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，我发现硝酸甘油（GTN）在体内显著降低肿瘤组织中的HIF-1 α、P-糖蛋白、VEGF、P-Akt和P-CREB，从而增强癌细胞对顺铂和多西他赛等抗癌药物的化疗敏感性。我开始并一直在进行三项关于GTN联合化疗的III期临床试验，如下：1）比较紫杉醇和卡铂与GTN与紫杉醇和卡铂单药治疗既往未经治疗的晚期非小细胞肺癌（NSCLC）患者的随机多中心II期试验; 2）氨柔比星和GTN作为第三方案在既往接受过治疗的晚期NSCLC患者中的单臂II期试验; 3）多西他赛和GTN在既往未接受过治疗的晚期NSCLC老年患者中的单臂II期试验。

项目成果

Carbocisteine inhibits oxidant‐induced apoptosis in cultured human airway epithelial cells

• DOI: 10.1111/j.1440-1843.2009.01594.x
• 发表时间: 2009-09
• 期刊: Respirology
• 影响因子: 6.9
• 作者: Motoki Yoshida;K. Nakayama;H. Yasuda;H. Kubo;K. Kuwano;H. Arai;M. Yamaya

Therapeutic Applications of Nitric Oxide for Malignant Tumor in Animal Models and Human Studies

一氧化氮在动物模型和人体研究中对恶性肿瘤的治疗应用

• DOI: 10.1007/978-1-4419-1432-3_22
• 发表时间: 2010
• 期刊: Gynecologic oncology
• 影响因子: 4.7
• 作者: H. Yasuda;K. Yanagihara;K. Nakayama;T. Mio;Takahiko Sasaki;M. Asada;M. Yamaya;M. Fukushima
• 通讯作者: M. Fukushima

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

Prolonged neutropenia after dose-dense chemo the rapy with pegfilgrastim

聚乙二醇化非格司亭剂量密集化疗后长期中性粒细胞减少症

• DOI: 10.1093/annonc/mdn051
• 发表时间: 2008
• 期刊: Ann Oncol
• 影响因子: 50.5
• 作者: Ishiguro H(1番目);Yanagihara K;et al
• 通讯作者: et al

Initial evaluation of dynamic human imaging using 18F-FRP170 as a new PET tracer for imaging hypoxia

• DOI: 10.1007/bf03033987
• 发表时间: 2007-02-01
• 期刊: ANNALS OF NUCLEAR MEDICINE
• 影响因子: 2.6
• 作者: Kaneta, Tomohiro;Takai, Yoshihiro;Yamada, Shogo
• 通讯作者: Yamada, Shogo