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. Author manuscript; available in PMC: 2022 Jul 31.
Published in final edited form as: Nat Cancer. 2022 Jan 31;3(3):318–336. doi: 10.1038/s43018-021-00326-1

Figure 4. The combination treatment prolongs survival and reprograms the tumor microenvironment in vivo .

Figure 4

a, Kaplan-Meier curve comparing the survival of classical and mesenchymal orthotopic PDAC models. The number of mice per treatment condition is indicated.

b, Quantification of tumor volume changes of the classical and mesenchymal subtype after one week of indicated treatment assessed by MRI. Each column represents one mouse, in comparison with baseline MRI measurement before treatment. Control, T, N and T/N cohorts are shown.

c, Representative MRI of vehicle (Control) and T/N treated mice before (week 2) and after 1 week of treatment (week 3). Scale bar, 5 mm.

d, Left and middle panel, Kaplan-Meier survival curve of classical and mesenchymal orthotopic models. The number of mice per treatment condition is indicated. Right, Comparison of the ratio between the survival of mice treated with T/N and the median survival of their respective vehicle treated controls.

e, Representative H&E and immunohistochemical staining for KI67 and CD31 of tumor sections from orthotopically transplanted classical and mesenchymal PDAC subtype models treated with vehicle (Control) or T/N for 1 week. Scale bars, 50 μm.

f, Quantification of KI67+ cells (classical: control n=6, T/N n=5; mesenchymal: control n=8, T/N n=7).

g, Quantification of the number of mitoses per high power field (classical: control n=6, T/N n=6; mesenchymal: control n=9, T/N n=8).

h, Quantification of vessels CD31+ (classical: control n=5, T/N n=5; mesenchymal: control n=9, T/N n=8).

i, Representative immunohistochemical staining for pPDGRFb-Tyr1021, pAMPKa-Thr172 and p-p44/42 (Thr202/Tyr204) of tumor sections from orthotopically transplanted classical and mesenchymal PDAC subtype models treated with vehicle (Control) or T/N for 1 week. Scale bars, 100 μm.

T: trametinib, N: nintedanib, T/N: trametinib+nintedanib.

P values in (b), (d, right), (f), (g) and (h) were calculated by two-tailed unpaired t test. P values in (a) and (d, left and middle) were calculated with log-rank (Mantel-Cox) test.

Note: The classical and mesenchymal cohorts in panel (a) are the same shown in panel (d). Vehicle and trametinib-treated cohorts shown in panel (b) are the same as shown in figure 1, panel (i).