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[PMID]:29446276
[Au] Autor:Yudina TV; Fedorova NE; Larkina MV; Egorchenkova OE; Rogacheva CK
[Ti] Título:[Determination of residual amounts of chlorothalonil in peaches: problems of gas chromatographic identification with the use of electron capture detector].
[So] Source:Gig Sanit;95(11):1108-12, 2016.
[Is] ISSN:0016-9900
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:In the work there are presented results of studies on the validation of the gas chromatographic (GC) methodfor the determination of chlorothalonil residue amounts in peaches with the use of electron capture detector (ECD). For the analytical control there was selected such stone fruit crop as the peach, referring to the crops, the most contaminated with residue amounts ofpesticides. There was justified the necessity of the inclusion in the procedure of the detection of the method of confirmation, based on mass spectrometry detection (MSD) (the type of ionization - electron impact). The significant source of the obtaining of incorrect data in the identification with the use of ECD of ions are shown to be phthalates, visualized in the chromatogram as intense and/or broad peaks. Mass spectra of compounds of the class ofphthalates are characterized by the dominant peak of the ion with the value of (mass/ charge) 149, just on this peak the detection of low molecular weight phthalates occurs in various matrices, on the spectrum there are also recorded typical ions corresponding to fragments of radical residues. The combination of the use of various types of the detection allows to prove that the revealed response (detector signal) is caused just by the analyte, but not the impurities, and optionally to optimize chromatographic conditions towards to the obtaining reliable results. The lower limit of the quantitation of chlorothalonil in peach fruits accounts for 0.01 mg/kg, determined with a signal/noise ratio of 10. The range of measured concentrations is volatile between 0.01-0.1 mg/kg, recovery rate of chlorothalonil from samples of peaches, established according to results of the analysis of model samples with the introduction of the substance in four points along the detection range, was 84-102%, the SD value of the repeatability varies in the range of 2.0-5.8%.
[Mh] Termos MeSH primário: Contaminação de Alimentos/análise
Cromatografia Gasosa-Espectrometria de Massas/métodos
Nitrilos/análise
Prunus persica/química
[Mh] Termos MeSH secundário: Fungicidas Industriais/análise
Seres Humanos
Limite de Detecção
Resíduos de Praguicidas/análise
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fungicides, Industrial); 0 (Nitriles); 0 (Pesticide Residues); J718M71A7A (tetrachloroisophthalonitrile)
[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:180216
[St] Status:MEDLINE


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[PMID]:28922787
[Au] Autor:Blok EJ; Kroep JR; Meershoek-Klein Kranenbarg E; Duijm-de Carpentier M; Putter H; van den Bosch J; Maartense E; van Leeuwen-Stok AE; Liefers GJ; Nortier JWR; Rutgers EJT; van de Velde CJH; IDEAL Study Group
[Ad] Endereço:Departments of Surgery, Medical Oncology, and Medical Statistics, Leiden University Medical Center, Leiden, Netherlands; Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, the Netherlands; Department of Internal Medicine, Reinier de Graaff Hospital, Delft, the Netherlands; Dutch
[Ti] Título:Optimal Duration of Extended Adjuvant Endocrine Therapy for Early Breast Cancer; Results of the IDEAL Trial (BOOG 2006-05).
