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[PMID]:28745319
[Au] Autor:D'Abronzo LS; Bose S; Crapuchettes ME; Beggs RE; Vinall RL; Tepper CG; Siddiqui S; Mudryj M; Melgoza FU; Durbin-Johnson BP; deVere White RW; Ghosh PM
[Ad] Endereço:VA Northern California Health Care System, University of California at Davis, Sacramento, CA, USA.
[Ti] Título:The androgen receptor is a negative regulator of eIF4E phosphorylation at S209: implications for the use of mTOR inhibitors in advanced prostate cancer.
[So] Source:Oncogene;36(46):6359-6373, 2017 Nov 16.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The antiandrogen bicalutamide is widely used in the treatment of advanced prostate cancer (PCa) in many countries, but its effect on castration-resistant PCa (CRPC) is limited. We previously showed that resistance to bicalutamide results from activation of mechanistic target of rapamycin (mTOR). Interestingly, clinical trials testing combinations of the mTOR inhibitor RAD001 with bicalutamide were effective in bicalutamide-naïve CRPC patients, but not in bicalutamide-pretreated ones. Here we investigate causes for their difference in response. Evaluation of CRPC cell lines identified resistant vs sensitive in vitro models, and revealed that increased eIF4E(S209) phosphorylation is associated with resistance to the combination. We confirmed using a human-derived tumor xenograft mouse model that bicalutamide pre-treatment is associated with an increase in eIF4E(S209) phosphorylation. Thus, AR suppressed eukaryotic initiation factor 4E (eIF4E) phosphorylation, while the use of antiandrogens relieved this suppression, thereby triggering its increase. Additional investigation in human prostatectomy samples showed that increased eIF4E phosphorylation strongly correlated with the cell proliferation marker Ki67. Small interfering RNA-mediated knockdown (k/d) of eIF4E-sensitized CRPC cells to RAD001+bicalutamide, whereas eIF4E overexpression induced resistance. Inhibition of eIF4E phosphorylation by treatment with CGP57380 (an inhibitor of mitogen-activated protein kinase-interacting serine-threonine kinases MAP kinase-interacting kinase 1 (Mnk1/2), the eIF4E upstream kinase) or inhibitors of extracellular signal-regulated kinase 1/2 (ERK1/2), the upstream kinase-regulating Mnk1/2, also sensitized CRPC cells to RAD001+bicalutamide. Examination of downstream targets of eIF4E-mediated translation, including survivin, demonstrated that eIF4E(S209) phosphorylation increased cap-independent translation, whereas its inhibition restored cap-dependent translation, which could be inhibited by mTOR inhibitors. Thus, our results demonstrate that while combinations of AR and mTOR inhibitors were effective in suppressing tumor growth by inhibiting both AR-induced transcription and mTOR-induced cap-dependent translation, pre-treatment with AR antagonists including bicalutamide increased eIF4E phosphorylation that induced resistance to combinations of AR and mTOR inhibitors by inducing cap-independent translation. We conclude that this resistance can be overcome by inhibiting eIF4E phosphorylation with Mnk1/2 or ERK1/2 inhibitors.
