lqirupdwlrq - disease models & mechanisms · han4.13 cells. there is mixed glandular and...
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Chemotherapy Drug Dose 1 (mg/kg) Dose 2 (mg/kg)
Ca Folinate 100 50
Oxaliplatin 5 2.5
Irinotecan 50 25
5-Fluorouracil 50 25
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Supplementary Figures
Disease Models & Mechanisms 11: doi:10.1242/dmm.034793: Supplementary information
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Supplementary Figure 1. Murine FOLIFIRINOX Dosing
(A) Kaplan-meier survival curve after two doses of FOLFIRINOX (n = 5 per experimental group). Fifty
percent of mice given the higher dose died within two weeks after the first dose of drug. No mice died
with the reduced dose. (B) All mice lost progressive weight starting after the first dose of FOLFIRINOX.
(C) FOLFIRINOX dosing regimens.
Disease Models & Mechanisms 11: doi:10.1242/dmm.034793: Supplementary information
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Supplementary Figure 2. Cytokeratin Staining of Pancreatitis-Related Ductal Metaplasia
Pan-cytokeratin staining of orthotopic tumor and surrounding pancreas with H&E co-staining. The tumor
mass (left side of image) stains uniformly positive for cytokeratin, as expected. Fibrosis surrounding the
tumor is delineated (dashed black line). Pancreas tissue is located on the right of the image, which is
inflamed with evidence of ductal metaplasia by cytokeratin staining (dashed red line).
Disease Models & Mechanisms 11: doi:10.1242/dmm.034793: Supplementary information
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10 Days
16 Days
30 Days
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B0 100 200 300 400 500 µm
Disease Models & Mechanisms 11: doi:10.1242/dmm.034793: Supplementary information
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Supplementary Figure 3. Characterization of Fibrosis Progression in Orthotopic Tumors Over
Time
(A) Collagen proportional area (CPA) quantification of tumor fibrosis at 10, 16 and 30 days after
implantation (n = 4 per experimental group, error bars represented as mean ± SD). Fibrosis significantly
increases up to postoperative day 16, after which collagen deposition relative to tumor mass appears to
stabilize as the CPA level for postoperative day 30 is similar to day 16. (B) Representative Sirius Red
staining of orthotopic tumors extracted at 10, 16, and 30 days after implantation. Although the
orthotopic model has a robust fibrotic response on the tumor periphery, intercalation of stromal cells
and collagen deposition occurs throughout the tumor bed as shown by the images. * p < 0.05, ** p <
0.01.
Disease Models & Mechanisms 11: doi:10.1242/dmm.034793: Supplementary information
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Disease Models & Mechanisms 11: doi:10.1242/dmm.034793: Supplementary information
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Supplementary Figure 4. Phenotypic Features of Orthotopic and Heterotopic Tumors Using
Han4.13 Cells
(A) Representative H&E and Sirius Red staining of an orthotopic tumor two weeks after implantation of
104 Han4.13 cells. There is mixed glandular and sarcomatoid morphologies distributed throughout the
tumor mass. Pancreatitis is present distal to the tumor along the length of the main pancreatic duct
(zoomed image). (B) Representative H&E and Sirius Red staining of a heterotopic tumor two weeks
after implantation of 104 Han4.13 cells. Similar to Hy15549 tumors of the flank, there is a dense fibrotic
response.
Disease Models & Mechanisms 11: doi:10.1242/dmm.034793: Supplementary information
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