Luk C K, Tannock I F
Physics Division, Ontario Cancer Institute, Toronto, Canada.
Br J Cancer. 1988 Aug;58(2):133-8. doi: 10.1038/bjc.1988.179.
The outcome of cancer chemotherapy is determined by an interplay of multiple factors between the host, the tumour, and the drugs administered. Most studies have emphasised the development or selection of drug resistant tumour cells. However, repeated drug treatment of the host may lead to changes (e.g. in pharmacokinetics, host defences, etc.) which can influence the subsequent response of the tumour. In this study, we present a model to investigate the role of the host in the development of drug resistance. A drug is administered repeatedly to animals prior to tumour implantation, and tumour response is then evaluated following treatment with the same drug in pretreated and control animals. To illustrate the method, cyclophosphamide was administered weekly for 4 weeks to C3H mice before implantation of the KHT tumour. Tumour growth delay was then compared after one further treatment of cyclophosphamide in this group of animals to that in control mice which had not received the cyclophosphamide pretreatment. Our results indicate that cyclophosphamide produces only a small effect on the host in this system, but the model is a potentially useful one to investigate the contribution of the host in the acquisition of drug resistance.
癌症化疗的结果取决于宿主、肿瘤和所施用药物之间多种因素的相互作用。大多数研究都强调了耐药肿瘤细胞的产生或选择。然而，对宿主进行反复的药物治疗可能会导致（例如在药代动力学、宿主防御等方面的）变化，这些变化会影响肿瘤随后的反应。在本研究中，我们提出了一个模型来研究宿主在耐药性发展中的作用。在肿瘤植入前对动物反复施用一种药物，然后在用相同药物治疗后，评估预处理动物和对照动物中的肿瘤反应。为了说明该方法，在植入KHT肿瘤前，每周给C3H小鼠施用环磷酰胺，持续4周。然后将该组动物再次接受一次环磷酰胺治疗后的肿瘤生长延迟与未接受环磷酰胺预处理的对照小鼠进行比较。我们的结果表明，在这个系统中环磷酰胺对宿主仅产生微小影响，但该模型对于研究宿主在获得耐药性中的作用可能是有用的。