[So] Source:J Natl Cancer Inst;110(1), 2018 Jan 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: The optimal duration of extended endocrine therapy beyond five years after initial aromatase inhibitor-based adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer is still unknown. Therefore, we conducted a clinical trial to compare two different extended endocrine therapy durations. Methods: In the randomized phase III IDEAL trial, postmenopausal patients with hormone receptor-positive breast cancer were randomly allocated to either 2.5 or five years of letrozole after the initial five years of any endocrine therapy. The primary end point was disease free survival (DFS), and secondary end points were overall survival (OS), distant metastasis-free interval (DMFi), new primary breast cancer, and safety. Hazard ratios (HRs) were determined using Cox regression analysis. All analyses were by intention-to-treat principle. Results: A total of 1824 patients were assigned to either 2.5 years (n = 909) or five years (n = 915) of letrozole, with a median follow-up of 6.6 years. A DFS event occurred in 152 patients in the five-year group, compared with 163 patients in the 2.5-year group (HR = 0.92, 95% confidence interval [CI] = 0.74 to 1.16). OS (HR = 1.04, 95% CI = 0.78 to 1.38) and DMFi (HR = 1.06, 95% CI = 0.78 to 1.45) were not different between both groups. A reduction in occurrence of second primary breast cancer was observed with five years of treatment (HR = 0.39, 95% CI = 0.19 to 0.81). Subgroup analysis did not identify patients who benefit from five-year extended therapy. Conclusion: This study showed no superiority of five years over 2.5 years of extended adjuvant letrozole after an initial five years of adjuvant endocrine therapy.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Neoplasias da Mama/terapia
Carcinoma Ductal de Mama/terapia
Carcinoma Intraductal não Infiltrante/terapia
Recidiva Local de Neoplasia/prevenção & controle
Segunda Neoplasia Primária/prevenção & controle
Nitrilos/administração & dosagem
Triazóis/administração & dosagem
[Mh] Termos MeSH secundário: Idoso
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Inibidores da Aromatase/administração & dosagem
Neoplasias da Mama/química
Neoplasias da Mama/patologia
Carcinoma Ductal de Mama/química
Carcinoma Ductal de Mama/prevenção & controle
Carcinoma Ductal de Mama/secundário
Carcinoma Intraductal não Infiltrante/prevenção & controle
Quimioterapia Adjuvante/efeitos adversos
Intervalo Livre de Doença
Feminino
Seguimentos
Seres Humanos
Mastectomia Segmentar
Meia-Idade
Nitrilos/efeitos adversos
Pós-Menopausa
Receptores Estrogênicos/análise
Receptores de Progesterona/análise
Taxa de Sobrevida
Tamoxifeno/administração & dosagem
Fatores de Tempo
Triazóis/efeitos adversos
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Aromatase Inhibitors); 0 (Nitriles); 0 (Receptors, Estrogen); 0 (Receptors, Progesterone); 0 (Triazoles); 094ZI81Y45 (Tamoxifen); 7LKK855W8I (letrozole)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx134


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[PMID]:28859291
[Au] Autor:Heindl A; Sestak I; Naidoo K; Cuzick J; Dowsett M; Yuan Y
[Ad] Endereço:Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK; Centre for Molecular Pathology, Royal Marsden Hospital, London, UK; Division of Molecular Pathology, The Institute of Cancer Research, London, UK; Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Qu
[Ti] Título:Relevance of Spatial Heterogeneity of Immune Infiltration for Predicting Risk of Recurrence After Endocrine Therapy of ER+ Breast Cancer.
[So] Source:J Natl Cancer Inst;110(2), 2018 Feb 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Despite increasing evidence supporting the clinical utility of immune infiltration in the estrogen receptor-negative (ER-) subtype, the prognostic value of immune infiltration for ER+ disease is not well defined. Methods: Quantitative immune scores of cell abundance and spatial heterogeneity were computed using a fully automated hematoxylin and eosin-stained image analysis algorithm and spatial statistics for 1178 postmenopausal patients with ER+ breast cancer treated with five years' tamoxifen or anastrozole. The prognostic significance of immune scores was compared with Oncotype DX 21-gene recurrence score (RS), PAM50 risk of recurrence (ROR) score, IHC4, and clinical treatment score, available for 963 patients. Statistical tests were two-sided. Results: Scores of immune cell abundance were not associated with recurrence-free survival. In contrast, high immune spatial scores indicating increased cell spatial clustering were associated with poor 10-year, early (0-5 years), and late (5-10 years) recurrence-free survival (Immune Hotspot: LR-χ2 = 14.06, P < .001, for 0-10 years; LR-χ2 = 6.24, P = .01, for 0-5 years; LR-χ2 = 7.89, P = .005, for 5-10 years). The prognostic value of spatial scores for late recurrence was similar to that of IHC4 and RS in both populations, but was not as strong as other tests in comparison for recurrence across 10 years. Conclusions: These results provide a missing link between tumor immunity and disease outcome in ER+ disease by examining tumor spatial architecture. The association between spatial scores and late recurrence suggests a lasting memory of protumor immunity that may impact disease progression and evolution of endocrine treatment resistance, which may be exploited for therapeutic advances.
