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[PMID]:29232583
[Au] Autor:Dai H; Ge S; Guo J; Chen S; Huang M; Yang J; Sun S; Ling Y; Shi Y
[Ad] Endereço:College of Chemistry and Chemical Engineering, Nantong University, Nantong, 226019, People's Republic of China; School of Pharmacy, Nantong University, Nantong, 226001, People's Republic of China.
[Ti] Título:Development of novel bis-pyrazole derivatives as antitumor agents with potent apoptosis induction effects and DNA damage.
[So] Source:Eur J Med Chem;143:1066-1076, 2018 Jan 01.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A series of bis-pyrazole derivatives were designed and synthesized, and their antitumor effects in vitro and in vivo were investigated. Several compounds displayed good antiproliferative activity with IC values in low-micromolar range against three human cancer cell lines in vitro, superior to 5-FU. The most potent compound 10M selectively inhibited human hepatocellular carcinoma cells but not non-tumor liver cell proliferation in vitro, and significantly triggered SMMC-7721 cell apoptosis by cleavage of both PARP and caspase-3 in a concentration-dependent manner. Further study revealed that the potent activity in the cell growth inhibition and apoptosis induction effects of 10M were related to DNA damage and activation of the p53 signaling pathway. Moreover, 10M showed low acute toxicity to mice and significant growth inhibition of the hepatoma tumor in vivo.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Pirazóis/farmacologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/síntese química
Antineoplásicos/química
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Dano ao DNA
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Feminino
Seres Humanos
Neoplasias Hepáticas Experimentais/tratamento farmacológico
Neoplasias Hepáticas Experimentais/patologia
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Estrutura Molecular
Pirazóis/síntese química
Pirazóis/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Pyrazoles)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE


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[PMID]:29078890
[Au] Autor:Kim M; Fisher DT; Powers CA; Gabriel EM; Korman AM; Sexton S; Gudkov AV; Skitzki JJ
[Ad] Endereço:Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York; Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York.
[Ti] Título:Novel mouse models of hepatic artery infusion.
[So] Source:J Surg Res;219:25-32, 2017 Nov.
[Is] ISSN:1095-8673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The liver has unique anatomy in that most blood flow to normal hepatocytes is derived from the portal venous system, whereas liver tumors obtain their nutrient blood supply exclusively from the hepatic artery. The focused arterial delivery of anticancer agents to liver tumors has been performed for decades; however, preclinical models to standardize drug regimens and examine novel agents have been lacking. The purpose of this study was to establish preclinical hepatic artery infusion (HAI) models in a mouse and to evaluate the safety and delivery capability of the models. MATERIAL AND METHODS: C57BL/6 and BALB/c mice were used to develop models of HAI via the hepatic artery (HA), superior pancreaticoduodenal artery (SPDA), or lienogastric artery (LGA). Success rates, distribution of perfusion, and associated morbidity and mortality were analyzed between groups. RESULTS: All three models were feasible and reproducible in mice, and there was no statistical difference on body weight change between models. The HA model had a 13.3% mortality from acute liver failure, and the SPDA model demonstrated duodenal and pancreatic toxicity. SPDA and LGA routes had the highest success rates (96.7% and 91.4%, respectively) with low mortality, better drug delivery, and preserved physiologic liver function compared with the HA model. CONCLUSIONS: The optimal route of HAI was mouse breed specific; SPDA access in BALB/c mice, and the LGA access in C57BL/6 mice. The described techniques serve as a reproducible platform for the identification and characterization of therapeutics for diverse metastatic liver tumors.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Neoplasias do Colo/patologia
Fluoruracila/administração & dosagem
Artéria Hepática
Neoplasias Hepáticas Experimentais/secundário
Neoplasias Hepáticas/secundário
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/uso terapêutico
Linhagem Celular Tumoral
Feminino
Fluoruracila/uso terapêutico
Infusões Intra-Arteriais
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Hepáticas Experimentais/tratamento farmacológico
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Reprodutibilidade dos Testes
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171029
[St] Status:MEDLINE


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[PMID]:29045226
[Au] Autor:Adam LC; Murali N; Chapiro J; Geschwind JF
[Ad] Endereço:Department of Radiology and Biomedical Imaging Yale University School of Medicine 300 Cedar St New Haven, CT 06520.
