Inflammatory Pathogenesis in Pancreatic Cancer Development and Its Therapy Strategy_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Hu ¹ , LIU Xubao. ²

Department of Gastroenterology, West China Hospital, Sichuan University， Chengdu 610041, China;

Corresponding author：

Keywords：

Pancreatic cancer Inflammatory pathogenesis Therapy

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【Abstract】Objective To investigate the relationship between the development of pancreatic cancer and inflammation, and the therapy strategy.
Methods Related articles were reviewed.
Results The pathogenesis of inflammation in pancreatic cancer development involves cytokines, NF-κB, COX-2, PPAR-γ, DNA damage, gene changes，etc. Based on these mechanisms some medications are under developing.
Conclusion Accumulative effects of pancreatic inflammation may lead to DNA changes, and even pancreatic cancer development. Medications aimed at suppressing pancreatic inflammation may help with prevention and treatment of pancreatic cancer.

Citation： ZHANG Hu,LIU Xubao.. Inflammatory Pathogenesis in Pancreatic Cancer Development and Its Therapy Strategy. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2004, 11(5): 470-472. doi: Copy

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2.	Lowenfels AB, Maisonneuve P, Cavallini G, et al. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group [J].N Engl J Med, 1993; 328(20)∶1433.
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7.	Wang W, Abbruzzese JL, Evans DB, et al. The nuclear factorkappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells [J]. Clin Cancer Res, 1999; 5(1)∶119.
8.	Shi Q, Abbruzzese JL, Huang S, et al. Constitutive and inducible interleukin 8 expression by hypoxia and acidosis renders human pancreatic cancer cells more tumorigenic and metastatic [J]. Clin Cancer Res, 1999; 5(11)∶3711.
9.	Kokawa A, Kondo H, Gotoda T, et al. Increased expression of cyclooxygenase2 in human pancreatic neoplasms and potential for chemoprevention by cyclooxygenase inhibitors [J]. Cancer, 2001; 91(2)∶333.
10.	Motomura W, Okumura T, Takahashi N, et al. Activation of peroxisome proliferatoractivated receptor gamma by troglitazone inhibits cell growth through the increase of p27KiP1 in human. Pancreatic carcinoma cells [J]. Cancer Res, 2000; 60(19)∶5558.
11.	Jackson AL, Loeb LA. The contribution of endogenous sources of DNA damage to the multiple mutations in cancer [J]. Mutat Res, 2001; 477(1-2)∶7.
12.	Wiseman H, Halliwell B. Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer [J]. Biochem J, 1996; 313 (Pt 1)∶17.
13.	Hussain SP, Amstad P, Raja K, et al. Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancerprone chronic inflammatory disease [J]. Cancer Res, 2000; 60(13)∶3333.
14.	Brentnall TA, Chen R, Lee JG, et al. Microsatellite instability and Kras mutations associated with pancreatic adenocarcinoma and pancreatitis [J]. Cancer Res, 1995; 55(19)∶4264.
15.	Jaffee EM, Schutte M, Gossett J, et al. Development and characterization of a cytokinesecreting pancreatic adenocarcinoma vaccine from primary tumors for use in clinical trials [J]. Cancer J Sci Am, 1998; 4(3)∶194.
16.	Yoshida Y, Tasaki K, Miyauchi M, et al. Impaired tumorigenicity of human pancreatic cancer cells retrovirally transduced with interleukin12 or interleukin15 gene [J]. Cancer Gene Ther, 2000; 7(2)∶324.
17.	Schwartz SA, Hernandez A, Mark Evers B. The role of NFkappaB/IkappaB proteins in cancer: implications for novel treatment strategies [J]. Surg Oncol, 1999; 8(3)∶143.
18.	Okami J, Yamamoto H, Fujiwara Y, et al. Overexpression of cyclooxygenase2 in carcinoma of the pancreas [J]. Clin Cancer Res, 1999; 5(8)∶2018.
19.	Suh N, Wang Y, Williams CR, et al. A new ligand for the peroxisome proliferatoractivated receptorgamma (PPARgamma), GW7845, inhibits rat mammary carcinogenesis [J]. Cancer Res, 1999; 59(22)∶5671.
20.	Woutersen RA, Appel MJ, Van GarderenHoetmer A. Modulation of pancreatic carcinogenesis by antioxidants [J]. Food Chem Toxicol, 1999; 37(9-10)∶981.

