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[PMID]:28559399
[Au] Autor:Dhruva SS; Huang C; Spatz ES; Coppi AC; Warner F; Li SX; Lin H; Xu X; Furberg CD; Davis BR; Pressel SL; Coifman RR; Krumholz HM
[Ad] Endereço:From the Robert Wood Johnson Foundation Clinical Scholars Program (S.S.D., H.M.K.), Section of Cardiovascular Medicine (E.S.S., A.C.C., F.W., H.M.K.), Department of Internal Medicine, and Department of Obstetrics, Gynecology and Reproductive Sciences (X.X.), Yale School of Medicine, New Haven, CT; D
[Ti] Título:Heterogeneity in Early Responses in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).
[So] Source:Hypertension;70(1):94-102, 2017 Jul.
[Is] ISSN:1524-4563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Randomized trials of hypertension have seldom examined heterogeneity in response to treatments over time and the implications for cardiovascular outcomes. Understanding this heterogeneity, however, is a necessary step toward personalizing antihypertensive therapy. We applied trajectory-based modeling to data on 39 763 study participants of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) to identify distinct patterns of systolic blood pressure (SBP) response to randomized medications during the first 6 months of the trial. Two trajectory patterns were identified: immediate responders (85.5%), on average, had a decreasing SBP, whereas nonimmediate responders (14.5%), on average, had an initially increasing SBP followed by a decrease. Compared with those randomized to chlorthalidone, participants randomized to amlodipine (odds ratio, 1.20; 95% confidence interval [CI], 1.10-1.31), lisinopril (odds ratio, 1.88; 95% CI, 1.73-2.03), and doxazosin (odds ratio, 1.65; 95% CI, 1.52-1.78) had higher adjusted odds ratios associated with being a nonimmediate responder (versus immediate responder). After multivariable adjustment, nonimmediate responders had a higher hazard ratio of stroke (hazard ratio, 1.49; 95% CI, 1.21-1.84), combined cardiovascular disease (hazard ratio, 1.21; 95% CI, 1.11-1.31), and heart failure (hazard ratio, 1.48; 95% CI, 1.24-1.78) during follow-up between 6 months and 2 years. The SBP response trajectories provided superior discrimination for predicting downstream adverse cardiovascular events than classification based on difference in SBP between the first 2 measurements, SBP at 6 months, and average SBP during the first 6 months. Our findings demonstrate heterogeneity in response to antihypertensive therapies and show that chlorthalidone is associated with more favorable initial response than the other medications.
[Mh] Termos MeSH primário: Anlodipino
Doenças Cardiovasculares/prevenção & controle
Clortalidona
Doxazossina
Hiperlipidemias
Hipertensão
Lisinopril
[Mh] Termos MeSH secundário: Idoso
Anlodipino/administração & dosagem
Anlodipino/efeitos adversos
Análise de Variância
Anti-Hipertensivos/administração & dosagem
Anti-Hipertensivos/efeitos adversos
Pressão Sanguínea/efeitos dos fármacos
Doenças Cardiovasculares/etiologia
Clortalidona/administração & dosagem
Clortalidona/efeitos adversos
Doxazossina/administração & dosagem
Doxazossina/efeitos adversos
Monitoramento de Medicamentos/métodos
Feminino
Seres Humanos
Hiperlipidemias/complicações
Hiperlipidemias/diagnóstico
Hiperlipidemias/tratamento farmacológico
Hipertensão/complicações
Hipertensão/diagnóstico
Hipertensão/tratamento farmacológico
Hipolipemiantes/uso terapêutico
Lisinopril/administração & dosagem
Lisinopril/efeitos adversos
Masculino
Meia-Idade
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antihypertensive Agents); 0 (Hypolipidemic Agents); 1J444QC288 (Amlodipine); E7199S1YWR (Lisinopril); NW1291F1W8 (Doxazosin); Q0MQD1073Q (Chlorthalidone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170601
[St] Status:MEDLINE
[do] DOI:10.1161/HYPERTENSIONAHA.117.09221


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[PMID]:28272220
[Au] Autor:Zhang M; Li H; Ji Z; Dong D; Yan S
[Ad] Endereço:Department of Urology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China.
[Ti] Título:Clinical study of duloxetine hydrochloride combined with doxazosin for the treatment of pain disorder in chronic prostatitis/chronic pelvic pain syndrome: An observational study.
