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ContextZD4054 is a specific endothelin A (ETA) receptor antagonist being investigated for the treatment of hormone-resistant prostate cancer (HRPC). ZD4054 binds specifically to the ETA receptor, with no detectable activity at the ETB receptor. In preclinical studies, ZD4054 inhibited endothelin (ET-1)-mediated changes in cellular invasiveness in vitro, and inhibited angiogenesis and growth of tumour xenografts in vivo. Consistent with its specific binding profile, ZD4054 inhibited ETA-receptor-mediated antiapoptotic events while allowing ETB-receptor-mediated proapoptotic signalling.Evidence acquisitionThe preclinical and clinical activity of ZD4054 is reviewed.Evidence synthesisIn the clinical setting, stable levels of circulating ET-1 following single ZD4054 doses up to 240 mg demonstrated the absence of ZD4054 activity at the ETB receptor. ZD4054 is cleared principally via the urine, with a terminal elimination half-life of approximately 8–12 hours and with little accumulation after once-daily oral dosing.In a Phase 2 trial, patients with metastatic HRPC who were pain free or mildly symptomatic for pain were randomized to once-daily oral tablets of ZD4054 10 mg (n = 107), or 15 mg (n = 98), or matched placebo (n = 107). ZD4054 was generally well tolerated in this population, with an adverse effect profile consistent with its known pharmacological activity. The most common adverse effects were headache, peripheral oedema and nasal congestion. At the primary analysis there was no statistically significant difference in time to progression between the ZD4054-treated groups and placebo (hazard ratio [HR]: ZD4054 10 mg, 0.88 [80% CI 0.71, 1.09]; ZD4054 15 mg, 0.83 [0.66, 1.03]). However, a promising signal for prolonged overall survival was observed, which was sustained at a subsequent analysis (HR versus placebo: ZD4054 10 mg, 0.55 [80% CI 0.41, 0.73]; ZD4054 15 mg, 0.65 [0.49, 0.86]).ConclusionsThese results support the strategy of targeting the ETA receptor in prostate cancer, and mandate further investigation of ZD4054 in Phase 3 clinical trials. 相似文献
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马金华 《中国药物应用与监测》2009,6(1):63-63
1临床资料
患者,女,43岁,因车祸致右胫腓骨骨折入住我院创伤骨科,一般情况良好,无食物、药物过敏史,入院后行腓骨复位固定术,3d后,伤口红肿并有脓液渗出,为预防和控制感染,静脉滴注硫酸奈替米星葡萄糖注射液每日200mL(每瓶100mL,硫酸奈替米星10万u,约相当于0.1g,葡萄糖5.0g,山东鲁抗辰欣药业有限公司,批号0803155209)分两次滴注,中间滴注含有4mL复方维生素注射液的10%葡萄糖注射液500mL(四川美大康佳乐有限公司,批号080125124)。 相似文献
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David Jiménez Castro Gema Díaz David Martí Carlos Escobar Javier Ortega Sergio García-Rull Joaquin Picher Antonio Sueiro 《Blood coagulation & fibrinolysis》2007,18(2):173-177
This study aimed to determine whether a weight-adjusted dose of subcutaneous enoxaparin is as effective and safe as oral acenocoumarol for the secondary prophylaxis of pulmonary embolism. Three hundred and eighty consecutive noncancer outpatients hospitalized with an episode of symptomatic pulmonary embolism selected treatment with acenocoumarol or enoxaparin at a dose of 1 mg/kg once daily after being informed of the type of administration and expected frequency of laboratory monitoring for both medicinal products. Endpoints were symptomatic recurrent thromboembolic events evaluated by standard objective testing, and a composite endpoint of recurrent venous thromboembolism, major bleeding, and death from any cause. One hundred and ninety-nine patients (52%) chose acenocoumarol therapy and 181 chose enoxaparin monotherapy. Four patients in the enoxaparin group (2.2%) and six patients in the acenocoumarol group (3%) had an objective thromboembolic recurrence (hazard ratio, 1.35; 95% confidence interval, 0.38-4.79; P = 0.64). Nine patients in the enoxaparin group (5.0%) had a hemorrhagic complication compared with 11 in the acenocoumarol group (5.5%) (P = 0.81). The hospital length of stay was shorter with enoxaparin compared with acenocoumarol (11 versus 16 days, P = 0.0001). Enoxaparin is as effective and safe as acenocoumarol in the secondary prevention of recurrent thromboembolic disease and is associated with shorter hospitalization. 相似文献
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在深静脉血栓—肺栓塞病程中腔静脉滤器的应用价值分析 总被引:1,自引:1,他引:0
目的:探讨腔静脉滤器(Vena cava filter VCF)在深静脉血栓(Deep venous thrombosis DVT)—肺栓塞(Pulmonary embolism PE)病程中的应用价值。方法:结合本组25例高危深静脉血栓一肺栓塞患者,对其中24例置放5种构型的永久型或临时型下腔静脉滤器(IVCF)26枚的临床疗效、影响病程与预后因素及病生理改变,复习文献分析讨论。结果:DVT有可能脱落导致PE或致死性肺栓塞;置放IVCF可有效预防肺栓塞,早期进行溶栓治疗,改变预后。结论:严格按适应证植入IVCF,对DVT—PE的早期治疗和预防致死性肺栓塞有重要意义,但其应用价值需进行综合评价和进一步探讨。 相似文献
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α-平滑肌肌动蛋白和β-肌动蛋白在瘢痕组织中的表达 总被引:4,自引:0,他引:4
目的 探讨α-平滑肌肌动蛋白(α-SMA)和β-肌动蛋白(β-actin)对增生性瘢痕形成的可能作用。方法 采用荧光定量PCR法检测10例增生性瘢痕和10例正常皮肤组织中α-SMA和β-actin的表达水平。结果 增生性瘢痕组织中α-SMA和β-actin表达水平均高于正常皮肤组织,差异有统计学意义(P<0.01)。结论 α-SMA和β-actin在瘢痕增生中起重要作用;由于β-actin在瘢痕组织和正常皮肤中的不恒定性,建议在瘢痕的mRNA定量研究中不作为内参照物。 相似文献
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