1. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY RUNX3 Controls a Metastatic Switch in Pancreatic Ductal Adenocarcinoma Cell, 2015, 161(6): 1345-60 肝胆胰外二科 1411110419 崔璨 导师：郝纯毅教授 2015.10.29

2. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Backgrounds Pancreatic Ductal Adenocarcinoma （ PDA ） Lethal Early and extreme penchant for dissemination 2 years >5years 20% >10years 2%

3. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Backgrounds Pancreatic Ductal Adenocarcinoma （ PDA ） KRAS >90% TP53 >75% DPC4/SMAD4 >50%

4. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Backgrounds Trp53 KPC ： Kras G12D/+,Trp53 R172H/+,Dpc4 +/+,p48 Cre/+ Cancer Cell, 2005, 7(5): 469-83

5. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Methods KPC ： Kras G12D/+,Trp53 R172H/+,Dpc4 +/+,p48 Cre/+ KPDC ： Kras G12D/+,Trp53 R172H/+,Dpc4 flox/+,p48 Cre/+

6. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Results

7. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Results

8. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Results KPC 、 KPDC Dpc4/Smad4 TGF-β pathway

9. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY KPC KPDC Results Runx3

10. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY KPC KPDC KPC Results Runx3

11. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY KPDC KPC Results Runx3

12. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Results Remodel the extracellular matrix

13. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Results Remodel the extracellular matrix Spp1

14. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Expel the seed and prepare the soil Results Remodel the extracellular matrix Col6a1

15. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Results Runx3:Tumor suppressor gene(TSG)

16. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Results KPDDC ： Kras G12D/+,Trp53 R172H/+,Dpc4 flox/flox,p48 Cre/+

17. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Results Dpc4 status and Runx3 levels

18. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Results Human PDA cell lines MiaPaCa-2 Panc-1 CFPAC-1 Panc-1 MiaPaCa-2 Panc-1

19. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Results Treatment

20. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Conclusions DPC4 dosage regulates RUNX3 levels in a biphasic manner RUNX3 functions as both tumor suppressor and tumor promoter in PDA DPC4 and RUNX3 levels can jointly inform clinical decision making

21. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Thought Biomarker Local growth Metastasis Clinical decision

22. 肝胆胰腺肿瘤外科 HEPATO-PANCREATO-BILIARY SURGERY Thank You! 肝胆胰外二科 1411110419 崔璨 导师：郝纯毅教授 2015.10.29