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  1 / 23190 MEDLINE  
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[PMID]:29364966
[Au] Autor:Maleki Vareki S; Salim KY; Danter WR; Koropatnick J
[Ad] Endereço:Cancer Research Laboratory Program, Lawson Health Research Institute, London, Ontario, Canada.
[Ti] Título:Novel anti-cancer drug COTI-2 synergizes with therapeutic agents and does not induce resistance or exhibit cross-resistance in human cancer cell lines.
[So] Source:PLoS One;13(1):e0191766, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Emerging drug-resistance and drug-associated toxicities are two major factors limiting successful cancer therapy. Combinations of chemotherapeutic drugs have been used in the clinic to improve patient outcome. However, cancer cells can acquire resistance to drugs, alone or in combination. Resistant tumors can also exhibit cross-resistance to other chemotherapeutic agents, resulting in sub-optimal treatment and/or treatment failure. Therefore, developing novel oncology drugs that induce no or little acquired resistance and with a favorable safety profile is essential. We show here that combining COTI-2, a novel clinical stage agent, with multiple chemotherapeutic and targeted agents enhances the activity of these drugs in vitro and in vivo. Importantly, no overt toxicity was observed in the combination treatment groups in vivo. Furthermore, unlike the tested chemotherapeutic drugs, cancer cells did not develop resistance to COTI-2. Finally, some chemo-resistant tumor cell lines only showed mild cross-resistance to COTI-2 while most remained sensitive to it.
[Mh] Termos MeSH primário: Aminoquinolinas/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Tiossemicarbazonas/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Carcinoma Pulmonar de Células não Pequenas/patologia
Linhagem Celular Tumoral
Cisplatino/administração & dosagem
Desoxicitidina/administração & dosagem
Desoxicitidina/análogos & derivados
Resistência a Medicamentos Antineoplásicos
Neoplasias Pulmonares/patologia
Camundongos
Paclitaxel/administração & dosagem
Vimblastina/administração & dosagem
Vimblastina/análogos & derivados
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aminoquinolines); 0 (COTI-2 compound); 0 (Thiosemicarbazones); 0W860991D6 (Deoxycytidine); 5V9KLZ54CY (Vinblastine); B76N6SBZ8R (gemcitabine); P88XT4IS4D (Paclitaxel); Q20Q21Q62J (Cisplatin); Q6C979R91Y (vinorelbine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191766


  2 / 23190 MEDLINE  
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[PMID]:29184405
[Au] Autor:Hureaux J; Lacoeuille F; Lagarce F; Rousselet MC; Contini A; Saulnier P; Benoit JP; Urban T
[Ad] Endereço:Unité Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire.
[Ti] Título:Absence of lung fibrosis after a single pulmonary delivery of lipid nanocapsules in rats.
[So] Source:Int J Nanomedicine;12:8159-8170, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Lipid nanocapsules (LNCs) are potential drug carriers for pulmonary delivery since they can be nebulized without any structural or functional changes, and the aerosols produced are highly compatible with pulmonary drug delivery in human beings. The alveolar surface tension, in vitro cytotoxicity, biodistribution and pulmonary toxicity in rats of a single endotracheal spray of LNCs or paclitaxel-loaded LNCs were studied. In vitro cytotoxicity of LNCs after a spray remained unchanged. Biodistribution study showed a homogeneous repartition in the lungs in rats with an improvement in lung retention of the radiolabeled tracer loaded in LNCs compared to the absence of LNCs with a lung half-time of 8.8±0.7 hours. Bronchoalveolar fluid analysis revealed transient 7-day alveolar inflammation, reaching a maximum between days 2 and 4, characterized by a peak of granulocytes at day 1 followed by a peak of lymphocytes at day 3. Alveolar protein levels were increased at days 3 and 7. Acute inflammation was increased with paclitaxel-loaded LNCs in comparison with blank LNCs but dropped out at day 7. No histological pulmonary lesion was observed at day 60. LNCs lowered surface tension to a greater degree than Curosurf in a physicochemical model of the pulmonary alveolus. A single pulmonary delivery of LNCs induces a short-term alveolar inflammation with no residual lesions in rats at day 60. These data permit to start the study of LNCs in surfactant replacement therapy.
