肿瘤
词汇介绍
拓展阅读
解析
Multidrug
释 义 n. 多药
例 句 The essence of the elimination strategy to cure leprosy, avoid disability andreduce the disease burden is to detect all patients as early as possible, and to treat them with multidrug treatment. 为治愈麻风、避免残疾和减轻疾病负担所制定的消灭战略,其精髓在于及早发现所有患者,并对他们采用多药性疗法进行治疗。
Resistance 英 /rɪ'zɪst(ə)ns/ 美 /rɪ'zɪstəns/
释 义 n. 阻力;电阻;抵抗;反抗;抵抗力;复数 resistances
同根词 resistant adj. 抵抗的,反抗的;顽固的;resistive adj. 有抵抗力的;resistible adj. 可抵抗的;resistless adj. 无抵抗力的;无法抗拒的;resist [助剂] n. 抗蚀剂;防染剂;resistant n. 抵抗者;
例 句 You have the ability to look here where there is not resistance. 你有能力在没有阻力的地方观察。
概述
概述
1970年,Biedle和Riehm用P388白血病细胞等与更生霉素(ACD)接触培养,观察到肿瘤细胞不但对ACD耐药,而且对结构不相似的药物,如柔红霉素和长春花碱也产生耐药,从而首先发现了多药耐药性现象。肿瘤多药耐药简写为MDR,是指肿瘤细胞对一种抗肿瘤药物产生抗药性的同时,对结构和作用机制不同的抗肿瘤药物产生交叉耐药性。典型的MDR指针对天然来源的抗肿瘤药物如阿霉素、柔红霉素、长春新碱、长春花碱、秋水仙碱、紫杉醇、依托泊甙、替尼泊甙等产生的交叉抗药性。MDR是肿瘤化疗失败的主要原因。也是肿瘤化疗急待解决的问题。MDR形成机制十分复杂,肿瘤细胞可通过不同途径导致MDR产生。单个MDR细胞可同时存在多种抗药性的机制。一种或多种机制联合作用均可导致MDR产生。MDR的形成使得肿瘤患者产生化学抵抗并导致预后较差。相关的评价标准包括:耐药倍数检测、耐药标志物检测和耐药机制检测。理论上克服多药耐药性主要有两种途径,一是寻找MDR的逆转剂与抗癌药物合用,恢复MDR细胞对抗癌药物的敏感性;二是开发对MDR细胞不具有抗药性的新抗癌药物。
原因
肿瘤多药抗药性的产生原因十分复杂,与细胞膜有关的主要因素有P-糖蛋白(P-gP)、多药抗药性相关蛋白、肺多药抗药性相关蛋白等;与细胞质、细胞核有关的主要因素有拓扑异构酶II、蛋白激酶C、谷胱甘肽氧化还原系统(谷胱甘三肽、谷胱甘肽S转移酶、谷胱甘肽过氧化物酶)、金属硫蛋白等,但最终要和最常用的是P-gP介导的多药抗药性,也称经典MDR。以肺多药抗药性相关蛋白为例说明其导致多药耐药性的机制,肺多药抗药性相关蛋白以囊泡的方式将药物及有害毒物包裹,阻断药物与细胞核作用靶点结合,从而介导肿瘤细胞产生MDR。
逆转策略
MDR的逆转是肿瘤治疗过程中不可回避的问题,目前逆转MDR的策略很多,都是针对MDR的一种或多种机制进行的。其中应用多药耐药逆转剂是解决肿瘤MDR的主要手段。现已发现大量具有MDR逆转活性的化合物,比如钙通道阻滞剂、Ca抑制剂等。另外,天然药物治疗、免疫治疗、基因治疗等也是一些逆转策略。
研究意义
研究MDR的形成机制,对研究新的肿瘤MDR判定标准以及有效逆转肿瘤MDR具有重要意义,并为进一步开发新一代化疗药物及MDR逆转药物指明新方向。随着高效低毒逆转剂的不断发现、基因治疗技术的不断发展以及应用循证医学指导临床实践,肿瘤对化疗药物的耐药性将会被克服。
Repurposing approved drugs on the pathway to novel therapies复制标题
将批准的药物重新用于新疗法的途径
发表时间:2019-08-20
影响指数:9.8
作者: Catherine H. Schein
期刊:Med Res Rev
The time and cost of developing new drugs have led many groups to limit their search for therapeutics to compounds that have previously been approved for human use. Many "repurposed" drugs, such as derivatives of thalidomide, antibiotics, and antivirals have had clinical success in treatment areas well beyond their original approved use. These include applications in treating antibiotic-resistant organisms, viruses, cancers and to prevent burn scarring. The major theoretical justification for reusing approved drugs is that they have known modes of action and controllable side effects. Coadministering antibiotics with inhibitors of bacterial toxins or enzymes that mediate multidrug resistance can greatly enhance their activity. Drugs that control host cell pathways, including inflammation, tumor necrosis factor, interferons, and autophagy, can reduce the "cytokine storm" response to injury, control infection, and aid in cancer therapy. An active compound, even if previously approved for human use, will be a poor clinical candidate if it lacks specificity for the new target, has poor solubility or can cause serious side effects. Synergistic combinations can reduce the dosages of the individual components to lower reactivity. Preclinical analysis should take into account that severely ill patients with comorbidities will be more sensitive to side effects than healthy trial subjects.
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