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[PMID]:29177545
[Au] Autor:Gu Y; Zhou Y; Shi X; Xin Y; Shan Y; Chen C; Cao T; Fang W; Li X
[Ad] Endereço:Institute of Preventive Veterinary Medicine, Zhejiang University, Hangzhou, 310058, China.
[Ti] Título:Porcine teschovirus 2 induces an incomplete autophagic response in PK-15 cells.
[So] Source:Arch Virol;163(3):623-632, 2018 Mar.
[Is] ISSN:1432-8798
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Autophagy is a homeostatic process that has been shown to be vital in the innate immune defense against pathogens. However, little is known about the regulatory role of autophagy in porcine teschovirus 2 (PTV-2) replication. In this study, we found that PTV-2 infection induces a strong increase in GFP-LC3 punctae and endogenous LC3 lipidation. However, PTV-2 infection did not enhance autophagic protein degradation. When cellular autophagy was pharmacologically inhibited by wortmannin or 3-methyladenine, PTV-2 replication increased. The increase in virus yield via autophagy inhibition was further confirmed by silencing atg5, which is required for autophagy. Furthermore, PTV-2 replication was suppressed when autophagy was activated by rapamycin. Together, the results suggest that PTV-2 infection activates incomplete autophagy and that autophagy then inhibits further PTV-2 replication.
[Mh] Termos MeSH primário: Proteína 5 Relacionada à Autofagia/antagonistas & inibidores
Autofagia/efeitos dos fármacos
Células Epiteliais/virologia
Interações Hospedeiro-Patógeno
Teschovirus/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adenina/análogos & derivados
Adenina/farmacologia
Androstadienos/farmacologia
Animais
Autofagia/genética
Proteína 5 Relacionada à Autofagia/genética
Proteína 5 Relacionada à Autofagia/metabolismo
Linhagem Celular
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/metabolismo
Regulação da Expressão Gênica
Genes Reporter
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Rim
Proteínas Associadas aos Microtúbulos/genética
Proteínas Associadas aos Microtúbulos/metabolismo
RNA Interferente Pequeno/genética
RNA Interferente Pequeno/metabolismo
Transdução de Sinais
Sirolimo/farmacologia
Suínos
Teschovirus/genética
Teschovirus/crescimento & desenvolvimento
Teschovirus/metabolismo
Replicação Viral/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androstadienes); 0 (Autophagy-Related Protein 5); 0 (Microtubule-Associated Proteins); 0 (RNA, Small Interfering); 147336-22-9 (Green Fluorescent Proteins); 5142-23-4 (3-methyladenine); JAC85A2161 (Adenine); W36ZG6FT64 (Sirolimus); XVA4O219QW (wortmannin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1007/s00705-017-3652-2


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[PMID]:28463012
[Au] Autor:Chirila C; Mitra D; Colosia A; Ling C; Odom D; Iyer S; Kaye JA
[Ad] Endereço:a RTI Health Solutions , RTP , NC , USA.
[Ti] Título:Comparison of palbociclib in combination with letrozole or fulvestrant with endocrine therapies for advanced/metastatic breast cancer: network meta-analysis.
[So] Source:Curr Med Res Opin;33(8):1457-1466, 2017 Aug.
