Bordonaro Michael, Lazarova Darina
Department of Basic Sciences, Geisinger Commonwealth School of Medicine, 525 Pine Street, Scranton, PA 18509, USA.
J Cancer. 2018 Jan 1;9(1):166-173. doi: 10.7150/jca.22593. eCollection 2018.
The signing of the National Cancer Act of 1971 by President Nixon marked the beginning of our war on cancer. More than 45 years later, the war is still going steady, with the enemy being almost as strong as in 1971. Furthermore, the increasing rates of obesity not only among adults, but among children and adolescents, are the likely cause for the 30-year trend of colon cancer (CC) becoming a disease of the younger population in the U.S. These trends, however, have not spurred the development of novel screening approaches for CC. Considering the need for a sensitive and non-invasive detection of early stage neoplastic lesions in the colon, we propose the development of a test based on a novel concept - the concept of induced biomarkers. The proposal is based upon our findings that the food additives propolis and gamma-cyclodextrin (gCD) (a) decrease the neoplastic burden in normal weight and obese mice, a model of early stage intestinal neoplasia, and (b) elicit significant changes in the serum proteome in mice. We posit that gCD and propolis induce the release of neoplasm-associated biomarkers in systemic circulation (e.g., metabolites, neoplastic, apoptotic, and immune response proteins), and these markers could be used to detect early stage intestinal neoplasms. Additional dietary bioactives may also elicit a complement of induced markers. The hypothesis could be ascertained by utilizing a mouse model, the mice, as well as through human subject studies that integrate proteomics and metabolomics analyses. The concept of detecting inducible markers of colonic neoplasms is novel, and is substantiated by the significant physiological effects of gCD and propolis on neoplastic colonic cells in culture and on early neoplastic development in mice. The long-term objective is to develop a minimally invasive method that detects early stage neoplastic development in the human colon.
尼克松总统签署1971年《国家癌症法案》标志着我们抗癌之战的开端。45年多过去了，这场战争仍在持续，敌人几乎仍如1971年时那般强大。此外，不仅成年人肥胖率在上升，儿童和青少年的肥胖率也在上升，这很可能是美国结肠癌（CC）在30年里成为一种年轻化疾病趋势的原因。然而，这些趋势并未促使针对CC的新型筛查方法得到发展。考虑到需要对结肠早期肿瘤性病变进行灵敏且非侵入性的检测，我们提议基于一个新概念——诱导生物标志物的概念来开发一种检测方法。该提议基于我们的研究发现：食品添加剂蜂胶和γ-环糊精（gCD）（a）在正常体重和肥胖小鼠（早期肠道肿瘤形成模型）中可减轻肿瘤负担，（b）可引起小鼠血清蛋白质组的显著变化。我们认为，gCD和蜂胶可诱导肿瘤相关生物标志物在体循环中释放（例如代谢物、肿瘤、凋亡和免疫反应蛋白），并且这些标志物可用于检测早期肠道肿瘤。其他膳食生物活性物质也可能引发一系列诱导标志物。这一假设可通过利用小鼠模型以及整合蛋白质组学和代谢组学分析的人体研究来确定。检测结肠肿瘤可诱导标志物的概念是新颖的，并且gCD和蜂胶对培养中的肿瘤性结肠细胞以及小鼠早期肿瘤发生具有显著生理效应，这为该概念提供了依据。长期目标是开发一种微创方法，用于检测人类结肠的早期肿瘤发展情况。
