The personalized therapy using Annexin II as a gemcitabine-resistant factor for pancreatic cancer patients after surgery.

使用膜联蛋白 II 作为吉西他滨耐药因子对胰腺癌患者术后进行个体化治疗。

• 批准号: 20591622
• 负责人: TAKANO Shigetsugu
• 金额: $ 3万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591622/
• 关键词: 膵臓外科学; 膵臓癌; 腫瘍マーカー; 抗癌剤耐性; 個別化治療

Background : Although gemcitabine has been widely used as a first-line chemo reagent for patients with pancreatic cancer, the response rate still remains low. We previously identified Annexin II as a factor involved in gemcitabine resistance against pancreatic cancer. The aim of this study was to elucidate the signaling mechanism by which Annexin II induces gemcitabine resistance and to develop a new therapy which overcomes the resistance against gemcitabine.Materials and methods : We comprehensively investigated and compared the specific profiles of 12 targeted phosphorylated signaling proteins in gemcitabine-resistant (GEM-MIA PaCa-2) and wild-type (WT-MIA PaCa-2) pancreatic cancer cell lines by the Bio-Plex phosphorylation protein assay system. We also evaluated the expression levels of Annexin II and two phosphoproteins, which showed different expression in these two cell lines, by immunohistochemistry of pancreatic cancer tissues.Results : Annexin II overexpression in cancer cells was significantly associated with rapid recurrence after gemcitabine-adjuvant chemotherapy in patients with resected pancreatic cancer (P=0.0118). Bio-Plex analysis showed upregulation of p-Akt in GEM-MIA PaCa-2 cells in which Annexin II is highly expressed. On immunohistochemistry, the expression level of p-Akt was significantly correlated with that of p-mTOR in pancreatic cancer tissues. Inhibition of mTOR phosphorylation canceled gemcitabine resistance in GEM-MIA PaCa-2 cells.Conclusion : The Akt/mTOR pathway is involved in the mechanisms of gemcitabine resistance induced by Annexin II in pancreatic cancer cells. Annexin II as an indicator for selection of gemcitabine resistance could thus be applied to the development of novel tailor-made approaches for pancreatic cancer treatment.

背景资料：虽然吉西他滨已被广泛用作胰腺癌患者的一线化疗药物，但其缓解率仍然很低。我们以前确定膜联蛋白II是吉西他滨对胰腺癌耐药的一个因素。本研究的目的是阐明膜联蛋白II诱导吉西他滨耐药的信号传导机制，并开发一种克服吉西他滨耐药的新疗法。我们全面研究并比较了吉西他滨耐药细胞中12种靶向磷酸化信号蛋白的特异性谱，通过Bio-Glycoprotein磷酸化蛋白测定系统，对GEM-MIA PaCa-2）和野生型（WT-MIA PaCa-2）胰腺癌细胞系进行比较。我们还评估了膜联蛋白II和两个磷蛋白的表达水平，这表明在这两个细胞系的表达不同，胰腺癌tissue.Results免疫组化：膜联蛋白II在癌细胞中的过度表达与吉西他滨辅助化疗后切除的胰腺癌患者的快速复发显着相关（P=0.0118）。生物荧光分析显示在膜联蛋白II高度表达的GEM-MIA PaCa-2细胞中p-Akt上调。免疫组化结果显示，胰腺癌组织中p-Akt和p-mTOR的表达水平显著相关。结论：Akt/mTOR通路参与了Annexin II诱导胰腺癌细胞吉西他滨耐药的机制。因此，膜联蛋白II作为选择吉西他滨耐药的指标可以应用于开发新的量身定制的胰腺癌治疗方法。

项目成果

効果的な個別化治療を目指した膵癌分子標的治療薬の選択

胰腺癌分子靶向药物的选择以实现有效的个体化治疗

• 发表时间: 2010
• 作者: Kikkawa Y;Sudo R;Kon J;Mizuguchi T;Nomizu M;Hirata K;Mitaka T.;高野重紹
• 通讯作者: 高野重紹

Increased circulating cell signaling phosphoproteins in sera are useful for the detection of pancreatic cancer.

血清中循环细胞信号磷蛋白的增加可用于检测胰腺癌。

• 发表时间: 2010
• 作者: Nobuoka T;Mizuguchi T;Oshima H;Shibata T;Kaji S;Nagayama M;Meguro M;Mitaka T;Hirata K.;高野重紹;Shigetsugu Takano
• 通讯作者: Shigetsugu Takano

膵癌用抗癌剤の耐性検査マーカー、膵癌用抗癌剤の補助治療薬

胰腺癌抗癌药耐药性检测标志物、胰腺癌抗癌药辅助治疗剂

• 发表时间: 2010

Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells

• DOI: 10.1038/sj.onc.1210951
• 发表时间: 2008-05-01
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Takano, S.;Yoshitomi, H.;Miyazaki, M.
• 通讯作者: Miyazaki, M.

The comprehensive measurement of serum cell signal phosphoproteins is useful for the detection of pancreatic cancer.

血清细胞信号磷蛋白的综合测定有助于胰腺癌的检测。

• 发表时间: 2010
• 作者: Mizuguchi T;et al.;Shigetsugu Takano
• 通讯作者: Shigetsugu Takano