Vnitřní lékařství 1/2021

REVIEW ARTICLES Is autoimmune pancreatitis a risk factor for pancreatic adenocarcinoma? E12 | VNITŘNÍ LÉKAŘSTVÍ / Vnitř Lék 2021; 67(1): e9–e13 / www.casopisvnitrnilekarstvi.cz nucleus, which in turn activates transcriptionof pro‑inflammatory cytokines, adhesionmolecules, chemokines, growth factors, anti‑apoptotic genes, and cyclinD1 (26,27). It shouldbe noted that NF‑kappaB induces the production of other proteins, such as COX-2 and nitric oxide synthetase. Thus, it can be deduced that NK‑kappaB forms themolecular link between the activation of inflammation and the simultaneous loss of the physiological cell cycle in carcinomas, which is referred to as a dualistic effect. The three findings that indicate that NF‑kappaB is an essential factor in pancreatic cancer are: „ 1) NF‑kappaB is activated in 70% of pancreatic cancers and in human pancreatic cell lines such as PANC-1 and BxPC-3 (28,29). „ 2) Supporting arguments fromexperimental studies – e.g. suppression of NF‑kappaB leads to re‑initiation of apoptosis in pancreatic tumor cells (30). „ 3) NF‑kappaB appears to be involved in the early stages of pancre- atic carcinogenesis, which is related to its relationship to the K‑ras oncogene and apoptotic resistance (31). K‑ras mutations play a prominent role in the induction of pan- creatic carcinogenesis. In 2009, Kamisawa et al. published a paper demonstrating high positive rates of K‑ras mutation in pancreatic tissue of individuals with AIP (32). He found positive rates in the tissue of all persons examined with an autoimmune form of pancreatitis. However, K‑ras mutation can be detected in 90% of cases of sporadic pancreatic cancer (33). Conclusion AIP, like sporadic chronic pancreatitis, is a risk factor for pancreatic cancer. Chronic inflammation is a precursor of tumor growth. Whereas in the case of chronic pancreatitis, the inflammation‑tumor sequence is only connected with pancreatic tissue, in the form of chronic AIP, which is one of the clinical manifestations of a group of diseases refe- rred to as IgG4-RD, malignancy may occur in an organ other than the pancreas. It seems that the appearance of such cancers occurs soon after the diagnosis of AIP. Fig. 1. The role of NF-kappaB in the inflammatory process and in the case of inflammation associated with carcinoma (modified according to Zhang et al. (24) – created in collaboration with Service Center for E-Learning at Masaryk University, Faculty of Informatics). A – Leukocytes and stromal cells secrete an abundance of proinflammatory proteins during inflammation. B – Proinflammatory factors in the microenvironment of latent pre-malignant cells lead to the accumulation of DNA damage, which, in turn, causes these cells to become malignant. C – Activation of NF-kappaB in pre-malignant cells induces anti-apoptotic signals, which prevents apoptosis and enhances their proliferation. D and E – Leukocytes and stromal cells secret proinflammatory proteins in their chronically inflamed microenvironment, which stimulates tumor progression and metastasis