Base de dados : MEDLINE
Pesquisa : D02.455.526.728.650.156 [Categoria DeCS]
Referências encontradas : 3401 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 341 ir para página                         

  1 / 3401 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28470340
[Au] Autor:Iyer PM; Karthikeyan S; Sanjay Kumar P; Krishnan Namboori PK
[Ad] Endereço:Department of Electronics and Communication Engineering, M.Tech-Biomedical Engineering Amrita School of Engineering, AMRITA Vishwa Vidyapeetham Amrita University, Amritanagar, Ettimadai, Coimbatore, Tamil Nadu, 641112, India.
[Ti] Título:Comprehensive strategy for the design of precision drugs and identification of genetic signature behind proneness of the disease-a pharmacogenomic approach.
[So] Source:Funct Integr Genomics;17(4):375-385, 2017 Jul.
[Is] ISSN:1438-7948
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The proneness of diseases and susceptibility towards drugs vary from person to person. At present, there is a strong demand for the personalization of drugs. The genetic signature behind proneness of the disease has been studied through a comprehensive 'octopodial approach'. All the genetic variants included in the approach have been introduced. The breast cancer associated with BRCA1 mutation has been taken as the illustrative example to introduce all these factors. The genetic variants associated with the drug action of tamoxifen have been fully illustrated in the manuscript. The design of a new personalized anti-breast cancer drug has been explained in the third phase. For the design of new personalized drugs, a metabolite of anti-cancer drug chlorambucil has been taken as the template. The design of drug has been made with respect to the protein 1T15 of BRCA1 gene corresponding to the genetic signature of rs28897696.
[Mh] Termos MeSH primário: Neoplasias da Mama/tratamento farmacológico
Desenho de Drogas
Predisposição Genética para Doença
Farmacogenética/métodos
Medicina de Precisão/métodos
[Mh] Termos MeSH secundário: Antineoplásicos/química
Antineoplásicos/farmacologia
Antineoplásicos/uso terapêutico
Proteína BRCA1/química
Proteína BRCA1/genética
Neoplasias da Mama/genética
Clorambucila/química
Clorambucila/farmacologia
Feminino
Seres Humanos
Polimorfismo de Nucleotídeo Único
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (BRCA1 Protein); 0 (BRCA1 protein, human); 18D0SL7309 (Chlorambucil)
[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:170505
[St] Status:MEDLINE
[do] DOI:10.1007/s10142-017-0559-7


  2 / 3401 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28916659
[Au] Autor:Chen F; Xu G; Qin X; Jin X; Gou S
[Ad] Endereço:Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing, China.
[Ti] Título:Hybrid of DNA-targeting Chlorambucil with Pt(IV) Species to Reverse Drug Resistance.
[So] Source:J Pharmacol Exp Ther;363(2):221-239, 2017 Nov.
[Is] ISSN:1521-0103
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Two hybrids of Pt(IV) species were designed and prepared by addition of a chlorambucil unit to the axial positions of the Pt(IV) complexes derived from DN603 and DN604. In vitro studies of two hybrids against two pairs of cisplatin sensitive and resistant cancer cell lines indicated that compound had superior antitumor activity to cisplatin and chlorambucil via suppressing DNA damage repair to reverse drug resistance. Mechanistic investigation suggested that the potent antitumor activity of compound arose from its major suppression of CK2-mediated MRE11-RAD50-NBS1(MRN) complex promotion of DNA double-strand break (DSB) repair. In nude mice with A549/CDDP xenografts, compound exhibited higher anticancer efficacy than cisplatin and chlorambucil by reversing drug resistance, displayed improved effectiveness, and had no toxicity effects. Overall, compound is a promising drug candidate, which could promote the anticancer activity and reverse drug resistance by attenuating CK2-induced MRN-dependent DSB repair.
[Mh] Termos MeSH primário: Antineoplásicos Alquilantes/farmacologia
Antineoplásicos/farmacologia
Clorambucila/farmacologia
DNA de Neoplasias/efeitos dos fármacos
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Compostos de Platina/farmacologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacocinética
Antineoplásicos Alquilantes/farmacocinética
Cálcio/metabolismo
Caseína Quinase II/antagonistas & inibidores
Linhagem Celular Tumoral
Clorambucila/farmacocinética
Cisplatino/farmacologia
Reparo do DNA/efeitos dos fármacos
Desenho de Drogas
Feminino
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Platina/metabolismo
Compostos de Platina/farmacocinética
Ratos Sprague-Dawley
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Antineoplastic Agents, Alkylating); 0 (DNA, Neoplasm); 0 (Platinum Compounds); 18D0SL7309 (Chlorambucil); 49DFR088MY (Platinum); EC 2.7.11.1 (Casein Kinase II); Q20Q21Q62J (Cisplatin); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170917
[St] Status:MEDLINE
[do] DOI:10.1124/jpet.117.243451


