doxazosin

多沙唑嗪
  • 文章类型: Journal Article
    良性前列腺增生是男性最常见的疾病之一,50多岁的患病率为50%,80多岁的患病率为80%,主要是用慢性药物治疗。这项研究的目的是分析2008年至2021年向HALMED报告的良性前列腺增生(BPH)治疗药物的不良反应(ADR)。克罗地亚的ADR报告数据来自VigiFlow国家数据库,克罗地亚的BPH药物使用数据来自HALMED的药物利用报告。在观察期间,每种BPH药物的报告数量,报告总数,报告的ADR的严重性,患者年龄和性别,记者的类型,并对大多数报告的ADR进行了分析。结果显示,共收到438份ADR报告,其中45.95%的坦索罗辛作为BPH最常用的药物。在所有报告中,84%是非严重的,男性报告了96%,45岁以上的患者报告了82%。最常报告的不良反应与BPH药物的已知安全性一致。药剂师是BPH药物ADR的最常见(47%)报告者,而33%是由医生报告的。对报告的ADR的分析表明,最常报告的ADR与BPH药物的已知安全性一致。然而,鉴于该疾病的患病率和BPH药物的使用程度,可以说,报告的数量可能会更高(即,34份报告/年)。报告药品不良反应是必要的,以更好地了解药物在授权后期间的安全性。通过提高医疗保健专业人员的认识,可以收集更多关于药物安全使用的信息。
    Benign prostatic hyperplasia is one of the most common diseases in men, with a prevalence rate of 50% in their 50s to 80% in their 80s, and is mostly treated with chronic drug therapy. The aim of this study was to analyze adverse drug reactions (ADR) to drugs used in benign prostate hyperplasia (BPH) treatment reported to HALMED from 2008 to 2021. Data on ADR reports in Croatia were obtained from the VigiFlow national database and on the use of drugs for BPH in Croatia from Drug Utilization Reports from HALMED. In the observed period, the number of reports on each BPH drug, total number of reports, seriousness of reported ADR, patient age and sex, type of reporter, and most reported ADRs were analyzed. Results showed that 438 ADR reports were received, of which 45.95% on tamsulosin as the most frequently used drug for BPH. Of all reports, 84% were non-serious, 96% were reported in men and 82% in patients older than 45 years. The most frequently reported ADRs were consistent with the known safety profile of BPH drugs. Pharmacists were the most common (47%) reporters of ADRs for BPH drugs, while 33% were reported by physicians. Analysis of the reported ADRs showed that most frequently reported ones were in line with the known safety profile of BPH drugs. However, given the prevalence of the disease and the extent of the use of BPH drugs, it could be argued that the number of reports could be higher (i.e., 34 reports/year). Reporting on ADRs is necessary to better understand the safety profile of drugs in the post-authorization period, and more information on the safe use of medicines could be collected by raising awareness of healthcare professionals.
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  • 文章类型: Journal Article
    目标:特拉唑嗪,多沙唑嗪,和阿夫唑嗪(Tz/Dz/Az)是α-1肾上腺素能受体拮抗剂,其也结合并激活糖酵解中的关键三磷酸腺苷(ATP)产生酶。据推测,大脑中能量可用性的增加可能会减缓或预防神经变性,可能通过减少α-突触核蛋白的积累。最近的工作表明,在动物和人类研究中,在帕金森氏症中使用Tz/Dz/Az具有潜在的神经保护作用。我们研究了Tz/Dz/Az在密切相关的疾病中的神经保护作用。路易体痴呆(DLB)。
    方法:我们在MerativeMarketscan数据库中使用了新的用户主动比较器设计,以识别新开始服用Tz/Dz/Az或2种比较药物的无DLB病史的男性。我们的比较药物是其他通常用于治疗良性前列腺增生但不增加ATP的药物:α-1肾上腺素能受体拮抗剂坦索罗辛或5α-还原酶抑制剂(5ARI)。我们在倾向评分和随访时间上对队列进行了匹配。我们对匹配的队列进行了随访,以使用Cox比例风险回归评估发展为DLB的风险。
    结果:新开始使用Tz/Dz/Az的男性患DLB的风险低于服用坦索罗辛的匹配男性(n=242,716,728,256人年,危险比[HR]0.60,95%CI0.50-0.71)或5ARI(n=130,872,399,316人年,HR0.73,95%CI0.57-0.93)。而服用坦索罗辛的男性的危害与服用5ARI的男性相似(n=159,596,482,280人年,HR1.17,95%CI0.96-1.42)。这些结果对一些敏感性分析是稳健的。
    结论:我们发现服用Tz/Dz/Az的男性与服用其他药物的类似男性相比,DLB的危害更低。当结合Tz/Dz/Az关于帕金森病的文献,我们的研究结果表明,糖酵解增强药物在神经退行性突触核蛋白病中可能具有广泛的保护作用.未来需要一项随机试验来评估这些因果关系。
    方法:本研究提供了III类证据,证明使用Tz/Dz/Az可降低成年男性患DLB的比率。
    OBJECTIVE: Terazosin, doxazosin, and alfuzosin (Tz/Dz/Az) are α-1 adrenergic receptor antagonists that also bind to and activate a key adenosine triphosphate (ATP)-producing enzyme in glycolysis. It is hypothesized that the increase in energy availability in the brain may slow or prevent neurodegeneration, potentially by reducing the accumulation of alpha-synuclein. Recent work has suggested a potentially neuroprotective effect of the use of Tz/Dz/Az in Parkinson disease in both animal and human studies. We investigated the neuroprotective effects of Tz/Dz/Az in a closely related disease, dementia with Lewy bodies (DLB).