[Mh] Termos MeSH primário: Portadores de Fármacos/efeitos adversos
Portadores de Fármacos/farmacocinética
Pulmão/efeitos dos fármacos
Pulmão/patologia
Nanocápsulas/efeitos adversos
[Mh] Termos MeSH secundário: Aerossóis/administração & dosagem
Aerossóis/efeitos adversos
Aerossóis/química
Animais
Produtos Biológicos
Linhagem Celular
Portadores de Fármacos/administração & dosagem
Sistemas de Liberação de Medicamentos/efeitos adversos
Sistemas de Liberação de Medicamentos/métodos
Feminino
Fibrose
Seres Humanos
Lipídeos/química
Nanocápsulas/administração & dosagem
Nanocápsulas/química
Paclitaxel/química
Paclitaxel/farmacocinética
Fosfolipídeos
Alvéolos Pulmonares/efeitos dos fármacos
Alvéolos Pulmonares/fisiopatologia
Ratos Sprague-Dawley
Tensão Superficial/efeitos dos fármacos
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aerosols); 0 (Biological Products); 0 (Drug Carriers); 0 (Lipids); 0 (Nanocapsules); 0 (Phospholipids); KE3U2023NP (poractant alfa); P88XT4IS4D (Paclitaxel)
[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:171130
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S146740


  3 / 23190 MEDLINE  
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[PMID]:29184399
[Au] Autor:Wu C; Xu J; Hao Y; Zhao Y; Qiu Y; Jiang J; Yu T; Ji P; Liu Y
[Ad] Endereço:Pharmacy School, Jinzhou Medical University, Jinzhou, China.
[Ti] Título:Application of a lipid-coated hollow calcium phosphate nanoparticle in synergistic co-delivery of doxorubicin and paclitaxel for the treatment of human lung cancer A549 cells.
[So] Source:Int J Nanomedicine;12:7979-7992, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:In this study, we developed a lipid-coated hollow calcium phosphate (LCP) nanoparticle for the combined application of two chemotherapeutic drugs to human lung cancer A549 cells. Hydrophilic doxorubicin (DOX) was incorporated into the hollow structure of hollow calcium phosphate (HCP), and a lipid bilayer containing hydrophobic paclitaxel (PTX) was subsequently coated on the surface of HCP. The study on combinational effects demonstrated that the combination of DOX and PTX at a mass ratio of 12:1 showed a synergistic effect against A549 cells. The particle size, zeta potential, and encapsulation efficiency were measured to obtain optimal values: particle size was 335.0 3.2 nm, zeta potential -41.1 mV, and encapsulation efficiency 80.40%±2.24%. An in vitro release study indicated that LCP produced a sustained drug release. A549 cells had a better uptake of LCP with good biocompatibility. Furthermore, in vitro cytotoxicity experiment, apoptosis analysis, in vivo anti-tumor efficacy and protein expression analysis of Bax, Bcl-2, and Caspase-3 demonstrated that the co-delivery system based on LCP had significant synergistic anti-tumor activity. All conclusions suggested that LCP is a promising platform for co-delivery of multiple anti-tumor drugs.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Sistemas de Liberação de Medicamentos/métodos
Nanopartículas/administração & dosagem
Nanopartículas/química
Fosfolipídeos/química
[Mh] Termos MeSH secundário: Células A549
Animais
Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética
Apoptose/efeitos dos fármacos
Fosfatos de Cálcio/química
Caspase 3/metabolismo
Preparações de Ação Retardada/administração & dosagem
Preparações de Ação Retardada/química
Doxorrubicina/administração & dosagem
Doxorrubicina/química
Seres Humanos
Camundongos Nus
Paclitaxel/administração & dosagem
Paclitaxel/química
Tamanho da Partícula
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Phosphates); 0 (Delayed-Action Preparations); 0 (Phospholipids); 80168379AG (Doxorubicin); 97Z1WI3NDX (calcium phosphate); EC 3.4.22.- (CASP3 protein, human); EC 3.4.22.- (Caspase 3); P88XT4IS4D (Paclitaxel)
[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:171130
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S140957


  4 / 23190 MEDLINE  
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[PMID]:28658975
[Au] Autor:Qiu WQ; Cui YM; Tang P; Qiu YY; Lin HX
[Ad] Endereço:a Department of Chemistry, Innovative Drug Research Center, College of Sciences , Shanghai University , Shanghai , China.
