Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors
Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors
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DOI：
10.1007/s00280-008-0729-3
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发表时间：
2009-01-01
影响因子：
3
通讯作者：
Dewhirst, Mark W.
中科院分区：
文献类型：
--
作者：
Hardee, Matthew E.;Eapen, Rose J.;Dewhirst, Mark W.
目的肿瘤缺氧会降低放疗和化疗的疗效，并改变促进细胞存活和转移的基因表达。生长因子受体 Her2/neu 在 25-30% 的乳腺肿瘤中过度表达。由于肿瘤生长速率和血管生成的差异，Her2(+) 肿瘤相对于 Her2(-) 肿瘤可能具有改变的氧合状态。方法 使用受体抗体（曲妥珠单抗；赫赛汀）实现 Her2 阻断。本研究探讨了 Her2 阻断对 Her2(+) 和 Her2(-) MCF7 异种移植肿瘤中肿瘤血管生成、血管结构和缺氧的影响。结果与对照治疗的 Her(2+) 肿瘤相比，曲妥珠单抗治疗 Her2(+) 肿瘤显着改善了肿瘤氧合、增加了微血管密度并改善了血管结构。与对照处理的异种移植物相比，用曲妥珠单抗处理的Her(2+)异种移植物也表现出增殖指数降低。这些结果表明，Her2 阻断可以通过减少耗氧量（减少肿瘤细胞增殖和诱导坏死）和增加氧输送（血管密度和结构）来改善肿瘤氧合。结论这些结果支持使用曲妥珠单抗作为化疗或放疗治疗乳腺肿瘤的辅助药物，因为肿瘤氧合的改善应转化为治疗的改善 回复。
Purpose Tumor hypoxia reduces the efficacy of radiation and chemotherapy as well as altering gene expression that promotes cell survival and metastasis. The growth factor receptor, Her2/neu, is overexpressed in 25-30% of breast tumors. Tumors that are Her2(+) may have an altered state of oxygenation, relative to Her2(-) tumors, due to differences in tumor growth rate and angiogenesis.Methods Her2 blockade was accomplished using an antibody to the receptor (trastuzumab; Herceptin). This study examined the effects of Her2 blockade on tumor angiogenesis, vascular architecture, and hypoxia in Her2(+) and Her2(-) MCF7 xenograft tumors.Results Treatment with trastuzumab in Her2(+) tumors significantly improved tumor oxygenation, increased microvessel density, and improved vascular architecture compared with the control-treated Her(2+) tumors. The Her(2+) xenografts treated with trastuzumab also demonstrated decreased proliferation indices when compared with control-treated xenografts. These results indicate that Her2 blockade can improve tumor oxygenation by decreasing oxygen consumption (reducing tumor cell proliferation and inducing necrosis) and increasing oxygen delivery (vascular density and architecture).Conclusions These results support the use of trastuzumab as an adjunct in the treatment of breast tumors with chemotherapy or radiotherapy, as improvements in tumor oxygenation should translate into improved treatment response.