[Is] ISSN:1473-4877
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Palbociclib is the first cyclin-dependent kinase 4/6 inhibitor approved in the United States for HR+/HER2- advanced/metastatic breast cancer, in combination with letrozole as initial endocrine-based therapy in postmenopausal women or with fulvestrant in women with disease progression following endocrine therapy. We compared progression-free survival (PFS) and discontinuations due to adverse events for palbociclib combinations against other endocrine therapies using a mixed-treatment comparison meta-analysis of randomized, controlled trials. METHODS: A systematic literature review identified relevant trials. Separate analyses were conducted for each palbociclib combination using a Bayesian approach. Treatment rankings were established using the surface under the cumulative ranking curve (SUCRA). RESULTS: Sixty-five unique studies met inclusion criteria. Palbociclib plus letrozole had the highest SUCRA value (99.9%) and was associated with significantly longer PFS than all comparators in treatment-naïve patients (hazard ratios [HRs] ranged from 0.41 to 0.58). Palbociclib plus fulvestrant had the second highest SUCRA value (93.9%) and, in previously treated patients, yielded significantly longer PFS than most comparators (HRs ranged from 0.26 to 0.46); the exception was everolimus plus exemestane, with similar PFS (HR, 1.04; 95% credible interval [CrI], 0.58-1.76). Palbociclib plus fulvestrant was associated with significantly lower odds of discontinuation due to adverse events than everolimus plus exemestane (odds ratio, 0.14; 95% CrI, 0.05-0.39). CONCLUSIONS: The results suggest that the two palbociclib combinations yielded significantly greater PFS than endocrine therapy in treatment-naïve and previously treated patients with advanced/metastatic breast cancer. Palbociclib plus fulvestrant was associated with significantly less toxicity than everolimus plus exemestane.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias da Mama/tratamento farmacológico
[Mh] Termos MeSH secundário: Androstadienos/administração & dosagem
Teorema de Bayes
Neoplasias da Mama/patologia
Intervalo Livre de Doença
Estradiol/administração & dosagem
Estradiol/análogos & derivados
Everolimo/administração & dosagem
Feminino
Seres Humanos
Metanálise em Rede
Nitrilos/administração & dosagem
Piperazinas/administração & dosagem
Piridinas/administração & dosagem
Ensaios Clínicos Controlados Aleatórios como Assunto
Triazóis/administração & dosagem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Androstadienes); 0 (Nitriles); 0 (Piperazines); 0 (Pyridines); 0 (Triazoles); 22X328QOC4 (fulvestrant); 4TI98Z838E (Estradiol); 7LKK855W8I (letrozole); 9HW64Q8G6G (Everolimus); G9ZF61LE7G (palbociclib); NY22HMQ4BX (exemestane)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1080/03007995.2017.1325730


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[PMID]:29179218
[Au] Autor:Wang L; Cui Y; Liu Q; Song Y; Hu Q; Tang M; Hescheler J; Xi J
[Ad] Endereço:Department of Physiology and Chinese-German Stem Cell Center, School of Basic Medicine, Huazhong University of Science and Technology, The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China.
[Ti] Título:Puerarin Enhances Ca2+ Reuptake and Ca2+ Content of Sarcoplasmic Reticulum in Murine Embryonic Stem Cell-Derived Cardiomyocytes via Upregulation of SERCA2a.
[So] Source:Cell Physiol Biochem;44(3):1199-1212, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: The embryonic stem cell-derived cardiomyocytes (ES-CMs) serve as potential sources for cardiac regenerative therapy. However, the immature sarcoplasmic reticulum (SR) function of ES-CMs prevents its application. In this report, we examined the effect of puerarin, an isoflavone compound, on SR function of murine ES-CMs. METHODS: Murine ES-CMs were harvested by embryoid body-based differentiation method. Confocal calcium imaging and whole-cell patch clamps were performed to assess the function of SR. The mRNA expression levels of SR-related genes were examined by quantitative PCR. The protein expression of sarcoplasmic reticulum calcium-ATPase 2a (SERCA2a) was evaluated by immunofluorescent and western blot. RESULTS: Long-term application of puerarin promotes basic properties of spontaneous calcium transient with increased amplitude, decay velocity, and decreased duration. Puerarin fails to alter ICa,L but increases the Ca2+ content of SR. Puerarin-treated ES-CMs have intact SR Ca2+ cycling with more SR Ca2+ reuptake. Long-term application of puerarin asynchronously upregulates the mRNA and protein expression of SERCA2a, as well as the transcripts of calsequestrin and triadin in developing ES-CMs. Application of puerarin during the stage of post-cardiac differentiation upregulates dose-dependently the transcripts of SERCA2a, phospholamban and tridin which can be reversed by the inhibitors of the PI3K/Akt and MAPK/ERK signaling pathways, but shows no effect on the protein expression of SERCA2a. CONCLUSION: This study demonstrates that long-term puerarin treatment enhances Ca2+ reuptake and Ca2+ content via upregulation of SERCA2a.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Isoflavonas/farmacologia
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
Regulação para Cima/efeitos dos fármacos
Vasodilatadores/farmacologia
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Androstadienos/farmacologia
Animais
Benzamidas/farmacologia
Proteínas de Ligação ao Cálcio/metabolismo
Calsequestrina/genética
Calsequestrina/metabolismo
Proteínas de Transporte/genética
Proteínas de Transporte/metabolismo
Diferenciação Celular/efeitos dos fármacos
Difenilamina/análogos & derivados
Difenilamina/farmacologia
Camundongos
Microscopia Confocal
Células-Tronco Embrionárias Murinas/citologia
Proteínas Musculares/genética
Proteínas Musculares/metabolismo
Miócitos Cardíacos/citologia
Miócitos Cardíacos/metabolismo
Técnicas de Patch-Clamp
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Fosfatidilinositol 3-Quinases/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Retículo Sarcoplasmático/metabolismo
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/antagonistas & inibidores
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética
Transdução de Sinais/efeitos dos fármacos
Tapsigargina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androstadienes); 0 (Benzamides); 0 (Calcium-Binding Proteins); 0 (Calsequestrin); 0 (Carrier Proteins); 0 (Isoflavones); 0 (Muscle Proteins); 0 (PD 0325901); 0 (Vasodilator Agents); 0 (phospholamban); 0 (triadin); 67526-95-8 (Thapsigargin); 9N3CBB0BIQ (Diphenylamine); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases); SY7Q814VUP (Calcium); XVA4O219QW (wortmannin); Z9W8997416 (puerarin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1159/000485450


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[PMID]:29271974
[Au] Autor:Sohal SS
[Ad] Endereço:Discipline of Laboratory Medicine, School of Health Sciences, Faculty of Health, University of Tasmania, Launceston, TAS, Australia.
[Ti] Título:Fluticasone propionate and increased risk of pneumonia in COPD: is it PAFR-dependent?
[So] Source:Int J Chron Obstruct Pulmon Dis;12:3425-3427, 2017.
[Is] ISSN:1178-2005
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Mh] Termos MeSH primário: Fluticasona
Doença Pulmonar Obstrutiva Crônica
[Mh] Termos MeSH secundário: Administração por Inalação
Albuterol
Androstadienos
Broncodilatadores
Método Duplo-Cego
Seres Humanos
Pneumonia
[Pt] Tipo de publicação:LETTER; COMMENT
[Nm] Nome de substância:
0 (Androstadienes); 0 (Bronchodilator Agents); CUT2W21N7U (Fluticasone); QF8SVZ843E (Albuterol)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171223
[St] Status:MEDLINE
[do] DOI:10.2147/COPD.S154897


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[PMID]:28464211
[Au] Autor:Lipton A; Chapman JW; Leitzel K; Garg A; Pritchard KI; Ingle JN; Budd GT; Ellis MJ; Sledge GW; Rabaglio M; Han L; Elliott CR; Shepherd LE; Goss PE; Ali SM
[Ad] Endereço:Penn State Hershey Cancer Institute, Penn State Hershey Medical Center, Hershey, Pennsylvania.
[Ti] Título:Osteoporosis therapy and outcomes for postmenopausal patients with hormone receptor-positive breast cancer: NCIC CTG MA.27.
[So] Source:Cancer;123(13):2444-2451, 2017 Jul 01.