  3 / 3401 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28898290
[Au] Autor:Ren S; Wang Y; Xian L; Toyama T; Jardine M; Li G; Perkovic V; Hong D
[Ad] Endereço:Renal Division and Institute of Nephrology, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
[Ti] Título:Comparative effectiveness and tolerance of immunosuppressive treatments for idiopathic membranous nephropathy: A network meta-analysis.
[So] Source:PLoS One;12(9):e0184398, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Immunosuppressive agents in general are shown to prevent renal progression and all-cause mortality in idiopathic membranous nephropathy (IMN) patients with nephrotic syndrome. However, the efficacy and safety of different immunosuppressive treatments have not been systematic assessed and compared. A network meta-analysis was performed to compare different immunosuppressive treatment in IMN. METHODS: Cochrane library, MEDLINE, EMBASE and trial register system were searched for randomized controlled trials reporting the treatments for IMN to May 3, 2016. Composite endpoint of mortality or end-stage kidney disease (ESKD), complete or partial proteinuria remission and withdrawal because of treatment adverse events were compared combing direct and indirect comparison using network meta-analysis. Ranking different immunosuppressive treatments in the outcomes were analyzed by using surface under the cumulative ranking curve (SUCRA). RESULTS: Total 36 randomized controlled trials (n = 2018) covering 11 kinds of treatments were included. Compared with non-immunosuppressive treatment, only cyclophosphamide (CTX) and chlorambucil significantly reduced the risk of composite outcome of mortality or ESKD while combining the direct and indirect comparison (OR = 0.31, 95%CI: 0.12-0.81 and OR = 0.33, 95%CI: 0.12-0.92). CTX increased the composite outcome of complete remission (CR) or partial remission (PR) (OR = 4.29, 95%CI: 2.30-8.00) but chlorambucil did not (OR = 1.58, 95%CI: 0.80-3.12) as compared with non-immunosuppressive treatment. Chlorambucil also significantly increased the withdrawal risk (OR = 3.34, 95%CI: 1.37-8.17) as compared to CTX. Both tacrolimus (OR = 3.10, 95%CI: 1.36-7.09) and cyclosporine (CsA) (OR = 2.81, 95%CI: 1.08-7.32) also significantly increased the rate of CR or PR as compared with non-immunosuppressive treatment (without significant difference as compared with CTX), while ranking results showed that cyclosporine or tacrolimus was with less possibility of drug withdrawal as compared to CTX. CONCLUSIONS: Cyclophosphamide and chlorambucil reduce risk of ESKD or death in IMN with nephrotic range proteinuria, but carry substantial toxicity that may be lower for cyclophosphamide. Tacrolimus and cyclosporine increase the possibility of proteinuria remission with less drug withdrawal, but the effects on kidney failure remain uncertain.
[Mh] Termos MeSH primário: Clorambucila/efeitos adversos
Ciclofosfamida/efeitos adversos
Ciclosporina/efeitos adversos
Glomerulonefrite Membranosa/tratamento farmacológico
Imunossupressores/efeitos adversos
Tacrolimo/efeitos adversos
[Mh] Termos MeSH secundário: Clorambucila/administração & dosagem
Clorambucila/uso terapêutico
Ciclofosfamida/administração & dosagem
Ciclofosfamida/uso terapêutico
Ciclosporina/administração & dosagem
Ciclosporina/uso terapêutico
Tolerância a Medicamentos
Feminino
Seres Humanos
Imunossupressores/administração & dosagem
Imunossupressores/uso terapêutico
Masculino
Ensaios Clínicos Controlados Aleatórios como Assunto
Tacrolimo/administração & dosagem
Tacrolimo/uso terapêutico
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (Immunosuppressive Agents); 18D0SL7309 (Chlorambucil); 83HN0GTJ6D (Cyclosporine); 8N3DW7272P (Cyclophosphamide); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184398


