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Chemoprevention of second primary cancer in the patients with lung cancer

肺癌患者第二原发癌的化学预防

基本信息

批准号：
16590746
负责人：
KIURA Katsuyuki
金额：
$ 2.18万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590746/
关键词：
AKT MAPK A J mouse NNK cisplatin ras lung cancer second malignancy

项目摘要

The risks of secondary lung cancer in patients with early stage non-small and small cell lung cancers are estimated to be 1-2% and 2-10% per patient per year, respectively. Surprisingly, the incidence of second primary cancer in locally advanced non-small cell lung cancer at 10 years, following cisplatin-based chemotherapy with concurrent radiotherapy, increases to 61%. Those patients, on the road to being cured, cannot overlook the possibility of developing a second primary cancer. We developed a second primary lung cancer model using cisplatin as a carcinogen in A/J mice to screen for chemopreventive agents for a second malignancy. In the primary lung tumour model, 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), benzo(a)pyrene (BaP), urethane induces specific K-ras mutations in codon 12, codon 13, and codon 61, respectively, in the A/J mice. In this study, we investigated the mechanisms of carcinogenicity by cisplatin in the A/J mice. In the cisplatin-induced tumours, we found no K-ras codon 12 mutation, which is the major mutation induced by NNK or BaP. K-ras gene mutations in codon 13 and codon 61 were found in one tumour (4%) and 5 tumours (17.8%), respectively. These findings suggest that cisplatin is partially related to K-ras codon 61 mutations, and that the mechanism of carcinogenicity by cisplatin is different from that by NNK or BaP

据估计，早期非小细胞肺癌和小细胞肺癌患者患继发性肺癌的风险分别为每名患者每年1-2%和2-10%。令人惊讶的是，在局部晚期非小细胞肺癌中，在以顺铂为基础的化疗和同步放射治疗后的10年内，第二原发癌的发生率上升到61%。这些患者在治愈的道路上，不能忽视发展成第二种原发癌症的可能性。我们用顺铂作为致癌物，在A/J小鼠体内建立了第二种原发肺癌模型，以筛选第二种恶性肿瘤的化学预防药物。在原发肺癌模型中，4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone(NNK)、苯并(A)芘(BaP)、氨基甲酸乙酯分别诱导A/J小鼠K-ras基因第12、13、61密码子的特异性突变。本研究探讨顺铂对A/J小鼠的致癌作用机制。在顺铂诱导的肿瘤中，我们没有发现K-ras密码子12突变，这是NNK或BaP诱发的主要突变。K-ras基因第13位密码子突变1例(4%)，61位密码子突变5例(17.8%)。提示顺铂与K-ras密码子61突变有一定关系，其致癌机制与NNK或BaP不同。

项目成果

期刊论文数量（36）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Can dose-dense chemotherapy improve outcome in patients with better prognosis small-cell lung cancer?

剂量密集化疗能否改善预后较好的小细胞肺癌患者的预后？

DOI：
发表时间：
2005
期刊：
Nat Clinic Pract Oncol 2・12
影响因子：
0
作者：
Kiura K;Saijo N
通讯作者：
Saijo N

The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers.

DOI：
发表时间：
2005-02
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
0
作者：
Masaki Tokumo;S. Toyooka;K. Kiura;H. Shigematsu;K. Tomii;M. Aoe;K. Ichimura;T. Tsuda;M. Yano
通讯作者：
Masaki Tokumo;S. Toyooka;K. Kiura;H. Shigematsu;K. Tomii;M. Aoe;K. Ichimura;T. Tsuda;M. Yano

Preoperative concurrent chemoradiotherapy with cisplatin and docetaxel in patients with locally advanced non-small-cell lung cancer