[So] Source:Medicine (Baltimore);96(10):e6243, 2017 Mar.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To explore the safety and efficacy of the selective 5-serotonin and norepinephrine reuptake inhibitor duloxetine hydrochloride and alpha-adrenergic receptor blocker (alpha-blocker) doxazosin mesylate-controlled tablets in the treatment of pain disorder in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).In all, 150 patients were enrolled and 126 patients completed the study (41 patients in the doxazosin group, 41 patients in the sertraline group, and 44 patients in the duloxetine group). This was an open randomized 6-month study. CP/CPPS patients who met the diagnostic criteria were randomized into 3 groups. The patients in the duloxetine group received doxazosin 4 mg + duloxetine 30 mg once a day, and the dosage of duloxetine was increased to 60 mg after a week. The patients in the doxazosin group received doxazosin 4 mg once a day. The patients in the sertraline group received doxazosin 4 mg + sertraline 50 mg once a day. National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, the short-form McGill Pain questionnaire (SF-MPQ), and the hospital anxiety and depression scale (HAD) were applied for evaluations during follow-up of 1, 3, and 6 months after treatment.There were slight positive significant correlations between NIH-CPSI scores and HAD scores, moderate positive significant correlations between the quality of life (QOL) and SF-MPQ, and slight positive significant correlations between HAD and QOL. The effective rate in the doxazosin group was 4.88%, 19.51%, and 56.10% after 1, 3, and 6 months, respectively (P < 0.05). The SF-MPQ score in the doxazosin group decreased to 1.80 ±â€Š1.29, 2.66 ±â€Š1.57, and 3.24 ±â€Š1.67 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the doxazosin group decreased to 2.24 ±â€Š2.17, 4 ±â€Š2.11, and 4.90 ±â€Š2.62 after 1, 3, and 6 months, respectively (P < 0.05). The effective rate in the sertraline group was 9.76%, 36.59%, and 63.41% after 1, 3, and 6 months, respectively. The SF-MPQ score in the sertraline group decreased to 1.76 ±â€Š1.28, 3.07 ±â€Š2, and 3.93 ±â€Š2.53 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the sertraline group decreased to 3.56 ±â€Š4.11, 5.73 ±â€Š5.26, and 7.27 ±â€Š6.50 after 1, 3, and 6 months, respectively (P < 0.05). The effective rate in the duloxetine group was 36.36%, 88.64%, and 88.64% after 1, 3, and 6 months, respectively. The SF-MPQ score in the duloxetine group decreased to 3.61 ±â€Š2.54, 6.05 ±â€Š3.66, and 7.41 ±â€Š4.26 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the duloxetine group decreased to 3.14 ±â€Š3.28, 6.93 ±â€Š3.90, and 9.43 ±â€Š4.67 after 1, 3, and 6 months, respectively (P < 0.05). There were significant differences in the reduction of the NIH-CPSI score and the SF-MPQ score between the duloxetine group and the sertraline group and between the duloxetine group and the doxazosin group (P < 0.01). There were significant differences in the reduction of the HAD score at 3 months between the duloxetine group and the doxazosin group, and there were significant differences in the reduction of the HAD score at 6 months among the groups (P < 0.05). The incidence rates of adverse reactions in the duloxetine group, the sertraline group, and the duloxetine group were 29.5%, 17%, and 7.3%, respectively, with adverse events ranging from mild to moderate.There was a clear relationship between the extent of pain and mental factors in CP/CPPS with the main symptom of pain. Doxazosin combined with duloxetine exhibited good safety and efficacy in the treatment of pain disorder in CP/CPPS.
[Mh] Termos MeSH primário: Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico
Doxazossina/uso terapêutico
Cloridrato de Duloxetina/uso terapêutico
Dor Pélvica/tratamento farmacológico
Prostatite/tratamento farmacológico
Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Idoso
Dor Crônica/tratamento farmacológico
Seres Humanos
Masculino
Meia-Idade
Estudos Prospectivos
Índice de Gravidade de Doença
Inquéritos e Questionários
Síndrome
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Adrenergic alpha-1 Receptor Antagonists); 0 (Serotonin and Noradrenaline Reuptake Inhibitors); 9044SC542W (Duloxetine Hydrochloride); NW1291F1W8 (Doxazosin)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170324
[Lr] Data última revisão:
170324
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000006243


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[PMID]:27992238
[Au] Autor:Guo J; Luo X; Liang J; Xiao M; Sun X
[Ad] Endereço:1 Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China .
[Ti] Título:Antiangiogenic Effects of Doxazosin on Experimental Choroidal Neovascularization in Mice.
[So] Source:J Ocul Pharmacol Ther;33(1):50-56, 2017 Jan/Feb.
