Pathophysiological and Clinical Significances of Specific Proteins which Are Related to Pancreatitis

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We developed an enzyme-immunoassay using monoclonal antibody specific for pancreatic stone protein/reg-protein (PSP/reg), and determined levels of this protein in sera to elucidate the clinical significances of PSP/reg. Frequencies of elevated levels of serum PSP/reg were 100% in acute pancreatitis (AP) and 59% in chronic relapsing pancreatitis (CRP), and were significantly higher in active pancreatic injury such as AP or CRP than those in chronic pancreatitis (CP). Elevated serum levels of this protein after attack of pancreatitis of ERCP tended to be more prolonged than those of amylase. Furthermore, the serum PSP/reg levels were also significantly increased in various cancers of the digestive system (54% in pancreatic cancer (PC), 33% in gastric cancer, 38% in hepatocellular carcinoma and 50% in biliary cancer), and decreased into the normal range after tumor resection in all cases with cancers. The immunohistochemical study demonstrated increased amounts of PSP/reg in pancreatic ti … More ssues from patients with CP associated with mild-to-moderate pancreatic damage, and decreased expression in CP associated with severe pancreatic damage. Moreover, 50 to 60% of cancer tissues from the digestive system expressed the PSP/reg-protein in malignant cells, although this protein was absent from almost all of the adjacent non-cancerous tissues. These results indicate that the serum PSP/reg levels may reflect pancreatic damage, espcially in AP or presence of digestive cancer, and may be as sensitive a marker for such lesions. On the other hand, there was no significant differences in levels of PSP/reg in pancreatic juice among the groups of control, non-calcitying CP,calcifying CP and PC.The expression of pancreatitis-associated protein (PAP) belonging to reg-gene family was investigated in tissues from various digestive diseases, using in situ hybridization and RT-PCR.Although PAP-mRNA was not detected in normal tissues except for small intestine, PAP-mRNA was expressed in some cases of digestive cancers, suggesting an ectopic or oncofetal induction of PAP in differentiated cancer cells. The expression of PAP was observed in spontaneous occurring CP model (male WBN/Kob rat) before a characteristic picture of the CP appeared, and was not detectable in the rats treated by sho-saiko-to (TJ-9) which showed mild changes of pancreatitis. Therefore, the expression of PAP may be a marker for early detection or therapeutic effect in CP Moreover, we have succeeded in preparing recombinant of human PAP,and are producing monoclonal antibody to PAP to apply it to clinical applications. Less