    METHODS: We used a new-user active comparator design in the Merative Marketscan database to identify men with no history of DLB who were newly started on Tz/Dz/Az or 2 comparator medications. Our comparator medications were other drugs commonly used to treat benign prostatic hyperplasia that do not increase ATP: the α-1 adrenergic receptor antagonist tamsulosin or 5α-reductase inhibitor (5ARI). We matched the cohorts on propensity scores and duration of follow-up. We followed up the matched cohorts forward to estimate the hazard of developing DLB using Cox proportional hazards regression.
    RESULTS: Men who were newly started on Tz/Dz/Az had a lower hazard of developing DLB than matched men taking tamsulosin (n = 242,716, 728,256 person-years, hazard ratio [HR] 0.60, 95% CI 0.50-0.71) or 5ARI (n = 130,872, 399,316 person-years, HR 0.73, 95% CI 0.57-0.93). while the hazard in men taking tamsulosin was similar to that of men taking 5ARI (n = 159,596, 482,280 person-years, HR 1.17, 95% CI 0.96-1.42). These results were robust to several sensitivity analyses.
    CONCLUSIONS: We find an association in men who are taking Tz/Dz/Az and a lower hazard of DLB compared with similar men taking other medications. When combined with the literature of Tz/Dz/Az on Parkinson disease, our findings suggest that glycolysis-enhancing drugs may be broadly protective in neurodegenerative synucleinopathies. A future randomized trial is required to assess these associations for causality.
    METHODS: This study provides Class III evidence that Tz/Dz/Az use reduces the rate of developing DLB in adult men.
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  • 文章类型: Journal Article
    最近的研究试图在良性前列腺增生(BPH)中使用α-1-肾上腺素能受体拮抗剂(A1ARAs)与PD风险之间建立关联。该研究的目的是比较特拉唑嗪/阿夫唑嗪/多沙唑嗪(TZ/AZ/DZ)使用者和坦索罗辛使用者患帕金森病(PD)的风险。
    PubMed,谷歌学者,和Embase从成立之初到2023年4月进行了系统搜索。荟萃分析包括比较使用不同类型A1ARAs的患者的PD风险的观察性研究。主要结果是两个不同类别的A1ARAs使用者发生PD的风险比(HR),CI为95%。
    这项研究基于总共678.433名BPH患者,其中287.080例患者属于TZ/AZ/DZ队列,391.353例患者属于坦索罗辛队列。坦索罗辛使用者的合并PD发病率较高(1.28%,95%CI:1.04-1.55%)比TZ/AZ/DZ吸毒者(1.11%,95%CI:0.83-1.42%)。服用TZ/AZ/DZ的患者发生PD的风险明显低于坦索罗辛(n=610,363,HR=0.82,95%CI=0.71-0.94,P=0.01;I2=87.4%)。
    这项荟萃分析表明,服用TZ/AZ/DZ的BPH患者发生PD的风险低于服用坦索罗辛的患者。
    UNASSIGNED: Recent studies have tried to establish an association between the use of alpha-1-adrenergic receptor antagonists (A1ARAs) used in benign prostatic hyperplasia (BPH) and the risk of PD. The objective of the study is to compare the risk of Parkinson\'s disease (PD) between terazosin/alfuzosin/doxazosin (TZ/AZ/DZ) users and tamsulosin users.
    UNASSIGNED: PubMed, Google Scholar, and Embase were systematically searched from inception to April 2023. Observational studies comparing the risk of PD among patients using different types of A1ARAs were included in the meta-analysis. The primary outcome was the hazard ratio (HR) with a 95% CI for the risk of occurrence of PD among A1ARAs users of two different classes.