[Is] ISSN:1097-0142
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Breast cancer patients in the MA.27 trial had similar outcomes with steroidal aromatase inhibitor (AI) exemestane and nonsteroidal anastrozole. AIs increase the risk of osteoporosis. This study examined the effects of self-reported osteoporosis and osteoporosis therapy (OPT) on outcomes. METHODS: The MA.27 phase 3 adjuvant trial enrolled 7576 postmenopausal women. The primary outcome was event-free survival (EFS), and the secondary outcome was distant disease-free survival (DDFS). Patients were permitted bisphosphonates to prevent or treat osteopenia/osteoporosis. In a multivariate, stratified Cox regression, factors were significant with a 2-sided Wald test P value ≤ .05. RESULTS: Osteoporosis was reported at the baseline by 654 of the 7576 women (8.6%) and in total by 1294 patients. Oral OPT was received at the baseline by 815 of the 7576 women (10.8%) and in total by 2711 patients (36%). With a median follow-up of 4.1 years, 693 EFS events (9.15%) and 321 DDFS events (4.2%) occurred. Osteoporosis was not associated with EFS or DDFS. Few EFS events occurred before the initiation of OPT, with no substantive evidence of a time-differing effect on outcomes (nonproportional hazards). OPT (yes vs no) was significantly associated with improved EFS (hazard ratio [HR] for yes vs no, 0.67; 95% confidence interval [CI], 0.57-0.80; P < .001) and DDFS (HR, 0.57; 95% CI, 0.44-0.73; P <. 001). Time-differing (time-dependent) OPT was not (EFS; P = .45). OPT did not alter the incidence of visceral-only metastasis (P = .31). CONCLUSIONS: Oral OPT, administered to postmenopausal breast cancer patients receiving adjuvant AI therapy, was associated with improved EFS and DDFS; the time of OPT initiation (a time-dependent effect) did not affect the outcome. OPT did not alter the risk of visceral metastasis. Cancer 2017;123:2444-51. © 2017 American Cancer Society.
[Mh] Termos MeSH primário: Androstadienos/uso terapêutico
Inibidores da Aromatase/uso terapêutico
Conservadores da Densidade Óssea/uso terapêutico
Neoplasias da Mama/tratamento farmacológico
Difosfonatos/uso terapêutico
Nitrilos/uso terapêutico
Osteoporose Pós-Menopausa/tratamento farmacológico
Triazóis/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Neoplasias da Mama/complicações
Neoplasias da Mama/metabolismo
Quimioterapia Adjuvante
Intervalo Livre de Doença
Feminino
Seres Humanos
Masculino
Mastectomia
Meia-Idade
Análise Multivariada
Osteoporose Pós-Menopausa/complicações
Modelos de Riscos Proporcionais
Radioterapia Adjuvante
Receptores Estrogênicos/metabolismo
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Androstadienes); 0 (Aromatase Inhibitors); 0 (Bone Density Conservation Agents); 0 (Diphosphonates); 0 (Nitriles); 0 (Receptors, Estrogen); 0 (Triazoles); 2Z07MYW1AZ (anastrozole); NY22HMQ4BX (exemestane)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180103
[Lr] Data última revisão:
180103
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1002/cncr.30682


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[PMID]:28974422
[Au] Autor:Taglieri L; Nardo T; Vicinanza R; Ross JM; Scarpa S; Coppotelli G
[Ad] Endereço:Department of Experimental Medicine, Sapienza University, Rome, Italy.
[Ti] Título:Thyroid hormone regulates fibronectin expression through the activation of the hypoxia inducible factor 1.
[So] Source:Biochem Biophys Res Commun;493(3):1304-1310, 2017 Nov 25.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Thyroid hormones regulate gene expression via both canonical and non-canonical signaling. Hyperthyroidism is associated with elevated plasma levels of fibronectin (FN): in this study we elucidate the molecular mechanism through which triiodothyronine (T3) regulates FN and demonstrate that T3 induces FN expression via a non-canonical pathway by activating hypoxia-inducible factor-1 (HIF-1). We found that T3 treatment increased cellular and secreted FN in human hepatoma cells (HepG2) and human dermal fibroblasts (HF) via the PI3K/Akt/HIF-1 pathway. The inhibition of either Akt phosphorylation with wortmannin or HIF-1 with YC1 in both cell types prevented HIF-1α synthesis and FN positive regulation upon T3 treatment. We showed that HIF-1α overexpression per se was sufficient to up-regulate FN in both cell lines as demonstrated by the transient transfection of both the constitutively active and wild-type forms of HIF-1α. Our data demonstrate the involvement of the PI3K/Akt/HIF-1 pathway in mediating T3 induced FN up-regulation.
