tailieunhanh - Báo cáo y học: "A tumor cord model for Doxorubicin delivery and dose optimization in solid tumors Steffen Eikenberry"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: A tumor cord model for Doxorubicin delivery and dose optimization in solid tumors Steffen Eikenberry. | Theoretical Biology and Medical Modelling Research A tumor cord model for Doxorubicin delivery and dose optimization in solid tumors Steffen Eikenberry BioMed Central Open Access Address Department of Mathematics and Statistics Arizona State University Tempe AZ 85287 USA Email Steffen Eikenberry - seikenbe@ Published 9 August 2009 Received 22 January 2009 Theoretical Biology and Medical Modelling 2009 6 16 doi 1742-4682-6-16 Accepted 9 August 2009 This article is available from http content 6 1 16 2009 Eikenberry licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Background Doxorubicin is a common anticancer agent used in the treatment of a number of neoplasms with the lifetime dose limited due to the potential for cardiotoxocity. This has motivated efforts to develop optimal dosage regimes that maximize anti-tumor activity while minimizing cardiac toxicity which is correlated with peak plasma concentration. Doxorubicin is characterized by poor penetration from tumoral vessels into the tumor mass due to the highly irregular tumor vasculature. I model the delivery of a soluble drug from the vasculature to a solid tumor using a tumor cord model and examine the penetration of doxorubicin under different dosage regimes and tumor microenvironments. Methods A coupled ODE-PDE model is employed where drug is transported from the vasculature into a tumor cord domain according to the principle of solute transport. Within the tumor cord extracellular drug diffuses and saturable pharmacokinetics govern uptake and efflux by cancer cells. Cancer cell death is also determined as a function of peak intracellular drug concentration. Results The model predicts that transport to the tumor cord from the .