  4 / 3401 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28845710
[Au] Autor:Klein C; Bacac M; Umana P; Fingerle-Rowson G
[Ad] Endereço:a Roche Pharmaceutical Research & Early Development , Roche Innovation Center Zurich , Zurich , Switzerland.
[Ti] Título:Combination therapy with the type II anti-CD20 antibody obinutuzumab.
[So] Source:Expert Opin Investig Drugs;26(10):1145-1162, 2017 Oct.
[Is] ISSN:1744-7658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Obinutuzumab is a novel humanized type II glycoengineered anti-CD20 antibody approved for first-line treatment of chronic lymphocytic leukemia (CLL) in combination with chlorambucil and for treatment of rituximab-refractory follicular lymphoma (FL). Areas covered: We describe current preclinical and clinical evidence supporting the combination of obinutuzumab with not only chemotherapy but also novel targeted therapies for B-cell hematologic malignancies, and its application in chemoimmunotherapy. We also provide an overview of the current clinical trial landscape investigating novel combination therapies based on obinutuzumab. Expert opinion: Within the next 10 years the treatment of B-cell malignancies with obinutuzumab is expected to increasingly move towards chemotherapy-free regimens. Novel combinations of obinutuzumab will be explored with targeted therapies, antibody-drug conjugates, and/or other immunotherapeutic agents, with the aim to achieve clinically meaningful improvements in efficacy and patient safety.
[Mh] Termos MeSH primário: Anticorpos Monoclonais Humanizados/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antígenos CD20/imunologia
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Clorambucila/administração & dosagem
Seres Humanos
Leucemia Linfocítica Crônica de Células B/imunologia
Leucemia Linfocítica Crônica de Células B/patologia
Terapia de Alvo Molecular
Rituximab/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Antigens, CD20); 18D0SL7309 (Chlorambucil); 4F4X42SYQ6 (Rituximab); O43472U9X8 (obinutuzumab)
[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:170829
[St] Status:MEDLINE
[do] DOI:10.1080/13543784.2017.1373087


  5 / 3401 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28818459
[Au] Autor:Liu T; Peng Y; Li X; Liu L; Liu F; He L
[Ad] Endereço:Department of Infectious Diseases and Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha 410008, PR China. Electronic address: liutengjy@126.com.
[Ti] Título:A novel delocalized lipophilic cation-chlorambucil conjugate inhibits P-glycoprotein in HepG2/ADM cells.
[So] Source:Bioorg Med Chem;25(20):5461-5467, 2017 Oct 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Multidrug resistance (MDR) limits the application of a large number of cancer-fighting agents in clinical therapy. One reason is that P-glycoprotein (Pgp) efflux pumps are usually overexpressed and lead to drug efflux in the cancer cells, which limits the viability of many chemotherapeutics. Current available inhibitors which block the Pgp pump efflux are usually not widely used in clinical practice, because they change other drug pharmacokinetic profiles or increase side effects. Here, through covalent linkage of cancer-targeting delocalized lipophilic cation FF and DNA-damaging drug nitrogen mustard chlorambucil (CLB), we rationally designed and synthesized a tumor-targeting anticancer agent FFCLB. And we found and proved that the FFCLB was capable of reducing the outflow of Pgp substrates efficiently. This conjugate selectively improves adriamycin uptake and toxicity through reducing MDR1 mRNA and Pgp protein expression. Based on molecular targeted strategy, this study can facilitate the discovery of superior MDR reducing agents to provide a more effective and safer way of resensitizing MDR.
[Mh] Termos MeSH primário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores
Clorambucila/farmacologia
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
Animais
Cátions/química
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Clorambucila/síntese química
Clorambucila/química
Relação Dose-Resposta a Droga
Células Hep G2
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Camundongos
Simulação de Acoplamento Molecular
Estrutura Molecular
Células NIH 3T3
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Cations); 18D0SL7309 (Chlorambucil)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170819
[St] Status:MEDLINE