[Ti] Título:Science to Practice: Molecular-targeted Drug Delivery in Combination with Radiofrequency Ablation of Liver Cancer: A Magic Bullet?
[So] Source:Radiology;285(2):333-335, 2017 Nov.
[Is] ISSN:1527-1315
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In an effort to improve the technical success rates and clinical outcomes of radiofrequency (RF) ablation, Yan et al validated the use of a tumor-penetrating peptide and thermosensitive doxorubicin (DOX)-loaded nanoparticles in combination with RF ablation in a hepatocellular carcinoma mouse model. By achieving higher chemotherapeutic drug concentrations in target lesions, fewer toxic effects, and improved survival end points in an animal tumor model, the authors conclude that superior tumor treatment with RF ablation is possible when combined with molecular-targeted drug delivery systems.
[Mh] Termos MeSH primário: Antineoplásicos
Ablação por Cateter/métodos
Portadores de Fármacos
Neoplasias Hepáticas Experimentais
Imagem Molecular/métodos
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/química
Antineoplásicos/uso terapêutico
Doxorrubicina/química
Doxorrubicina/uso terapêutico
Portadores de Fármacos/química
Portadores de Fármacos/uso terapêutico
Neoplasias Hepáticas Experimentais/diagnóstico por imagem
Neoplasias Hepáticas Experimentais/tratamento farmacológico
Camundongos
Nanopartículas/química
Nanopartículas/uso terapêutico
Peptídeos/química
Peptídeos/uso terapêutico
Nanomedicina Teranóstica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Drug Carriers); 0 (Peptides); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171121
[Lr] Data última revisão:
171121
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171019
[St] Status:MEDLINE
[do] DOI:10.1148/radiol.2017171527


  4 / 14234 MEDLINE  
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[PMID]:28985870
[Au] Autor:Nirei T; Ishihara S; Tanaka T; Kiyomatsu T; Kawai K; Hata K; Nozawa H; Watanabe T
[Ad] Endereço:Faculty of Medical Sciences, Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.
[Ti] Título:Polymeric micelles loaded with (1,2-diaminocyclohexane)platinum(II) against colorectal cancer.
[So] Source:J Surg Res;218:334-340, 2017 Oct.
[Is] ISSN:1095-8673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: We investigated the potential of nanomedicine in loading the oxaliplatin parent complex (1,2-diaminocyclohexane)platinum(II)-loaded polymeric micelles (DACHPt/m) against multiple liver metastases from colon cancer in a mouse model. MATERIALS AND METHODS: The efficacy of DACHPt/m or oxaliplatin (on days 14 and 21 after inoculation of tumor cells) was evaluated in a mouse model of liver metastasis for murine colon adenocarcinoma C26 cells. In vivo antitumor effects were evaluated by recording the number of liver metastases and weights of metastatic livers after treatment (day 28). The accumulation of drugs in tumors and liver parenchyma was analyzed using ion coupled plasma-mass spectrometry 24 h after administration of DACHPt/m or oxaliplatin (n = 5). We assessed renal and hepatic toxicities through changes in creatinine, aspartate transaminase, and alanine transaminase on the last day of the antitumor activity experiment. RESULTS: Mice receiving DACHPt/m had significantly fewer metastatic nodules (P = 0.038) and lower liver weights (P = 0.038) than those receiving oxaliplatin. The accumulation of DACHPt/m in the metastatic liver was significantly higher than that of oxaliplatin, whereas the distribution of micelles in healthy liver tissues was limited. Mice treated with DACHPt/m also showed significantly lower serum creatinine levels than those treated with oxaliplatin (P = 0.007), whereas serum aspartate transaminase and alanine transaminase levels for both drugs were not different. CONCLUSIONS: High levels of DACHPt/m accumulate in metastatic livers, producing a strong antitumor effect without severe adverse effects. DACHPt/m is a safe approach for managing liver metastasis from colorectal cancer.
