Supplementary Figures from Agonists of the TRAIL Death Receptor DR5 Sensitize Intestinal Stem Cells to Chemotherapy-Induced Cell Death and Trigger Gastrointestinal Toxicity

Supplementary Figures 1-9. Sup. Fig. 1: IV injections of the monoclonal DR5-targeting MD5-1 antibody in combination with fluorouracil (5-FU) and CPT-11 sensitizes mice to chemotherapy-induced toxicity. Area-under-the curve (AUC) analysis of weight loss curves following different doses of fluorouracil (5-FU). Sup. Fig. 2: High dose treatment with the DR5-targeting antibody MD5-1 in combination with low-dose CPT-11 triggers liver toxicity whereas low dose MD5-1-treatment combined with high dose chemo triggers GI-toxicity in mouse strains known to be resistant to TRAIL-R-targeting. Sup. Fig. 3: Targeting of DR5 in combination with radiochemotherapy does not trigger synergistic bone marrow toxicity. Sup. Fig. 4: DR5-targeting sensitizes human small intestinal epithelial cells to cell death following chemotherapy. Sup. Fig. 5: DR5-targeting in combination with chemotherapy triggers cell death in the crypts of the GI tract in mice in vivo. Sup. Fig. 6: P53-dependent gene expression changes in the mouse colonic epithelium following fluorouracil and irinotecan. Affymetrix gene expression mRNA data on p53-responsive genes in the colon of mice treated with 5-FU (A) and CPT-11 (B). Sup. Fig. 7: Chemotherapy-dependent reliance on cell cycle regulating- and apoptosis-signaling genes for the toxic response following chemotherapy and DR5-targeting. Sup. Fig. 8: Chk2 is a modulator GIT following combined chemotherapy and DR5-targeting. Sup. Fig. 9: Pharmacologic targeting of Chk2 countermeasure GIT without impacting the anti-tumor response following chemotherapy and DR5-targeting.