  6 / 3401 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28818449
[Au] Autor:Xie R; Li Y; Tang P; Yuan Q
[Ad] Endereço:Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, 15 Beisanhuan East Road, Beijing 100029, China.
[Ti] Título:Rational design, synthesis and preliminary antitumor activity evaluation of a chlorambucil derivative with potent DNA/HDAC dual-targeting inhibitory activity.
[So] Source:Bioorg Med Chem Lett;27(18):4415-4420, 2017 09 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Histone deacetylases (HDACs) play a pivotal role not only in gene expression but also in DNA repair. Herein, we report the successful design, synthesis and evaluation of a chlorambucil derivative named vorambucil with a hydroxamic acid tail as a DNA/HDAC dual-targeting inhibitor. Vorambucil obtained both potent DNA and HDACs inhibitory activities. Molecular docking results supported the initial pharmacophoric hypothesis and rationalized the potent inhibitory activity of vorambucil against HDAC1, HDAC2 and HDAC6. Vorambucil showed potent antiproliferative activity against all the test four cancer cell lines with IC values of as low as 3.2-6.2µM and exhibited 5.0-18.3-fold enhanced antiproliferative activity than chlorambucil. Vorambucil also significantly inhibits colony formation of A375 cancer cells. Further investigation showed that vorambucil remarkably induced apoptosis and arrested the cell cycle of A375 cells at G2/M phase. Vorambucil could be a promising candidate and a useful tool to elucidate the role of those DNA/HDAC dual-targeting inhibitors for cancer therapy.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Clorambucila/farmacologia
DNA/efeitos dos fármacos
Desenho de Drogas
Inibidores de Histona Desacetilases/farmacologia
Histona Desacetilases/metabolismo
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Clorambucila/síntese química
Clorambucila/química
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Inibidores de Histona Desacetilases/síntese química
Inibidores de Histona Desacetilases/química
Seres Humanos
Simulação de Acoplamento Molecular
Estrutura Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Histone Deacetylase Inhibitors); 18D0SL7309 (Chlorambucil); 9007-49-2 (DNA); EC 3.5.1.98 (Histone Deacetylases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170819
[St] Status:MEDLINE


  7 / 3401 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28586717
[Au] Autor:Qin X; Fang L; Chen F; Gou S
[Ad] Endereço:Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
[Ti] Título:Conjugation of platinum(IV) complexes with chlorambucil to overcome cisplatin resistance via a "joint action" mode toward DNA.
[So] Source:Eur J Med Chem;137:167-175, 2017 Sep 08.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Two platinum(IV) complexes were designed and prepared by conjugation of cisplatin and oxaliplatin units with a DNA-damaging agent, chlorambucil, respectively. By taking a joint action to enhance the damage of DNA, the conjugates displayed potent antitumor activity against all the tested cancer cell lines comparable to cisplatin and oxaliplatin, and notably could overcome cisplatin resistance at certain degree. Complex 4, a hybrid of cisplatin and chlorambucil, arrested the cell cycle at the S and G2 phases, distinctive from those of cisplatin and oxaliplatin. Apoptosis studies revealed that complex 4 could induce cell apoptosis significantly in both SGC7901 and SGC7901/CDDP cells. Moreover, further investigation indicated that complex 4 suppressed the drug resistance by the improvement of the platinum uptake and the inhibition of PRAP-1 protein. These results show that the "joint action" on DNA is an effective strategy to overcome cisplatin resistance.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Clorambucila/farmacologia
Cisplatino/farmacologia
DNA de Neoplasias/efeitos dos fármacos
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Compostos Organoplatínicos/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Apoptose/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Clorambucila/química
Cisplatino/química
Relação Dose-Resposta a Droga
Seres Humanos
Estrutura Molecular
Compostos Organoplatínicos/síntese química
Compostos Organoplatínicos/química
Relação Estrutura-Atividade
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (DNA, Neoplasm); 0 (Organoplatinum Compounds); 18D0SL7309 (Chlorambucil); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170607
[St] Status:MEDLINE


