POWRE: Mathematical Models for Optimization of Anti-Cancer Chemotherapy

POWRE：优化抗癌化疗的数学模型

• 批准号: 0074985
• 负责人: Ardith Elkareh
• 金额: $ 7.5万
• 依托单位: University of Arizona
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0074985&HistoricalAwards=false
• 关键词: POWRE; Mathematical; Models; Optimization; Anti

The overall objective of the project is to apply engineering methods for modeling mass transport to the problem of optimizing delivery of several commonly used anti-cancer drugs to tumor cells. The models will provide a rational basis for selecting among treatment options. An important feature will be consideration of the kinetics of cellular influx in addition to transport across microvessels and through tissue. Because of the wide variation in transport properties between different drugs, the models are specialized to the drugs melphalan, methotrexate, cisplatin, doxorubicin and 5-fluorouracil, all of which are widely used. Where necessary, spatial gradients of the drug within the compartments will be accounted for. Transport equations for processes such as diffusion and convection within and between the body compartments will be developed. All values of transport parameters will be taken from data in the biological literature. The resulting systems of ordinary or partial differential equations will be solved numerically.The three specific objectives are: (1) to determine the optimal schedule of intravenous infusion for the drugs melphalan, methotrexate and 5-fluorouracil, for both well-vascularized and poorly vascularized tumors; (2) to study the effects of spontaneously occurring intermittent flow, as well as artificially induced alterations in tumor blood flow, on the delivery of melphalan, methotrexate, doxorubicin and5-fluorouracil. Connections between time-varying blood flow and such phenomena as drug trapping, long tumor half-life of drug, or enhanced retention will be investigated; (3) to develop spatially distributed models to compare cellular delivery of the drug cisplatin to abdominal tumors (such as ovarian or colorectal) when administered intra-peritoneally or intravenously. These models will be used to examine the theoreticalrationale behind intra-peritoneal chemotherapy.One of the PI's career objectives is to apply theoretical principles and modeling to improve cancer therapies. She feels strongly that there is a need for a better understanding of drug delivery, and that theoretical studies have lagged behind experimental work and development of new therapies. The PI's work in this area was interrupted when she recently took two maternity leave. This POWRE grant at this point in her career will help her to regain momentum as an independent researcher in this area and to become competitive for standrad federal grant programs.

该项目的总体目标是将工程方法应用于模拟质量运输，以优化几种常用抗癌药物向肿瘤细胞的输送。 这些模型将为治疗方案的选择提供合理的依据。 一个重要的特征是除了跨微血管和通过组织的运输之外，还要考虑细胞流入的动力学。 由于不同药物之间的转运特性差异很大，因此模型专门用于药物美法仑、甲氨蝶呤、顺铂、阿霉素和5-氟尿嘧啶，所有这些药物都被广泛使用。 必要时，考虑隔室内药物的空间梯度。 运输方程的过程，如扩散和对流内和之间的身体隔间将开发。所有运输参数值均取自生物学文献中的数据。 本文的三个具体目标是：（1）确定药物美法仑、甲氨蝶呤和5-氟尿嘧啶静脉输注的最佳时间表，包括血管化良好和血管化不良的肿瘤;（2）研究自发发生的间歇流动以及人工诱导的肿瘤血流改变对美法仑递送的影响，甲氨蝶呤、阿霉素和5-氟尿嘧啶。 将研究随时间变化的血流与药物捕获、药物的长肿瘤半衰期或增强的保留等现象之间的联系;（3）开发空间分布模型，以比较腹膜内或静脉内给药时药物顺铂与腹部肿瘤（如卵巢或结肠直肠）的细胞递送。 这些模型将被用于研究腹膜内化疗背后的理论基础。PI的职业目标之一是应用理论原理和模型来改善癌症治疗。 她强烈认为，有必要更好地了解药物输送，理论研究已经落后于实验工作和新疗法的开发。 PI在这方面的工作因她最近休了两次产假而中断。 在她职业生涯的这一点上，这项POWRE资助将帮助她重新获得这一领域独立研究人员的动力，并成为标准联邦资助项目的竞争力。