[Mh] Termos MeSH primário: Neoplasias da Mama/imunologia
Neoplasias da Mama/patologia
Linfócitos do Interstício Tumoral/imunologia
Recidiva Local de Neoplasia/imunologia
Receptores Estrogênicos/análise
[Mh] Termos MeSH secundário: Idoso
Antineoplásicos/uso terapêutico
Biomarcadores Tumorais/imunologia
Neoplasias da Mama/química
Neoplasias da Mama/tratamento farmacológico
Intervalo Livre de Doença
Feminino
Seres Humanos
Contagem de Linfócitos
Meia-Idade
Nitrilos/uso terapêutico
Fatores de Risco
Tamoxifeno/uso terapêutico
Triazóis/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Biomarkers, Tumor); 0 (Nitriles); 0 (Receptors, Estrogen); 0 (Triazoles); 094ZI81Y45 (Tamoxifen); 2Z07MYW1AZ (anastrozole)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170902
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx137


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[PMID]:29334634
[Au] Autor:Hansson A; Knych H; Stanley S; Berndtson E; Jackson L; Bondesson U; Thevis M; Hedeland M
[Ad] Endereço:Division of Analytical Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Box 574, SE-75123, Uppsala, Sweden. Electronic address: Annelie.Hansson@farmkemi.uu.se.
[Ti] Título:Equine in vivo-derived metabolites of the SARM LGD-4033 and comparison with human and fungal metabolites.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1074-1075:91-98, 2018 Feb 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:LGD-4033 has been found in human doping control samples and has the potential for illicit use in racehorses as well. It belongs to the pharmacological class of selective androgen receptor modulators (SARMs) and can stimulate muscle growth, much like anabolic steroids. However, SARMs have shown superior side effect profiles compared to anabolic steroids, which arguably makes them attractive for use by individuals seeking an unfair advantage over their competitors. The purpose of this study was to investigate the metabolites formed from LGD-4033 in the horse in order to find suitable analytical targets for doping controls. LGD-4033 was administered to three horses after which plasma and urine samples were collected and analyzed for metabolites using ultra high performance liquid chromatography coupled to a high resolution mass spectrometer. In horse urine, eight metabolites, both phase I and phase II, were observed most of which had not been described in other metabolic systems. Six of these were also detected in plasma. The parent compound was detected in plasma, but not in non-hydrolyzed urine. The longest detection times were observed for unchanged LGD-4033 in plasma and in urine hydrolyzed with ß-glucuronidase and is thus suggested as the analytical target for doping control in the horse. The metabolite profile determined in the horse samples was also compared to those of human urine and fungal incubate from Cunninghamella elegans. The main human metabolite, dihydroxylated LGD-4033, was detected in the horse samples and was also produced by the fungus. However, it was a not a major metabolite for horse and fungus, which highlights the importance of performing metabolism studies in the species of interest.
[Mh] Termos MeSH primário: Cunninghamella/metabolismo
Nitrilos/análise
Nitrilos/metabolismo
Pirrolidinas/análise
Pirrolidinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Cavalos
Seres Humanos
Limite de Detecção
Nitrilos/química
Pirrolidinas/química
Extração em Fase Sólida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-(2-(2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-2-(trifluoromethyl)benzonitrile); 0 (Nitriles); 0 (Pyrrolidines)
[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:180116
[St] Status:MEDLINE


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[PMID]:29183075
[Au] Autor:Van Wagoner RM; Eichner A; Bhasin S; Deuster PA; Eichner D
[Ad] Endereço:Sports Medicine Research and Testing Laboratory, Salt Lake City, Utah.
[Ti] Título:Chemical Composition and Labeling of Substances Marketed as Selective Androgen Receptor Modulators and Sold via the Internet.
