The basic and clinical research regarding development of combinationalchemotherapy with nitric oxide donating drugs for non-small cell lung cancer

一氧化氮供体药物联合化疗治疗非小细胞肺癌的基础与临床研究

• 批准号: 19689018
• 负责人: YASUDA Hiroyasu
• 金额: $ 17.22万
• 依托单位: Tohoku University (2008-2009)Kyoto University (2007)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (A)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19689018/
• 关键词: 非小細胞肺癌; 低酸素誘導性抗がん薬耐性化機序; 低酸素誘導因子; 腫瘍内微小循環; 一酸化窒素; ニトログリセリン; 多施設第II相proof of concept臨床試験; P糖蛋白; 血管内皮成長因子; 生存シグナル; 化学療法; 多施設無作為化臨床試験; 腫瘍内低酸素; 腫瘍微小循環; 腫瘍循環; P糖蛋白質

In basic science, I showed that nitroglycerin (GTN) significantly reduced HIF-1 alpha, P-glycoprotein, VEGF, P-Akt, and P-CREB in tumor tissues in vivo, resulting in enhancing chemosensitivity of cancer cells to anti-cancer drugs including cisplatin and docetaxel. I started and have been performing three clinical trials regarding combinational chemotherapy with GTN for the next phase III trials, as following : 1) Randomized multicenter phase II trial comparing paclitaxel and carboplatin with GTN with paclitaxel and carboplatin alone in patients with previously untreated advanced non-small cell lung cancer (NSCLC) ; 2) Single arm phase II trial of amrubicin and GTN in patients with previously treated advanced NSCLC as third regimen ; 3) Single arm phase II trial of docetaxel and GTN in elderly patients with previously untreated advanced NSCLC.

在基础科学中，我表明硝酸甘油（GTN）显着降低了体内肿瘤组织中的HIF-1α，P-糖蛋白，VEGF，P-AKT和P-CREB包括顺铂和多西他赛。我开始并一直在进行三项临床试验，以进行下一个III期试验的GTN与GTN结合化化疗，如下：1）与先前未经固定的高级非培训的高级先进的高级高级先进的高级非甲甲烷和卡泊蛋白相比，与GTN与GTN与GTN与GTN与GTN与GTN的随机多中心II期试验进行了比较。小细胞肺癌（NSCLC）； 2）AMRUBICIN和GTN的单臂II期试验在先前治疗的NSCLC作为第三个方案的患者中； 3）多西他赛和GTN的单臂II期试验对先前未经治疗的晚期NSCLC的老年患者。

项目成果

肺線癌症例におけるニトログリセリン使用による腫瘍内HIF-1 pathwayの抑制効果

硝酸甘油对肺癌瘤内HIF-1通路的抑制作用

• 发表时间: 2007
• 作者: 安田浩康、中山勝敏、浅田成紀;ら
• 通讯作者: ら

Glyceryl Trinitrate may enhance chemosensitivity to cisplatin and docetaxel via inhibitions of Akt signaling pathway and HIF-1 pathway and via activation of p53 in murine syngraft solid cancer model

在小鼠同种移植实体瘤模型中，三硝酸甘油酯可能通过抑制 Akt 信号通路和 HIF-1 通路以及激活 p53 来增强对顺铂和多西紫杉醇的化疗敏感性

• 发表时间: 2008
• 作者: Yasuda H;et.al.
• 通讯作者: et.al.

Interleukin-1beta gene polymorphisms associated with risk of lung cancwe in Japanese

白介素-1β基因多态性与日本肺癌风险相关

• 发表时间: 2007
• 作者: Asada M;Yasuda H;Ebihara S;et al.
• 通讯作者: et al.

Partial response by nitroglycerin plus amrubicin regimen in patients with refractory and recurrent advanced non-small cell lung cancer who had received at least third-line chemotherapy

硝酸甘油加氨柔比星方案对至少接受过三线化疗的难治性和复发性晚期非小细胞肺癌患者有部分缓解

• 发表时间: 2007
• 期刊: Cancer Therapy 5
• 作者: Yasuda H;et. al.
• 通讯作者: et. al.

The effects of low-dose inhaled carbon monoxide on the dyspnea in patients with chronic obstructive pulmonary disease

小剂量吸入一氧化碳对慢性阻塞性肺疾病患者呼吸困难的影响

• 发表时间: 2009
• 作者: Ohshima S;Yamamoto S;Yamaji T;Suzuki M;Mutoh M;Iwasaki M;Sasazuki S;Kotera K;Tsugane S;Muramatsu Y;Moriyama N.;安田浩康
• 通讯作者: 安田浩康