Boston University School of Medicine, Boston Medical Center, 650 Albany Street, Suite 526, Boston, MA 02118.
Cancer Prev Res (Phila). 2013 Oct;6(10):1111-9. doi: 10.1158/1940-6207.CAPR-13-0138. Epub 2013 Aug 27.
Current fecal tests (occult blood, methylation, DNA mutations) target minute amounts of tumor products among a large amount of fecal material and thus have suboptimal performance. Our group has focused on exploiting field carcinogenesis as a modality to amplify the neoplastic signal. Specifically, we have shown that endoscopically normal rectal brushings have striking nano-architectural alterations which are detectable using a novel optical technique, partial wave spectroscopic microscopy (PWS). We therefore wished to translate this approach to a fecal assay. We examined mucus layer fecal colonocytes (MLFC) at preneoplastic and neoplastic time points (confirmed with rat colonoscopy) in the azoxymethane (AOM)-treated rat model and conducted PWS analysis to derive the nano-architectural parameter, disorder strength (Ld). We confirmed these results with studies in a genetic model (the Pirc rat). We showed that MLFC appeared microscopically normal, consistent with field carcinogenesis. Ld was elevated at an early time point (5 weeks post-AOM injection, effect size = 0.40, P = 0.024) and plateaued before adenoma formation (10 weeks post-AOM, effect size = 0.66, P = 0.001), with no dramatic increase once tumors developed. We replicated these data in the preneoplastic Pirc rat with an effect size in the MLFC that replicated the rectal brushings (increase vs. age-matched controls of 62% vs. 74%, respectively). We provide the first demonstration of a biophotonics approach to fecal assay. Furthermore, targeting the nano-architectural changes of field carcinogenesis rather than the detection of tumor products may provide a novel paradigm for colorectal cancer screening.
当前的粪便检测（潜血、甲基化、DNA 突变）针对的是粪便中大量物质中的微量肿瘤产物，因此性能不佳。我们的团队专注于利用现场癌变作为一种放大肿瘤信号的方式。具体来说，我们已经表明，在内镜正常的直肠刷检中，存在明显的纳米结构改变，这些改变可以使用一种新的光学技术，部分波谱显微镜（PWS）来检测。因此，我们希望将这种方法转化为粪便检测。我们在奥沙米妥（AOM）处理的大鼠模型中检查了癌前和肿瘤时间点（通过大鼠结肠镜检查确认）的粘液层粪便结肠细胞（MLFC），并进行了 PWS 分析，以得出纳米结构参数，无序强度（Ld）。我们在遗传模型（Pirc 大鼠）中进行了研究，证实了这些结果。我们发现 MLFC 在显微镜下看起来正常，与现场癌变一致。Ld 在早期（AOM 注射后 5 周，效应大小=0.40，P=0.024）升高，并在腺瘤形成前趋于平稳（AOM 注射后 10 周，效应大小=0.66，P=0.001），一旦肿瘤形成，就没有明显增加。我们在癌前 Pirc 大鼠中复制了这些数据，MLFC 的效应大小与直肠刷检相似（与年龄匹配的对照组相比，分别增加了 62%和 74%）。我们首次证明了一种生物光子学方法用于粪便检测。此外，靶向现场癌变的纳米结构变化而不是肿瘤产物的检测可能为结直肠癌筛查提供一种新的范例。