    UNASSIGNED: This study was based on a total of 678 433 BPH patients, out of which 287 080 patients belonged to the TZ/AZ/DZ cohort and 391 353 patients belonged to the tamsulosin cohort. The pooled incidence of PD was higher in tamsulosin users (1.28%, 95% CI: 1.04-1.55%) than in TZ/AZ/DZ drug users (1.11%, 95% CI: 0.83-1.42%). The risk of occurrence of PD was significantly lower in patients taking TZ/AZ/DZ than tamsulosin (n= 610,363, HR = 0.82, 95% CI = 0.71-0.94, P = 0.01; I2 = 87.4%).
    UNASSIGNED: This meta-analysis demonstrated that patients with BPH who take TZ/AZ/DZ have a lower risk for developing PD than those who take tamsulosin.
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  • 文章类型: Journal Article
    背景:本研究调查了热休克蛋白27(HSP27)的表达,细胞FLICE样抑制蛋白(cFLIP),和聚集素(CLU)影响癌细胞的进展及其对多沙唑嗪诱导的凋亡的敏感性。通过单独沉默这些基因中的每一个,研究了其对多沙唑嗪治疗后前列腺癌细胞活力的影响.方法:培养PC-3前列腺癌细胞,然后使用靶向HSP27,cFLIP的siRNA进行基因沉默,和CLU,无论是单独的,成对,或全部在一起。然后用各种浓度的多沙唑嗪处理细胞,并通过MTT测定评估它们的活力。结果:研究发现,沉默PC-3细胞中的CLU基因可显着降低25µM多沙唑嗪处理后的细胞活力。此外,cFLIP和CLU的双重沉默降低了10µM多沙唑嗪时的细胞活力。值得注意的是,沉默HSP27,cFLIP,即使在较低的多沙唑嗪浓度为1µM时,CLU也是最有效的,并且降低了细胞活力。结论:综合来看,这些结果表明,同时沉默的HSP27,cFLIP,和CLU基因可能是促进前列腺癌细胞凋亡的潜在策略,这可以为未来的恶性前列腺癌治疗研究提供信息。
    Background: This study investigated how the expression of heat shock protein 27 (HSP27), cellular FLICE-like inhibitory protein (cFLIP), and clusterin (CLU) affects the progression of cancer cells and their susceptibility to doxazosin-induced apoptosis. By silencing each of these genes individually, their effect on prostate cancer cell viability after doxazosin treatment was investigated. Methods: PC-3 prostate cancer cells were cultured and then subjected to gene silencing using siRNA targeting HSP27, cFLIP, and CLU, either individually, in pairs, or all together. Cells were then treated with doxazosin at various concentrations and their viability was assessed by MTT assay. Results: The study found that silencing the CLU gene in PC-3 cells significantly reduced cell viability after treatment with 25 µM doxazosin. In addition, the dual silencing of cFLIP and CLU decreased cell viability at 10 µM doxazosin. Notably, silencing all three genes of HSP27, cFLIP, CLU was most effective and reduced cell viability even at a lower doxazosin concentration of 1 µM. Conclusions: Taken together, these findings suggest that the simultaneous silencing of HSP27, cFLIP, and CLU genes may be a potential strategy to promote apoptosis in prostate cancer cells, which could inform future research on treatments for malignant prostate cancer.
