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Class Changes Untreated + Gem/Pac Untreated + Gem/Pac Lean Obese A. B Class Changes Untreated + Gem/Pac Untreated + Gem/Pac Lean Animals 500000 L4 400000 L3 L2 L1 300000 200000 100000 Relative Abundance Relative 0 Bacilli Clostridia Bacteroidia Actinobacteria errucomicrobiae V Gammaproteobacteria Obese Animals O4 800000 O3 O2 O1 600000 400000 200000 Relative Abundance Relative 0 Bacilli Clostridia Bacteroidia Actinobacteria errucomicrobiae V Gammaproteobacteria A. B. C. 40 * 4 400 Day1 * * Day 30 ) 30 l 300 ) 3 s m s m L g/ / a l ide u r r o g 20 e 200 ( 2 c ol ( r y l e ht mm g ig st i r e T le 100 W 10 1 ho C 0 0 0 Adjusted Control High Fat (Lean) Diet (Obesogenic) Diet Lean Mice Lean Mice Obese Mice Obese Mice Tumor Take D. 250 E. * 100 r ) o L 200 m d u 80 t g/ m 150 ith e ( s 60 o c 100 lu mals w i G 40 d 50 f an o 20 Bloo % 0 0 Adjusted Control High Fat (Lean) Diet (Obesogenic) Diet Lean Mice Obese Mice High Fat Diet F. Tumor progression G. Adjusted Control Diet 4000 * ) 3000 2000 olume (mm v 1000 umor T 0 0 10 20 30 Days after tumor implantation Adjusted Control H&E staining of representative tumors High Fat Diet A. B. MIA-PaCa2 S2VP10 4 4 ) ) * * 3 3 2 2 Absorbance Absorbance 1 1 (function of cell growth (function of cell growth 0 0 20 40 60 0 0 20 40 60 Time in hours Time in hours Control Pre Q1 100nM Fold change over Fold change over control control 0.0 0.5 1.0 1.5 2.0 2.5 Fold change in mRNA expression (Normalized to Control) 0 1 2 3 4 0.0 0.5 1.0 1.5 AKR1C2 BAG2 SiPRDX1 eciency APOE FHL2 ATOX1 GCLM Pathway CAT GLA CCL5 HMOX1 CYGB HSP90AA1 DHCR24 LHPP DUOX1 Activit DUOX2 NCOA7 DUSP1 NQO1 EPX PTGR1 FOXM1 SLC7A11 y FTH1 SPINK1 GCLC TRAPPC6A GCLM Oxidative stressrespons TXN GPX1 GPX2 TXNRD1 20n 10n N GPX3 S GPX4 M siPRDX1 M siPRDX1 GPX5 GSR GSS HMOX1 HSPA1A KRT LPO MBL2 Fold change over MPO MSRA control 0.0 0.5 1.0 1.5 2.0 NQ01 10 12 14 16 18 20 NUDT1 PDLIM1 e SOD1 Viability PRDX2 SOD2 Normalized to untreated PRDX5 SOD3 0.0 0.5 1.0 1.5 PRDX6 ALOX12 PRNP CCS R RNF7 DUOX1 O S Control SELENEP DUOX2 SELENOS MT3 meta SIRT2 NCF1 SOD1 NCF2 SOD2 boli siPrdx1 NOS2 (iNOS) SQSTM1 NOX4 s PreQ 5 Control SRXN1 NOX5 TPO UCP2 m TTN AOX1 0 nM TXNRD1 BNIP3 TXNRd2 EPHX2 TXN MPV17 SFTPD Fold change over E. control C. A. 0 1 2 3 4 % of CD133+ event Cytokines 0.0 0.5 1.0 1.5 ng/ml ABCB5 0 2 4 6 ABCG2 AC ALCAM Control ALDH1A1 M IL6 ATM CD13 ATXN1 AXL BMI1 3 ACM TNFα BMP7 CD24 Fl CD34 o CD38 w CD44 IFNγ DACH1 DDR1 DLL4 EGF IL17A ENG EPCAM ERBB2 D. FGFR2 withPre-Q after treatment CSC PCRarray IL17F FLOT2 FOXA2 FOXP1 GSK3B Cytokines (ng/ml) IL22 HDAC1 0 1 2 3 IL8 ITGA2 media Adipocyte conditioned JAG1 JAK2 IL6 KIT KITLG TNFα KLF4 H L F LIN28B IFNγ F MUC1 MYC IL17A MYCN NANOG B NFKB1 IL17F . NOS2 NOTCH1 IL22 NOTCH2 Ratio of CD133+/Perilipin+ events PECAM1 0.0 0.5 1.0 1.5 PLAT PLAUR POU5F1 CD13 PROM1 PTCH1 Lean SMO 3 SNAI1 / SOX2 Pe Obese STAT3 r i TAZ li * TGFBR1 p i THY1 n WEE1 WNT1 WWC1 YAP1 ZEB1 ZEB2.
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