Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polymyositis

Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polymyositis
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DOI:
10.1002/ijc.21118
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发表时间:
2005-10-10
影响因子:
6.4
通讯作者:
Kawakami, Y
Kawakami, Y
中科院分区:
医学1区
文献类型:
--
作者:
Okada, T;Noji, S;Kawakami, Y

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为了鉴定可用于胰腺导管腺癌患者的诊断和免疫治疗的肿瘤抗原,我们应用 SEREX 方法,使用由 5 个胰腺癌细胞系和从 8 名胰腺癌患者获得的血清制成的 cDNA 文库,分离出总共 32 个基因,包括 14 个先前鉴定的基因和 18 个功能未知的基因。在这些分离的抗原中,在胰腺导管腺癌、皮肌炎 (DM) 和多发性肌炎 (PM) 患者中检测到 2 种分离的 DNA 错配修复酶(智人 mutS 同源物 2 (hMSH2) 和智人减数分裂后分离增加 1 (hPMS1))的血清 IgG 抗体,但在健康个体的血清中未检测到。免疫组织化学研究表明,与正常胰管相比,hMSH2 和 hPMS1 在胰腺导管腺癌中过度表达。这些结果表明,hMSH2和hPMS1可作为CD4+辅助T细胞抗原用于胰腺癌患者的免疫治疗,并且血清IgG抗体可用于诊断胰腺导管腺癌和DM/PM患者。 (C) 2005 Wiley-Liss, Inc.
To identify tumor antigens useful for diagnosis and immunotherapy of patients with pancreatic ductal adenocarcinoma, we applied a SEREX approach with a cDNA library made from 5 pancreatic cancer cell lines and sera obtained from 8 patients with pancreatic cancer, and isolated total 32 genes, including 14 previously characterized genes and 18 genes with unknown functions. Among these isolated antigens, serum IgG antibodies for 2 isolated DNA mismatch repair enzymes, Homo sapiens mutS homolog 2 (hMSH2) and Homo sapiens postmeiotic segregation increased 1 (hPMS1), were detected in patients with pancreatic ductal adenocarcinoma and dermatomyositis (DM), and polymyositis (PM), but not in sera from healthy individuals. Immunohistochemical study demonstrated that hMSH2 and hPMS1 were over-expressed in pancreatic ductal adenocarcinoma compared to normal pancreatic ducts. These results suggested that hMSH2 and hPMS1 may be useful as CD4+ helper T cell antigens for immunotherapy of pancreatic cancer patients and that serum IgG antibodies may be useful for diagnosis of patients with pancreatic ductal adenocarcinoma and DM/PM. (C) 2005 Wiley-Liss, Inc.