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

胰腺炎相关特定蛋白的病理生理学及临床意义

• 批准号: 07670578
• 负责人: SAWABU Norio
• 金额: $ 1.6万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670578/
• 关键词: pancreatitis-associated protein (PAP); pancreatic stone protein (PSP); reg-protein; acute pancreatitis; pancreatic cancer; chronic pancreatitis; digestive cancer; spontaneous occurring chronic pancreatitis of rat; Pancreatition-associated protein

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

我们用胰石蛋白/reg蛋白（PSP/reg）单克隆抗体建立了酶免疫分析法，并测定了血清中PSP/reg的水平，以阐明PSP/reg的临床意义。血清PSP/reg升高的频率在急性胰腺炎（AP）为100%，在慢性复发性胰腺炎（CRP）为59%，活动性胰腺损伤（AP、CRP）患者的血清CRP水平明显高于慢性胰腺炎（CP）患者。ERCP胰腺炎发作后血清中这种蛋白的升高比淀粉酶的升高更持久。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（PC）54%，胃癌33%，肝细胞癌38%和胆管癌50%），并且在所有癌症病例中在肿瘤切除术后均降至正常范围。免疫组织化学研究显示胰腺组织中PSP/reg的含量增加， ...更多信息 与轻度至中度胰腺损伤相关的CP患者的胰腺癌，以及与重度胰腺损伤相关的CP中的表达降低。此外，50%至60%的消化系统癌组织在恶性细胞中表达PSP/reg蛋白，尽管几乎所有邻近的非癌组织都不存在这种蛋白。提示血清PSP/reg水平可反映胰腺损害，尤其是AP或消化道癌，并可作为胰腺损害的敏感指标。应用原位杂交和RT-PCR技术检测了reg基因家族的胰腺炎相关蛋白（PAP）在各种消化系统疾病组织中的表达，结果表明，在正常组织中除小肠外均未检测到PAP-mRNA的表达，而在正常组织中仅检测到PAP-mRNA的表达。PAP-mRNA在某些消化道癌中表达，提示PAP在分化的癌细胞中的异位或癌胚诱导。在自发性CP模型（雄性WBN/Kob大鼠）中，在CP特征性图像出现之前观察到PAP的表达，而在经小柴胡汤（TJ-9）治疗的大鼠中未检测到PAP的表达，表现出轻度的胰腺炎变化。因此，PAP的表达可能是CP早期检测或治疗效果的标志。此外，我们已成功地制备了人PAP重组体，并正在制备抗PAP的单克隆抗体，以应用于临床。少

项目成果

Satomura Y,et al.: "Measurement of serum PSP reg-protein concentration in various disease with a newly developed enzymed-linked immunosorbent assay" J.Gastroenterol. 30・5. 643-650 (1995)

Satomura Y等人：“用新开发的酶联免疫吸附测定法测量各种疾病中的血清PSP reg蛋白浓度”J.Gastroenterol 30・5（1995）。

Watanabe H, et al: "Detection K-ras point mutations at codon 12 in pure pancreatic juice for the diagnosis of pancreatic cancer by analysis of PCR-RFLP method" Pancreas. 12. 18-24 (1996)

Watanabe H 等人：“通过 PCR-RFLP 方法分析，检测纯胰液中密码子 12 处的 K-ras 点突变，用于诊断胰腺癌”《胰腺》。

澤武紀雄, ほか: "新しい膵関連蛋白と遺伝子研究の進歩:reg遺伝ファミリー" 臨床消化器内科. 70. 913-920 (1995)

Takeo Sawa 等人：“新的胰腺相关蛋白和基因研究进展：reg 基因家族”《临床胃肠病学》70. 913-920 (1995)。

澤武紀雄,ほか: "膵癌のK-ras癌遺伝子の点突然変異とその膵液中分析の膵癌診断への応用" 日本臨床. 53. 511-517 (1995)

Takeo Sawa 等人：“胰腺癌中 K-ras 癌基因的点突变及其在胰液分析中诊断胰腺癌的应用”，53. 511-517 (1995)。

Satomura Y, et al.: "Measurement of serum PSP reg-protein concentration in various diseasa with a newly developed enzymed-linked immunosorbent assay" J. Gastroenterol. 30. 643-650 (1995)

Satomura Y 等人：“使用新开发的酶联免疫吸附测定法测量各种疾病中的血清 PSP reg 蛋白浓度”J. Gastroenterol。