Breakthrough Breast Cancer Research Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Biomaterials. 2012 Jan;33(3):907-15. doi: 10.1016/j.biomaterials.2011.10.028. Epub 2011 Nov 1.
We developed a three-dimensional assay prepared from primary breast cancer tissue and quantified tumor response to tamoxifen therapy. Freshly harvested breast cancer biopsies obtained at the time of curative surgical resection were fragmented and embedded into collagen I cushions. Changes in proliferation, apoptosis and tumor volume in response to tamoxifen treatment were quantified using image analysis software and optical projection tomography. Individual and collective invasion of epithelial cells into the surrounding collagen I was observed over the course of the experiment using phase contrast light microscopy and histopathological methods. Addition of tamoxifen to preparations derived from ER+ tumors demonstrated a range of response as measured by proliferative and apoptotic markers. In keeping with published data, tamoxifen reduced the percentage of apoptotic cells expressing cleaved caspase-3 (p = 0.02, Poisson regression analysis). Tamoxifen also reduced residual epithelial volume in ER+ tumors (p = 0.001, Mann-Whitney test), but not in ER low/- tumors (p = 0.78). Changes in tumor volume, as measured by optical projection tomography, allowed stratification into responsive and non-responsive tumors. The model mirrors observations of breast cancer response and histopathological changes to tamoxifen in neo-adjuvant trials. This assay provides a method of screening a battery of therapeutics against individual cancers, informing subsequent design of neo-adjuvant trials.
我们开发了一种源自原发性乳腺癌组织的三维分析方法，并对他莫昔芬治疗的肿瘤反应进行了定量。在根治性手术切除时采集的新鲜乳腺癌活检组织被分割并嵌入 I 型胶原垫中。使用图像分析软件和光学投影断层扫描技术定量测量增殖、凋亡和肿瘤体积对他莫昔芬治疗的反应。使用相差显微镜和组织病理学方法，在实验过程中观察到上皮细胞个体和集体侵入周围 I 型胶原的情况。在 ER+肿瘤来源的制剂中添加他莫昔芬，通过增殖和凋亡标志物测量，显示出一系列的反应。与已发表的数据一致，他莫昔芬减少了表达 cleaved caspase-3 的凋亡细胞的百分比（p=0.02，泊松回归分析）。他莫昔芬还减少了 ER+肿瘤中的残余上皮体积（p=0.001，Mann-Whitney 检验），但在 ER 低/-肿瘤中没有（p=0.78）。光学投影断层扫描测量的肿瘤体积变化允许对反应性和非反应性肿瘤进行分层。该模型反映了新辅助试验中对乳腺癌对他莫昔芬的反应和组织病理学变化的观察。该分析方法提供了一种针对个体癌症筛选一系列治疗方法的方法，为随后的新辅助试验设计提供信息。
