Chan K C, Knox W F, Gandhi A, Slamon D J, Potten C S, Bundred N J
Department of Surgery, University Hospital of South Manchester, Manchester, UK.
Br J Surg. 2001 Mar;88(3):412-8. doi: 10.1046/j.1365-2168.2001.01686.x.
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 (HerceptinTM), or of EGFR with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), ZD1839 (IressaTM), would decrease epithelial proliferation in DCIS.
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 immuno- staining.
ZD1839 inhibited proliferation compared with that in controls after 14 days (P < 0.01), whereas 4D5 did not.
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.
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一种人源化单克隆抗体4D5（赫赛汀）阻断c-erbB-2受体，或用一种表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）ZD1839（易瑞沙）阻断EGFR，是否会减少DCIS中的上皮细胞增殖。
将18例接受手术的女性的DCIS组织，每次实验植入16至20只无胸腺裸鼠体内（每只小鼠8个异种移植物）。植入后2周开始治疗，包括每周两次腹腔注射10mg/kg的4D5，或每天灌胃100 - 200mg/kg的ZD1839，持续14天；设置了适当的对照组。在第14、21和28天取出异种移植物。通过对Ki67免疫染色后的1000个上皮细胞进行计数来评估增殖情况。
与对照组相比，ZD1839在14天后抑制了增殖（P < 0.01），而4D5没有。
DCIS中的增殖通过EGFR酪氨酸激酶抑制而降低，但c-erbB-2受体阻断没有此作用。ZD1839，一种口服活性且选择性的EGFR-TKI，有作为DCIS辅助治疗的潜力。