[Mh] Termos MeSH primário: Adenocarcinoma/tratamento farmacológico
Antineoplásicos/administração & dosagem
Neoplasias Hepáticas Experimentais/tratamento farmacológico
Compostos Organoplatínicos/administração & dosagem
[Mh] Termos MeSH secundário: Adenocarcinoma/secundário
Animais
Antineoplásicos/efeitos adversos
Linhagem Celular Tumoral
Neoplasias Colorretais/tratamento farmacológico
Neoplasias Colorretais/patologia
Ensaios de Seleção de Medicamentos Antitumorais
Neoplasias Hepáticas Experimentais/secundário
Camundongos
Camundongos Endogâmicos BALB C
Micelas
Compostos Organoplatínicos/efeitos adversos
Compostos Organoplatínicos/uso terapêutico
Distribuição Aleatória
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (((1R,2R)-1,2-diaminocyclohexane)platinum(II)); 0 (Antineoplastic Agents); 0 (Micelles); 0 (Organoplatinum Compounds); 04ZR38536J (oxaliplatin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171008
[St] Status:MEDLINE


  5 / 14234 MEDLINE  
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[PMID]:28943392
[Au] Autor:Romualdo GR; Grassi TF; Goto RL; Tablas MB; Bidinotto LT; Fernandes AAH; Cogliati B; Barbisan LF
[Ad] Endereço:Department of Pathology, Botucatu Medical School, São Paulo State University (UNESP), Botucatu - SP, Brazil.
[Ti] Título:An integrative analysis of chemically-induced cirrhosis-associated hepatocarcinogenesis: Histological, biochemical and molecular features.
[So] Source:Toxicol Lett;281:84-94, 2017 Nov 05.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:This study aimed the integrative characterization of morphological, biochemical and molecular features of chemically-induced cirrhosis-associated hepatocarcinogenesis. Thus, male Wistar rats were submitted to a diethylnitrosamine (DEN)/thioacetamide (TAA)-induced model. Liver tissue was processed for global gene expression, histopathological and collagen evaluations; as well as immunohistochemical and oxidative stress analysis. Gene Ontology and functional analysis showed the upregulation of extracellular matrix deposition genes, such as collagen type I alpha 1 and 2 (Col1α1 and Col1α2) and tissue inhibitor of metalloproteinase 1 and 2 genes (Timp1 and Timp2). In agreement these findings, animals presented extensive liver cirrhosis with increased collagen deposition (Sirius red). Besides, the animals developed many glutathione S-transferase pi (GST-P)-positive preneoplastic lesions showing high cell proliferation (Ki-67), in keeping with the Gstp1 and Gstp2 increased gene expression. DEN/TAA-treated rats also showed the upregulation of tumorigenesis-related annexin A2 gene (Anxa2) and few neoplastic lesions (hepatocellular adenomas, carcinomas, and cholangiocarcinoma). In contrast, gene expression and activity of antioxidant enzymes were decreased (glutathione peroxidase, total glutathione-S-transferase, and catalase). The model featured remarkable similarities to human hepatocarcinogenesis. Our findings could bring up new molecular insights into cirrhosis-associated hepatocarcinogenesis, and provide a suitable animal model for the establishment of further diagnostic, preventive and therapeutic approaches.