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  • 文章类型: Journal Article
    肺癌是全球癌症相关死亡的主要原因,约85%的肺癌是非小细胞肺癌(NSCLC),5年总生存率低,死亡率高。已经开发了几种治疗策略,比如靶向治疗,免疫肿瘤治疗和联合治疗。然而,低生存率表明迫切需要新的NSCLC治疗.血管生成拟态(VM)是在肿瘤新血管形成过程中存在的侵袭性和转移性肿瘤细胞的无内皮细胞肿瘤血液供应系统。VM在临床上负责肿瘤转移和耐药,并且与NSCLC的不良预后相关,使其成为潜在的治疗靶点。在本研究中,A549细胞形成富含糖蛋白的内衬管状结构,VM相关基因的转录水平在VM形成细胞中显著上调。基于药物再利用策略,研究表明,在非细胞毒性浓度下,多沙唑嗪(一种抗高血压药物)对VM形成显示抑制活性.在VM形成过程中,多沙唑嗪显着降低了细胞培养基中血管内皮生长因子A(VEGF-A)和基质金属蛋白酶2(MMP-2)的水平。进一步的实验表明,VEGF-A和血管内皮钙粘蛋白(VE-cadherin)的蛋白表达水平,这有助于肿瘤的侵袭性和VM的形成,在多沙唑嗪治疗后下调。此外,下游信号EphrinA型受体2(EphA2)/AKT/mTOR/MMP/层粘连蛋白-5γ2网络在多沙唑嗪治疗后受到抑制.总之,本研究表明,多沙唑嗪通过下调VEGF-A和VE-cadherin水平在NSCLC细胞模型中显示出抗VM活性,以及与受体酪氨酸激酶相关的信号通路的抑制,EphA2,蛋白激酶,AKT和mTOR,和蛋白酶,MMP-2和MMP-9。这些结果支持多沙唑嗪作为抗NSCLC的潜在药物的附加抗VM作用。
    Lung cancer is the leading cause of cancer-related death worldwide, and ~85% of lung cancers are non-small cell lung cancer (NSCLC), which has a low 5-year overall survival rate and high mortality. Several therapeutic strategies have been developed, such as targeted therapy, immuno-oncotherapy and combination therapy. However, the low survival rate indicates the urgent need for new NSCLC treatments. Vasculogenic mimicry (VM) is an endothelial cell-free tumor blood supply system of aggressive and metastatic tumor cells present during tumor neovascularization. VM is clinically responsible for tumor metastasis and resistance, and is correlated with poor prognosis in NSCLC, making it a potential therapeutic target. In the present study, A549 cells formed glycoprotein-rich lined tubular structures, and transcript levels of VM-related genes were markedly upregulated in VM-forming cells. Based on a drug repurposing strategy, it was demonstrated that doxazosin (an antihypertensive drug) displayed inhibitory activity on VM formation at non-cytotoxic concentrations. Doxazosin significantly reduced the levels of vascular endothelial growth factor A (VEGF-A) and matrix metalloproteinase-2 (MMP-2) in the cell media during VM formation. Further experiments revealed that the protein expression levels of VEGF-A and vascular endothelial-cadherin (VE-cadherin), which contribute to tumor aggressiveness and VM formation, were downregulated following doxazosin treatment. Moreover, the downstream signaling Ephrin type-A receptor 2 (EphA2)/AKT/mTOR/MMP/Laminin-5γ2 network was inhibited in response to doxazosin treatment. In conclusion, the present study demonstrated that doxazosin displayed anti-VM activity in an NSCLC cell model through the downregulation of VEGF-A and VE-cadherin levels, and the suppression of signaling pathways related to the receptor tyrosine kinase, EphA2, protein kinases, AKT and mTOR, and proteases, MMP-2 and MMP-9. These results support the add-on anti-VM effect of doxazosin as a potential agent against NSCLC.
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  • 文章类型: Journal Article
    背景:先前已经报道了地塞米松诱导的神经毒性。然而,分子机制仍未完全了解。
    目的:本研究旨在研究α-和β-肾上腺素受体对地塞米松所致大鼠神经毒性的调节作用,重点是β-arrestin2和大脑皮质神经损伤分子标志物的变化。
    方法:雄性Wistar大鼠皮下注射地塞米松(10mg/kg/天)7天,引起大脑皮质神经损伤。实验涉及5组:对照组,地塞米松,卡维地洛,普萘洛尔,还有多沙唑嗪.在最后三组中,地塞米松注射前2小时给予药物治疗.实验结束时,收集脑样本用于测量脑源性神经营养因子(BDNF),胶质纤维酸性蛋白(GFAP),蛋白激酶B(Akt)的激酶活性,二酰基甘油(DAG),α-平滑肌肌动蛋白(α-SMA),Smad3,β-淀粉样蛋白和磷酸-tau蛋白水平,除了使用苏木精-伊红对脑组织进行组织病理学检查外,Nissl,和小天狼星的红色污渍。此外,使用免疫组织化学检查测量大脑皮层中的β-arrestin2水平。
    结果:地塞米松轻微减轻脑重量,显著降低BDNF,Akt激酶活性和β-arrestin2但显著诱导皮层神经元变性和显著增加GFAP,DAG,α-SMA,与对照相比,Smad3、β-淀粉样蛋白和磷酸-tau蛋白水平。卡维地洛,普萘洛尔,多沙唑嗪逆转了所有地塞米松诱导的分子变化,并轻微改善了组织病理学变化。与地塞米松相比,卡维地洛显著增加脑重量和β-arrestin2水平,普萘洛尔,和多沙唑嗪组。
    结论:阻断α-和/或β-肾上腺素能受体减轻了地塞米松诱导的神经毒性,尽管它们对大脑皮质中的β-arrestin2水平有明显影响。
    BACKGROUND: Dexamethasone-induced neurotoxicity has been previously reported. However, the molecular mechanisms are still not completely understood.