[Is] ISSN:1557-7732
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: The present study was designed to evaluate the effects of doxazosin on experimental choroidal neovascularization (CNV) in mice. METHODS: Six- to 8-week-old male C57BL/6 mice were divided into a control group and a doxazosin-treated group (5 mg/kg, i.p., daily). Experimental CNV was induced by laser photocoagulation. Seven and 14 days after laser induction, fluorescein angiography, choroidal flat mounts, and histological studies were performed to evaluate the fluorescence leakage, area, and thickness of CNV lesions, respectively. In addition, western blot analysis was carried out to assess the inhibitory effects of doxazosin on the PI3K/Akt/mTOR signaling pathway and the expression levels of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), which are involved in CNV model. RESULTS: Compared with the control group, the doxazosin-treated group demonstrated significantly less fluorescence leakage on day 7 and 14 after laser induction. Both the area and the thickness of CNV lesions in the doxazosin-treated group were significantly decreased. Mechanistically, PI3K/Akt/mTOR signaling pathway activation was significantly suppressed in the doxazosin-treated group. The expression of HIF-1α and VEGF was also notably reduced by systemic doxazosin treatment. CONCLUSIONS: Doxazosin exerts antiangiogenic actions in an experimental mouse model of CNV and may be a potential adjunctive therapy for neovascular age-related macular degeneration in humans.
[Mh] Termos MeSH primário: Inibidores da Angiogênese/farmacologia
Neovascularização de Coroide/tratamento farmacológico
Doxazossina/farmacologia
[Mh] Termos MeSH secundário: Inibidores da Angiogênese/administração & dosagem
Animais
Neovascularização de Coroide/patologia
Modelos Animais de Doenças
Doxazossina/administração & dosagem
Lasers
Masculino
Camundongos
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); NW1291F1W8 (Doxazosin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161220
[St] Status:MEDLINE
[do] DOI:10.1089/jop.2016.0153


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[PMID]:27987130
[Au] Autor:Liu Q; Zhu Y; Liu J; Qi J; Kang J
[Ad] Endereço:Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Rd, Shanghai, 200092, China.
[Ti] Título:Ultrasound image features of intravesical prostatic protrusion indicated failure of medication therapy of finasteride and doxazosin in patients with benign prostatic hyperplasia (LUTS/BPH).
[So] Source:Int Urol Nephrol;49(3):399-404, 2017 Mar.
[Is] ISSN:1573-2584
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Intravesical prostatic protrusion (IPP) is a type of benign prostatic hyperplasia (BPH) adenoma, and it plays a critical role in the pathogenesis of bladder outlet obstruction in patients with lower urinary tract syndromes (LUTS/BPH). AIMS: The goal of this study was to investigate the effect of a combination therapy with finasteride and doxazosin on IPP in BPU/LUTS patients. METHODS: A total of 322 BPH patients with enlarged prostatic volume as well as moderate to severe symptom scores were enrolled and divided into four groups according to the degree of IPP (IPP > 10 mm, 5-10 mm, <5 mm and no IPP) in this study. Aggravated International Prostatic Symptom Score (IPSS), acute urinary retention or relevant urinary complications were considered as failure of the therapy. The degrees of IPP were recorded before and after 6 months of treatment. Student's t test and χ were performed between the baseline and endpoint of the therapy. RESULTS: The results showed that the total prostate volume (TPV) and transition zone volume (TZV) of the prostate decreased significantly after 6-month combination therapy (P < 0.05), while no significant changes in IPP were observed at that point (P > 0.05). Failure rates of the medication differed significantly among the four groups. CONCLUSIONS: The study indicated that the combination therapy using finasteride and doxazosin could not reduce the degree of IPP. LUTS/BPH patients with IPP which contributes to the failure of medication tend to have a higher risk of progression.
