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增强泌尿系统癌症治疗效果:利用血管舒张剂与5-氟尿嘧啶的协同潜力以改善治疗结果。

Enhancing Urological Cancer Treatment: Leveraging Vasodilator Synergistic Potential with 5-FU for Improved Therapeutic Outcomes.

作者信息

Ribeiro Eduarda, Costa Barbara, Marques Lara, Vasques-Nóvoa Francisco, Vale Nuno

机构信息

PerMed Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.

CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal.

出版信息

J Clin Med. 2024 Jul 14;13(14):4113. doi: 10.3390/jcm13144113.

DOI:10.3390/jcm13144113
PMID:39064153
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11277888/
Abstract

: This study investigates the potential of vasodilator drugs as additive therapy in the treatment of urological cancers, particularly in combination with the antineoplastic agent 5-fluorouracil (5-FU). : The study evaluated the cytotoxic effects of sildenafil, tezosentan and levosimendan alone and in combination with 5-FU on urological cancer cell lines. The assessment included MTT assays, colony formation assays and wound healing assays to determine cell viability, proliferative capacity, and migratory behavior, respectively. : Sildenafil and tezosentan showed limited cytotoxic effects, while levosimendan demonstrated moderate anticancer activity. The combination of levosimendan and 5-FU exhibited an additive interaction, enhancing cytotoxicity against cancer cells while sparing normal cells. Levosimendan also inhibited cell migration and proliferation, potentially through mechanisms involving the modulation of cAMP levels and nitric oxide production. : The findings suggest that levosimendan can be used in conjunction with 5-FU to reduce the required dose of 5-FU, thereby minimizing side effects without compromising therapeutic efficacy. This study offers a new perspective for enhancing therapeutic outcomes in patients with urological cancers.

摘要

本研究探讨血管扩张剂药物作为辅助治疗手段用于治疗泌尿系统癌症的潜力,特别是与抗肿瘤药物5-氟尿嘧啶(5-FU)联合使用时的潜力。本研究评估了西地那非、替唑生坦和左西孟旦单独使用以及与5-FU联合使用对泌尿系统癌细胞系的细胞毒性作用。评估包括MTT试验、集落形成试验和伤口愈合试验,分别用于确定细胞活力、增殖能力和迁移行为。西地那非和替唑生坦显示出有限的细胞毒性作用,而左西孟旦表现出中等程度的抗癌活性。左西孟旦与5-FU联合使用表现出相加作用,增强了对癌细胞的细胞毒性,同时对正常细胞具有保护作用。左西孟旦还抑制细胞迁移和增殖,可能是通过涉及调节环磷酸腺苷(cAMP)水平和一氧化氮生成的机制实现的。研究结果表明,左西孟旦可与5-FU联合使用,以降低5-FU的所需剂量,从而在不影响治疗效果的情况下将副作用降至最低。本研究为提高泌尿系统癌症患者的治疗效果提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/002e/11277888/6ec9f9098859/jcm-13-04113-g012.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/002e/11277888/a139dfe4baf5/jcm-13-04113-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/002e/11277888/122e5161b746/jcm-13-04113-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/002e/11277888/2b339b475176/jcm-13-04113-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/002e/11277888/74d3a1f81c53/jcm-13-04113-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/002e/11277888/6ec9f9098859/jcm-13-04113-g012.jpg

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本文引用的文献

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CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.
2
Understanding the Clinical Use of Levosimendan and Perspectives on its Future in Oncology.了解左西孟旦的临床应用及其在肿瘤学领域的未来前景。
Biomolecules. 2023 Aug 24;13(9):1296. doi: 10.3390/biom13091296.
3
Exploring the Role of Drug Repurposing in Bridging the Hypoxia-Depression Connection.
探索药物重新利用在弥合缺氧与抑郁症关联方面的作用。
Membranes (Basel). 2023 Sep 17;13(9):800. doi: 10.3390/membranes13090800.
4
Repurposing approved non-oncology drugs for cancer therapy: a comprehensive review of mechanisms, efficacy, and clinical prospects.重新利用已批准的非肿瘤学药物治疗癌症:机制、疗效和临床前景的综合综述。
Eur J Med Res. 2023 Sep 14;28(1):345. doi: 10.1186/s40001-023-01275-4.
5
Advancements in Drug Repurposing: Examples in Psychiatric Medications.药物再利用的进展:精神药物的实例。
Int J Mol Sci. 2023 Jul 1;24(13):11000. doi: 10.3390/ijms241311000.
6
Prediction of CYP-Mediated Drug Interaction Using Physiologically Based Pharmacokinetic Modeling: A Case Study of Salbutamol and Fluvoxamine.使用基于生理的药代动力学模型预测细胞色素P450介导的药物相互作用:沙丁胺醇与氟伏沙明的案例研究
Pharmaceutics. 2023 May 24;15(6):1586. doi: 10.3390/pharmaceutics15061586.
7
Insights into Urologic Cancer.泌尿系统癌症洞察
Cancers (Basel). 2023 Jun 8;15(12):3108. doi: 10.3390/cancers15123108.
8
Repurposing of the Drug Tezosentan for Cancer Therapy.将药物替唑生坦重新用于癌症治疗。
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The Involvement of Hypoxia in the Response of Neuroblastoma Cells to the Exposure of Atorvastatin.缺氧在神经母细胞瘤细胞对阿托伐他汀暴露反应中的作用
Curr Issues Mol Biol. 2023 Apr 11;45(4):3333-3346. doi: 10.3390/cimb45040218.
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The Effects of the Levosimendan Metabolites OR-1855 and OR-1896 on Endothelial Pro-Inflammatory Responses.左西孟旦代谢物OR-1855和OR-1896对内皮促炎反应的影响。
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