[Mh] Termos MeSH primário: Carcinogênese/genética
Regulação Neoplásica da Expressão Gênica
Cirrose Hepática/genética
Neoplasias Hepáticas Experimentais/genética
[Mh] Termos MeSH secundário: Alanina Transaminase/metabolismo
Animais
Anexina A2/genética
Anexina A2/metabolismo
Aspartato Aminotransferases/metabolismo
Carcinogênese/induzido quimicamente
Colágeno/genética
Colágeno/metabolismo
Dietilnitrosamina/toxicidade
Glutationa Peroxidase/genética
Glutationa Peroxidase/metabolismo
Glutationa Transferase/genética
Glutationa Transferase/metabolismo
Cirrose Hepática/induzido quimicamente
Neoplasias Hepáticas Experimentais/induzido quimicamente
Masculino
Metaloproteinases da Matriz/genética
Metaloproteinases da Matriz/metabolismo
Estresse Oxidativo/efeitos dos fármacos
Ratos
Ratos Wistar
Tioacetamida/toxicidade
Inibidores Teciduais de Metaloproteinases/genética
Inibidores Teciduais de Metaloproteinases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Annexin A2); 0 (Tissue Inhibitor of Metalloproteinases); 075T165X8M (Thioacetamide); 3IQ78TTX1A (Diethylnitrosamine); 9007-34-5 (Collagen); EC 1.11.1.9 (Glutathione Peroxidase); EC 2.5.1.18 (Glutathione Transferase); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase); EC 3.4.24.- (Matrix Metalloproteinases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE


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[PMID]:28869588
[Au] Autor:Xu G; Ye J; Liu XJ; Zhang NP; Zhao YM; Fan J; Liu XP; Wu J
[Ad] Endereço:Department of Medical Microbiology, Key Laboratory of Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
[Ti] Título:Activation of pluripotent genes in hepatic progenitor cells in the transition of nonalcoholic steatohepatitis to pre-malignant lesions.
[So] Source:Lab Invest;97(10):1201-1217, 2017 Oct.
[Is] ISSN:1530-0307
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nonalcoholic steatohepatitis is considered as a precancerous condition. However, hepatic carcinogenesis from NASH is poorly understood. This study aims to investigate the activation of pluripotent genes (c-Myc, Oct-4, KLF-4, and Nanog) and morphogenic gene (Gli-1) in hepatic progenitor cells from patient specimens and in an animal model to determine the possibility of normal stem/progenitor cells becoming the origin of NASH-HCC. In this study, expression of pluripotent and morphogenic genes in human NASH-HCC tissues was significantly upregulated compared to adjacent non-tumor liver tissues. After feeding high-fat/calorie diet plus high fructose/glucose in drinking water (HFC diet plus HF/G) for up to 12 months, mice developed obesity, insulin resistance, and steatohepatitis with significant necroptotic inflammation and fibrotic progression, as well as occurrence of hyperplastic nodules with dysplasia; and this model represents pathohistologically as a transition from NASH to NASH-HCC in a pre-carcinomatous stage. High expression of pluripotent and morphogenic genes was immunohistochemically visualized in the dysplasia areas of mouse liver, where there were many OV-6-positive cells, indicating proliferation of HOCs in NASH with fibrotic progression. Moreover, oncogenic transcription factors (c-Myc, KLF-4, and Nanog) were co-localized in these hepatic progenitor cells. In conclusion, pluripotent and morphogenic genes may contribute to the reprogramming of hepatic progenitor cells in driving these cells to be the origin of NASH-HCC in a steatotic and inflamed microenvironment.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/metabolismo
Proteínas de Ligação a DNA/metabolismo
Hepatócitos/metabolismo
Neoplasias Hepáticas Experimentais/metabolismo
Hepatopatia Gordurosa não Alcoólica/metabolismo
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Animais
Carcinoma Hepatocelular/química
Carcinoma Hepatocelular/genética
Proteínas de Ligação a DNA/genética
Dieta Hiperlipídica
Intolerância à Glucose/metabolismo
Hepatócitos/química
Seres Humanos
Resistência à Insulina
Fatores de Transcrição Kruppel-Like
Neoplasias Hepáticas Experimentais/química
Neoplasias Hepáticas Experimentais/genética
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Proteína Homeobox Nanog
Hepatopatia Gordurosa não Alcoólica/genética
Obesidade/metabolismo
Fator 3 de Transcrição de Octâmero
Proteínas Proto-Oncogênicas c-myc
Fatores de Transcrição/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (GKLF protein); 0 (Kruppel-Like Transcription Factors); 0 (NANOG protein, human); 0 (Nanog Homeobox Protein); 0 (Octamer Transcription Factor-3); 0 (Proto-Oncogene Proteins c-myc); 0 (Transcription Factors)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170905
[St] Status:MEDLINE
[do] DOI:10.1038/labinvest.2017.84


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[PMID]:28829785
[Au] Autor:Kuruvilla SP; Tiruchinapally G; Crouch AC; ElSayed MEH; Greve JM
[Ad] Endereço:Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI United States of America.