    OBJECTIVE: The current work aimed to investigate the modulatory effects of α- and β-adrenergic receptors on dexamethasone-induced neurotoxicity in rats focused on changes in β-arrestin2 and molecular markers of neural injury in cerebral cortex.
    METHODS: Male Wistar rats were subcutaneously injected with dexamethasone (10 mg/kg/day) for 7 days to induce neural injury in the cerebral cortex. The experiment involved 5 groups: control, dexamethasone, carvedilol, propranolol, and doxazosin. In the last 3 groups, drugs were given 2 hours before dexamethasone injection. At the end of experiment, brain samples were collected for measurement of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), kinase activity of protein kinase B (Akt), diacylglycerol (DAG), α-smooth muscle actin (α-SMA), Smad3, β-amyloid and phospho-tau protein levels in addition to histopathological examination of brain tissue using hematoxylin-eosin, Nissl, and Sirius red stains. Moreover, β-arrestin2 levels in the cerebral cortex were measured using immunohistochemical examination.
    RESULTS: Dexamethasone slightly reduced brain weight and significantly decreased BDNF, Akt kinase activity and β-arrestin2 but markedly induced degeneration of cortical neurons and significantly increased GFAP, DAG, α-SMA, Smad3, β-amyloid and phospho-tau protein levels compared to controls. Carvedilol, propranolol, and doxazosin reversed all dexamethasone-induced molecular changes and slightly ameliorated the histopathological changes. Carvedilol significantly increased brain weight and β-arrestin2 levels compared to dexamethasone, propranolol, and doxazosin groups.
    CONCLUSIONS: blocking α- and/or β-adrenergic receptors alleviate dexamethasone-induced neurotoxicity despite their distinct effects on β-arrestin2 levels in the cerebral cortex.
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  • 文章类型: Journal Article
    背景:三阴性乳腺癌(TNBC)的特征是侵袭性生长和高复发和转移倾向。在TNBC中c-MET和EGFR的同时过度表达与更差的临床病理特征和不利的结果相关。尽管新的c-MET抑制剂的开发和第三代EGFR抑制剂的出现代表了有希望的治疗选择,高昂的费用限制了这些药物的可获得性.在本研究中,我们试图研究多沙唑嗪(DOXA)的治疗潜力,一种治疗良性前列腺增生的仿制药,针对TNBC。
    方法:根据细胞活力评估DOXA对体外TNBC细胞系的影响,凋亡,c-MET/EGFR信号通路,分子对接研究及其对癌症干细胞(CSC)样特性的影响。使用具有CSC的体内转移模型来评估DOXA的功效。
    结果:DOXA通过激活caspase诱导细胞凋亡,对TNBC细胞具有显著的抗增殖作用。分子对接研究揭示了DOXA与c-MET和EGFR的酪氨酸激酶结构域的直接相互作用。因此,DOXA破坏了包括AKT在内的重要生存途径,MEK/ERK,和JAK/STAT3,同时抑制CSC样特征,包括CD44high/CD24low亚群,醛脱氢酶1(ALDH1)活性和乳腺球的形成。发现DOXA给药抑制肿瘤生长,具有CSC富集群体的原位同种异体移植模型中的肿瘤内和肿瘤周围血管生成和远处转移。此外,未观察到DOXA对肝或肾功能的毒性作用。
    结论:我们的发现强调了DOXA作为转移性TNBC的治疗选择的潜力,保证进一步调查。
    BACKGROUND: Triple-negative breast cancer (TNBC) is characterized by aggressive growth and a high propensity for recurrence and metastasis. Simultaneous overexpression of c-MET and EGFR in TNBC is associated with worse clinicopathological features and unfavorable outcomes. Although the development of new c-MET inhibitors and the emergence of 3rd-generation EGFR inhibitors represent promising treatment options, the high costs involved limit the accessibility of these drugs. In the present study, we sought to investigate the therapeutic potential of doxazosin (DOXA), a generic drug for benign prostate hyperplasia, in targeting TNBC.
    METHODS: The effect of DOXA on TNBC cell lines in vitro was evaluated in terms of cell viability, apoptosis, c-MET/EGFR signaling pathway, molecular docking studies and impact on cancer stem cell (CSC)-like properties. An in vivo metastatic model with CSCs was used to evaluate the efficacy of DOXA.
