leukemia (AML) have improved over the past 20 years even though the medications used for induction therapy have not changed. METHODS: This study analyzed data from patients with AML who were enrolled in successive protocols (AML97 and AML02) to determine the contributors to the improved outcomes of the latter clinical trial. RESULTS: There were significant improvements in 5-year overall survival (48.9% vs 71.2%; P < .0001) and event-free survival (43.5% vs 61.8%; P = .002) from AML97 to AML02. The 5-year cumulative incidence of early death (ED)/treatment-related mortality (TRM) was reduced for patients treated in AML02 (18.5% vs 7.9%; P = .007). Although the overall incidence of refractory disease (6.5% vs 5.6%; P = .736) and relapse (29.3% vs 21.0%; P = .12) did not differ between the 2 studies, patients with low-risk AML who were treated in AML02 had a reduced incidence of relapse (27.3% vs 8.8%; P = .036). CONCLUSIONS: The improved outcomes of the AML02 trial resulted from improved disease control for low-risk patients and overall decreased ED/TRM. These results emphasize the importance of supportive-care measures throughout chemotherapy courses and hematopoietic cell transplantation and the value of treatment intensity for patients with low-risk AML while underscoring the need for novel therapy, rather than increased therapy intensity, for children with high-risk AML. Cancer 2017;123:3791-3798. © 2017 American Cancer Society.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Quimioterapia de Indução/métodos
Leucemia Mieloide Aguda/tratamento farmacológico
Leucemia Mieloide Aguda/mortalidade
[Mh] Termos MeSH secundário: Adolescente
Aminoglicosídeos/administração & dosagem
Anticorpos Monoclonais Humanizados/administração & dosagem
Asparaginase/administração & dosagem
Criança
Pré-Escolar
Cladribina/administração & dosagem
Protocolos Clínicos
Quimioterapia de Consolidação/métodos
Citarabina/administração & dosagem
Daunorrubicina/administração & dosagem
Intervalo Livre de Doença
Etoposídeo/administração & dosagem
Feminino
Transplante de Células-Tronco Hematopoéticas
Seres Humanos
Lactente
Recém-Nascido
Masculino
Mitoxantrona/administração & dosagem
Neoplasia Residual
Recidiva
Estudos Retrospectivos
Análise de Sobrevida
Fatores de Tempo
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Aminoglycosides); 0 (Antibodies, Monoclonal, Humanized); 0 (Antineoplastic Agents); 04079A1RDZ (Cytarabine); 47M74X9YT5 (Cladribine); 6PLQ3CP4P3 (Etoposide); 93NS566KF7 (gemtuzumab); BZ114NVM5P (Mitoxantrone); EC 3.5.1.1 (Asparaginase); ZS7284E0ZP (Daunorubicin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE
[do] DOI:10.1002/cncr.30791


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[PMID]:28505160
[Au] Autor:Karathedath S; Rajamani BM; Musheer Aalam SM; Abraham A; Varatharajan S; Krishnamurthy P; Mathews V; Velayudhan SR; Balasubramanian P
[Ad] Endereço:Department of Haematology, Christian Medical College, Vellore, India.
[Ti] Título:Role of NF-E2 related factor 2 (Nrf2) on chemotherapy resistance in acute myeloid leukemia (AML) and the effect of pharmacological inhibition of Nrf2.
[So] Source:PLoS One;12(5):e0177227, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cytarabine (Ara-C) and Daunorubicin (Dnr) forms the backbone of acute myeloid leukemia (AML) therapy. Drug resistance and toxic side effects pose a major threat to treatment success and hence alternate less toxic therapies are warranted. NF-E2 related factor-2 (Nrf2), a master regulator of antioxidant response is implicated in chemoresistance in solid tumors. However, little is known about the role of Nrf2 in AML chemoresistance and the effect of pharmacological inhibitor brusatol in modulating this resistance. Primary AML samples with high ex-vivo IC50 to Ara-C, ATO, Dnr had significantly high NRF2 RNA expression. Gene-specific knockdown of NRF2 improved sensitivity to these drugs in resistant AML cell lines by decreasing the expression of downstream antioxidant targets of Nrf2 by compromising the cell's ability to scavenge the ROS. Treatment with brusatol, a pharmacological inhibitor of Nrf2, improved sensitivity to Ara-C, ATO, and Dnr and reduced colony formation capacity. AML cell lines stably overexpressing NRF2 showed increased resistance to ATO, Dnr and Ara-C and increased expression of downstream targets. This study demonstrates that Nrf2 could be an ideal druggable target in AML, more so to the drugs that function through ROS, suggesting the possibility of using Nrf2 inhibitors in combination with chemotherapeutic agents to modulate drug resistance in AML.
[Mh] Termos MeSH primário: Resistência a Medicamentos Antineoplásicos/genética
Leucemia Mieloide Aguda/genética
Fator 2 Relacionado a NF-E2/genética
[Mh] Termos MeSH secundário: Antineoplásicos/farmacologia
Antineoplásicos/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Antioxidantes/metabolismo
Apoptose/efeitos dos fármacos
Apoptose/genética
Linhagem Celular Tumoral
Citarabina/farmacologia
Citarabina/uso terapêutico
Daunorrubicina/farmacologia
Daunorrubicina/uso terapêutico
Expressão Gênica
Técnicas de Silenciamento de Genes
Seres Humanos
Concentração Inibidora 50
Proteína 1 Associada a ECH Semelhante a Kelch/genética
Leucemia Mieloide Aguda/tratamento farmacológico
Mutação
Fator 2 Relacionado a NF-E2/antagonistas & inibidores
Fator 2 Relacionado a NF-E2/metabolismo
Transporte Proteico
Elementos de Resposta
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Antioxidants); 0 (Kelch-Like ECH-Associated Protein 1); 0 (NF-E2-Related Factor 2); 04079A1RDZ (Cytarabine); ZS7284E0ZP (Daunorubicin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171104
[Lr] Data última revisão:
171104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177227



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