Chemoprevention of cancer of the upper respiratory tract of the Syrian golden hamster by aerosol administration of difluoromethylornithine and 5-fluorouracil.
Chemoprevention of cancer of the upper respiratory tract of the Syrian golden hamster by aerosol administration of difluoromethylornithine and 5-fluorouracil.
复制标题
通过雾化二氟甲基鸟氨酸和 5-氟尿嘧啶对叙利亚金仓鼠上呼吸道癌症进行化学预防。
DOI：
10.1158/0008-5472.can-03-4032
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发表时间：
2004
期刊：
影响因子：
11.2
通讯作者：
Estensen,RichardD
中科院分区：
文献类型：
--
作者：
Wattenberg,LeeW;Wiedmann,TimothyS;Estensen,RichardD
Research aimed at identifying effective chemopreventive compounds active against carcinogenesis of the upper respiratory tract (URT) has been largely unsuccessful. We are addressing this problem by efforts at agent identification and by using aerosol delivery. Two compounds, difluoromethylornithine (DFMO) and 5-fluorouracil (5-FU) were investigated. DFMO is an irreversible inhibitor of ornithine decarboxylase, an enzyme important in cell proliferation. It has been used widely by oral administration for chemoprevention. 5-FU is a pyrimidine analog used extensively as a chemotherapeutic agent. It is generally administered i.v. and can cause considerable toxicity. However, aerosol administration for therapy of lung cancer in humans has been reported to be without adverse effects (Tatsumuraet al., Br J Cancer 1993;68:1146–9). The experimental model used herein entailed six intratracheal administrations of methylnitrosourea (MNU) to hamsters. Each of the test agents was started about 1 week after MNU and was continued for 29 weeks with DFMO. Infiltrating squamous cell carcinomas of the URT occurred in 92% of the controls and were reduced by 50% in animals receiving DFMO (P= 0.0001). The experiment with 5-FU was of shorter duration being terminated 20 weeks after MNU. Thirty percent of the controls had infiltrating carcinomas and were reduced by 60% in animals receiving 5-FU (P= 0.0274). Both compounds resulted in a significant increase in the percent of cancer-free animals. These two agents may have selected use in subjects at high risk of cancer of the URT.
