Biomedical Engineering Reference
In-Depth Information
proliferation and promotes differentiation can be effective. Simulation results of this
combinational therapy showed that it can indeed successfully eradicate tumor cells
of all cell types.
5.4
Model Prediction of Power Law Tumor Growth Rate
and Supporting Experimental Results
Examining the simulated macroscopic dynamics of tumor growth reveals an
interesting result regarding tumor growth rate. Model dynamics in the intermediate
stage of accelerated growth support previous results, suggesting power law tumor
growth [ 26 , 31 , 36 ], as opposed to the widely accepted assumption that the tumor
growth rate is exponential or Gompertzian (e.g., [ 49 ]). In the simulation results
for the two-dimensional CA, the total number of cells is well approximated by a
parabola, i.e., it is proportional to the square of time [ 90 ]. Similar model simulations
of a one-dimensional automaton show that growth of the total number of cells is
linear [ 48 ]. Therefore, the model suggests that a tumor radius should grow linearly
with time. This is corroborated by experimental findings in breast cancer [ 36 ]and
malignant glioma [ 82 ].
To test this, in vitro experiments [ 48 ] have been conducted in a breast cancer
MCF-7 cell line. Small colonies of these cells were seeded in a thin channel or
a Petri dish, and their growth was monitored for several days. One-dimensional
growth of cells in channels showed that the progression rate of the cell-colony front
line was linear (Fig. 3 ). The two-dimensional area growth of cell colonies showed
good fit with the model's prediction of quadratic growth (Fig. 4 ). Measurements of
3D tumor growth, done in a mouse xenograft model of human breast cancer cells,
also support this hypothesis of linear growth of tumor radius [ 48 ]. Analysis of these
results and of the possible implications of power law tumor growth rate on clinical
therapy is to be published in [ 48 ].
5.5
Experimental Results Supporting the Quorum Sensing
Concept
In vitro experiments [ 3 ] with CSCs or “stem-like cells” from the breast cancer
MCF-7 cell line were conducted in order to test the theory of the QS control
mechanism underlying the model. CSCs, or “stem-like cells” positive for the CD44
marker, were isolated from the breast cancer cell line and plated at different
proportions with remaining cell populations. The proportion of CSCs was evaluated
several times, until the culture was confluent, and cell populations' proportions
reached equilibrium.
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