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Analysis of combined effects of Discodermolide withclinical anticancer agent, Paclitaxel

Lo, Wan-chen (2009) Analysis of combined effects of Discodermolide withclinical anticancer agent, Paclitaxel. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Study of multiple drug usage is common in chemotherapy. Many research studies examine the effect multiple usage of these anticancer drugs. The study of these drugs together could help clarify the biological effects of agents that affect microtubules. This could guide future cancer treatment for patients especially these with breast cancer, an important public health issue. The main purpose of this paper is to apply and compare methods for examining the combined effects of anticancer drugs. We focus on Paclitaxel and Discodermolide. While in the process of modeling the single drug effect, we noticed that these anticancer drugs may be unable to kill all the cells even at high concentration, or that, some subpopulation is far less sensitive: there may be a mixed population of two types of cells with very different sensitivities. According to this description, one population of cell is very sensitive to the drug and the other one is nearly resistant to the drug. This model is difficult to fit. One approach is to fit the low-concentration and high-concentration portion of the dose-response curve separately, and then combine them. We constructed a simple method to predict the combined drug effects while adjusting for the assumption of mixed cell populations. We will summarize the commonly used methods for evaluating drug combination. Two models are commonly used as reference models to test the drug additive effect, which are dose-additive models and effect-additive models. For effect-additive models, we focus on the "mutually exclusive" and "mutually non-exclusive" additive effect models, and another additive effect model based on a population log kill mixture model.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lo, Wan-chencathylljc@hotmail.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberYouk, Adaayouk@pitt.eduAYOUK
Committee MemberVogt, Andreasavogt@pitt.eduAVOGT
Committee MemberDay, Rogerday@upci.pitt.eduDAY01
Date: 29 January 2009
Date Type: Completion
Defense Date: 10 December 2008
Approval Date: 29 January 2009
Submission Date: 31 July 2008
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Biostatistics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: combination index; synergism; dose additive; effect additive; median effect
Other ID: http://etd.library.pitt.edu/ETD/available/etd-07312008-221427/, etd-07312008-221427
Date Deposited: 10 Nov 2011 19:55
Last Modified: 15 Nov 2016 13:47
URI: http://d-scholarship.pitt.edu/id/eprint/8778

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