[Ti] Título:Dendrimer-doxorubicin conjugates exhibit improved anticancer activity and reduce doxorubicin-induced cardiotoxicity in a murine hepatocellular carcinoma model.
[So] Source:PLoS One;12(8):e0181944, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatocellular carcinoma (HCC) is the 2nd leading cause of cancer-related deaths every year globally. The most common form of treatment, hepatic arterial infusion (HAI), involves the direct injection of doxorubicin (DOX) into the hepatic artery. It is plagued with limited therapeutic efficacy and the occurrence of severe toxicities (e.g. cardiotoxicity). We aim to improve the therapeutic index of DOX delivered via HAI by loading the drug onto generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers targeted to hepatic cancer cells via N-acetylgalactosamine (NAcGal) ligands. DOX is attached to the surface of G5 molecules via two different enzyme-sensitive linkages, L3 or L4, to achieve controllable drug release inside hepatic cancer cells. We previously reported on P1 and P2 particles that resulted from the combination of NAcGal-targeting with L3- or L4-DOX linkages, respectively, and showed controllable DOX release and toxicity towards hepatic cancer cells comparable to free DOX. In this study, we demonstrate that while the intratumoral delivery of free DOX (1 mg/kg) into HCC-bearing nod scid gamma (NSG) mice achieves a 2.5-fold inhibition of tumor growth compared to the saline group over 30 days, P1 and P2 particles delivered at the same DOX dosage achieve a 5.1- and 4.4-fold inhibition, respectively. Incubation of the particles with human induced pluripotent stem cell derived cardiomyocytes (hiPSC CMs) showed no effect on monolayer viability, apoptosis induction, or CM electrophysiology, contrary to the effect of free DOX. Moreover, magnetic resonance imaging revealed that P1- and P2-treated mice maintained cardiac function after intraperitoneal administration of DOX at 1 mg/kg for 21 days, unlike the free DOX group at an equivalent dosage, confirming that P1/P2 can avoid DOX-induced cardiotoxicity. Taken together, these results highlight the ability of P1/P2 particles to improve the therapeutic index of DOX and offer a replacement therapy for clinical HCC treatment.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/química
Carcinoma Hepatocelular/tratamento farmacológico
Dendrímeros/química
Doxorrubicina/química
Coração/efeitos dos fármacos
Neoplasias Hepáticas Experimentais/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antibióticos Antineoplásicos/farmacologia
Doxorrubicina/farmacologia
Feminino
Células Hep G2
Seres Humanos
Masculino
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Dendrimers); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181944


  8 / 14234 MEDLINE  
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[PMID]:28811106
[Au] Autor:Machihara K; Tanaka H; Hayashi Y; Murakami I; Namba T
[Ad] Endereço:Science Research Center, Kochi University, Kochi 783-8505, Japan.
[Ti] Título:Questiomycin A stimulates sorafenib-induced cell death via suppression of glucose-regulated protein 78.
