Caffeic acid phenethyl ester decreases acute pneumonitis after irradiation in vitro and in vivo.

Caffeic acid phenethyl ester decreases acute pneumonitis after irradiation in vitro and in vivo.
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咖啡酸苯乙酯在体外和体内辐射后降低急性肺炎。

DOI:
10.1186/1471-2407-5-158
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发表时间:
2005-12-09
期刊:
影响因子:
3.8
通讯作者:
Chen, WC
Chen, WC
中科院分区:
医学2区
文献类型:
--
作者:
Chen, MF;Keng, PC;Lin, PY;Yang, CT;Liao, SK;Chen, WC

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肺癌对放射治疗相对抵抗,放射性肺炎是增加放射剂量的主要障碍。我们以前发现,咖啡酸苯乙酯(CAPE)诱导细胞凋亡,增加肺癌的放射敏感性。为了确定CAPE,一种抗氧化剂和NF-κ B抑制剂,是否可以作为肺癌治疗的一种有用的辅助剂,我们在这项研究中检测了CAPE对照射后的正常肺组织的影响。我们比较了CAPE对正常肺成纤维细胞和肺癌细胞系的细胞毒性和细胞内氧化应激的影响。对于体内分析,在有或没有CAPE预处理的情况下,向BALB/c雄性小鼠递送全胸辐射(单剂量10戈伊和20戈伊)。检测照射后小鼠NF-κ B活化和急性炎症细胞因子的表达水平。体外研究表明,CAPE对正常肺组织的细胞毒性与肺癌细胞相比不明显。这可能是由于正常和恶性肺细胞之间NF-κ B B表达的差异效应。体内研究结果表明,CAPE治疗降低了照射后炎性细胞因子包括IL-1 α和β、IL-6、TNF-α和TGF-β的表达。此外,组织学和免疫化学数据显示,CAPE降低辐射诱导的间质性肺炎和TGF-β表达。这项研究表明,CAPE降低胸部照射诱导的炎症反应级联反应,而不会引起正常肺组织的毒性。这为在进一步的临床研究中结合CAPE和胸部放疗治疗肺癌提供了理论基础。
Lung cancer is relatively resistant to radiation treatment and radiation pneumonitis is a major obstacle to increasing the radiation dose. We previously showed that Caffeic acid phenethyl ester (CAPE) induces apoptosis and increases radiosensitivity in lung cancer. To determine whether CAPE, an antioxidant and an inhibitor of NF-kappa B, could be a useful adjuvant agent for lung cancer treatment, we examine the effects of CAPE on irradiated normal lung tissue in this study. We compared the effects of CAPE on cytotoxicity and intracellular oxidative stress in normal lung fibroblast and a lung cancer cell line. For in vivo analysis, whole thorax radiation (single dose 10 Gy and 20 Gy) was delivered to BALB/c male mice with or without CAPE pretreatment. NF- kappaB activation and the expression levels of acute inflammatory cytokines were evaluated in mice after irradiation. The in vitro studies showed that CAPE cause no significant cytotoxicity in normal lung as compared to lung cancer cells. This is probably due to the differential effect on the expression of NF-kappa B between normal and malignant lung cells. The results from in vivo study showed that CAPE treatment decreased the expression of inflammatory cytokines including IL-1 alpha and beta, IL-6, TNF-alpha and TGF- beta, after irradiation. Moreover, histological and immunochemical data revealed that CAPE decreased radiation- induced interstitial pneumonitis and TGF-beta expression. This study suggests that CAPE decreases the cascade of inflammatory responses induced by thoracic irradiation without causing toxicity in normal lung tissue. This provides a rationale for combining CAPE and thoracic radiotherapy for lung cancer treatment in further clinical studies.
DOI: 10.1016/0167-5699(91)90107-5
发表时间: 1991-01-01
期刊: IMMUNOLOGY TODAY
影响因子: --
作者:
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通讯作者: KOVACS, EJ
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发表时间: 2000-07-01
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影响因子: 7
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