[So] Source:JAMA;318(20):2004-2010, 2017 11 28.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Recent reports have described the increasing use of nonsteroidal selective androgen receptor modulators, which have not been approved by the US Food and Drug Administration (FDA), to enhance appearance and performance. The composition and purity of such products is not known. Objective: To determine the chemical identity and the amounts of ingredients in dietary supplements and products marketed and sold through the internet as selective androgen receptor modulators and compare the analyzed contents with product labels. Design and Setting: Web-based searches were performed from February 18, 2016, to March 25, 2016, using the Google search engine on the Chrome and Internet Explorer web browsers to identify suppliers selling selective androgen receptor modulators. The products were purchased and the identities of the compounds and their amounts were determined from April to August 2016 using chain-of-custody and World Anti-Doping Association-approved analytical procedures. Analytical findings were compared against the label information. Exposures: Products marketed and sold as selective androgen receptor modulators. Main Outcomes and Measures: Chemical identities and the amount of ingredients in each product marketed and sold as selective androgen receptor modulators. Results: Among 44 products marketed and sold as selective androgen receptor modulators, only 23 (52%) contained 1 or more selective androgen receptor modulators (Ostarine, LGD-4033, or Andarine). An additional 17 products (39%) contained another unapproved drug, including the growth hormone secretagogue ibutamoren, the peroxisome proliferator-activated receptor-δ agonist GW501516, and the Rev-ErbA agonist SR9009. Of the 44 tested products, no active compound was detected in 4 (9%) and substances not listed on the label were contained in 11 (25%). In only 18 of the 44 products (41%), the amount of active compound in the product matched that listed on the label. The amount of the compounds listed on the label differed substantially from that found by analysis in 26 of 44 products (59%). Conclusions and Relevance: In this limited investigation involving chemical analyses of 44 products marketed as selective androgen receptor modulators and sold via the internet, most products contained unapproved drugs and substances. Only 52% contained selective androgen receptor modulators and many were inaccurately labeled.
[Mh] Termos MeSH primário: Anabolizantes/química
Comércio
Rotulagem de Medicamentos
Internet
Substâncias para Melhoria do Desempenho/química
Receptores Androgênicos
[Mh] Termos MeSH secundário: Acetamidas/análise
Aminofenóis/análise
Anilidas/análise
Aprovação de Drogas
Tráfico de Drogas
Nitrilos/análise
Pirrolidinas/análise
Estados Unidos
United States Food and Drug Administration
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (4-(2-(2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-2-(trifluoromethyl)benzonitrile); 0 (Acetamides); 0 (Aminophenols); 0 (Anabolic Agents); 0 (Anilides); 0 (Nitriles); 0 (Performance-Enhancing Substances); 0 (Pyrrolidines); 0 (Receptors, Androgen); 7UT2HAH49H (andarine); O3571H3R8N (ostarine)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.17069


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[PMID]:29231935
[Au] Autor:Roy S; Samanta D; Kumar P; Maji TK
[Ad] Endereço:Molecular Materials Laboratory, Chemistry and Physics of Materials Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore-560064, India. tmaji@jncasr.ac.in.
[Ti] Título:Pure white light emission and charge transfer in organogels of symmetrical and unsymmetrical π-chromophoric oligo-p-(phenyleneethynylene) bola-amphiphiles.
[So] Source:Chem Commun (Camb);54(3):275-278, 2018 Jan 02.
[Is] ISSN:1364-548X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Two novel bola-amphiphilic oligo-p-(phenyleneethynylene) (OPE) dicarboxylates have been synthesized having non-polar and mixed-polar side chains. This led to gelation in both with vesicular morphology. Upon in situ loading of a suitable dye and redox-active molecule, pure white light emitting and charge transfer (CT)-gels, respectively, were realized.
[Mh] Termos MeSH primário: Alquinos/química
Derivados de Benzeno/química
Substâncias Luminescentes/química
Tensoativos/química
[Mh] Termos MeSH secundário: Alquinos/síntese química
Alquinos/efeitos da radiação
Compostos Azo/química
Derivados de Benzeno/síntese química
Derivados de Benzeno/efeitos da radiação
Géis
Luz
Substâncias Luminescentes/síntese química
Substâncias Luminescentes/efeitos da radiação
Nitrilos/química
Tensoativos/síntese química
Tensoativos/efeitos da radiação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkynes); 0 (Azo Compounds); 0 (Benzene Derivatives); 0 (Gels); 0 (Luminescent Agents); 0 (Nitriles); 0 (Surface-Active Agents); 1518-16-7 (tetracyanoquinodimethane); 69083AX1ZX (methyl red)
[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:171213
[St] Status:MEDLINE
[do] DOI:10.1039/c7cc08046h


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[PMID]:27770345
[Au] Autor:Whitworth P; Beitsch P; Mislowsky A; Pellicane JV; Nash C; Murray M; Lee LA; Dul CL; Rotkis M; Baron P; Stork-Sloots L; de Snoo FA; Beatty J
[Ad] Endereço:Nashville Breast Center, Nashville, TN, USA. patwhitworth@gmail.com.
[Ti] Título:Chemosensitivity and Endocrine Sensitivity in Clinical Luminal Breast Cancer Patients in the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST) Predicted by Molecular Subtyping.
