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

我们建立了胰石蛋白/reg蛋白（PSP/reg）特异性单克隆抗体的酶免疫分析法，并测定了该蛋白在血清中的水平，以阐明PSP/reg的临床意义。急性胰腺炎（AP）患者血清PSP/reg水平升高的频率为100%，慢性复发性胰腺炎（CRP）患者为59%，活动性胰腺损伤（如AP或CRP）患者明显高于慢性胰腺炎（CP）患者。ERCP型胰腺炎发作后血清中该蛋白水平升高的时间比淀粉酶水平升高的时间更长。此外，血清PSP/reg水平在各种消化系统癌症中也显著升高（胰腺癌为54%，胃癌为33%，肝细胞癌为38%，胆道癌为50%），所有癌症患者肿瘤切除后均降至正常范围。免疫组化研究表明，胰腺组织中PSP/reg的含量增加，在轻度至中度胰腺损伤的CP患者中出现更多的问题，而在重度胰腺损伤的CP中表达减少。此外，消化系统中50% - 60%的癌组织在恶性细胞中表达PSP/reg蛋白，尽管该蛋白在几乎所有邻近的非癌组织中都不存在。这些结果表明，血清PSP/reg水平可能反映胰腺损伤，特别是在AP或消化道癌症存在时，并且可能是此类病变的敏感标志物。对照组、非钙化CP组、钙化CP组和钙化CP组胰腺液中PSP/reg水平无显著差异。应用原位杂交和RT-PCR技术，研究了reg基因家族中胰腺炎相关蛋白（PAP）在各种消化系统疾病组织中的表达。虽然PAP- mrna在除小肠外的正常组织中未被检测到，但PAP- mrna在一些消化道肿瘤中表达，提示PAP在分化的癌细胞中有异位或癌胎诱导作用。自发性CP模型（雄性WBN/Kob大鼠）在CP特征性图像出现前观察到PAP的表达，而在显示轻度胰腺炎变化的sho-saiko-to （TJ-9）治疗的大鼠中未检测到PAP的表达。因此，PAP的表达可能是早期发现或治疗CP效果的标志。此外，我们已经成功制备了人PAP重组蛋白，并正在生产PAP单克隆抗体，将其应用于临床。少

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