[Ti] Título:Synthesis and biological evaluation of novel A-seco-taxoids derived from 1-deoxybaccatin VI.
[So] Source:Nat Prod Res;32(2):121-127, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Three novel nor-seco-taxoids 13, 15, 23 in which the A rings are cleaved but the B, C, and D rings are retained were prepared from 1-deoxybaccatin VI via its nor-dioxo derivative and their structures were confirmed by H NMR, C NMR and high resolution MS. Oxidative introduction of C-1 hydroxyl to 1-deoxybaccatin VI with oxidising agent KBrO and catalyst RuCl led to the dioxo derivative 6 and its structure is determined by X-ray crystallographic analysis. A-seco taxoids 13, 15, 23 with a C-13 ester linkage were tested for cytotoxic activity and all compounds showed no measurable cytotoxic activity against HCT-116 cell line. However, 1-deoxy-9a-dihydrotaxane analogue 4 semi-synthesised from 1-deoxybaccatin VI is 10-fold less cytotoxic than paclitaxel, indicating the indispensible nature of the A ring double bond for the bioactivity of paclitaxel.
[Mh] Termos MeSH primário: Taxoides/síntese química
Taxoides/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/farmacologia
Linhagem Celular Tumoral
Cristalografia por Raios X
Células HCT116
Seres Humanos
Estrutura Molecular
Oxirredução
Paclitaxel/farmacologia
Análise Espectral
Taxoides/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-deoxybaccatin VI); 0 (Antineoplastic Agents); 0 (Taxoids); P88XT4IS4D (Paclitaxel)
[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:170630
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1340281


  5 / 23190 MEDLINE  
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[PMID]:29442003
[Au] Autor:Li Z; Shu J; Yang B; Xu C; Zou Y; Sun W
[Ti] Título:Evaluating the relationship between cell viability and volatile organic compound production following DMSO treatment of cultured human cells.
[So] Source:Pharmazie;71(12):727-732, 2016 12 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Methylsulfinylmethane (dimethyl sulfoxide; DMSO) is widely used in clinical treatment and bioresearch. Moreover, there is bioconversion between methylsulfanylmethane (dimethyl sulfide; DMS), DMSO, and methylsulfonylmethane (DMSO2) in mammalian metabolism. Due to the real-time detection limits for volatile compounds, most research has focused on DMSO2 as a stable byproduct of DMSO. Therefore, details about the production of DMS as a byproduct of DMSO metabolism remain to be elucidated. Here, we report the characterization of trace-level volatile organic compounds (VOCs) produced following DMSO treatment of cultured human cells using an ultrasensitive vacuum ultraviolet photoionization mass spectrometer (VUV-PIMS). Using this approach, 24 h after DMSO treatment we detected 16.9 and 21 parts per billion by volume (ppbv) DMS in the atmosphere above the cells (headspace) within HeLa and 293T tissue culture flasks, respectively. When simultaneously exposed to 50 nM paclitaxel (PTX), 17.6 and 22.3 ppbv DMS were detected in the headspace of HeLa and 293T culture flasks, respectively. Nevertheless, at doses of PTX more or less than 50 nM, the detectable levels of DMS were reduced to as low as 8.4 ppbv. Our experimental results demonstrate that by co-administering 5 to 10 nM PTX with DMSO, it is possible to moderate the production of DMS considerably. However, at higher doses of PTX, increased apoptosis was observed that likely contributed to higher DMS production by cells.
