Blockade of growth factor receptors in ductal carcinoma in situ inhibits epithelial proliferation
Blockade of growth factor receptors in ductal carcinoma in situ inhibits epithelial proliferation
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DOI：
10.1046/j.1365-2168.2001.01686.x
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发表时间：
2001-03-01
影响因子：
9.6
通讯作者：
Bundred, NJ
中科院分区：
文献类型：
--
作者：
Chan, KC;Knox, WF;Bundred, NJ
背景：导管原位癌（DCIS）表达c-erbB-2受体和表皮生长因子受体（EGFR）。本研究的目的是确定用人源化单克隆抗体4D5（赫赛汀（TM））阻断c-erbB-2受体，或用表皮生长因子受体酪氨酸激酶抑制剂（EGFR- tki） ZD1839（易瑞沙（TM））阻断EGFR，是否会减少DCIS中上皮细胞的增殖。方法：将18例接受手术的女性DCIS组织植入16 ~ 20只胸腺裸鼠体内，每只小鼠8只异种移植。治疗于植入后2周开始，包括每周两次腹腔注射4D5 10 mg/kg或每天灌胃100-200 mg/kg的ZD1839，持续14天；包括适当的控制。异种移植物于第14、21和28天切除。Ki67免疫染色后，通过计数1000个上皮细胞来评估增殖情况。结果：14d后，与对照组相比，ZD1839对细胞增殖有抑制作用（P < 0.01），而4D5无抑制作用。结论：EGFR酪氨酸激酶抑制可抑制DCIS细胞的增殖，而c-erbB-2受体阻断对DCIS细胞增殖无抑制作用。ZD1839是一种口服活性和选择性EGFR-TKI，具有作为DCIS辅助治疗的潜力。
Background: Ductal carcinoma in situ (DCIS) expresses c-erbB-2 receptor and epidermal growth factor receptor (EGFR). The aim of this study was to determine whether blocking of c-erbB-2 receptor with a humanized monoclonal antibody, 4D5 (Herceptin(TM)), or of EGFR with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), ZD1839 (Iressa(TM)), would decrease epithelial proliferation in DCIS.Methods: DCIS tissue from 18 women undergoing surgery was implanted into 16 to 20 athymic nude mice per experiment (eight xenografts per mouse). Treatment commenced 2 weeks after implantation and consisted either of twice-weekly intraperitoneal injections of 4D5 10 mg/kg or of daily gavage with ZD1839 at 100-200 mg/kg for 14 days; appropriate controls were included. Xenografts were removed on days 14, 21 and 28. Proliferation was assessed by counting 1000 epithelial cells after Ki67 immunostaining.Results: ZD1839 inhibited proliferation compared with that in controls after 14 days (P < 0.01), whereas 4D5 did not.Conclusion: Proliferation in DCIS was decreased by EGFR tyrosine kinase inhibition but not by c-erbB-2 receptor blockade. ZD1839, an orally active and selective EGFR-TKI, has potential as adjuvant therapy in DCIS.