1. Lowenfels AB, Maisonneuve P, DiMagno EP, et al. Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group [J]. J Natl Cancer Inst, 1997; 89(6)∶442.
2. Lowenfels AB, Maisonneuve P, Cavallini G, et al. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group [J].N Engl J Med, 1993; 328(20)∶1433.
3. Friess H, Guo XZ, Nan BC, et al. Growth factors and cytokines in pancreatic carcinogenesis [J]. Ann N Y Acad Sci， 1999; 880∶110.
4. Kleeff J, Kusama T, Rossi DL, et al. Detection and localization of Mip3alpha/LARC/Exodus, a macrophage proinflammatory chemokine, and its CCR6 receptor in human pancreatic cancer [J]. Int J Cancer, 1999; 81(4)∶650.
5. McCawley LJ, Matrisian LM. Tumor progression: defining the soil round the tumor seed [J]. Curr Biol, 2001; 11(1)∶R25.
6. Kornmann M, Ishiwata T, Itakura J, et al. Increased cyclin D1 in human pancreatic cancer is associated with decreased postoperative survival [J]. Oncology, 1998; 55(4)∶363.
7. Wang W, Abbruzzese JL, Evans DB, et al. The nuclear factorkappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells [J]. Clin Cancer Res, 1999; 5(1)∶119.
8. Shi Q, Abbruzzese JL, Huang S, et al. Constitutive and inducible interleukin 8 expression by hypoxia and acidosis renders human pancreatic cancer cells more tumorigenic and metastatic [J]. Clin Cancer Res, 1999; 5(11)∶3711.
9. Kokawa A, Kondo H, Gotoda T, et al. Increased expression of cyclooxygenase2 in human pancreatic neoplasms and potential for chemoprevention by cyclooxygenase inhibitors [J]. Cancer, 2001; 91(2)∶333.
10. Motomura W, Okumura T, Takahashi N, et al. Activation of peroxisome proliferatoractivated receptor gamma by troglitazone inhibits cell growth through the increase of p27KiP1 in human. Pancreatic carcinoma cells [J]. Cancer Res, 2000; 60(19)∶5558.
11. Jackson AL, Loeb LA. The contribution of endogenous sources of DNA damage to the multiple mutations in cancer [J]. Mutat Res, 2001; 477(1-2)∶7.
12. Wiseman H, Halliwell B. Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer [J]. Biochem J, 1996; 313 (Pt 1)∶17.
13. Hussain SP, Amstad P, Raja K, et al. Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancerprone chronic inflammatory disease [J]. Cancer Res, 2000; 60(13)∶3333.
14. Brentnall TA, Chen R, Lee JG, et al. Microsatellite instability and Kras mutations associated with pancreatic adenocarcinoma and pancreatitis [J]. Cancer Res, 1995; 55(19)∶4264.
15. Jaffee EM, Schutte M, Gossett J, et al. Development and characterization of a cytokinesecreting pancreatic adenocarcinoma vaccine from primary tumors for use in clinical trials [J]. Cancer J Sci Am, 1998; 4(3)∶194.
16. Yoshida Y, Tasaki K, Miyauchi M, et al. Impaired tumorigenicity of human pancreatic cancer cells retrovirally transduced with interleukin12 or interleukin15 gene [J]. Cancer Gene Ther, 2000; 7(2)∶324.
17. Schwartz SA, Hernandez A, Mark Evers B. The role of NFkappaB/IkappaB proteins in cancer: implications for novel treatment strategies [J]. Surg Oncol, 1999; 8(3)∶143.
18. Okami J, Yamamoto H, Fujiwara Y, et al. Overexpression of cyclooxygenase2 in carcinoma of the pancreas [J]. Clin Cancer Res, 1999; 5(8)∶2018.
19. Suh N, Wang Y, Williams CR, et al. A new ligand for the peroxisome proliferatoractivated receptorgamma (PPARgamma), GW7845, inhibits rat mammary carcinogenesis [J]. Cancer Res, 1999; 59(22)∶5671.
20. Woutersen RA, Appel MJ, Van GarderenHoetmer A. Modulation of pancreatic carcinogenesis by antioxidants [J]. Food Chem Toxicol, 1999; 37(9-10)∶981.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Inflammatory Pathogenesis in Pancreatic Cancer Development and Its Therapy Strategy

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