[So] Source:Biochem Biophys Res Commun;492(1):33-40, 2017 Oct 07.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatocellular carcinoma (HCC) is one of the most difficult cancers to treat owing to the lack of effective chemotherapeutic methods. Sorafenib, the first-line and only available treatment for HCC, extends patient overall survival by several months, with a response rate below 10%. Thus, the identification of an agent that enhances the anticancer effect of sorafenib is critical for the development of therapeutic options for HCC. Endoplasmic reticulum (ER) stress response is one of the methods of sorafenib-induced cell death. Here we report that questiomycin A suppresses expression of GRP78, a cell-protective ER chaperone protein. Analysis of the molecular mechanisms of questiomycin A revealed that this compound stimulated GRP78 protein degradation in an ER stress response-independent manner. Cotreatment with sorafenib and questiomycin A suppressed GRP78 protein expression, which is essential for the stimulation of sorafenib-induced cell death. Moreover, our in vivo study demonstrated that the coadministration of sorafenib and questiomycin A suppressed tumor formation in HCC-induced xenograft models. These results suggest that cotreatment with sorafenib and questiomycin A is a novel therapeutic strategy for HCC by enhancing sorafenib-dependent ER stress-induced cell death, and downregulation of GRP78 is a new target for the stimulation of the therapeutic effects of sorafenib in HCC.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Morte Celular/efeitos dos fármacos
Proteínas de Choque Térmico/antagonistas & inibidores
Niacinamida/análogos & derivados
Oxazinas/farmacologia
Compostos de Fenilureia/farmacologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/química
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Proteínas de Choque Térmico/genética
Proteínas de Choque Térmico/metabolismo
Seres Humanos
Neoplasias Hepáticas Experimentais/tratamento farmacológico
Neoplasias Hepáticas Experimentais/metabolismo
Neoplasias Hepáticas Experimentais/patologia
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Niacinamida/química
Niacinamida/farmacologia
Oxazinas/química
Compostos de Fenilureia/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Heat-Shock Proteins); 0 (Oxazines); 0 (Phenylurea Compounds); 0 (molecular chaperone GRP78); 1916-59-2 (3-aminophenoxazone); 25X51I8RD4 (Niacinamide); 9ZOQ3TZI87 (sorafenib)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170817
[St] Status:MEDLINE


  9 / 14234 MEDLINE  
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[PMID]:28720064
[Au] Autor:Medhat A; Mansour S; El-Sonbaty S; Kandil E; Mahmoud M
[Ad] Endereço:1 Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
[Ti] Título:Evaluation of the antitumor activity of platinum nanoparticles in the treatment of hepatocellular carcinoma induced in rats.
[So] Source:Tumour Biol;39(7):1010428317717259, 2017 Jul.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study aimed to evaluate the antitumor activity of platinum nanoparticles compared with cis-platin both in vitro and in vivo in the treatment of hepatocellular carcinoma induced in rats. The treatment efficacy of platinum nanoparticles was evaluated by measuring antioxidant activities against oxidative stress caused by diethylnitrosamine in liver tissue. The measurements included reduced glutathione content and superoxide dismutase activity, as well as malondialdehyde level. Liver function tests were also determined, in addition to the evaluation of serum alpha-fetoprotein, caspase-3, and cytochrome c in liver tissue. Total RNA extraction from liver tissue samples was also done for the relative quantification of B-cell lymphoma 2, matrix metallopeptidase 9, and tumor protein p53 genes. Histopathological examination was also performed for liver tissue. Results showed that platinum nanoparticles are more potent than cis-platin in treatment of hepatocellular carcinoma induced by diethylnitrosamine in rats as it ameliorated the investigated parameters toward normal control animals. These findings were well appreciated with histopathological studies of diethylnitrosamine group treated with platinum nanoparticles, suggesting that platinum nanoparticles can serve as a good therapeutic agent for the treatment of hepatocellular carcinoma which should attract further studies.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/tratamento farmacológico