  8 / 3401 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28479418
[Au] Autor:Valdez BC; Hassan M; Andersson BS
[Ad] Endereço:Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX. Electronic address: bvaldez@mdanderson.org.
[Ti] Título:Development of an assay for cellular efflux of pharmaceutically active agents and its relevance to understanding drug interactions.
[So] Source:Exp Hematol;52:65-71, 2017 Aug.
[Is] ISSN:1873-2399
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Drug interactions may dictate the failure or success of a treatment. Patients undergoing hematopoietic stem cell transplantation (HSCT) are exposed to various types of drugs, and understanding how these drugs interact is of the utmost importance. The pharmacokinetics of busulfan, melphalan, and cyclophosphamide, drugs commonly used for HSCT, are known to be affected by a variety of other drugs with differing molecular structures. We hypothesized that these structurally unrelated drugs affect the transport of DNA-alkylating agents. To test this hypothesis, we developed a flow cytometry assay that used 5-carboxyfluorescein diacetate acetoxymethyl ester, which is cleaved by nonspecific intracellular esterases to 5-carboxyfluorescein (5-CF), a fluorescent ligand for the drug transporter MRP1. A decreased 5-CF efflux in the presence of a test compound suggests competitive inhibition. We demonstrated that chlorambucil, 4-hydroperoxycyclophosphamide, ketoconazole, ethacrynic acid, everolimus, and sirolimus strongly inhibited 5-CF efflux in lymphoma and leukemia cell lines. The efflux of these drugs partially depends on the glutathione (GSH) level, and their cytotoxicity is synergistic with inhibited GSH synthesis. This is consistent with the hypothesis that their GSH-conjugated products are ligands of a common cellular drug transporter. Our results may explain clinical observations on the effects of various drugs on the pharmacokinetics and pharmacodynamics of alkylating agents, and the assay may be used to deduce interaction mechanisms of drugs transported by a common system.
[Mh] Termos MeSH primário: Ciclofosfamida/farmacologia
Interações Medicamentosas
Citometria de Fluxo/métodos
Fluoresceínas/metabolismo
[Mh] Termos MeSH secundário: Antineoplásicos Alquilantes/farmacocinética
Antineoplásicos Alquilantes/farmacologia
Transporte Biológico/efeitos dos fármacos
Bussulfano/farmacocinética
Bussulfano/farmacologia
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Clorambucila/farmacocinética
Clorambucila/farmacologia
Ciclofosfamida/análogos & derivados
Ciclofosfamida/farmacocinética
Ácido Etacrínico/farmacocinética
Ácido Etacrínico/farmacologia
Everolimo/farmacocinética
Everolimo/farmacologia
Fluoresceínas/química
Seres Humanos
Cetoconazol/farmacocinética
Cetoconazol/farmacologia
Melfalan/farmacocinética
Melfalan/farmacologia
Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo
Reprodutibilidade dos Testes
Sirolimo/farmacocinética
Sirolimo/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5-carboxyfluorescein diacetate acetoxymethyl ester); 0 (Antineoplastic Agents, Alkylating); 0 (Fluoresceins); 0 (Multidrug Resistance-Associated Proteins); 18D0SL7309 (Chlorambucil); 76823-03-5 (4-carboxyfluorescein); 8N3DW7272P (Cyclophosphamide); 9HW64Q8G6G (Everolimus); G1LN9045DK (Busulfan); M5DP350VZV (Ethacrynic Acid); Q41OR9510P (Melphalan); R9400W927I (Ketoconazole); U880A4FUDA (perfosfamide); W36ZG6FT64 (Sirolimus); Y49M64GZ4Q (multidrug resistance-associated protein 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170509
[St] Status:MEDLINE