[Mh] Termos MeSH primário: Fibronectinas/metabolismo
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Tri-Iodotironina/metabolismo
[Mh] Termos MeSH secundário: Androstadienos/farmacologia
Fibroblastos/efeitos dos fármacos
Fibroblastos/metabolismo
Fibronectinas/genética
Células Hep G2
Seres Humanos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética
Fosfatidilinositol 3-Quinases/metabolismo
Fosforilação/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-akt/metabolismo
Transdução de Sinais/efeitos dos fármacos
Tri-Iodotironina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androstadienes); 0 (Fibronectins); 0 (HIF1A protein, human); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 06LU7C9H1V (Triiodothyronine); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); XVA4O219QW (wortmannin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE


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[PMID]:28953959
[Au] Autor:Kim J; Montagne K; Nemoto H; Ushida T; Furukawa KS
[Ad] Endereço:Department of Mechanical Engineering, Graduate School of Engineering, University of Tokyo, Tokyo, Japan.
[Ti] Título:Hypergravity down-regulates c-fos gene expression via ROCK/Rho-GTP and the PI3K signaling pathway in murine ATDC5 chondroprogenitor cells.
[So] Source:PLoS One;12(9):e0185394, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chondrocytes are known to be physiologically loaded with diverse physical factors such as compressive stress, shear stress and hydrostatic pressure. Although the effects of those mechanical stimuli onto various cell models have been widely studied, those of hypergravity have not yet been revealed clearly. Hereby, we hypothesized that the hypergravity affects relative positions of intracellular elements including nucleus and cytoskeletons due to their density differences, triggering mechanotransduction in the cell. The aim of this study was to investigate the effect of hypergravity on c-fos expression in the murine ATDC5 chondroprogenitor cells, as c-fos is a well known key regulator of cell proliferation and differentiation, including in chondrocytes. We first found that hypergravity down-regulated c-fos expression transiently via ROCK/Rho-GTP and PI3K signaling, and the down-regulation was suppressed by inhibition of actin polymerization.
[Mh] Termos MeSH primário: Condrócitos/citologia
Regulação para Baixo
Guanosina Trifosfato/metabolismo
Hipergravidade
Fosfatidilinositol 3-Quinases/metabolismo
Proteínas Proto-Oncogênicas c-fos/genética
Proteínas rho de Ligação ao GTP/metabolismo
Quinases Associadas a rho/metabolismo
[Mh] Termos MeSH secundário: Citoesqueleto de Actina/metabolismo
Androstadienos/farmacologia
Animais
Linhagem Celular
Condrócitos/efeitos dos fármacos
Condrócitos/metabolismo
Regulação para Baixo/efeitos dos fármacos
Regulação da Expressão Gênica/efeitos dos fármacos
Camundongos
Modelos Biológicos
Proteínas Proto-Oncogênicas c-fos/metabolismo
Transdução de Sinais/efeitos dos fármacos
Células-Tronco/citologia
Células-Tronco/efeitos dos fármacos
Células-Tronco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androstadienes); 0 (Proto-Oncogene Proteins c-fos); 86-01-1 (Guanosine Triphosphate); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (rho-Associated Kinases); EC 3.6.5.2 (rho GTP-Binding Proteins); XVA4O219QW (wortmannin)
[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:170928
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185394


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[PMID]:28816986
[Au] Autor:Zhang J; Huang Y; Wang C; He Y; Zheng S; Wu K
[Ad] Endereço:aDepartment of Preventive Medicine, Shantou University Medical College, Xinling Road bMental Health Center, Shantou University Medical College, North Taishan Road, Shantou cDepartment of Non-communicable Disease Control and Prevention, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, Guangdong, China.
[Ti] Título:Efficacy and safety of endocrine monotherapy as first-line treatment for hormone-sensitive advanced breast cancer: A network meta-analysis.