[Mh] Termos MeSH primário: Fator de Iniciação 4E em Eucariotos/metabolismo
Neoplasias de Próstata Resistentes à Castração/metabolismo
Receptores Androgênicos/metabolismo
Serina-Treonina Quinases TOR/metabolismo
[Mh] Termos MeSH secundário: Anilidas/administração & dosagem
Compostos de Anilina/administração & dosagem
Animais
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Western Blotting
Linhagem Celular Tumoral
Everolimo/administração & dosagem
Seres Humanos
Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Masculino
Camundongos Nus
Nitrilos/administração & dosagem
Fosforilação/efeitos dos fármacos
Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico
Proteínas Serina-Treonina Quinases/antagonistas & inibidores
Proteínas Serina-Treonina Quinases/metabolismo
Purinas/administração & dosagem
Serina/metabolismo
Sirolimo/administração & dosagem
Serina-Treonina Quinases TOR/antagonistas & inibidores
Compostos de Tosil/administração & dosagem
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AR protein, human); 0 (Anilides); 0 (Aniline Compounds); 0 (CGP 57380); 0 (Eukaryotic Initiation Factor-4E); 0 (Intracellular Signaling Peptides and Proteins); 0 (Nitriles); 0 (Purines); 0 (Receptors, Androgen); 0 (Tosyl Compounds); 452VLY9402 (Serine); 9HW64Q8G6G (Everolimus); A0Z3NAU9DP (bicalutamide); EC 2.7.1.- (MKNK1 protein, human); EC 2.7.1.1 (MTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171201
[Lr] Data última revisão:
171201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2017.233


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[PMID]:29017178
[Au] Autor:Haque R; UlcickasYood M; Xu X; Cassidy-Bushrow AE; Tsai HT; Keating NL; Van Den Eeden SK; Potosky AL
[Ad] Endereço:Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA 91101, USA.
[Ti] Título:Cardiovascular disease risk and androgen deprivation therapy in patients with localised prostate cancer: a prospective cohort study.
[So] Source:Br J Cancer;117(8):1233-1240, 2017 Oct 10.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: As androgen deprivation therapy (ADT) is increasingly being used in men with localised prostate cancer, our goal was to examine the association between ADT and the risk of cardiovascular disease (CVD). METHODS: We conducted a prospective cohort study using records of a large health-care system in California. The study included men with newly diagnosed localised prostate cancer (1998-2008) who initially underwent active surveillance (N=7637) and were followed through 2010. We examined 10 individual CVD outcomes. Cox proportional hazard models incorporated time-varying treatment variables and controlled for race/ethnicity, age, and tumour characteristics, recurrence risk, CVD medication use, and CVD risk factors. RESULTS: Of the 7637 subjects, nearly 30% were exposed to ADT. In the multivariable analyses, ADT was associated with an increased risk of heart failure (adjusted HR=1.81, 95% CI 1.40-2.32) in men without preexisting CVD. Elevated risks of arrhythmia (adjusted HR=1.44, 95% CI 1.02-2.01), and conduction disorder (adjusted HR=3.11, 95% CI 1.22, 7.91) were only observed among patients with preexisting CVD. CONCLUSIONS: In men with clinically localised prostate cancer who were initially under active surveillance, ADT was associated with a greater risk of heart failure in men without any preexisting CVD. We also found an increased risk of arrhythmia and conduction disorder in men with preexisting CVD. This study provides the basis for identifying high-risk men treated with ADT who might benefit from regular cardiac monitoring and lifestyle modification recommendations.
[Mh] Termos MeSH primário: Antagonistas de Androgênios/uso terapêutico
Antineoplásicos Hormonais/uso terapêutico
Arritmias Cardíacas/epidemiologia
Insuficiência Cardíaca/epidemiologia
Neoplasias da Próstata/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Anilidas/uso terapêutico
California/epidemiologia
Doenças Cardiovasculares/epidemiologia
Estudos de Coortes
Flutamida/uso terapêutico
Hormônio Liberador de Gonadotropina/agonistas
Gosserrelina/uso terapêutico
Seres Humanos
Imidazolidinas/uso terapêutico
Leuprolida/uso terapêutico
Masculino
Meia-Idade
Análise Multivariada
Gradação de Tumores
Nitrilos/uso terapêutico
Modelos de Riscos Proporcionais
Estudos Prospectivos
Neoplasias da Próstata/epidemiologia
Neoplasias da Próstata/patologia
Fatores de Risco
Compostos de Tosil/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androgen Antagonists); 0 (Anilides); 0 (Antineoplastic Agents, Hormonal); 0 (Imidazolidines); 0 (Nitriles); 0 (Tosyl Compounds); 0F65R8P09N (Goserelin); 33515-09-2 (Gonadotropin-Releasing Hormone); 51G6I8B902 (nilutamide); 76W6J0943E (Flutamide); A0Z3NAU9DP (bicalutamide); EFY6W0M8TG (Leuprolide)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171011
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2017.280


  3 / 2900 MEDLINE  
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[PMID]:28768934
[Au] Autor:Nakahara K; Kitazawa C; Mineno T
[Ad] Endereço:Laboratory of Medicinal Chemistry, Faculty of Pharmacy, Takasaki University of Health and Welfare.