[Mh] Termos MeSH primário: Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico
Doxazossina/uso terapêutico
Finasterida/uso terapêutico
Próstata/patologia
Hiperplasia Prostática/diagnóstico por imagem
Hiperplasia Prostática/tratamento farmacológico
Agentes Urológicos/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Quimioterapia Combinada
Seres Humanos
Masculino
Meia-Idade
Tamanho do Órgão
Próstata/diagnóstico por imagem
Antígeno Prostático Específico/sangue
Hiperplasia Prostática/complicações
Hiperplasia Prostática/patologia
Prostatismo/tratamento farmacológico
Prostatismo/etiologia
Falha de Tratamento
Ultrassonografia
Bexiga Urinária/diagnóstico por imagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic alpha-1 Receptor Antagonists); 0 (Urological Agents); 57GNO57U7G (Finasteride); EC 3.4.21.77 (Prostate-Specific Antigen); NW1291F1W8 (Doxazosin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161218
[St] Status:MEDLINE
[do] DOI:10.1007/s11255-016-1478-6


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[PMID]:27709382
[Au] Autor:Kirpatovskii VI; Mudraya IS; Revenko SV; Bablumyan AY; Adamyan NK; Ivanov VP
[Ad] Endereço:Department of Experimental Modeling of Urological Diseases, N. Lopatkin Research Institute of Urology - Affiliated Branch of National Medical Research Radiology Centre, Ministry of Health of the Russian Federation, Moscow, Russia. vladkirp@yandex.ru.
[Ti] Título:Effect of Doxazosin on Autonomic Nervous Control and Urodynamics of Rat Urinary Bladder during Modeled Infravesical Obstruction.
[So] Source:Bull Exp Biol Med;161(5):657-661, 2016 Sep.
[Is] ISSN:1573-8221
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The therapeutic effect of doxazosin (40 µg/kg/day over one month) on urinary bladder was examined in female rats with modeled chronic infravesical obstruction (IVO) produced by graduated mechanical constriction of the proximal urethral segment. In one month, IVO induced a pronounced vesical hypertrophy both in treated and untreated rats that manifested in increased bladder weight and capacity, the latter increment being pronouncedly greater in treated rats. In untreated IVO rats, infusion cystometry revealed elevated basal intravesical pressure of void bladder P , markedly increased maximal (premicturitional) pressure P , and increased amplitude of spontaneous oscillations of intravesical pressure ΔP in filled bladder. Doxazosin produced no significant effect on P rise during IVO, but prevented elevation of P and increment of ΔP in filled bladder. During gradual filling of urinary bladder in control (intact) rats, the parasympathetic vesical influences increased progressively, while in untreated IVO rats, the adrenergic influences prevailed even at maximal filling of the bladder. In IVO rats, doxazosin prevented the bias of the sympathetic-parasympathetic balance in the filled bladder in favor of sympathetic influences, but did not prevent this bias in a void bladder. It is hypothesized that α-adrenoblockers improve micturition during IVO caused by benign prostatic hyperplasia not only by decreasing the urethral resistance to urine flow due to down-regulation of prostate smooth muscle tone, but also by a direct action of these blockers on detrusor adrenergic receptors and central structures involved in urinary bladder control.
[Mh] Termos MeSH primário: Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia
Doxazossina/farmacologia
Obstrução Uretral/tratamento farmacológico
Micção/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico
Animais
Doxazossina/uso terapêutico
Avaliação Pré-Clínica de Medicamentos
Feminino
Masculino
Tamanho do Órgão/efeitos dos fármacos
Hiperplasia Prostática
Ratos
Fibras Simpáticas Pós-Ganglionares/efeitos dos fármacos
Fibras Simpáticas Pós-Ganglionares/fisiopatologia
Obstrução Uretral/fisiopatologia
Bexiga Urinária/efeitos dos fármacos
Bexiga Urinária/inervação
Bexiga Urinária/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic alpha-1 Receptor Antagonists); NW1291F1W8 (Doxazosin)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170214
[Lr] Data última revisão:
170214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161007
[St] Status:MEDLINE


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[PMID]:27629686
[Au] Autor:Belayneh M; Korownyk C
[Ad] Endereço:Medical student at the University of Alberta in Edmonton.
[Ti] Título:Treatment of lower urinary tract symptoms in benign prostatic hypertrophy with α-blockers.
[So] Source:Can Fam Physician;62(9):e523, 2016 Sep.
[Is] ISSN:1715-5258
[Cp] País de publicação:Canada
[La] Idioma:eng
[Mh] Termos MeSH primário: Antagonistas Adrenérgicos alfa/uso terapêutico
Doxazossina/uso terapêutico
Sintomas do Trato Urinário Inferior/tratamento farmacológico
Prazosina/análogos & derivados
Hiperplasia Prostática/complicações
[Mh] Termos MeSH secundário: Antagonistas Adrenérgicos alfa/efeitos adversos
Tontura/etiologia
Doxazossina/efeitos adversos
Seres Humanos
Hipotensão/etiologia
Masculino
Prazosina/efeitos adversos
Prazosina/uso terapêutico
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Adrenergic alpha-Antagonists); 8L5014XET7 (Terazosin); NW1291F1W8 (Doxazosin); XM03YJ541D (Prazosin)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160916
[St] Status:MEDLINE


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[PMID]:27564283
[Au] Autor:Zhang L; Li J; Pan M; Han W; Liu S; Xiao Y
[Ad] Endereço:Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
[Ti] Título:Doxazosin oral intake therapy to relieve stent - related urinary symptoms and pain: a prospective, randomized, controlled study.