[So] Source:Ann Surg Oncol;24(3):669-675, 2017 Mar.
[Is] ISSN:1534-4681
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Hormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. In the Neoadjuvant Breast Registry Symphony Trial (NBRST) patients were classified according to MammaPrint/BluePrint subtyping to provide insight into the response to neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NCT). OBJECTIVE: The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity. METHODS: NBRST IHC/FISH HR+/HER2- breast cancer patients (n = 474) were classified into four molecular subgroups by MammaPrint/BluePrint subtyping: Luminal A, Luminal B, HER2, and Basal type. Pathological complete response (pCR) rates were compared with conventional IHC/FISH subtype. RESULTS: The overall pCR rate for 'clinical luminal' patients to NCT was 11 %; however, 87 of these 474 patients were reclassified as Basal type by BluePrint, with a high pCR rate of 32 %. The MammaPrint index was highly associated with the likelihood of pCR (p < 0.001). Fifty-three patients with BluePrint Luminal tumors received NET with an aromatase inhibitor and 36 (68 %) had a clinical response. CONCLUSIONS: With BluePrint subtyping, 18 % of clinical 'luminal' patients are classified in a different subgroup, compared with conventional assessment, and these patients have a significantly higher response rate to NCT compared with BluePrint Luminal patients. MammaPrint/BluePrint subtyping can help allocate effective treatment to appropriate patients. In addition, accurate identification of subtype biology is important in the interpretation of neoadjuvant treatment response since lack of pCR in luminal patients does not portend the worse prognosis associated with residual disease in Basal and HER2 subtypes.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias da Mama/classificação
Neoplasias da Mama/tratamento farmacológico
Perfilação da Expressão Gênica
Tipagem Molecular/métodos
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Inibidores da Aromatase/uso terapêutico
Neoplasias da Mama/genética
Neoplasias da Mama/metabolismo
Hidrocarbonetos Aromáticos com Pontes/administração & dosagem
Quimioterapia Adjuvante
Tomada de Decisão Clínica
Ciclofosfamida/administração & dosagem
Doxorrubicina/administração & dosagem
Feminino
Seres Humanos
Imuno-Histoquímica
Hibridização in Situ Fluorescente
Mastectomia Segmentar
Meia-Idade
Terapia Neoadjuvante
Nitrilos/administração & dosagem
Estudos Prospectivos
Receptor ErbB-2/metabolismo
Receptores Estrogênicos/metabolismo
Receptores de Progesterona/metabolismo
Sistema de Registros
Tamoxifeno/administração & dosagem
Taxoides/administração & dosagem
Resultado do Tratamento
Triazóis/administração & dosagem
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE IV; COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Aromatase Inhibitors); 0 (Bridged-Ring Compounds); 0 (Nitriles); 0 (Receptors, Estrogen); 0 (Receptors, Progesterone); 0 (Taxoids); 0 (Triazoles); 094ZI81Y45 (Tamoxifen); 15H5577CQD (docetaxel); 1605-68-1 (taxane); 2Z07MYW1AZ (anastrozole); 7LKK855W8I (letrozole); 80168379AG (Doxorubicin); 8N3DW7272P (Cyclophosphamide); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE
[do] DOI:10.1245/s10434-016-5600-x


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[PMID]:29037849
[Au] Autor:Li Q; Zhao X; Wang S; Zhou Z
[Ad] Endereço:College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China.
[Ti] Título:Letrozole induced low estrogen levels affected the expressions of duodenal and renal calcium-processing gene in laying hens.
[So] Source:Gen Comp Endocrinol;255:49-55, 2018 Jan 01.