[So] Source:Medicine (Baltimore);96(33):e7846, 2017 Aug.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Endocrine therapy was recommended as the preferred first-line treatment for hormone receptor-positive (HR+, i.e., ER+ and/or PgR+), human epidermal growth factor receptor-2-negative (HER2-) postmenopausal advanced breast cancer (ABC), but which endocrine monotherapy is optimal lacks consensus. We aimed to identify the optimal endocrine monotherapy with a network meta-analysis. METHODS: We performed a network meta-analysis for a comprehensive analysis of 6 first-line endocrine monotherapies (letrozole, anastrozole, exemestane, tamoxifen, fulvestrant 250 mg and 500 mg) for HR+ HER2- metastatic or locally advanced breast cancer in postmenopausal patients. The main outcomes were objective response rate (ORR), time to progression (TTP), and progression-free survival (PFS). Secondary outcomes were adverse events. RESULTS: We identified 27 articles of 8 randomized controlled trials including 3492 patients in the network meta-analysis. For ORR, the treatments ranked in descending order of effectiveness were letrozole > exemestane > anastrozole > fulvestrant 500 mg > tamoxifen > fulvestrant 250 mg. For TTP/PFS, the order was fulvestrant 500 mg > letrozole > anastrozole > exemestane > tamoxifen > fulvestrant 250 mg. We directly compared adverse events and found that tamoxifen produced more hot flash events than fulvestrant 250 mg. CONCLUSIONS: Fulvestrant 500 mg and letrozole might be optimal first-line endocrine monotherapy choices for HR+ HER2- ABC because of efficacious ORR and TTP/PFS, with a favorable tolerability profile. However, direct comparisons among endocrine monotherapies in the first-line therapy setting are still required to robustly demonstrate any differences among these endocrine agents. Clinical choices should also depend on the specific disease situation and duration of endocrine therapy.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Neoplasias da Mama/tratamento farmacológico
[Mh] Termos MeSH secundário: Androstadienos/uso terapêutico
Antineoplásicos/administração & dosagem
Antineoplásicos/efeitos adversos
Intervalo Livre de Doença
Estradiol/análogos & derivados
Estradiol/uso terapêutico
Feminino
Seres Humanos
Neoplasias Hormônio-Dependentes
Metanálise em Rede
Nitrilos/uso terapêutico
Receptor ErbB-2
Tamoxifeno/uso terapêutico
Triazóis/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (Androstadienes); 0 (Antineoplastic Agents); 0 (Nitriles); 0 (Triazoles); 094ZI81Y45 (Tamoxifen); 22X328QOC4 (fulvestrant); 2Z07MYW1AZ (anastrozole); 4TI98Z838E (Estradiol); 7LKK855W8I (letrozole); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2); NY22HMQ4BX (exemestane)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000007846


  9 / 7916 MEDLINE  
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[PMID]:28770835
[Au] Autor:Abderrahman B; Jordan VC
[Ad] Endereço:University of Texas MD Anderson Cancer Center, Houston, Texas. V.C.J. met Angela at the Worcester Foundation in 1972. They remained lifelong friends.
[Ti] Título:Angela M. Hartley Brodie (1934-2017).
[So] Source:Nature;548(7665):32, 2017 08 02.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Inibidores da Aromatase/história
[Mh] Termos MeSH secundário: Androstadienos/história
Androstadienos/farmacologia
Androstadienos/uso terapêutico
Androstenodiona/análogos & derivados
Androstenodiona/história
Androstenodiona/farmacologia
Benzimidazóis/história
Benzimidazóis/farmacologia
Benzimidazóis/uso terapêutico
Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/enzimologia
Neoplasias da Mama/metabolismo
Estrogênios/biossíntese
Feminino
História do Século XX
História do Século XXI
Seres Humanos
Masculino
Maryland
Neoplasias da Próstata/tratamento farmacológico
Neoplasias da Próstata/enzimologia
Neoplasias da Próstata/metabolismo
[Pt] Tipo de publicação:BIOGRAPHY; HISTORICAL ARTICLE; JOURNAL ARTICLE; PORTRAITS
[Ps] Nome de pessoa como assunto:Brodie AMH
[Nm] Nome de substância:
0 (Androstadienes); 0 (Aromatase Inhibitors); 0 (Benzimidazoles); 0 (Estrogens); 409J2J96VR (Androstenedione); PUB9T8T355 (formestane); WA33E149SW (3-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1038/548032a


  10 / 7916 MEDLINE  
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[PMID]:28732650
[Au] Autor:Derks MGM; Blok EJ; Seynaeve C; Nortier JWR; Kranenbarg EM; Liefers GJ; Putter H; Kroep JR; Rea D; Hasenburg A; Markopoulos C; Paridaens R; Smeets JBE; Dirix LY; van de Velde CJH
[Ad] Endereço:Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.