[So] Source:Int Braz J Urol;42(4):727-33, 2016 Jul-Aug.
[Is] ISSN:1677-6119
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To assess the impact of Doxazosin Oral Intake Therapy on urinary symptoms and pain in patients with indwelling ureteral stents Patients and Methods: A total of 239 patients with ureteral stone-related hydronephrosis who underwent a double-J stent insertion after ureteroscopic lithotripsy were enrolled. Patients were randomized to receive doxazosin cotrolled release 4 mg once daily for 4 weeks or matching placebo. Patients completed the brief-form Chinese version Ureteric Stent Symptom Questionnaire (USSQ) and quality of life (QoL) score 2 weeks and 4 weeks after stent placement and 4 weeks after stent withdrawal. The analgesic use was also recorded during the stenting period. RESULTS: Patients in Doxazosin Oral Intake Therapy group, in the first 2 weeks and second 2 weeks with the stent in situ, expressed significant lower daytime frequency (p=0.028 and p=0.038), nocturia (p=0.021 and p=0.008) and urgency (p=0.012 and p=0.014), respectively. Similarly, flank pain score, QoL score and analgesic use were also significant less in the stenting period. There was no significant difference in scores of urinary symptoms, pain and QoL during the post-stent period between two cohorts. CONCLUSIONS: Doxazosin Oral Intake Therapy reduced stent-related urinary symptoms, pain and the negative impact on QoL.
[Mh] Termos MeSH primário: Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem
Doxazossina/administração & dosagem
Sintomas do Trato Urinário Inferior/tratamento farmacológico
Dor/tratamento farmacológico
Qualidade de Vida
Stents/efeitos adversos
[Mh] Termos MeSH secundário: Administração Oral
Adulto
Idoso
Feminino
Seres Humanos
Litotripsia/métodos
Masculino
Meia-Idade
Período Pós-Operatório
Estudos Prospectivos
Inquéritos e Questionários
Resultado do Tratamento
Ureteroscopia/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Adrenergic alpha-1 Receptor Antagonists); NW1291F1W8 (Doxazosin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160827
[St] Status:MEDLINE


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[PMID]:27537875
[Au] Autor:Batty M; Pugh R; Rathinam I; Simmonds J; Walker E; Forbes A; Anoopkumar-Dukie S; McDermott CM; Spencer B; Christie D; Chess-Williams R
[Ad] Endereço:School of Pharmacy, Griffith University, Gold Coast, QLD 4222, Australia. mallory.batty@griffithuni.edu.au.
[Ti] Título:The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers.
[So] Source:Int J Mol Sci;17(8), 2016 Aug 16.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers.
[Mh] Termos MeSH primário: Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico
Neoplasias da Próstata/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/uso terapêutico
Doxazossina/uso terapêutico
Feminino
Seres Humanos
Masculino
Prazosina/análogos & derivados
Prazosina/uso terapêutico
Neoplasias da Próstata/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Adrenergic alpha-1 Receptor Antagonists); 0 (Antineoplastic Agents); 8L5014XET7 (Terazosin); NW1291F1W8 (Doxazosin); XM03YJ541D (Prazosin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170417
[Lr] Data última revisão:
170417
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160819
[St] Status:MEDLINE


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[PMID]:27323967
[Au] Autor:de Marcondes PG; Bastos LG; de-Freitas-Junior JC; Rocha MR; Morgado-Díaz JA
[Ad] Endereço:Cellular Biology Program, Brazilian National Cancer Institute (INCA), 37 André Cavalcanti Street, 5th Floor, Rio de Janeiro, RJ, 20230-051, Brazil.
[Ti] Título:EphA4-mediated signaling regulates the aggressive phenotype of irradiation survivor colorectal cancer cells.