[Is] ISSN:1095-6840
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Estrogen regulates the calcium homeostasis in hens, but the mechanisms involved are still unclear fully. In this study, we investigated whether letrozole (LZ) induced low estrogen levels affected the calcium absorption and transport in layers. In the duodenum, we observed a significant decrease of mRNA expressions of Calbindin-28k (CaBP-28k) and plasma membrane Ca -ATPase (PMCA 1b) while CaBP-28k protein expression was declined in birds with LZ treatment, and the mRNA levels of duodenal transient receptor potential vanilloid 6 (TRPV6) and Na /Ca exchanger 1 (NCX1) were not affected. Interestingly, we observed the different changes in the kidney. The renal mRNA expressions of TRPV6 and NCX1 were unregulated while the PMCA1b was down-regulated in low estrogen layers, however, the CaBP-28k gene and protein expressions were no changed in the kidney. Furthermore, it showed that the duodenal estradiol receptor 2 (ESR2) transcripts rather than parathyroid hormone 1 receptor (PTH1R) and calcitonin receptor (CALCR) played key roles to down-regulate calcium transport in LZ-treated birds. In conclusion, CaBP-28k, PMCA 1b and ESR2 genes in the duodenum may be primary targets for estrogen regulation in order to control calcium homeostasis in hens.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Galinhas/genética
Duodeno/metabolismo
Estrogênios/metabolismo
Regulação da Expressão Gênica/efeitos dos fármacos
Rim/metabolismo
Nitrilos/farmacologia
Triazóis/farmacologia
[Mh] Termos MeSH secundário: Animais
Cálcio/sangue
Proteínas de Ligação ao Cálcio/metabolismo
Galinhas/sangue
Galinhas/metabolismo
Duodeno/efeitos dos fármacos
Estrogênios/sangue
Feminino
Rim/efeitos dos fármacos
Hormônio Paratireóideo/sangue
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium-Binding Proteins); 0 (Estrogens); 0 (Nitriles); 0 (Parathyroid Hormone); 0 (RNA, Messenger); 0 (Triazoles); 7LKK855W8I (letrozole); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171018
[St] Status:MEDLINE


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[PMID]:28469997
[Au] Autor:Zhao M; Zhang L; Lv S; Zhang C; Wang L; Chen H; Zhou Y; Lou J
[Ad] Endereço:Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong UniversityShanghai, China.
[Ti] Título:IQGAP1 Mediates Hcp1-Promoted Meningitis by Stimulating the MAPK Pathway.
[So] Source:Front Cell Infect Microbiol;7:132, 2017.
[Is] ISSN:2235-2988
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:-induced meningitis remains a life-threatening disease despite recent advances in the field of antibiotics-based therapeutics, necessitating continued research on its pathogenesis. The current study aims to elucidate the mechanism through which hemolysin-coregulated protein 1 (Hcp1) induces the apoptosis of human brain microvascular endothelial cells (HBMEC). Co-immunoprecipitation coupled with mass spectrometric (MS) characterization led to the identification of IQ motif containing GTPase activating protein 1 (IQGAP1) as a downstream target of Hcp1. IQGAP1 was found to be up-regulated by Hcp1 treatment and mediate the stimulation of HBMEC apoptosis. It was shown that Hcp1 could compete against Smurf1 for binding to IQGAP1, thereby rescuing the latter from ubiquitin-dependent degradation. Subsequent study suggested that IQGAP1 could stimulate the MAPK signaling pathway by promoting the phosphorylation of ERK1/2, an effect that was blocked by U0126, an MAPK inhibitor. Furthermore, U0126 also demonstrated therapeutic potential against meningitis in a mouse model. Taken together, our results suggested the feasibility of targeting the MAPK pathway as a putative therapeutic strategy against bacterial meningitis.
[Mh] Termos MeSH primário: Proteínas de Escherichia coli/farmacologia
Escherichia coli/metabolismo
Meningite devida a Escherichia coli/metabolismo
Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo
Fatores de Virulência/farmacologia
Proteínas Ativadoras de ras GTPase/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Encéfalo
Butadienos/antagonistas & inibidores
Linhagem Celular
Citocinas/análise
Modelos Animais de Doenças
Células Endoteliais/efeitos dos fármacos
Seres Humanos
Meningite devida a Escherichia coli/tratamento farmacológico
Camundongos
Camundongos Endogâmicos C57BL
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Nitrilos/antagonistas & inibidores
Fosforilação
RNA Interferente Pequeno
Transdução de Sinais
Ubiquitina-Proteína Ligases
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Butadienes); 0 (Cytokines); 0 (Escherichia coli Proteins); 0 (HCP1 protein, E coli); 0 (IQ motif containing GTPase activating protein 1); 0 (Nitriles); 0 (RNA, Small Interfering); 0 (U 0126); 0 (Virulence Factors); 0 (ras GTPase-Activating Proteins); EC 2.3.2.26 (SMURF1 protein, human); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3); EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.3389/fcimb.2017.00132


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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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