[Ti] Título:Chloramine-T-Mediated Oxidation of Benzylic Alcohols Using Indium(III) Triflate.
[So] Source:Chem Pharm Bull (Tokyo);65(8):801-804, 2017.
[Is] ISSN:1347-5223
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:The efficient oxidation of benzylic alcohols to carbonyl compounds was performed using chloramine-T and a catalytic amount of indium(III) triflate. The primary benzylic alcohols were converted to the corresponding aldehydes in a good yield, and the secondary benzylic alcohols were oxidized to ketones in a high yield. The optimized reaction conditions required 0.3 eq of indium(III) triflate and the use of acetonitrile as a solvent.
[Mh] Termos MeSH primário: Álcool Benzílico/química
Cloraminas/química
Cetonas/síntese química
Compostos de Tosil/química
[Mh] Termos MeSH secundário: Cetonas/química
Estrutura Molecular
Oxirredução
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chloramines); 0 (Ketones); 0 (Tosyl Compounds); 4IU6VSV0EI (chloramine-T); LKG8494WBH (Benzyl Alcohol)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1248/cpb.c17-00061


  4 / 2900 MEDLINE  
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[PMID]:28704421
[Au] Autor:Tosetti V; Sassone J; Ferri ALM; Taiana M; Bedini G; Nava S; Brenna G; Di Resta C; Pareyson D; Di Giulio AM; Carelli S; Parati EA; Gorio A
[Ad] Endereço:Department of Cerebrovascular Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
[Ti] Título:Transcriptional role of androgen receptor in the expression of long non-coding RNA Sox2OT in neurogenesis.
[So] Source:PLoS One;12(7):e0180579, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The complex architecture of adult brain derives from tightly regulated migration and differentiation of precursor cells generated during embryonic neurogenesis. Changes at transcriptional level of genes that regulate migration and differentiation may lead to neurodevelopmental disorders. Androgen receptor (AR) is a transcription factor that is already expressed during early embryonic days. However, AR role in the regulation of gene expression at early embryonic stage is yet to be determinate. Long non-coding RNA (lncRNA) Sox2 overlapping transcript (Sox2OT) plays a crucial role in gene expression control during development but its transcriptional regulation is still to be clearly defined. Here, using Bicalutamide in order to pharmacologically inactivated AR, we investigated whether AR participates in the regulation of the transcription of the lncRNASox2OTat early embryonic stage. We identified a new DNA binding region upstream of Sox2 locus containing three androgen response elements (ARE), and found that AR binds such a sequence in embryonic neural stem cells and in mouse embryonic brain. Our data suggest that through this binding, AR can promote the RNA polymerase II dependent transcription of Sox2OT. Our findings also suggest that AR participates in embryonic neurogenesis through transcriptional control of the long non-coding RNA Sox2OT.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica no Desenvolvimento
Neurogênese
RNA Longo não Codificante/genética
Receptores Androgênicos/metabolismo
Ativação Transcricional
[Mh] Termos MeSH secundário: Antagonistas de Androgênios/farmacologia
Anilidas/farmacologia
Animais
Encéfalo/embriologia
Encéfalo/metabolismo
Células Cultivadas
Feminino
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Células-Tronco Neurais/efeitos dos fármacos
Células-Tronco Neurais/metabolismo
Nitrilos/farmacologia
RNA Longo não Codificante/metabolismo
Elementos de Resposta
Compostos de Tosil/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androgen Antagonists); 0 (Anilides); 0 (Nitriles); 0 (RNA, Long Noncoding); 0 (Receptors, Androgen); 0 (Tosyl Compounds); 0 (long noncoding RNA Sox2OT, mouse); A0Z3NAU9DP (bicalutamide)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170714
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180579


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[PMID]:28581399
[Au] Autor:Morote J; Tabernero ÁJ; Álvarez Ossorio JL; Ciria JP; Domínguez-Escrig JL; Vázquez F; Angulo J; López FJ; de La Iglesia R; Romero J; ANAMEM Investigator Group
[Ad] Endereço:Department of Urology, Hospital Universitario Vall D'Hebrón, Barcelona, Spain. Electronic address: jmorote@vhebron.net.
