Kinetic heterogeneity of an experimental tumour revealed by BrdUrd incorporation and mathematical modelling

Bulletin of Mathematical Biology
A BertuzziPaolo Ubezio

Abstract

In the present paper we propose a method of analysis of the cell kinetic characteristics of in vivo experimental tumours, that uses DNA-BrdUrd flow cytometry data at various times after the bromodeoxyuridine (BrdUrd) injection and mathematical modelling. The model of the cell population takes into account the cell-cell heterogeneity of the progression rate across cell cycle phases within the tumour, and assumes a strict correlation between the durations of S and G2M phases. The model also allows for a nonconstant DNA synthesis rate across S phase. In addition, the measurement process is modelled, considering the possibility of nonimpulsive labelling and providing a representation of the time course of the bivariate DNA-BrdUrd fluorescence distribution. Sequential DNA-BrdUrd distributions were obtained in vivo from a human ovarian carcinoma transplanted in mice and, for comparison, in vitro from a cell line of the same origin. From these data, that included the fractional density and the mean BrdUrd-fluorescence of BrdUrd-positive cells as a function of the DNA-fluorescence, kinetic parameters such as the potential doubling time (Tpot) and the mean and variance of the transit times in S and G2M phases, were estimated. This study...Continue Reading

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Citations

Mar 4, 2005·Medical & Biological Engineering & Computing·K J Rounseville, P C Chau
Sep 27, 2008·Bulletin of Mathematical Biology·Sara LarssonMaria Johansson
Aug 24, 2012·Bulletin of Mathematical Biology·Liene DauksteDavid J N Wall
Jun 24, 2004·Bulletin of Mathematical Biology·John D Nagy
Apr 25, 2008·Mathematical Biosciences·Sara LarssonMaria Johansson
Oct 19, 2007·Mathematical Biosciences·Sara LarssonMaria Johansson
Apr 6, 2005·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Sara LarssonUlla Holst
Feb 3, 2015·Asian Pacific Journal of Cancer Prevention : APJCP·Vassilis KoulouliasAristofanis Papaloucas
Sep 28, 2017·Cancer Research·Francesca FalcettaPaolo Ubezio
Mar 7, 2012·Medical Hypotheses·Carla C C R de Carvalho, Maria José Caramujo

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