Biomedical Engineering Reference
In-Depth Information
fluid flux
Cell flux
Cell flux
fluid flux
distance from tumor center
Fig. 1 Left: Proliferation in the viable rim (yellow cells) generates a cell flux (dark gray arrows)
that can balance with fluid flux (pale blue arrows) created by lysing cells in the necrotic core
(brown cell debris), resulting in steady tumor sizes. Adapted with permission from [
52
]. Right:
Typical ductal carcinoma in situ (DCIS) duct cross-sections showing the outer viable rim, inner
necrotic core, calcifications, and an inflammatory response. Adapted from [
56
] with permission
In
Sect. 4
, we present a multiscale agent-based cell model [
56
] by Macklin and
colleagues and apply it to ductal carcinoma in situ. The model is the first to
incorporate the vast range of time scales of necrosis and calcification; tissue-scale
biomechanics emerge from interactions among time-varying forces, adhesion
characteristics, and individual cell volumes. This work, which included the first
patient-specific calibration to pathology, gave new mechanistic insights on the
impact of multiscale necrotic and calcified tissue biomechanics on features
observed in patient pathology and mammography. We conclude by discussing the
next steps in multiscale modeling of necrotic and calcified tissues, and we outline
our vision for the future of clinically-focused integrative computational oncology.
It is our belief that integrative modeling will increasingly push the envelope to
advance the state-of-the-art across biology, engineering, mathematics, computing,
and the clinical sciences.
2 Biological Background
2.1 Basic Biology of Apoptosis
Apoptosis is a tightly-regulated, energy-consuming process [
25
,
36
] that begins
when intrinsic or extrinsic signals activate initiator caspases (e.g., Caspase-9) in
the cytoplasm [
25
,
38
]. This is generally regulated in one of two ways. In the first,
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