[Ti] Título:Cognitive Function in Patients With Prostate Cancer Receiving Luteinizing Hormone-Releasing Hormone Analogues: A Prospective, Observational, Multicenter Study.
[So] Source:Int J Radiat Oncol Biol Phys;98(3):590-594, 2017 Jul 01.
[Is] ISSN:1879-355X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: The effect of androgen deprivation therapy (ADT) on cognitive performance (CP) in prostate cancer (PCa) patients is not well understood. We evaluated changes in CP after 6 months of medical castration with luteinizing hormone-releasing hormone (LHRH) analogues. METHODS AND MATERIALS: We performed a prospective, observational, multicenter, open-label study of PCa patients scheduled to receive LHRH analogues for ≥6 months. We assessed 4 domains of CP at baseline and after 6 months of ADT: (1) working memory, assessed with the Wechsler Adult Intelligence Scale III (WAIS III) Digit Span subtest; (2) visual memory, assessed with an ad hoc visual memory test; (3) visuospatial ability, assessed with the Judgment of Line Orientation test and Mental Rotation of Three-Dimensional Objects test; and (4) nonverbal analytical reasoning, assessed with the WAIS III Matrix Reasoning test. Changes outside the baseline 95% confidence intervals were considered significant. RESULTS: A total of 308 patients completed the study. Of these, 245 (79.6%) experienced no statistically significant changes on any test whereas 63 (20.4%) experienced significant changes on ≥1 test. Most of these patients showed a change on only 1 test, distributed evenly between improvement (58 patients, 18.8%) and worsening (56 patients, 18.2%). For individual tests, most patients (87.8%-91.8%) had no change from baseline; however, the significant changes (improvement vs deterioration) were as follows: WAIS III Digit Span subtest (6.3% vs 5.9%), visual memory (5.3% vs 5.7%), Judgment of Line Orientation test (5.3% vs 4.5%), Mental Rotation of Three-Dimensional Objects test (4.1% vs 4.1%), and WAIS III Matrix Reasoning test (4.8% vs 5.8%). CONCLUSIONS: CP in patients with PCa does not appear to be adversely affected by 6 months of LHRH analogue administration.
[Mh] Termos MeSH primário: Antagonistas de Androgênios/uso terapêutico
Antineoplásicos Hormonais/uso terapêutico
Cognição/efeitos dos fármacos
Hormônio Liberador de Gonadotropina/agonistas
Memória/efeitos dos fármacos
Neoplasias da Próstata/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Anilidas/uso terapêutico
Cognição/fisiologia
Seres Humanos
Masculino
Memória/fisiologia
Meia-Idade
Gradação de Tumores
Nitrilos/uso terapêutico
Estudos Prospectivos
Neoplasias da Próstata/patologia
Análise de Regressão
Compostos de Tosil/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Androgen Antagonists); 0 (Anilides); 0 (Antineoplastic Agents, Hormonal); 0 (Nitriles); 0 (Tosyl Compounds); 33515-09-2 (Gonadotropin-Releasing Hormone); A0Z3NAU9DP (bicalutamide)
[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:170606
[St] Status:MEDLINE


  6 / 2900 MEDLINE  
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Vieira, Ana Claudia
Texto completo
[PMID]:28433972
[Au] Autor:Vieira AC; Alvarenga MJ; Santos JC; Silva AM
[Ad] Endereço:Pneumologia, Hospital de Egas Moniz, Lisboa, Portugal.
[Ti] Título:Paraneoplastic jaundice and prostate cancer.
[So] Source:BMJ Case Rep;2017, 2017 Apr 22.