[Mh] Termos MeSH primário: Sobrevivência Celular/efeitos dos fármacos
Dimetil Sulfóxido/farmacologia
Substâncias Protetoras/farmacologia
Compostos Orgânicos Voláteis/metabolismo
[Mh] Termos MeSH secundário: Antineoplásicos Fitogênicos/antagonistas & inibidores
Antineoplásicos Fitogênicos/toxicidade
Células Cultivadas
Células HEK293
Células HeLa
Seres Humanos
Paclitaxel/antagonistas & inibidores
Paclitaxel/toxicidade
Sulfonas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Protective Agents); 0 (Sulfones); 0 (Volatile Organic Compounds); 9H4PO4Z4FT (dimethyl sulfone); P88XT4IS4D (Paclitaxel); YOW8V9698H (Dimethyl Sulfoxide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6075


  6 / 23190 MEDLINE  
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[PMID]:29180863
[Au] Autor:Liu K; Chen W; Yang T; Wen B; Ding D; Keidar M; Tang J; Zhang W
[Ad] Endereço:College of Pharmacy, Weifang Medical University, Weifang.
[Ti] Título:Paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery.
[So] Source:Int J Nanomedicine;12:8239-8255, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:High drug resistance, poor water solubility, short half-life, and low local drug concentration are obstacles for successful delivery of chemotherapeutic drugs for lung cancer. A new method involving the use of nanoparticles (NPs) for pulmonary delivery is proposed. However, use of NPs is limited by the particle size range for pulmonary drug delivery considering that NPs cannot be deposited directly into the lungs. NPs polymerized into microspheres (polymeric microspheres, PMs) will result in suitable particle sizes and retain the advantages of nanodrugs after redispersion when applied in pulmonary delivery. We report the development of novel NPs in the form of PMs loaded with paclitaxel (PTX) and quercetin (QUE) double drugs based on the synthesis of oleic acid-conjugated chitosan (OA-CTS) for pulmonary delivery. This approach is aimed toward prolonging PTX retention time in the presence of QUE and bypassing P-glycoprotein drug efflux pumps. NPs loaded with PTX or QUE were prepared with 11% substitution degree using OA-CTS as the carrier by ionic cross-linking method, which NPs loaded with PTX or QUE were used in the preparation of PMs by spray-drying. The diameters of the PMs ranged from 1 to 5 µm which had uniform size range. Scanning electron microscopy showed that PMs were polymers formed by a large number of NPs and readily redispersed (after redispersion, size of NPs ranged between 250 and 350 nm) in water within 1 h. PMs displayed slow-release characteristics at pH 4.5 and 7.4. The in vivo pharmacokinetic and biodistribution studies suggested that PMs exhibit prolonged circulation time and a markedly high accumulation in the lung. The obtained results indicate that PMs can serve as a promising pulmonary delivery system for combined pharmacotherapy using hydrophobic anticancer drugs.
[Mh] Termos MeSH primário: Pulmão/efeitos dos fármacos
Nanopartículas/química
Paclitaxel/administração & dosagem
Quercetina/administração & dosagem
[Mh] Termos MeSH secundário: Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
Animais
Antineoplásicos/administração & dosagem
Quitosana/química
Sistemas de Liberação de Medicamentos
Liberação Controlada de Fármacos
Feminino
Meia-Vida
Masculino
Microesferas
Ácido Oleico/química
Paclitaxel/farmacocinética
Tamanho da Partícula
Quercetina/farmacocinética
Ratos Wistar
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Antineoplastic Agents); 2UMI9U37CP (Oleic Acid); 9012-76-4 (Chitosan); 9IKM0I5T1E (Quercetin); P88XT4IS4D (Paclitaxel)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S147028


  7 / 23190 MEDLINE  
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[PMID]:28449309
[Au] Autor:Zanella S; Angerani S; Pina A; López Rivas P; Giannini C; Panzeri S; Arosio D; Caruso M; Gasparri F; Fraietta I; Albanese C; Marsiglio A; Pignataro L; Belvisi L; Piarulli U; Gennari C
[Ad] Endereço:Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133, Milano, Italy.
