Biomedical Engineering Reference
In-Depth Information
Modeling Multiscale Necrotic
and Calcified Tissue Biomechanics
in Cancer Patients: Application to Ductal
Carcinoma In Situ (DCIS)
Paul Macklin, Shannon Mumenthaler
and John Lowengrub
Abstract Tissue necrosis and calcification significantly affect cancer progression
and clinical treatment decisions. Necrosis and calcification are inherently multi-
scale processes, operating at molecular to tissue scales with time scales ranging
from hours to months. This chapter details key insights we have gained through
mechanistic continuum and discrete multiscale models, including the first mod-
eling of necrotic cell swelling, lysis, and calcification. Among our key findings:
necrotic volume loss contributes to steady tumor sizes but can destabilize tumor
morphology; steady necrotic fractions can emerge even during unstable growth;
necrotic volume loss is responsible for linear ductal carcinoma in situ (DCIS)
growth; fast necrotic cell swelling creates mechanical tears at the perinecrotic
boundary; multiscale interactions give rise to an age-structured, stratified necrotic
core; and mechanistic, patient-calibrated DCIS modeling allows us to assess our
working biological assumptions and better interpret pathology and mammography.
We finish by outlining our integrative computational oncology approach to
developing computational tools that we hope will one day assist clinicians and
patients in their treatment decisions.
P. Macklin (
&
)
S. Mumenthaler
Keck School of Medicine, Center for Applied Molecular Medicine,
University of Southern California, Los Angeles, CA, USA
e-mail: Paul.Macklin@usc.edu
URL: http://MathCancer.org
J. Lowengrub
Departments of Mathematics, Chemical Engineering and Materials Science,
and Biomedical Engineering, University of California, Irvine, CA, USA
URL: http://math.uci.edu/*lowengrb
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