Analysis of stress-inducible genes as predictive markers for response to chemotherapeutic drug in gastrointestinal cancer

应激诱导基因分析作为胃肠癌化疗药物反应的预测标记

• 批准号: 18591492
• 负责人: UEDA Shugo
• 金额: $ 2.49万
• 依托单位: Tazuke Kofukai Medical Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591492/
• 关键词: anticancer drug; chemosensitivity; predictive marker; galectin-7; thioredoxin; adverse event; stress; cisplatin; 進行胃癌; 感受性マーカー; 肺癌; 間質性肺炎

Chemotherapeutic agents have an important role in treatment for advanced cancer, and it is necessary to develop predictive markers for the drug response. The purpose of this research was to identify the predictive markers among stress-inducible genes that regulate apoptosis signal using clinical cancer samples.We showed that neoadjuvant chemotherapy with S-1 and cisplatin was effective for advanced gastric cancer patients. Although we examined the gene expression in the cancer samples collected endoscopically before chemotherapy, we could not specify genes that predict the chemo-sensitivity. We demonstrated that stress-inducible galectin-7 gene was highly expressed in cisplatin-sensitive urinary bladder cancer, and that galectin-7 augmented the cisplatin-induced apoptosis by generation of reactive oxygen species (ROS) and activation of c-Jun N-terminal kinase (JNK).We measured plasma thioredoxin levels in non-small-cell lung cancer patients to identify predictive marker for adverse events during chemotherapy. We showed the plasma thioredoxin levels were high in patients with interstitial lung disease, severe adverse event associated with treatment with epidermal growth factor receptor (EGFR) inhibitor, gefitinib.Our results suggest the future possibility of developing novel tailored therapeutic strategy for cancer by monitoring redox-regulating molecule and stress-inducible gene expression.

化学治疗剂在治疗晚期癌症中具有重要作用，因此有必要为药物反应开发预测标记。这项研究的目的是确定使用临床癌症样本调节凋亡信号的应激诱导基因之间的预测标记。我们表明，新辅助化疗S-1和顺铂对晚期胃癌患者有效。尽管我们在化学疗法之前通过内镜收集的癌症样品检查了基因表达，但我们无法指定预测化学敏感性的基因。我们证明，在顺铂敏感的尿膀胱癌中高度表达应激诱导的乳糖素-7基因，乳肠蛋白-7通过产生反应性氧（ROS）（ROS）增强了顺铂诱导的凋亡，并激活了C-Jun N-末端末端激酶（JNK）。化学疗法期间不良事件的预测标记。我们显示，间质肺疾病患者的血浆硫氧还蛋白水平很高，与表皮生长因子受体（EGFR）抑制剂治疗相关的严重不良事件Gefitinib。

项目成果

Recombinant human thioredoxin-1 becomes oxidized in circulation and suppresses bleomycin-induced neutrophil recruitment in the rat airway

• DOI: 10.1080/10715760701487682
• 发表时间: 2007-01-01
• 期刊: FREE RADICAL RESEARCH
• 影响因子: 3.3
• 作者: Nakamura, Takayuki;Hoshino, Yuma;Nakamura, Hajime
• 通讯作者: Nakamura, Hajime

Sensitizing effect of galectin-7 in urothelial cancer to cisplatin through the accumulation of intracellular reactive oxygen species

• DOI: 10.1158/0008-5472.can-06-3283
• 发表时间: 2007-02-01
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Matsui, Yoshiyuki;Ueda, Shugo;Nishiyama, Hiroyuki
• 通讯作者: Nishiyama, Hiroyuki

Sensitizing effect of galectin-7 in urothelial cancer to cisplatin throuth the accumulation of intracellular reactive oxygen species

半乳糖凝集素7通过细胞内活性氧积累对尿路上皮癌顺铂增敏作用

• 发表时间: 2007
• 期刊: Cancer Research 67
• 作者: Matsui Y;et. al.
• 通讯作者: et. al.

Recombinant human thioredoxin suppresses lipopolysaccharide-induced bronchoalveolar neutrophil infiltration in rat

• DOI: 10.1016/j.lfs.2006.03.026
• 发表时间: 2006-08-15
• 期刊: LIFE SCIENCES
• 影响因子: 6.1
• 作者: Ueda, Shugo;Nakamura, Takayuki;Nakamura, Hajime
• 通讯作者: Nakamura, Hajime

Elevation of serum thioredoxin in patients with gefitinib-induced interstitial lung disease

• DOI: 10.2169/internalmedicine.46.0220
• 发表时间: 2007-01-01
• 期刊: INTERNAL MEDICINE
• 影响因子: 1.2
• 作者: Sakuma, Keiichiro;Nakamura, Hajime;Mio, Tadashi
• 通讯作者: Mio, Tadashi