The focus of Project 1 is the development of stochastic models of carcinogenesis and experimental data using these models.
The specific aims of this project fall into three groups. 1. The hazard function and analyses of time to tumor data. In this part of the project, we will investigate the properties of the hazard function of the two-mutation clonal expansion model and extensions of it. In particular, we propose to investigate issues of identifiability, goodness- of-fit, incorporation of time to tumor-detection, patterns of exposure to environmental agents, approximations to the hazard function, and covariate measurement errors. 2. Number and size distribution of intermediate (premalignant) lesions and analyses of initiation-promotion experiments. In this part of the project, we will develop models for the analyses of altered foci in the rodent liver or papillomas on the mouse skin. In particular, we will investigate shape-free methods for stereological reconstruction and analyses of foci in the rodent liver and methods for analyses of correlated longitudinal data on papillomas on the mouse skin. 3. Development of efficient computational algorithms. We intend to develop efficient computer algorithms and software, including highly computer-intensive methods such as Markov Chain Monte Carlo methods, for analyzing data using the models developed in 1 and 2.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA076466-02
Application #
6103456
Study Section
Project Start
1998-09-30
Project End
1999-09-29
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
Wick, David; Self, Steven G (2004) On simulating strongly-interacting, stochastic population models. Math Biosci 187:1-20
Wick, David; Self, Steven G (2004) On simulating strongly interacting, stochastic population models. II. Multiple compartments. Math Biosci 190:127-43
de Gunst, Mathisca C M; Dewanji, Anup; Luebeck, E Georg (2003) Exploring heterogeneity in tumour data using Markov chain Monte Carlo. Stat Med 22:1691-707
Curtis, S B; Luebeck, E G; Hazelton, W D et al. (2002) A new perspective of carcinogenesis from protracted high-LET radiation arises from the two-stage clonal expansion model. Adv Space Res 30:937-44
Wick, David; Self, Steven G (2002) What's the matter with HIV-directed killer T cells? J Theor Biol 219:19-31
Luebeck, E Georg; Moolgavkar, Suresh H (2002) Multistage carcinogenesis and the incidence of colorectal cancer. Proc Natl Acad Sci U S A 99:15095-100
Gregori, Giovanni; Hanin, Leonid; Luebeck, Georg et al. (2002) Testing goodness of fit for stochastic models of carcinogenesis. Math Biosci 175:13-29
Hazelton, W D; Luebeck, E G; Heidenreich, W F et al. (2001) Analysis of a historical cohort of Chinese tin miners with arsenic, radon, cigarette smoke, and pipe smoke exposures using the biologically based two-stage clonal expansion model. Radiat Res 156:78-94
Curtis, S B; Luebeck, E G; Hazelton, W D et al. (2001) The role of promotion in carcinogenesis from protracted high-LET exposure. Phys Med 17 Suppl 1:157-60
Wick, D; Self, S G (2000) Early HIV infection in vivo: branching-process model for studying timing of immune responses and drug therapy. Math Biosci 165:115-34

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