Studies on effective molecular targeted therapy for head and neck cancer

头颈癌有效分子靶向治疗研究

• 批准号: 18591877
• 负责人: TSUKUDA Mamoru
• 金额: $ 2.53万
• 依托单位: Yokohama City University
• 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-18591877/
• 关键词: Head and Neck Cancer; molecular-targeted therapy; EGFR; VEGF; HER2

All the 16 head and neck squamous cell carcinoma (HNSCC) established in our institute expressed EGFR protein and mRNA. Silent heterogous mutation on exon 20 of EGFR gene was detected in all the 16 cell lines, however mutation on exon 19 or exon 20 associated with sensitivity to EGFR inhibitor was not observed in these 16 HNSCC lines.The cell lines with mutation on exon 20 was more sensitive to gefitinib, one of EGFR inhibitors, than the cell lines without mutation (wild type).The exprssions of HER2 protein and mRNA were observed in these 16 cell lines hoeever the growth of these cell lines was not inhibited by the treatment of herceptin, monoclonal antibody against HER2, alone. In 6 of 16 cell lines, the combined treatment of gefitinib and herceptin showed a higher growth inhibition than the treatment of gefitinib alone. The anti-tumor mechanism of the combined treatment is thought to be a blockage of heterodimarization between EGFR and HER.2.On the other hand bevacizumab which is a dual inhibitor of EGFR and VEGF, showed a strong anti-tumor effect in a model using nude mice transplanted with a human HNSCC line. Especially, the tumor treated with bevacizumab and paclitaxel completely disappeared. The induction of apoptosis and inhibition of angiogenesis were confirmed in terms of the anti-tumor mechanisms.

本院16例头颈部鳞状细胞癌（HNSCC）均表达EGFR蛋白和mRNA。16株HNSCC细胞系中均检测到EGFR基因外显子20的沉默异质突变，但未发现与EGFR抑制剂敏感性相关的外显子19或外显子20的突变。外显子20突变的细胞系对EGFR抑制剂吉非替尼的敏感性高于未突变的细胞系（野生型）。HER2单克隆抗体herceptin对16株细胞株的生长均无抑制作用，但HER2蛋白和mRNA在16株细胞株中均有表达。在16个细胞系中的6个中，吉非替尼和赫赛汀联合治疗显示出比吉非替尼单独治疗更高的生长抑制作用。联合治疗的抗肿瘤机制被认为是阻断EGFR和her之间的异源二聚化。另一方面，贝伐单抗是EGFR和VEGF的双重抑制剂，在移植人HNSCC细胞系的裸鼠模型中显示出很强的抗肿瘤作用。特别是贝伐单抗联合紫杉醇治疗后肿瘤完全消失。在抗肿瘤机制方面，证实了其诱导细胞凋亡和抑制血管生成的作用。

项目成果

Anti-tumor effects of bevacizumab in combination with paclitaxel in head and neck squamous cell carcinoma.

贝伐珠单抗联合紫杉醇治疗头颈鳞状细胞癌的抗肿瘤作用。

• 发表时间: 2007
• 期刊: oncology report 18(1)(in press)
• 作者: Tsukuda M;Fujita K
• 通讯作者: Fujita K

New approaches to preserve functions in head and neck cancer

保留头颈癌功能的新方法

• 发表时间: 2007
• 作者: Tsukuda;M
• 通讯作者: M

Relationship between p21 and p53 expression, human papilloma virus infection and malignant transformation in sinonasal-inverted papilloma

• DOI: 10.1016/j.clon.2005.11.001
• 发表时间: 2006-05-01
• 期刊: CLINICAL ONCOLOGY
• 影响因子: 3.4
• 作者: Katori, H;Nozawa, A;Tsukuda, M
• 通讯作者: Tsukuda, M

Head and Neck 頭頸部癌 IV.頭頸部癌に対する分子標的療法

头颈 头颈癌 四、头颈癌分子靶向治疗

• 发表时间: 2007
• 期刊: 癌と化学療法 34巻7号
• 作者: Tsukuda;M;Taguchi;T;佃 守
• 通讯作者: 佃 守

Antitumor effect of gefitinib on head and neck squamous cell carcinoma enhanced by trastuzumab

• DOI: 10.3892/or_00000017
• 发表时间: 2008-08-01
• 期刊: ONCOLOGY REPORTS
• 影响因子: 4.2
• 作者: Kondo, Norio;Ishiguro, Yukari;Tsukuda, Mamoru
• 通讯作者: Tsukuda, Mamoru