    RESULTS: DOXA exhibits notable anti-proliferative effects on TNBC cells by inducing apoptosis via caspase activation. Molecular docking studies revealed the direct interaction of DOXA with the tyrosine kinase domains of c-MET and EGFR. Consequently, DOXA disrupts important survival pathways including AKT, MEK/ERK, and JAK/STAT3, while suppressing CSC-like characteristics including CD44high/CD24low subpopulations, aldehyde dehydrogenase 1 (ALDH1) activity and formation of mammospheres. DOXA administration was found to suppress tumor growth, intra- and peri-tumoral angiogenesis and distant metastasis in an orthotopic allograft model with CSC-enriched populations. Furthermore, no toxic effects of DOXA were observed in hepatic or renal function.
    CONCLUSIONS: Our findings highlight the potential of DOXA as a therapeutic option for metastatic TNBC, warranting further investigation.
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  • 文章类型: Case Reports
    副神经节瘤是一种不太普遍的疾病,和仅分泌白细胞介素-6(IL-6)的副神经节瘤以前没有报道。一名64岁的男性患者带着发烧和心悸的主要投诉来到医院。峰值体温为38.7°C(101.66°F)。心率是110bpm,而血压在正常范围内。抗生素和抗病毒治疗无效。血IL-6、C反应蛋白(CRP)水平,碱性磷酸酶(ALP),血小板(PLT),谷氨酰转移酶(GGT),纤维蛋白原,D-二聚体均升高。传染病,自身免疫性疾病,和恶性血液病均被排除。近10年前,意外发现患者的腹膜后大肿块。幸运的是,定期随访后,过去10年没有出现特殊症状。这次入院后,进行PET-CT检查。在腹部和腹膜后区域的上部可见一个大的混杂密度肿块,并考虑了副神经节瘤的可能性。然而,血液和尿液儿茶酚胺及其代谢物包括肾上腺素的生化测定,去甲肾上腺素,3-甲氧基酪胺,甲氧基肾上腺素,甲氧基去甲肾上腺素,尽管多巴胺轻度升高,但扁桃酸和香草酸都在正常范围内。患者基因组DNA的全外显子组捕获和测序显示KIF1B基因编码位点的杂合突变(编码:NM_015047.3:c.460G>C,突变:p.Val1554Leu;染色体位置为chr1:10428570)。在KIF1B的该基因座处的突变以前没有报道过。患者拒绝手术治疗。因为肿块负担了包括胰腺在内的几个重要器官,手术的风险很高。然后向患者施用多沙唑嗪。服用多沙唑嗪后,症状迅速消失。体温在3天内恢复到正常范围。心率降至约90bpm。在接下来的日子里,IL-6,CPR,ALP,血小板,GGT纤维蛋白原,D-二聚体持续下降。服用多沙唑嗪63天后,IL-6水平完全正常。服药190天后,血红蛋白(Hb)和GGT水平也恢复到正常范围。发病1年后,病人再次接受了血液检查。包括IL-6在内的几乎所有血液指标均在正常范围内。
    Paraganglioma is a less prevalent disease, and paraganglioma with only secreting interleukin-6 (IL-6) has not been previously reported. A 64-year-old male patient came to the hospital with the chief complaints of fever and palpitations. The peak body temperature was 38.7°C (101.66°F). Heart rate was 110 bpm, while blood pressure was in the normal range. Antibiotics and antiviral therapies were ineffective. The levels of blood IL-6, C-reactive protein (CRP), alkaline phosphatase (ALP), platelets (PLT), glutamyltransferase (GGT), fibrinogen, and D-dimer were all elevated. Infectious diseases, auto-immune diseases, and hematological malignancy were all excluded. Nearly 10 years ago, a large retroperitoneal mass of the patient was detected by accident. Fortunately, there have been no special symptoms for the past 10 years after regular follow-up. After admission this time, PET-CT was performed. A large confounding density mass at the upper part of the abdominal and retroperitoneal area was seen, and the possibility of paraganglioma was considered. However, biochemical assays for blood and urine catecholamine and their metabolites including adrenaline, norepinephrine, 3-methoxytyramine, methoxyepinephrine, methoxynorepinephrine, and vanillylmandelic acid were all in normal range in spite of mild elevated dopamine with no significance. The whole-exome capture and sequencing of the genomic DNA of the patient showed a heterozygous mutation in the coding site of KIF1B gene (Coding: NM_015047.3:c.4660G>C, Mutation: p.Val1554Leu; chromosomal location was chr1: 10428570). The mutation at this locus of KIF1B has not been reported previously. The patient refused the surgical treatment. Because the mass burdens several important organs including the pancreas, the risk of surgery was high. Doxazosin was then administered to the patient. After taking doxazosin, the symptoms disappeared rapidly. Body temperature returned to normal range in 3 days. Heart rate decreased to approximately 90 bpm. In the following days, the levels of IL-6, CPR, ALP, platelets, GGT fibrinogen, and D-dimer continued to decrease. After 63 days of taking doxazosin, IL-6 level was completely normal. After 190 days of medication, hemoglobin (Hb) and GGT levels also returned to the normal range. After 1 year onset, the patient again underwent a blood test. Almost all blood indexes were in the normal range including IL-6.