[So] Source:Tumour Biol;37(9):12411-12422, 2016 Sep.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Radiotherapy is widely used for advanced rectal tumors. However, tumor recurrence after this treatment tends to be more aggressive and is associated with a poor prognosis. Uncovering the molecular mechanism that controls this recurrence is essential for developing new therapeutic applications. In the present study, we demonstrated that radiation increases the EphA4 activation level of the survivor progeny of colorectal cancer cells submitted to this treatment and that such activation promoted the internalization of a complex E-cadherin-EphA4, inducing cell-cell adhesion disruption. Moreover, EphA4 knockdown in the progeny of irradiated cells reduced the migratory and invasive potentials and metalloprotease activity induced by irradiation. Finally, we demonstrated that the cell migration and invasion potential were regulated by AKT and ERK1/2 signaling, with the ERK1/2 activity being dependent on EphA4. In summary, our study demonstrates that these signaling pathways could be responsible for the therapeutic failure, thereby promoting local invasion and metastasis in rectal cancer after radiotherapy. We also postulate that EphA4 is a potential therapeutic target for colorectal cancer treatment.
[Mh] Termos MeSH primário: Neoplasias Colorretais/radioterapia
Receptor EphA4/fisiologia
Transdução de Sinais/fisiologia
[Mh] Termos MeSH secundário: Caderinas/análise
Neoplasias Colorretais/patologia
Doxazossina/farmacologia
MAP Quinases Reguladas por Sinal Extracelular/fisiologia
Células HT29
Seres Humanos
Invasividade Neoplásica
Proteínas Proto-Oncogênicas c-akt/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CDH1 protein, human); 0 (Cadherins); EC 2.7.10.1 (Receptor, EphA4); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); NW1291F1W8 (Doxazosin)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160622
[St] Status:MEDLINE


  10 / 1216 MEDLINE  
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[PMID]:27260129
[Au] Autor:Cao Y; Wang Y; Guo L; Yang X; Chen T; Niu H
[Ad] Endereço:Department of Urology, Qingdao University Affiliated Hospital, Qingdao, Shandong, China (mainland).
[Ti] Título:A Randomized, Open-Label, Comparative Study of Efficacy and Safety of Tolterodine Combined with Tamsulosin or Doxazosin in Patients with Benign Prostatic Hyperplasia.
[So] Source:Med Sci Monit;22:1895-902, 2016 Jun 04.
[Is] ISSN:1643-3750
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND Benign prostatic hyperplasia (BPH), a common disease in men over age 50 years, often causes bladder outlet obstruction and lower urinary tract symptoms (LUTS). Alpha blockers in combination with muscarinic receptor antagonists may have the potential to improve symptoms. This study aimed to assess the efficacy and safety of doxazosin or tamsulosin combined with tolterodine extend release (ER) in patients with BPH and LUTS. MATERIAL AND METHODS In a prospective, randomized, open-label study (ChiCTR-IPR-15005763), 220 consecutive men with BPH and LUTS were allocated to receive doxazosin 4 mg and tolterodine ER 4 mg per day (doxazosin group) or tamsulosin 0.2 mg and tolterodine ER 4 mg per day (tamsulosin group). Treatment lasted 12 weeks. The primary endpoint was the international prostatic symptom score (IPSS). Secondary endpoints were quality of life (QoL) and maximum flow rate (Qmax), which were evaluated at 0, 6, and 12 weeks, and urodynamic parameters assessed at 0 and 12 weeks. RESULTS A total of 192 patients completed the trial. Baseline measurements showed no differences between the groups. After 6 weeks, IPSS improved in both groups and QoL was significantly better in the doxazosin group (P=0.01). After 12 weeks, Qmax, IPSS, QoL, intravesical pressure (Pves), and bladder compliance (BC) in the doxazosin group were significantly better than in the tamsulosin group (P=0.03, P<0.001, P<0.001, P=0.027, and P=0.044, respectively). CONCLUSIONS Administration of alpha blockers combined with muscarinic receptor blocker for 12 weeks improved LUTS in men with BPH.
[Mh] Termos MeSH primário: Doxazossina/uso terapêutico
Hiperplasia Prostática/tratamento farmacológico
Sulfonamidas/uso terapêutico
Tartarato de Tolterodina/uso terapêutico
[Mh] Termos MeSH secundário: Antagonistas Adrenérgicos alfa/uso terapêutico
Idoso
Quimioterapia Combinada
Seres Humanos
Masculino
Meia-Idade
Estudos Prospectivos
Qualidade de Vida
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Adrenergic alpha-Antagonists); 0 (Sulfonamides); 5T619TQR3R (Tolterodine Tartrate); G3P28OML5I (tamsulosin); NW1291F1W8 (Doxazosin)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170303
[Lr] Data última revisão:
170303
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160605
[St] Status:MEDLINE



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