[Ti] Título:Tumor Targeting with an isoDGR-Drug Conjugate.
[So] Source:Chemistry;23(33):7910-7914, 2017 Jun 12.
[Is] ISSN:1521-3765
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Herein we report the first example of an isoDGR-drug conjugate (2), designed to release paclitaxel selectively within cancer cells expressing integrin α ß . Conjugate 2 was synthesized by connecting the isoDGR peptidomimetic 5 with paclitaxel via the lysosomally cleavable Val-Ala dipeptide linker. Conjugate 2 displayed a low nanomolar affinity for the purified integrin α ß receptor (IC =11.0 nm). The tumor targeting ability of conjugate 2 was assessed in vitro in anti-proliferative assays on two isogenic cancer cell lines characterized by different integrin α ß expression: human glioblastoma U87 (α ß +) and U87 ß -KO (α ß -). The isoDGR-PTX conjugate 2 displayed a remarkable targeting index (TI=9.9), especially when compared to the strictly related RGD-PTX conjugate 4 (TI=2.4).
[Mh] Termos MeSH primário: Oligopeptídeos/química
Paclitaxel/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Seres Humanos
Concentração Inibidora 50
Integrina alfaVbeta3/antagonistas & inibidores
Integrina alfaVbeta3/genética
Integrina alfaVbeta3/metabolismo
Peptidomiméticos/química
Peptidomiméticos/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Integrin alphaVbeta3); 0 (Oligopeptides); 0 (Peptidomimetics); 78VO7F77PN (arginyl-glycyl-aspartic acid); P88XT4IS4D (Paclitaxel)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1002/chem.201701844


  8 / 23190 MEDLINE  
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[PMID]:29223048
[Au] Autor:Zheng N; Lian B; Du W; Xu G; Ji J
[Ad] Endereço:Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), National Drug Clinical Trial Center, Peking University Cancer Hospital & Institute, Beijing 100142, China.
[Ti] Título:Extraction protocol and liquid chromatography/tandem mass spectrometry method for determining micelle-entrapped paclitaxel at the cellular and subcellular levels: Application to a cellular uptake and distribution study.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1072:347-354, 2018 Jan 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Paclitaxel-loaded polymeric micelles (PTX-PM) are commonly used as tumor-targeted nanocarriers and display outstanding antitumor features in clinic, but its accumulation and distribution in vitro are lack of investigation. It is probably due to the complex micellar system and its low concentration at the cellular or subcellular levels. In this study, we developed an improved extraction method, which was a combination of mechanical disruption and liquid-liquid extraction (LLE), to extract the total PTX from micelles in the cell lysate and subcellular compartments. An ultra-performance liquid chromatography tandem mass spectroscopy (UPLC-MS/MS) method was optimized to detect the low concentration of PTX at cellular and subcellular levels simultaneously, using docetaxel as internal standard (IS). The method was proved to release PTX totally from micelles (≥95.93%) with a consistent and reproducible extraction recovery (≥75.04%). Good linearity was obtained at concentrations ranging from 0.2 to 20ng/mL. The relative error (RE%) for accuracy varied from 0.68 to 7.56%, and the intra- and inter-precision (relative standard deviation, RSD%) was less than 8.64% and 13.14%, respectively. This method was fully validated and successfully applied to the cellular uptake and distribution study of PTX-loaded PLGA-PEG micelles in human breast cancer cells (MCF-7).
