Table 1.
Parameter | Value | Units | Source | |
---|---|---|---|---|
r1 | 1.2924 | per day | [16] | |
C1 | 0.1 | Oxygen concentration | [16] | |
r2 | 0.001 | per Tumor cell density per day | [16] | |
σ | 1.0029 | dimensionless | [16] | |
C2 | 0.054 | Oxygen concentration | [16] | |
Cm | 0.2 | Oxygen concentration | [16] | |
k | 16.0 | # Microvessels per mm3 | 1 | |
μa | 12.8810 | # HDMECs per pg of Da per day | [11]2 | |
μl | 806.9190 | # HDMECs per pg of Cl per day | [11]2 | |
ad | 3.8780×10−6 | per day | [11], [21]3 | |
bd | 1.7329 | per Bad concentration | [11], [21]3 | |
α1 | 30.0 | # HDMECs per Microvessel | [16] | |
M0 | 17×103 | # HDMECs per mm3 | [16] | |
α2 | 0.2984 | # Microvessels per pg of Da per day | [22]2 | |
α3 | 6.5757 | # Microvessels per pg of Cl per day | [22]2 | |
0.2250 | pg VEGF per pg Ra | [16] | ||
0.1837 | pg VEGF per pg Ca | [16] | ||
0.8163 | pg Ra per pg Ca | [16] | ||
0.4494 | pg Ra per pg Da | [16] | ||
1.2250 | pg Ca per pg Ra | [16] | ||
0.5506 | pg Ca per pg Da | [16] | ||
2.2250 | pg Da per pg Ra | [16] | ||
λa | 15.5958 | per day | [16] | |
r3 | 0.1507 | pg VEGF per Tumor cell per day | [12]4 | |
1.6232 | per VEGF concentration per day | [16] | ||
49.3025 | per day | [16] | ||
162.32 | per Ca concentration per day | [16] | ||
0.493025 | per day | [16] | ||
16.0 | per day | [16] | ||
Vchar | 55.0 | # Microvessels per mm3 | [16] | |
V0 | 2.0 | # Microvessels per mm3 | [16] | |
∊ | 1.0 | # Microvessels per mm3 | [16] | |
6.7587 | per CXCL8 concentration per day | [16] | ||
43.2557 | per day | [16] | ||
24.0 | per day | [16] | ||
0.1311 | pg CXCL8 per pg Rl | [16] | ||
0.1159 | pg CXCL8 per pg Cl | [16] | ||
0.8841 | pg Rl per pg Cl | [16] | ||
1.1311 | pg Cl per pg Rl | [16] | ||
λl | 15.5958 | per day | [16] | |
βm | 8.1139×10−4 | pg of CXCL8 per HDMEC per day | [11] [16]2,5 | |
ap | 6.9620×10−4 | pg of CXCL8 per HDMEC per day | [11] [16]2,5 | |
bp | 1.6185 | per Bcl-2 concentration | [11] [16]2,5 | |
α4 | 0.24845 | # Microvessels per HDMEC | [16] | |
4 | per Bad concentration per day | 1 | ||
8.832 | per day | [3] | ||
40 | per BL193 concentration per day | [3]6 | ||
2.56 | per day | [3]6 | ||
βa | 40 | fg of Bcl-2 per pg Da | [12] | |
Di | 3.4650 | per day | 1 |
In the absence of experimental data, biologically realistic values for these parameters were chosen so that the solution profiles best fit experimental observations.
The parameters associated with CXCL8 production, and CXCL8 and VEGF effect on HDMEC proliferation, and microvessel formation were estimated using least squares fits of experimental data in [11, 22].
We know that the normal death rate of HDMECs is 0.12 per day [21]. Further, in the presence of 50 ng per ml VEGF, Bcl-2 is up-regulated 3.1 fold, and consequently the level of Bad falls by a factor of 0.77. We assume a very low HDMEC death rate corresponding to this low level of Bad. From these two observations, the constants ad and bd may be determined.
Keeping all other parameter values fixed, VEGF production rate by tumor cells was determined by fitting the microvessel density after 21 days with that observed experimentally in a (control) tumor that was allowed to grow without the application of any anti-cancer therapy [12].
A relation between the constants βm, ap and bp may be found by observing that at constitutive Bcl-2 levels, the production rate of CXCL8 is 0.0358 pg of CXCL8 per HDMEC per day [16]. Note that at constitutive levels of Bcl-2 and Bad, the cell death rate is taken to be 0.12 per day [21] and HDMEC CXCL8 production rate is fit to experiments in [12]
It was assumed that rate of forward reaction of BL193 with Bcl-2 was higher than that of Bad binding to Bcl-2, due to the much smaller size of BL193.