[Is] ISSN:1757-790X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cholestasis has numerous causes. We present the case of a 78-year-old man with a common diagnosis in this age group and gender but with an unusual presentation. There are only 11 articles published of patients with jaundice due to a paraneoplastic syndrome associated with prostate cancer. Interleukin 6 and other proinflammatory cytokines appear to contribute to the pathophysiology of this syndrome. Our patient remains symptom free 4 months after treatment initiation.
[Mh] Termos MeSH primário: Anilidas/administração & dosagem
Icterícia/etiologia
Nitrilos/administração & dosagem
Síndromes Paraneoplásicas/diagnóstico
Neoplasias da Próstata/diagnóstico
Compostos de Tosil/administração & dosagem
[Mh] Termos MeSH secundário: Idoso
Anilidas/uso terapêutico
Seres Humanos
Masculino
Metástase Neoplásica
Nitrilos/uso terapêutico
Síndromes Paraneoplásicas/tratamento farmacológico
Neoplasias da Próstata/tratamento farmacológico
Compostos de Tosil/uso terapêutico
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anilides); 0 (Nitriles); 0 (Tosyl Compounds); A0Z3NAU9DP (bicalutamide)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170628
[Lr] Data última revisão:
170628
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170424
[St] Status:MEDLINE


  7 / 2900 MEDLINE  
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[PMID]:28409246
[Au] Autor:Onal C; Dolek Y; Ozdemir Y
[Ad] Endereço:Faculty of Medicine, Adana Dr. Turgut Noyan Research and Treatment Centre, Department of Radiation Oncology, Baskent University, 01120, Adana, Turkey. hcemonal@hotmail.com.
[Ti] Título:The impact of androgen deprivation therapy on setup errors during external beam radiation therapy for prostate cancer.
[Ti] Título:Einfluss der Androgendeprivationstherapie auf Konfigurationsfehler bei der externen Strahlentherapie des Prostatakarzinoms..
[So] Source:Strahlenther Onkol;193(6):472-482, 2017 Jun.
[Is] ISSN:1439-099X
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To determine whether setup errors during external beam radiation therapy (RT) for prostate cancer are influenced by the combination of androgen deprivation treatment (ADT) and RT. MATERIALS AND METHODS: Data from 175 patients treated for prostate cancer were retrospectively analyzed. Treatment was as follows: concurrent ADT plus RT, 33 patients (19%); neoadjuvant and concurrent ADT plus RT, 91 patients (52%); RT only, 51 patients (29%). Required couch shifts without rotations were recorded for each megavoltage (MV) cone beam computed tomography (CBCT) scan, and corresponding alignment shifts were recorded as left-right (x), superior-inferior (y), and anterior-posterior (z). The nonparametric Mann-Whitney test was used to compare shifts by group. Pearson's correlation coefficient was used to measure the correlation of couch shifts between groups. Mean prostate shifts and standard deviations (SD) were calculated and pooled to obtain mean or group systematic error (M), SD of systematic error (Σ), and SD of random error (σ). RESULTS: No significant differences were observed in prostate shifts in any direction between the groups. Shifts on CBCT were all less than setup margins. A significant positive correlation was observed between prostate volume and the z­direction prostate shift (r = 0.19, p = 0.04), regardless of ADT group, but not between volume and x­ or y­direction shifts (r = 0.04, p = 0.7; r = 0.03, p = 0.7). Random and systematic errors for all patient cohorts and ADT groups were similar. CONCLUSION: Hormone therapy given concurrently with RT was not found to significantly impact setup errors. Prostate volume was significantly correlated with shifts in the anterior-posterior direction only.
