Biomedical Engineering Reference
In-Depth Information
Tumour advance:
τ
NL
= 15 days
Rate of tumour advance vs. duct radius
1400
160
1200
140
1000
120
800
100
600
80
400
60
200
40
0
20
0
5
10
15
20
25
30
50
100
150
200
Time (days)
Duct radius (
μ
m)
Fig. 10 Left: Delaying cell lysis leads to a completely filled necrotic core, which redirects
proliferative cell flux along the duct. This results in exponential-like growth (blue curve). Right:
Larger ducts have a greater ''reservoir'' available to absorb proliferative cell flux through necrotic cell
lysis, leading to slower growth than in smaller ducts. Figures reproduced from [
56
] with permission
still from the leading edge in Slice c, there has been sufficient cell flux to fill the lumen
with necrotic material; an outermost band of intact necrotic nuclei encircles a central
region of mostly degraded nuclei (modeled here simply as partly calcified). Farther
from the leading edge in Slice d, a thin outermost band of relatively intact necrotic
nuclei surrounds an inner band of mostly degraded necrotic material and an inner
core of microcalcification. In Slice e, the microcalcification is larger, and the out-
ermost band of intact necrotic nuclei is largely gone. The necrotic core is increasingly
calcified with distance from the tumor leading edge.
Overall, the model predicts an age-ordered necrotic core microstructure, with
oldest material in the center surrounded by increasingly newer, less-degraded, and
less-calcified material. Indeed, all these cross-sections can be found in our patient.
See the hematoxylin and eosin (H&E) stained section in Fig.
11
(bottom). Slice b
corresponds to Duct 1, where a ring of relatively intact necrotic debris (red arrows)
surrounds an as-yet unfilled lumen. Slice c corresponds to Duct 2, where the entire
lumen has been filled necrotic debris, which is more intact at its outer edge (red
arrow), and increasingly degraded in its center (green arrow). Slice d corresponds
to Duct 3, where a thinner ring of mostly intact nuclei (red arrows) surrounds an
intermediate layer of mostly degraded debris (green arrows) and a central core of
microcalcifications (white arrows). (Note that Duct 3 is likely the intersection of
two or more ducts near a branch point.) Slice e corresponds to Duct 4, where a ring
of degraded necrotic debris (green arrow) surrounds a larger calcification (white
arrow). The inset shows a different duct from the patient that is similar to slice a.
This stratified structure arises from the overall flux of cells from the viable rim
into the necrotic core, working in concert with the multiple time scales during
Search WWH ::
Custom Search