[Ti] Título:Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial.
[So] Source:Lancet Oncol;18(9):1211-1220, 2017 Sep.
[Is] ISSN:1474-5488
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: After 5 years of median follow-up, the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial reported no difference in disease-free survival between exemestane monotherapy and a sequential scheme of tamoxifen followed by exemestane in postmenopausal patients with early-stage, hormone receptor-positive breast cancer. As recurrence risk in hormone receptor-positive breast cancer remains linear beyond 5 years after diagnosis, we analysed long-term follow-up outcomes of this trial. METHODS: The TEAM trial, a multicentre, open-label, randomised, controlled, phase 3 trial, included postmenopausal patients with early-stage hormone receptor-positive breast cancer from nine countries. Patients were randomly allocated (1:1) by a computer-generated random permuted block method (block sizes 4-8) to either 5 years of oral exemestane monotherapy (25 mg once a day) or a sequential scheme of oral tamoxifen (20 mg once a day) followed by exemestane for a total duration of 5 years. After the publication of the IES trial, the protocol was amended (Dec 13, 2004). Patients assigned to tamoxifen were switched after 2·5-3·0 years to exemestane therapy for a total duration of 5·0 years of treatment. Randomisation was done centrally in each country. Long-term follow-up data for disease recurrence and survival was collected in six participating countries and analysed by intention to treat. The primary endpoint was disease-free survival at 10 years of follow-up. The trial is registered with ClinicalTrials.gov, numbers NCT00279448 and NCT00032136; with Netherlands Trial Register, number NTR 267; and the Ethics Commission Trial, number 27/2001. FINDINGS: 6120 patients of the original 9776 patients in the TEAM trial were included in the current intention-to-treat analysis. Median follow-up was 9·8 years (IQR 8·0-10·3). During follow-up, 921 (30%) of 3075 patients in the exemestane group and 929 (31%) of 3045 patients in the sequential group had a disease-free survival event. Disease-free survival at 10 years was 67% (95% CI 65-69) for the exemestane group and 67% (65-69) for the sequential group (hazard ratio 0·96, 0·88-1·05; p=0·39). INTERPRETATION: The long-term findings of the TEAM trial confirm that both exemestane alone and sequential treatment with tamoxifen followed by exemestane are reasonable options as adjuvant endocrine therapy in postmenopausal patients with hormone receptor-positive early breast cancer. These results suggest that the opportunity to individualise adjuvant endocrine strategy accordingly, based on patient preferences, comorbidities, and tolerability might be possible. FUNDING: Pfizer, Dutch Cancer Foundation.
[Mh] Termos MeSH primário: Adenocarcinoma/terapia
Androstadienos/uso terapêutico
Antineoplásicos Hormonais/uso terapêutico
Neoplasias da Mama/terapia
Tamoxifeno/uso terapêutico
[Mh] Termos MeSH secundário: Adenocarcinoma/mortalidade
Adenocarcinoma/patologia
Idoso
Neoplasias da Mama/mortalidade
Neoplasias da Mama/patologia
Quimioterapia Adjuvante
Intervalo Livre de Doença
Quimioterapia Combinada
Feminino
Seguimentos
Seres Humanos
Masculino
Mastectomia
Meia-Idade
Pós-Menopausa
Fatores de Tempo
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Androstadienes); 0 (Antineoplastic Agents, Hormonal); 094ZI81Y45 (Tamoxifen); NY22HMQ4BX (exemestane)
[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:170723
[St] Status:MEDLINE



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