[Mh] Termos MeSH primário: Antagonistas de Androgênios/uso terapêutico
Artefatos
Marcadores Fiduciais
Posicionamento do Paciente
Neoplasias da Próstata/radioterapia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Anilidas/uso terapêutico
Quimiorradioterapia
Terapia Combinada
Tomografia Computadorizada de Feixe Cônico
Hormônio Liberador de Gonadotropina/agonistas
Seres Humanos
Masculino
Meia-Idade
Terapia Neoadjuvante
Nitrilos/uso terapêutico
Tamanho do Órgão
Próstata/efeitos da radiação
Neoplasias da Próstata/diagnóstico por imagem
Neoplasias da Próstata/tratamento farmacológico
Estudos Retrospectivos
Compostos de Tosil/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androgen Antagonists); 0 (Anilides); 0 (Nitriles); 0 (Tosyl Compounds); 33515-09-2 (Gonadotropin-Releasing Hormone); A0Z3NAU9DP (bicalutamide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170916
[Lr] Data última revisão:
170916
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170415
[St] Status:MEDLINE
[do] DOI:10.1007/s00066-017-1131-z


  8 / 2900 MEDLINE  
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[PMID]:28394498
[Au] Autor:Mason M; Richaud P; Bosnyak Z; Malmberg A; Neijber A
[Ad] Endereço:School of Medicine, Institute of Cancer and Genetics, Cardiff University, Cardiff, UK.
[Ti] Título:Degarelix Versus Goserelin Plus Bicalutamide in the Short-Term Relief of Lower Urinary Tract Symptoms in Prostate Cancer Patients: Results of a Pooled Analysis.
[So] Source:Low Urin Tract Symptoms;9(2):82-88, 2017 May.
[Is] ISSN:1757-5672
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: In patients with prostate cancer (PCa), prostate enlargement may give rise to lower urinary tract symptoms (LUTS); many patients suffer from moderate-to-severe symptoms. We compare the efficacy of degarelix and goserelin plus bicalutamide in improving LUTS in PCa patients. METHODS: Data were pooled from three Phase 3, randomized clinical trials of once-monthly treatment for 12 weeks with degarelix (240/80 mg; n = 289) or goserelin (3.6 mg) plus bicalutamide (50 mg; n = 174) for initial flare protection. LUTS at weeks 4, 8, and 12 were compared to baseline. Clinically relevant LUTS relief was a ≥3-point International Prostate Symptom Score (IPSS) decrease. Adverse events were assessed throughout the trials. RESULTS: Patients receiving degarelix had significantly greater decreases in IPSS vs. goserelin at week 12 (adjusted difference: -1.24; 95% CI -2.33 to -0.14, P = 0.03). Clinically relevant LUTS relief with degarelix was especially pronounced in patients with moderate-to-severe LUTS (baseline IPSS ≥13) (odds ratio; OR 2.31; 95% CI 1.19-4.47, P = 0.01) and advanced PCa (OR 2.36; 95% CI 1.10-5.04, P = 0.03). A twofold higher OR for early (week 4) LUTS relief was seen with degarelix vs. goserelin (OR 2.03; 95% CI 1.14-3.60, P = 0.02). No difference in total prostate volume or urinary tract infection-related adverse events (2%) was seen between treatment groups. CONCLUSION: An early, significant and clinically more pronounced improvement of LUTS, especially in patients with moderate-to-severe LUTS or advanced PCa, was seen with degarelix vs. goserelin plus bicalutamide.