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  • 文章类型: Journal Article
    背景:嗜铬细胞瘤(PHEO)和副神经节瘤(PGL)是以血流动力学不稳定为特征的罕见神经内分泌肿瘤,由儿茶酚胺的阵发性释放引起的。由于儿茶酚胺的大量释放,患者在围手术期可能会出现心血管并发症,特别是在肿瘤的麻醉诱导和手术操作期间。这项回顾性研究的目的是评估接受嗜铬细胞瘤手术的患者围手术期血流动力学不稳定的危险因素。
    方法:2011年1月至2016年12月,40名患者(中位年龄55[36.50-64.50])在AOUCareggi接受了PHEO/腹部PGL手术(佛罗伦萨,意大利)进行了回顾性评估。收缩压,舒张压,在基线和手术过程中考虑平均血压.手术前血压稳定<140/90mmHg的患者被认为是“充分准备”。术前使用多沙唑嗪治疗,选择性α-1阻断剂,所有患者在手术前至少14天开始。据报道存在血液动力学不稳定。
    结果:比较男性和女性,多沙唑嗪日剂量存在显着差异(p=0.018),收缩压(p=0.048),以及充分准备的患者比例(p=0.031)出现。术前每日剂量多沙唑嗪,肿瘤大小(B=0.60,p<0.001),还观察到尿中去甲肾上腺素水平(B=0.64,p<0.001)。30.0%的患者发生血流动力学不稳定。手术前没有足够的准备(p=0.012),尿中去甲肾上腺素水平(NMNurp=0.039),和手术时间(分钟)(p=0.021)是我们系列中血流动力学不稳定的危险因素。血流动力学不稳定患者术中药物使用率较高(p<0.001)。术前SBP水平>133mmHg(OR=6CI95%1.37-26.20,p=0.017),术中SBP和MBP水平>127mmHg(OR=28.80CI95%2.23-371.0,p=0.010)和>90mmHg(OR=18.90CI95%1.82-196.0,p=0.014),分别,被确定为识别高HI风险患者的有效阈值。
    结论:术前使用α-受体阻滞剂治疗是有用的,但不足以避免手术风险。NMNur术前水平较高的患者,术前SBP>133mmHg,和/或术中SBP>127mmHg和MBP>90mmHg,应该仔细监控。多学科方法对于优化PHEO/腹部PGL的管理以减少手术并发症是必不可少的。
    BACKGROUND: Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors characterized by hemodynamic instability, caused by the paroxysmal release of catecholamines. Patients may develop cardiovascular complications in the perioperative phase due to the massive release of catecholamines, particularly during anesthetic induction and surgical manipulation of the tumor. The aim of this retrospective study was to evaluate the risk factors involved in perioperative hemodynamic instability in patients who underwent surgery for chromaffin tumors.
    METHODS: Forty patients (median age 55 [36.50-64.50]) undergone surgery for PHEO/abdominal PGL from January 2011 to December 2016 at the AOU Careggi (Florence, Italy) were retrospectively evaluated. Systolic, diastolic, and mean blood pressure were considered at baseline and during surgery. Patients with blood pressure steadily < 140/90 mmHg before surgery were considered \"adequately prepared\". A preoperative therapy with doxazosin, a selective alpha-1 blocker, was started in all patients for at least 14 days prior to the surgery. The presence of hemodynamic instability was reported.
    RESULTS: Comparing males and females, a significant difference in doxazosin daily dose (p = 0.018), systolic blood pressure (p = 0.048), and in the proportion of adequately prepared patients (p = 0.031) emerged. A positive correlation between preoperative daily dose of doxazosin, tumor size (B = 0.60, p < 0.001), and urinary normetanephrine levels (B = 0.64, p < 0.001) was also observed. Hemodynamic instability occurred in 30.0% of patients. The absence of adequate preparation (p = 0.012) before surgery, urinary normetanephrine levels (NMNur p = 0.039), and surgery time (minutes) (p = 0.021) resulted as risk factors of hemodynamic instability in our series. The use of intraoperative drugs was higher in patients with hemodynamic instability (p < 0.001). A pre-surgical SBP level of > 133 mmHg (OR = 6 CI95% 1.37-26.20, p = 0.017) and an intraoperative SBP and MBP levels of > 127 mmHg (OR = 28.80 CI95% 2.23-371.0, p = 0.010) and > 90 mmHg (OR = 18.90 CI95% 1.82-196.0, p = 0.014), respectively, were identified as effective thresholds to recognize patients at higher risk of HI.