  9 / 3401 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28421390
[Au] Autor:Hatake K; Ogura M; Takada K; Taniwaki M; Zhang F; Fujita T; Ando K
[Ad] Endereço:Department of Hematology and Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan. khatake@jfcr.or.jp.
[Ti] Título:Ofatumumab combined with chlorambucil for previously untreated chronic lymphocytic leukemia: a phase I/II, open-label study in Japan.
[So] Source:Int J Hematol;106(2):240-247, 2017 Aug.
[Is] ISSN:1865-3774
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Elderly/comorbid patients with chronic lymphocytic leukemia (CLL) require low-toxicity treatments. Internationally, the standard treatment for such patients is chlorambucil and an anti-CD20 therapy; however, chlorambucil is not approved in Japan. The aim of the present study was to evaluate the safety, efficacy and pharmacokinetics of ofatumumab in combination with chlorambucil in Japanese patients with previously untreated CLL who were inappropriate for fludarabine-based therapy. Ten patients were enrolled and treated in this study, all of whom received at least one dose of the study drugs. The tolerability of the treatment was confirmed initially with three patients. The overall response rate was 50%, as determined by the Independent Review Committee (IRC) with computerized tomography. All patients were alive at follow-up, and only one patient had progressive disease. The most common treatment-related adverse events (AEs) were thrombocytopenia (n = 10), neutropenia (n = 9) and rash (n = 6). One grade 3 serious AE related to the study drug occurred (hypoxia). The results indicate that ofatumumab combined with chlorambucil is an effective treatment for Japanese CLL patients, with a manageable safety profile.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Anticorpos Monoclonais/administração & dosagem
Anticorpos Monoclonais/efeitos adversos
Anticorpos Monoclonais/farmacocinética
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Grupo com Ancestrais do Continente Asiático
Clorambucila/administração & dosagem
Clorambucila/efeitos adversos
Clorambucila/farmacocinética
Exantema/induzido quimicamente
Feminino
Seres Humanos
Japão
Masculino
Meia-Idade
Neutropenia/induzido quimicamente
Trombocitopenia/induzido quimicamente
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 18D0SL7309 (Chlorambucil); M95KG522R0 (ofatumumab)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170420
[St] Status:MEDLINE
[do] DOI:10.1007/s12185-017-2233-1


  10 / 3401 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28355112
[Au] Autor:Zucca E; Conconi A; Martinelli G; Bouabdallah R; Tucci A; Vitolo U; Martelli M; Pettengell R; Salles G; Sebban C; Guillermo AL; Pinotti G; Devizzi L; Morschhauser F; Tilly H; Torri V; Hohaus S; Ferreri AJM; Zachée P; Bosly A; Haioun C; Stelitano C; Bellei M; Ponzoni M; Moreau A; Jack A; Campo E; Mazzucchelli L; Cavalli F; Johnson P; Thieblemont C
[Ad] Endereço:Emanuele Zucca and Franco Cavalli, Oncology Institute of Southern Switzerland, Bellinzona; Luca Mazzucchelli, Cantonal Institute of Pathology, Locarno, Switzerland; Annarita Conconi, Ospedale degli Infermi, Biella; Giovanni Martinelli, European Institute of Oncology; Liliana Devizzi, Fondazione Isti
[Ti] Título:Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy.
[So] Source:J Clin Oncol;35(17):1905-1912, 2017 Jun 10.
[Is] ISSN:1527-7755
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m /d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Clorambucila/uso terapêutico
Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico
Rituximab/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Clorambucila/administração & dosagem
Clorambucila/efeitos adversos
Intervalo Livre de Doença
Determinação de Ponto Final
Feminino
Seres Humanos
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Rituximab/administração & dosagem
Rituximab/efeitos adversos
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
18D0SL7309 (Chlorambucil); 4F4X42SYQ6 (Rituximab)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170330
[St] Status:MEDLINE
[do] DOI:10.1200/JCO.2016.70.6994



página 1 de 341 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde