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伊立替康的治疗效果增强与药物蓄积增加有关。

Augmented therapeutic efficacy of irinotecan is associated with enhanced drug accumulation.

机构信息

Department of Cancer Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.

出版信息

Cancer Lett. 2011 Dec 8;311(2):219-29. doi: 10.1016/j.canlet.2011.07.023. Epub 2011 Aug 6.

DOI:10.1016/j.canlet.2011.07.023
PMID:21872389
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3183362/
Abstract

The goal of this study is to determine whether treatment with methylselenocysteine (MSC) results in differential uptake of irinotecan and its active metabolite (SN-38) between tumors of head and neck squamous cell carcinomas and normal tissue. The in vivo synergy between MSC and irinotecan is influenced by treatment schedule and associated with enhancement of tumor vessel maturation, intra-tumor concentration of SN-38 and apoptotic death of tumor cells. Normal tissue drug concentrations were not impacted by selenium treatment. The finding is of clinical relevance for enabling the delivery of higher doses of irinotecan to reverse tumor resistance, recurrence and ultimately enhancing cure rates.

摘要

本研究旨在确定甲基硒代半胱氨酸 (MSC) 的治疗是否会导致头颈部鳞状细胞癌肿瘤和正常组织之间伊立替康及其活性代谢物 (SN-38) 的摄取存在差异。MSC 和伊立替康的体内协同作用受治疗方案的影响，并与增强肿瘤血管成熟、SN-38 在肿瘤内的浓度和肿瘤细胞的凋亡死亡有关。硒处理不会影响正常组织的药物浓度。这一发现对临床具有重要意义，因为它可以使更高剂量的伊立替康用于逆转肿瘤耐药、复发，并最终提高治愈率。

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1
Augmented therapeutic efficacy of irinotecan is associated with enhanced drug accumulation.伊立替康的治疗效果增强与药物蓄积增加有关。
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2
Potentiation of irinotecan sensitivity by Se-methylselenocysteine in an in vivo tumor model is associated with downregulation of cyclooxygenase-2, inducible nitric oxide synthase, and hypoxia-inducible factor 1alpha expression, resulting in reduced angiogenesis.在体内肿瘤模型中，硒代甲基硒代半胱氨酸增强伊立替康敏感性与环氧合酶-2、诱导型一氧化氮合酶和缺氧诱导因子1α表达下调相关，从而导致血管生成减少。
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3
Hypoxia-specific drug tirapazamine does not abrogate hypoxic tumor cells in combination therapy with irinotecan and methylselenocysteine in well-differentiated human head and neck squamous cell carcinoma a253 xenografts.在高分化人头颈鳞状细胞癌A253异种移植瘤中，缺氧特异性药物替拉扎明与伊立替康和甲基硒代半胱氨酸联合治疗时，并不会消除缺氧肿瘤细胞。
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本文引用的文献

1
Tumor vascular maturation and improved drug delivery induced by methylselenocysteine leads to therapeutic synergy with anticancer drugs.甲基硒代半胱氨酸诱导的肿瘤血管成熟及药物递送改善导致与抗癌药物产生治疗协同作用。
Clin Cancer Res. 2008 Jun 15;14(12):3926-32. doi: 10.1158/1078-0432.CCR-08-0212.
2
Irinotecan pharmacokinetic and pharmacogenomic alterations induced by methylselenocysteine in human head and neck xenograft tumors.甲基硒代半胱氨酸在人源头颈异种移植瘤中诱导的伊立替康药代动力学和药物基因组学改变
Mol Cancer Ther. 2005 May;4(5):843-54. doi: 10.1158/1535-7163.MCT-04-0315.
3
Lack of microvessels in well-differentiated regions of human head and neck squamous cell carcinoma A253 associated with functional magnetic resonance imaging detectable hypoxia, limited drug delivery, and resistance to irinotecan therapy.
可药物治疗的生物标志物在透明细胞肾细胞癌中的改变：基于机制的联合治疗的开发策略。
Int J Mol Sci. 2023 Jan 4;24(2):902. doi: 10.3390/ijms24020902.
4
Potential Role of Selenium in the Treatment of Cancer and Viral Infections.硒在癌症和病毒感染治疗中的潜在作用。
Int J Mol Sci. 2022 Feb 17;23(4):2215. doi: 10.3390/ijms23042215.
5
Non-Coding Micro RNAs and Hypoxia-Inducible Factors Are Selenium Targets for Development of a Mechanism-Based Combination Strategy in Clear-Cell Renal Cell Carcinoma-Bench-to-Bedside Therapy.非编码 microRNAs 和缺氧诱导因子是硒在开发用于透明细胞肾细胞癌的基于机制的联合治疗策略中的靶点——从基础到临床的研究。
Int J Mol Sci. 2018 Oct 29;19(11):3378. doi: 10.3390/ijms19113378.
6
Selenium targets resistance biomarkers enhancing efficacy while reducing toxicity of anti-cancer drugs: preclinical and clinical development.硒靶向耐药生物标志物，提高抗癌药物疗效并降低毒性：临床前和临床开发
Oncotarget. 2018 Jan 23;9(12):10765-10783. doi: 10.18632/oncotarget.24297. eCollection 2018 Feb 13.
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Selenium compounds, apoptosis and other types of cell death: an overview for cancer therapy.硒化合物、细胞凋亡及其他类型的细胞死亡：癌症治疗概述
Int J Mol Sci. 2012;13(8):9649-9672. doi: 10.3390/ijms13089649. Epub 2012 Aug 2.
在人类头颈部鳞状细胞癌A253的高分化区域微血管缺乏，这与功能磁共振成像可检测到的缺氧、有限的药物递送以及对伊立替康治疗的耐药性相关。
Clin Cancer Res. 2004 Dec 1;10(23):8005-17. doi: 10.1158/1078-0432.CCR-04-1306.
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Clin Cancer Res. 2004 Apr 1;10(7):2561-9. doi: 10.1158/1078-0432.ccr-03-0268.
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Therapeutic synergy between irinotecan and 5-fluorouracil against human tumor xenografts.伊立替康与5-氟尿嘧啶对人肿瘤异种移植瘤的治疗协同作用。
Clin Cancer Res. 2004 Feb 1;10(3):1121-9. doi: 10.1158/1078-0432.ccr-0913-3.
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Lessons learned from the irinotecan metabolic pathway.从伊立替康代谢途径中吸取的经验教训。
Curr Med Chem. 2003 Jan;10(1):41-9. doi: 10.2174/0929867033368619.
7
Lessons from basic research in selenium and cancer prevention.硒与癌症预防基础研究的经验教训。
J Nutr. 1998 Nov;128(11):1845-54. doi: 10.1093/jn/128.11.1845.
8
Simple and versatile high-performance liquid chromatographic method for the simultaneous quantitation of the lactone and carboxylate forms of camptothecin anticancer drugs.用于同时定量喜树碱抗癌药物内酯形式和羧酸盐形式的简单通用高效液相色谱法。
J Chromatogr B Biomed Sci Appl. 1997 Mar 28;691(1):161-71. doi: 10.1016/s0378-4347(96)00426-4.
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Irinotecan (CPT-11): a brief overview.
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Conversion of irinotecan (CPT-11) to its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), by human liver carboxylesterase.人肝脏羧酸酯酶将伊立替康（CPT-11）转化为其活性代谢产物7-乙基-10-羟基喜树碱（SN-38）。
Biochem Pharmacol. 1996 Oct 11;52(7):1103-11. doi: 10.1016/0006-2952(96)00457-1.