[Mh] Termos MeSH primário: Cromatografia Líquida/métodos
Paclitaxel/análise
Paclitaxel/farmacocinética
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Cromatografia Líquida de Alta Pressão
Estabilidade de Medicamentos
Seres Humanos
Limite de Detecção
Modelos Lineares
Extração Líquido-Líquido
Células MCF-7
Micelas
Paclitaxel/química
Paclitaxel/isolamento & purificação
Poliésteres/química
Polietilenoglicóis/química
Reprodutibilidade dos Testes
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Micelles); 0 (Polyesters); 0 (polyethylene glycol-poly(lactide-co-glycolide)); 30IQX730WE (Polyethylene Glycols); P88XT4IS4D (Paclitaxel)
[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:171210
[St] Status:MEDLINE


  9 / 23190 MEDLINE  
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[PMID]:29221445
[Au] Autor:Kawamoto Y; Komatsu Y; Yuki S; Sawada K; Muranaka T; Harada K; Nakatsumi H; Fukushima H; Ishiguro A; Dazai M; Hatanaka K; Nakamura M; Iwanaga I; Uebayashi M; Sogabe S; Kobayashi Y; Miyagishima T; Ono K; Sakamoto N; Sakata Y
[Ad] Endereço:Department of Cancer Center, Hokkaido University Hospital, Sapporo, Japan.
[Ti] Título:Study protocol of HGCSG1404 SNOW study: a phase I/II trial of combined chemotherapy of S-1, nab-paclitaxel and oxaliplatin administered biweekly to patients with advanced gastric cancer.
[So] Source:BMC Cancer;17(1):837, 2017 12 08.
[Is] ISSN:1471-2407
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In Japan, S-1 plus cisplatin (SP) regimen has become a standard therapy for patients with advanced gastric cancer. Moreover, the S-1 plus oxaliplatin regimen is now a standard treatment. Nab-paclitaxel was developed for chemotherapy of gastric cancer in Japanese clinical practice. Nab-paclitaxel, created with albumin-bound paclitaxel particles, has high transferability to tumour tissues and does not cause hypersensitivity reactions because of a different chemical composition compared with docetaxel and paclitaxel. A combination of S-1, nab-paclitaxel and oxaliplatin (which we named 'SNOW regimen') can be a promising triplet therapy for advanced gastric cancer. Although we have to pay attention to chemotherapy-induced neuropathy, we aim to investigate the recommended dose of this regimen in a phase I study. Furthermore, we will investigate its efficacy and toxicity in a phase II study. METHODS: The phase I study is a dose-escalation study using a standard 3 plus 3 design, followed by expansion cohorts. The SNOW regimen involves 28-day cycles with escalated doses of nab-paclitaxel (100-175 mg/m on days 1 and 15) and fixed doses of oxaliplatin (65 mg/ m on days 1 and 15) and S-1 (80 mg/m /day on day 1 to 14). The primary endpoints are assessment of dose limiting toxicities and determination of maximum tolerated dose to investigate the recommended dose in the subsequent phase II study. In the phase II study, the primary endpoint is objective response rate. Secondary endpoints are assessment of safety, progression-free survival, disease control rate, overall survival and time to treatment failure. Adverse events were monitored and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. DISCUSSION: Triplet therapies for advanced gastric cancer patients have been evaluated in clinical trials. The SNOW regimen can be a promising new triplet therapy. TRIAL REGISTRATION: This study is performed at institutes that participate in Hokkaido Gastrointestinal Cancer Study Group (HGCSG) and registered as UMIN000016788 . Registrated 16 March 2015.
[Mh] Termos MeSH primário: Albuminas
Protocolos de Quimioterapia Combinada Antineoplásica
Compostos Organoplatínicos
Ácido Oxônico
Paclitaxel
Neoplasias Gástricas/tratamento farmacológico
Tegafur
[Mh] Termos MeSH secundário: Adulto
Albuminas/administração & dosagem
Albuminas/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Combinação de Medicamentos
Seres Humanos
Compostos Organoplatínicos/administração & dosagem
Compostos Organoplatínicos/uso terapêutico
Ácido Oxônico/administração & dosagem
Ácido Oxônico/uso terapêutico
Paclitaxel/administração & dosagem
Paclitaxel/uso terapêutico
Neoplasias Gástricas/mortalidade
Tegafur/administração & dosagem
Tegafur/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (130-nm albumin-bound paclitaxel); 0 (Albumins); 0 (Drug Combinations); 0 (Organoplatinum Compounds); 04ZR38536J (oxaliplatin); 150863-82-4 (S 1 (combination)); 1548R74NSZ (Tegafur); 5VT6420TIG (Oxonic Acid); P88XT4IS4D (Paclitaxel)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180217
[Lr] Data última revisão:
180217
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171210
[St] Status:MEDLINE
[do] DOI:10.1186/s12885-017-3850-z


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[PMID]:29390553
[Au] Autor:Ryu H; Song IC; Choi YS; Yun HJ; Jo DY; Kim JM; Ko YB; Lee HJ
[Ad] Endereço:Department of Internal Medicine.
[Ti] Título:ERCC1 expression status predicts the response and survival of patients with metastatic or recurrent cervical cancer treated via platinum-based chemotherapy.
[So] Source:Medicine (Baltimore);96(51):e9402, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The deoxyribonucleic acid (DNA) repair gene encoding the excision-repair cross-complementation group 1 (ERCC1) protein is known to predict the response to platinum-based chemotherapy. Our aim was to explore whether ERCC1 expression predicted tumor response and survival in patients with recurrent or metastatic cervical cancer treated via platinum-based chemotherapy. We analyzed 32 such patients. ERCC1 expression was assessed immunohistochemically in pretreatment biopsy samples. Of the 32 patients, 13 (40.6%) were ERCC1 high. ERCC1-low patients exhibited a significantly higher response rate (73.7%) than did others (15.4%). The median progression-free survival differed significantly by ERCC1 status, being 135 days in ERCC1-high and 242 days in ERCC1-low patients (hazard ratio, 2.428; 95% confidence interval, 1.145-5.148, P = .032). Overall survival was significantly longer in ERCC1-low (617 days) than in ERCC1-high (320 days) patients (hazard ratio, 2.322; 95% confidence interval, 1.051-5.29; P = .037). Thus, pretreatment ERCC1 expression status can be used to predict tumor response and survival of patients with recurrent or metastatic uterine cervical cancer receiving platinum-based chemotherapy.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Biomarcadores Tumorais/metabolismo
Carcinoma/tratamento farmacológico
Proteínas de Ligação a DNA/metabolismo
Endonucleases/metabolismo
Neoplasias do Colo do Útero/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Antineoplásicos/uso terapêutico
Carboplatina/uso terapêutico
Carcinoma/metabolismo
Carcinoma/mortalidade
Carcinoma/secundário
Cisplatino/uso terapêutico
Feminino
Fluoruracila/uso terapêutico
Seguimentos
Seres Humanos
Imuno-Histoquímica
Meia-Idade
Recidiva Local de Neoplasia/tratamento farmacológico
Recidiva Local de Neoplasia/metabolismo
Recidiva Local de Neoplasia/mortalidade
Paclitaxel/uso terapêutico
Neoplasias Pélvicas/patologia
Estudos Retrospectivos
Análise de Sobrevida
Topotecan/uso terapêutico
Resultado do Tratamento
Neoplasias do Colo do Útero/metabolismo
Neoplasias do Colo do Útero/mortalidade
Neoplasias do Colo do Útero/secundário
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Biomarkers, Tumor); 0 (DNA-Binding Proteins); 7M7YKX2N15 (Topotecan); BG3F62OND5 (Carboplatin); EC 3.1.- (ERCC1 protein, human); EC 3.1.- (Endonucleases); P88XT4IS4D (Paclitaxel); Q20Q21Q62J (Cisplatin); U3P01618RT (Fluorouracil)
[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.0000000000009402



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