Pathways Linking Chronic Pancreatitis to Pancrea...
The concept of the strong link between inflammation and cancer was first proposed in the nineteenth century by Virchow，who observed the presence of inflammation cells within neoplastic tissues（Balkwill and Mantovani 2001）.Epidemiological and clinical researches support his hypothesis and reveal the causal link between chronic inflammation and cancer.For example，the ulcerative colitis，which is a common chronic inflammatory disease affecting the large bowel mucosa，may provide the strongest evidence to whether and how inflammation affect carcinogenesis progress.Patients with ulcerative colitis are more predisposed to colorectal cancer，which is in the order of tenfold greater than that in the general Western population（Itzkowitz and Yio 2004）.Inflammation-cancer connection is not unique to a subset of tumors，but universally identified within different cancer types，including lung，bladder，gastrointestinal tract，skin and vulva.Use of anti-inflammatory medications，e.g.，aspirin，is usually associated with protection against various tumors，which to some extent substantiate that inflammation is a risk factor for many types of cancer（McKay et al.2008）.While the link between inflammation and cancer is clearly strong，detailed mechanisms underlying this connection warrant more studies.The chronic pancreatitis-pancreatic cancer link has also been established in different ethnic cohorts independently by different groups.Nonetheless，“chronic pancreatitis-pancreatic cancer”connection holds certain traits different from other cancer types.For example，COX-2 levels were significantly elevated in chronic pancreatitis patients，and targeted therapy against COX-2 appears be a good therapeutic strategy to treat chronic pancreatitis（Reding et al.2006）.However，aspirin，the most commonly used COX-2 inhibitor，exhibits controversial effects to pancreatic cancer（Jacobs et al.2004）.Extended periods of regular aspirin use may likely increase risk of pancreatic cancer among women（Schernhammer et al.2004）.These inconsistent results suggested that there exist a complex network among pancreatic cells and inflammatory milieu，and a list of comprehensive studies is needed to explore or validate current knowledge framework concerning“inflammationcancer”connection in pancreatic cancer.To this end，multiple animal models have been established for dissecting the effects of inflammatory mediators and anti-inflammatory drugs on“chronic pancreatitis-pancreatic cancer”progression（Mazur et al.2015）.Currently used animal models are primarily developed based on the genetic activation of resident K-ras oncogenes knocked-in within the endogenous K-ras locus（Olive et al.2009）.These models faithfully recapitulate the histological lesions that characterize many aspects of human pancreatic tumors，including a desmoplastic stroma and inflammatory responses that closely resemble those observed in human patients.Of particular interest，these animals will not develop into pancreatic cancer，unless undergo pancreatic damage in the form of pancreatitis（Hingorani et al.2003）.These results further confirm the indispensable functions of inflammation in pancreatic carcinogenesis.Many insightful mechanisms have been identified linking pancreatitis and pancreatic cancer by using the genetic animal models and can be arguably grouped into intrinsic pathway and extrinsic pathway.(https://www.daowen.com)