Neoplasias Hepáticas Experimentais/tratamento farmacológico
Neoplasias Hepáticas/tratamento farmacológico
Nanopartículas Metálicas/administração & dosagem
Platina/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Antioxidantes/metabolismo
Carcinoma Hepatocelular/induzido quimicamente
Carcinoma Hepatocelular/genética
Carcinoma Hepatocelular/patologia
Dietilnitrosamina/toxicidade
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Neoplasias Hepáticas/induzido quimicamente
Neoplasias Hepáticas/genética
Neoplasias Hepáticas/patologia
Neoplasias Hepáticas Experimentais/induzido quimicamente
Neoplasias Hepáticas Experimentais/genética
Neoplasias Hepáticas Experimentais/patologia
Masculino
Metaloproteinase 9 da Matriz/biossíntese
Estresse Oxidativo/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-bcl-2/biossíntese
Ratos
Proteína Supressora de Tumor p53/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Tumor Suppressor Protein p53); 3IQ78TTX1A (Diethylnitrosamine); 49DFR088MY (Platinum); EC 3.4.24.35 (Matrix Metalloproteinase 9)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170726
[Lr] Data última revisão:
170726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170720
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317717259


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[PMID]:28699238
[Au] Autor:Zhang R; Ma M; Dong G; Yao RR; Li JH; Zheng QD; Dong YY; Ma H; Gao DM; Cui JF; Ren ZG; Chen RX
[Ad] Endereço:Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
[Ti] Título:Increased matrix stiffness promotes tumor progression of residual hepatocellular carcinoma after insufficient heat treatment.
[So] Source:Cancer Sci;108(9):1778-1786, 2017 Sep.
[Is] ISSN:1349-7006
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Aggravated behaviors of hepatocellular carcinoma (HCC) will occur after inadequate thermal ablation. However, its underlying mechanisms are not fully understood. Here, we assessed whether the increased matrix stiffness after thermal ablation could promote the progression of residual HCC. Heat-treated residual HCC cells were cultured on tailorable 3D gel with different matrix stiffness, simulating the changed physical environment after thermal ablation, and then the mechanical alterations of matrix stiffness on cell phenotypes were explored. Increased stiffness was found to significantly promote the proliferation of the heat-treated residual HCC cells when the cells were cultured on stiffer versus soft supports, which was associated with stiffness-dependent regulation of ERK phosphorylation. Heat-exposed HCC cells cultured on stiffer supports showed enhanced motility. More importantly, vitamin K1 reduced stiffness-dependent residual HCC cell proliferation by inhibiting ERK phosphorylation and suppressed the in vivo tumor growth, which was further enhanced by combining with sorafenib. Increased matrix stiffness promotes the progression of heat-treated residual HCC cells, proposing a new mechanism of an altered biomechanical environment after thermal ablation accelerates HCC development. Vitamin K1 plus sorafenib can reverse this protumor effect.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/patologia
Matriz Extracelular/patologia
Neoplasias Hepáticas Experimentais/patologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Carcinoma Hepatocelular/terapia
Linhagem Celular Tumoral
Movimento Celular
Proliferação Celular
Terapia Combinada
Progressão da Doença
Ativação Enzimática
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Seres Humanos
Hipertermia Induzida
Neoplasias Hepáticas Experimentais/terapia
Masculino
Camundongos Endogâmicos BALB C
Camundongos Nus
Neoplasia Residual
Células-Tronco Neoplásicas/fisiologia
Niacinamida/análogos & derivados
Niacinamida/farmacologia
Compostos de Fenilureia/farmacologia
Transdução de Sinais
Vitamina K 1/farmacologia
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Phenylurea Compounds); 25X51I8RD4 (Niacinamide); 84-80-0 (Vitamin K 1); 9ZOQ3TZI87 (sorafenib); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170713
[St] Status:MEDLINE
[do] DOI:10.1111/cas.13322



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