    CONCLUSIONS: A preoperative therapy with alpha-blockers is useful, but not sufficient to avoid surgical risks. Patients with higher pre-surgical levels of NMNur, pre-surgical SBP > 133 mmHg, and/or intraoperative SBP > 127 mmHg and MBP > 90 mmHg, should be carefully monitored. A multidisciplinary approach is indispensable to optimize the management of PHEOs/abdominal PGLs in order to reduce surgical complications.
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  • 文章类型: Journal Article
    口腔鳞状细胞癌(OSCC),一种全球性的威胁疾病,据报道,主要在中老年男性人群中。尽管OSCC的确切原因尚不清楚,据报道,大多数OSCC患者都食用任何形式的烟草。OSCC是一种巨大的侵袭性癌症,很容易扩散到远处的器官。因此,在适当的时间进行治疗是必要的,并且OSCC的发生率也在不断增加。目前,放化疗是针对OSCC患者的唯一处方疗法,会产生各种副作用。因此,副作用较小的治疗是目前的研究兴趣.多沙唑嗪(α1肾上腺素拮抗剂)已被证明可在前列腺中产生抗癌作用,肾,肝,和卵巢癌,但其在口腔癌细胞中的作用尚未阐明。因此,我们已经评估了多沙唑嗪通过诱导细胞凋亡对口腔鳞状细胞癌细胞的抗癌作用,和抗氧化性能。MTT法分析多沙唑嗪对正常Vero细胞的细胞保护作用和对口腔癌KB细胞的抗癌作用。通过FRAP方法,通过对自由基和金属离子的反应性来分析多沙唑嗪的抗氧化活性,DPPH,化学发光,和ORAC测定。抗氧化剂水平也通过TBARS评估,SOD,和谷胱甘肽水平,以及后来的细胞凋亡染色技术,如DCFH-DA,进行罗丹明123和AO/EtBr染色。通过ELISA方法估计多沙唑嗪处理的KB人口腔癌细胞中凋亡蛋白的水平来确认凋亡。我们的研究结果表明,多沙唑嗪是一种有效的抗氧化剂,它通过改变下游信号的各种细胞分子显着诱导人类口腔癌的细胞凋亡,这已在结果中描述。我们的研究证明多沙唑嗪是一种有效的抗癌药物,可用于口腔癌的治疗。如果使用人体临床试验进行进一步研究。
    Oral squamous cell carcinoma (OSCC), a global threatening disease, is reported mostly in the middle and elderly male population. Even though the exact cause of OSCC was not known, consumption of tobacco in any form has been reported in most of OSCC patients. OSCC is a massive invasive type of cancer which easily spreads to the distant organs. Hence treating it at appropriate time is necessary and the rate of OSCC incidence is also constantly increasing. At present, chemoradiation is the only therapy prescribed for OSCC patients which renders various side effects. Hence, the treatment with lesser side effect was of current research interest. Doxazosin (α1 adrenorecptor antagonist) had been proven to render anticancer effect in prostate, renal, hepatic, and ovarian cancers but its role in oral cancer cells was not been elucidated. Therefore, we have assessed the anticancer effect of doxazosin on oral squamous cancer cells via through the induction of apoptosis, and antioxidant property. The cytoprotective effect of doxazosin on normal Vero cells and anticancer effect on oral cancer KB cells were analyzed with MTT assay. Doxazosin antioxidant activity were analyzed by their reactivity with free radicals and metal ions by the method of FRAP, DPPH, chemilumiscence, and ORAC assay. The antioxidant levels were also assessed by TBARS, SOD, and glutathione levels, and later on apoptosis staining techniques like DCFH-DA, Rhodamine 123, and AO/EtBr stain were conducted. Apoptosis was confirmed by estimating the levels of apoptotic proteins in doxazosin-treated KB human oral cancer cells by ELISA method. The results from our study show that doxazosin is a potent antioxidant and it significantly induces apoptosis in human oral cancer by altering various cellular molecules at downstream signaling which has been depict in the results. Our study proves doxazosin as a potent anticancer drug which may be used in the treatment of oral carcinoma, if it is subjected to further research using human clinical trials.
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