[Mh] Termos MeSH primário: Antagonistas de Androgênios/administração & dosagem
Anilidas/administração & dosagem
Antineoplásicos Hormonais/administração & dosagem
Gosserrelina/administração & dosagem
Sintomas do Trato Urinário Inferior/tratamento farmacológico
Nitrilos/administração & dosagem
Oligopeptídeos/administração & dosagem
Compostos de Tosil/administração & dosagem
[Mh] Termos MeSH secundário: Idoso
Análise de Variância
Esquema de Medicação
Seres Humanos
Sintomas do Trato Urinário Inferior/etiologia
Sintomas do Trato Urinário Inferior/patologia
Masculino
Tamanho do Órgão
Próstata/patologia
Antígeno Prostático Específico/metabolismo
Neoplasias da Próstata/complicações
Neoplasias da Próstata/tratamento farmacológico
Neoplasias da Próstata/patologia
Testosterona/metabolismo
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Androgen Antagonists); 0 (Anilides); 0 (Antineoplastic Agents, Hormonal); 0 (Nitriles); 0 (Oligopeptides); 0 (Tosyl Compounds); 0 (acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide); 0F65R8P09N (Goserelin); 3XMK78S47O (Testosterone); A0Z3NAU9DP (bicalutamide); EC 3.4.21.77 (Prostate-Specific Antigen)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170411
[St] Status:MEDLINE
[do] DOI:10.1111/luts.12114


  9 / 2900 MEDLINE  
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[PMID]:28323339
[Au] Autor:Hurwitz MD; Harris J; Sartor O; Xiao Y; Shayegan B; Sperduto PW; Badiozamani KR; Lawton CAF; Horwitz EM; Michalski JM; Roof K; Beyer DC; Zhang Q; Sandler HM
[Ad] Endereço:Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
[Ti] Título:Adjuvant radiation therapy, androgen deprivation, and docetaxel for high-risk prostate cancer postprostatectomy: Results of NRG Oncology/RTOG study 0621.
[So] Source:Cancer;123(13):2489-2496, 2017 Jul 01.
[Is] ISSN:1097-0142
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Phase 3 trials have demonstrated a benefit from adjuvant radiation therapy (ART) for men who have adverse factors at radical prostatectomy (RP). However, some patients have a high risk of progression despite ART. The role of systemic therapy with ART in this high-risk group remains to be defined. METHODS: Patients who had either a post-RP prostate-specific antigen (PSA) nadir > 0.2 ng/mL and a Gleason score ≥7 or a PSA nadir ≤0.2 ng/mL, a Gleason score ≥8, and a pathologic tumor (pT) classification ≥ pT3 received 6 months of androgen-deprivation therapy (ADT) plus radiotherapy and 6 cycles of docetaxel. The primary objective was to assess whether the addition of ADT and docetaxel to ART resulted in a freedom from progression (FFP) rate ≥ 70% compared with an expected rate of 50%. Multivariate logistic and Cox regression analyses were used to model associations between factors and outcomes. RESULTS: In total, 74 patients were enrolled. The median follow-up was 4.4 years. The pathologic tumor classification was pT2 in 4% of patients, pT3 in 95%, and pT4 in 1%. The Gleason score was 7 in 18% of patients and ≥8 in 82%. Post-RP PSA levels were ≤0.2 ng/mL in 53% of patients and >0.2 ng/mL in 47%. The 3-year FFP rate was 73% (95% confidence interval, 61%-83%), and the 3-year cumulative incidence of biochemical, distant, and local failure was 26%, 7%, and 0%, respectively. In multivariate models, postprostatectomy PSA nadir was associated with 3-year FFP, Gleason score, and PSA with biochemical failure. Grade 3 and 4 neutropenia was common; however, only 3 episodes of febrile neutropenia occurred. Late toxicities were not impacted by the addition of systemic therapy. CONCLUSIONS: Combined ADT, docetaxel, and ART for men with high-risk prostate cancer after prostatectomy exceeded the prespecified study endpoint of 70% 3-year FFP. Phase 3 trials assessing combined local and systemic therapies for these high-risk patients are warranted. Cancer 2017;123:2489-96. © 2017 American Cancer Society.
