Roy Hemant K, Liu Yang, Wali Ramesh K, Kim Young L, Kromine Alexei K, Goldberg Michael J, Backman Vadim
Department of Internal Medicine, Evanston-Northwest Healthcare, Northwestern Univerity, IL 60201, USA.
Gastroenterology. 2004 Apr;126(4):1071-81; discussion 948. doi: 10.1053/j.gastro.2004.01.009.
BACKGROUND & AIMS: Identification of preneoplastic changes in histologically normal epithelium (the "field effect") could provide a powerful screening tool for colorectal cancer. However, to date, reliable detection has not been possible. We have recently developed a new generation of optical technology, 4-dimensional elastic light-scattering fingerprinting (4D-ELF), which enables us to probe the nanoscale/microscale architecture of living cells. We therefore investigated whether 4D-ELF would be able to identify preneoplastic changes in the colonocytes of the azoxymethane (AOM)-treated rat model of colon carcinogenesis.
Forty-eight Fisher 344 rats were randomized to either 2 weekly injections of AOM or saline. Animals were killed 2-20 weeks after the second injection of AOM. Colons were removed and subjected to 4D-ELF analysis, with a subset undergoing assessment of aberrant crypt foci (ACF). All AOM-treated animals were compared with age-matched saline-treated controls.
AOM-induced ACF became apparent at approximately 4-6 weeks and continued to increase over time. ACF were predominantly located in the distal colon. At 2 weeks (before development of ACF), there were marked changes in a number of 4D-ELF signatures. The relevance to carcinogenesis of these 4D-ELF-detected microarchitectural abnormalities is supported by their spatial and temporal correlation with subsequent development of ACF. All changes reported were highly statistically significant.
We show that probing the nanoscale cellular architecture with 4D-ELF provided an unprecedented tool for detecting the earliest stages of colon carcinogenesis. Future studies are necessary to explore the clinical applicability of this technology and elucidate the biological determinants of these microarchitectural changes.
识别组织学正常上皮中的癌前变化（“场效应”）可为结直肠癌提供强大的筛查工具。然而，迄今为止，可靠的检测尚无法实现。我们最近开发了新一代光学技术，即四维弹性光散射指纹图谱（4D-ELF），它使我们能够探测活细胞的纳米级/微米级结构。因此，我们研究了4D-ELF是否能够识别经偶氮甲烷（AOM）处理的结肠癌发生大鼠模型结肠细胞中的癌前变化。
48只Fisher 344大鼠被随机分为两组，分别接受每周2次的AOM注射或生理盐水注射。在第二次注射AOM后2至20周处死动物。取出结肠并进行4D-ELF分析，其中一部分进行异常隐窝灶（ACF）评估。将所有接受AOM处理的动物与年龄匹配的生理盐水处理对照组进行比较。
AOM诱导的ACF在大约4至6周时变得明显，并随时间持续增加。ACF主要位于结肠远端。在2周时（ACF出现之前），一些4D-ELF特征有明显变化。这些4D-ELF检测到的微结构异常与致癌作用的相关性得到了它们与ACF后续发展的时空相关性的支持。报告的所有变化均具有高度统计学意义。
我们表明，用4D-ELF探测纳米级细胞结构为检测结肠癌发生的最早阶段提供了前所未有的工具。未来有必要开展研究以探索该技术的临床适用性，并阐明这些微结构变化的生物学决定因素。
