Abstract 4554: Unified theoretical algorithms for graphics dynamic multiple transformations of dose-effect relationships with computer simulation

Abstract

Abstract Based on physico-chemical principle of the mass-action law, bio-system analysis (arrangement & combinatorial) several hundred rate equations have been derived and published. Mathematical induction allows the deduction of them into the unified general median-effect equation (MEE) that makes dose & effect “interchangeable” for the 1st order and higher order dynamics. Based on the MEE plot, all dose-effect curves can be “linealized” which allows the quantitative determination of x-intercept (log Dm which signifies potency) and slope (m which signifies shape or dynamic order). Extension of MEE to multi-drug combinations resulted the combination index (CI) theorem which quantifies synergism (CI<1), additive effect (CI=1), and antagonism (CI>1). This unprecedented approach and multi-step logics have been summarized in [Chou TC. Pharmacol Rev 58: 621-681, 2006] which has been cited 1,261 times in 485 bio-medical journals (http://www.researcherid.com/rid/B4111-2009 as of 10.19.2016). Dose-effect curves (single & multi-drugs) can be quantitatively transformed into the MEE plot, Fa-CI plot, isobologram, Fa-DRI Plot for dose-reduction index, and when n>2, the polygonogram. This presentation will illustrate of combinations (1:5) of docetaxel (TXT) with T-compound against HCT-116 colon carcinoma xenograft in nude mice. In all, only 66 nude mice have been used, i.e. TXT 3 doses, T 3 doses and TXT+T 4 doses, plus a control group, each N=6. The MEE “Linearization” allows the “Econo-Green Bio-research”, with small experimental size and small number of data points, using small number of animals. The algorithms based computer simulation using CompuSyn software can be completed within one second after the dose and effect data entries. The CompuSyn has been offered for free download upon registration via www.combosyn.com. Note: This abstract was not presented at the meeting. Citation Format: Ting-Chao Chou. Unified theoretical algorithms for graphics dynamic multiple transformations of dose-effect relationships with computer simulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4554. doi:10.1158/1538-7445.AM2017-4554