Biomedical Engineering Reference
In-Depth Information
on
(i) Aberrant activation of signal transduction pathways that control cell
growth and survival,
(ii) Genetic changes, distortion in the cell cycle and loss of apoptosis,
(iii) Response of the cellular activity to the signals received,
(iv) Absorption of vital nutrients. A large amount of literature related to
the above features can be found.
Several interesting papers are cited in the review paper by Lustig and
Behrens (2003), focusing on the dependence of cancer development on the
aberrant activation of signal pathways that control cell growth and survival.
Subcellular scale models deal with models concerning the intra-celllular
origin of cancer, which involves genetic changes and distortion in the cell
cycle. They refer to the origins of unlimited and inappropriate cell prolif-
eration, loss of apoptosis, and the production, release and recognition of
messenger substances such as interleukins.
Micro environment study of multicellular tumor spheroids is a good
place to start. There is some data evidence that growth inhibitors are due
to small protein factors
21;38
. The desire to understand tumor complexity
has given rise to mathematical models to describe the tumor microenvi-
ronment. New mathematical models for avascular tumor growth and devel-
opment that spans three distinct scales can be developed. At the cellular
level, a lattice Monte Carlo model describes cellular dynamics (prolifera-
tion, adhesion, and viability). At the subcellular level, a network regulates
the expression of proteins that control the cell cycle. At the extracellular
level, reaction-diusion equations describe the chemical dynamics (nutrient,
waste, growth promoter, and inhibitor concentrations). Reaction diusion
equation coupled with an integro dierential equation describing tumor ra-
dius response to externally supplied nutrient.
Data from experiments with multicellular spheroids are used to deter-
mine the parameters of the simulations. Starting with a single tumor cell,
these models produce an avascular tumor that quantitatively mimics experi-
mental measurements in multicellular spheroids. Based on the simulations,
these models predict: 1), the microenvironmental conditions required for
tumor cell survival; and 2), growth promoters and inhibitors have diu-
sion coecients, corresponding to molecules. Using the same parameters,
the model also accurately predicts spheroid growth curves under dierent
external nutrient supply conditions.
Search WWH ::
Custom Search