[Mh] Termos MeSH primário: Adenocarcinoma/terapia
Antagonistas de Androgênios/uso terapêutico
Anilidas/uso terapêutico
Antineoplásicos/uso terapêutico
Quimiorradioterapia Adjuvante/métodos
Nitrilos/uso terapêutico
Prostatectomia
Neoplasias da Próstata/terapia
Taxoides/uso terapêutico
Compostos de Tosil/uso terapêutico
[Mh] Termos MeSH secundário: Adenocarcinoma/sangue
Adenocarcinoma/patologia
Adulto
Idoso
Intervalo Livre de Doença
Hormônio Liberador de Gonadotropina/agonistas
Seres Humanos
Calicreínas/sangue
Masculino
Meia-Idade
Análise Multivariada
Gradação de Tumores
Estadiamento de Neoplasias
Modelos de Riscos Proporcionais
Antígeno Prostático Específico/sangue
Neoplasias da Próstata/sangue
Neoplasias da Próstata/patologia
Radioterapia Conformacional
Radioterapia de Intensidade Modulada
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androgen Antagonists); 0 (Anilides); 0 (Antineoplastic Agents); 0 (Nitriles); 0 (Taxoids); 0 (Tosyl Compounds); 15H5577CQD (docetaxel); 33515-09-2 (Gonadotropin-Releasing Hormone); A0Z3NAU9DP (bicalutamide); EC 3.4.21.- (Kallikreins); EC 3.4.21.- (kallikrein-related peptidase 3, human); EC 3.4.21.77 (Prostate-Specific Antigen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171114
[Lr] Data última revisão:
171114
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1002/cncr.30620


  10 / 2900 MEDLINE  
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[PMID]:28219796
[Au] Autor:Kim KP; Parise RA; Holleran JL; Lewis LD; Appleman L; van Erp N; Morris MJ; Beumer JH
[Ad] Endereço:Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine,
[Ti] Título:Simultaneous quantitation of abiraterone, enzalutamide, N-desmethyl enzalutamide, and bicalutamide in human plasma by LC-MS/MS.
[So] Source:J Pharm Biomed Anal;138:197-205, 2017 May 10.
[Is] ISSN:1873-264X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Inhibiting the androgen receptor (AR) pathway is an important clinical strategy in metastatic prostate cancer. Novel agents including abiraterone acetate and enzalutamide have been shown to prolong life in men with metastatic, castration-resistant prostate cancer (mCRPC). To evaluate the pharmacokinetics of AR-targeted agents, we developed and validated an LC-MS/MS assay for the quantitation of enzalutamide, N-desmethyl enzalutamide, abiraterone and bicalutamide in 0.05mL human plasma. After protein precipitation, chromatographic separation was achieved with a Phenomenex Synergi Polar-RP column and a linear gradient of 0.1% formic acid in methanol and water. Detection with an ABI 4000Q mass spectrometer utilized electrospray ionization in positive multiple reaction monitoring mode. The assay was linear over the ranges of 1-1000ng/mL for abiraterone and bicalutamide and 100-30,000ng/mL for N-desmethyl enzalutamide and enzalutamide and proved to be accurate (92.8-107.7%) and precise (largest was 15.3% CV at LLOQ for bicalutamide), and fulfilled FDA criteria for bioanalytical method validation. We demonstrated the suitability of this assay in plasma from patients who were administered enzalutamide 160mg, abiraterone 1000mg and bicalutamide 50mg once a day as monotherapy or in combination. The LC-MS/MS assay that has been developed will be an essential tool that further defines the pharmacology of the combinations of androgen synthesis or AR-receptor targeted agents.
[Mh] Termos MeSH primário: Androstenos/sangue
Androstenos/química
Anilidas/sangue
Anilidas/química
Nitrilos/sangue
Nitrilos/química
Feniltioidantoína/análogos & derivados
Compostos de Tosil/sangue
Compostos de Tosil/química
[Mh] Termos MeSH secundário: Androstenos/uso terapêutico
Anilidas/uso terapêutico
Cromatografia Líquida/métodos
Seres Humanos
Masculino
Nitrilos/uso terapêutico
Feniltioidantoína/sangue
Feniltioidantoína/química
Feniltioidantoína/uso terapêutico
Neoplasias de Próstata Resistentes à Castração/sangue
Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico
Receptores Androgênicos/metabolismo
Espectrometria de Massas por Ionização por Electrospray/métodos
Compostos de Tosil/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androstenes); 0 (Anilides); 0 (MDV 3100); 0 (Nitriles); 0 (Receptors, Androgen); 0 (Tosyl Compounds); 2010-15-3 (Phenylthiohydantoin); A0Z3NAU9DP (bicalutamide); G819A456D0 (abiraterone)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170628
[Lr] Data última revisão:
170628
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170222
[St] Status:MEDLINE



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