Nanoscale/Molecular analysis of Fecal Colonocytes for Colorectal Cancer Screening

用于结直肠癌筛查的粪便结肠细胞的纳米级/分子分析

• 批准号: 9102020
• 负责人: Vadim Backman
• 金额: $ 54.37万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9102020
• 关键词: Age; Algorithms; American; Animals; Architecture; Biological; Biophotonics; Cancer Etiology; Cells; Cervical Cancer Screening; Cessation of life; Characteristics; Clinical; Colon; Colon Carcinoma; Colonoscopy; Colorectal Cancer; Colposcopy; Contrast Media; Data; Data Analyses; Demographic Aging; Detection; Development; Disease; Distal; Dysplasia; Endoscopy; Ensure; Epigenetic Process; Epithelial Cells; Epithelium; Feces; Fingerprint; Funding; Future; Gender; General Population; Genetic; Goals; Guidelines; Health; Hemorrhage; Histologic; Image; Individual; Lead; Lesion; Life; Location; Lung; Malignant Neoplasms; Measures; Methods; MicroRNAs; Microsatellite Instability; Microscopy; Modeling; Molecular; Molecular Analysis; Mucous Membrane; Mucous body substance; Neoplasms; Optics; Pancreas; Pap smear; Pathway interactions; Patients; Performance; Polypectomy; Population; Populations at Risk; Procedures; Protocols documentation; Refractive Indices; Risk; Specimen Handling; Stratification; Techniques; Technology; Testing; Tobacco; Translating; Ursidae Family; Validation; Variant; Villous; adenoma; base; cancer risk; carcinogenesis; clinical application; colon carcinogenesis; colorectal cancer screening; cost; cost effective; improved; innovation; instrument; minimally invasive; molecular marker; nanoscale; neoplastic; neoplastic cell; non-compliance; novel; patient population; personalized medicine; pre-clinical; rectal; screening; statistics; technology development; technology validation; tool

DESCRIPTION (provided by applicant): Existing guidelines recommend colorectal cancer (CRC) screening for all patients over age 50. However, CRC remains the second leading cause of cancer death among Americans largely because colonoscopic screening of all the >100 million Americans over age 50 is unfeasible for both patient-related (non-compliance) and societal (inadequate endoscopic capacity and funding) reasons. Furthermore, the current practice of colonoscopy on the 3average risk4 population is remarkably inefficient2only ~6% of the screening population has significant neoplasia (advanced adenomas). Thus, a simple, non-invasive risk-stratification technique is critical to better target patients for colonoscopy. Stool analysis would be an ideal test that would engender the best patients6 compliance, although current stool tests assessing tumor cells or blood loss have dismal sensitivity. We propose a novel, more robust approach that utilizes mucus layer fecal colonocytes which are abraded from the epithelium and thus represent field carcinogenesis (the genetic/environmental fingerprint of neoplastic risk). Based on our preliminary data (156 patients), we hypothesize that the analysis of two complementary facets, nanostructural and molecular (microRNA) alterations, in mucus layer fecal colonocytes will serve as a highly accurate means of identifying field carcinogenesis and thereby serve as a non-invasive CRC screening test. Our approach is based on the combination of a novel biophotonics technology, partial wave spectroscopic microscopy (PWS), that is uniquely capable of imaging and quantification of the statistics of cell nanoscale organization and a new method to get high quality non-apoptotic fecal colonocytes in a practical fashion. In preclinical and clinical models, the performance characteristics of PWS and microRNA were outstanding, thus providing promise for a screening test. There are several requisite steps prior to the future definitive clinical validation. We will develop high-throughput PWS technology and identify the cellular location of the nanoarchitectural alterations. We will formulate and prospectively test a prediction rule that combines both nanostructural and molecular alterations. This project will confirm that nanostructural/ molecular stool analysis may provide sensitive, non-invasive risk-stratification tool, thereby heralding the era of personalized medicine for CRC population screening.

描述（由申请人提供）：现有指南建议对所有50岁以上患者进行大肠癌（CRC）筛查。但是，CRC仍然是美国人癌症死亡的第二大主要原因，主要是因为对50岁以上的所有> 1亿美国人的结肠镜检查筛查对于患者相关的（不合格）和社会上的（不适当的）和不足的内窥镜和Funsing）。此外，当前对3A级风险人群的结肠镜检查的做法明显效率低约6％，占筛查人群的6％具有明显的肿瘤（晚期腺瘤）。因此，一种简单的非侵入性风险分层技术对于更好地靶向结肠镜检查至关重要。尽管当前评估肿瘤细胞或失血的粪便测试的敏感性降低，但粪便分析将是一项理想的测试，它会产生最佳患者6的依从性。我们提出了一种新型，更健壮的方法，该方法利用粘液粪便结肠细胞，从上皮磨损，因此代表了野外致癌（肿瘤风险的遗传/环境指纹）。根据我们的初步数据（156名患者），我们假设对两个互补面，纳米结构和分子（microRNA）的分析进行分析，在粘液层粪便结肠细胞中，将用作高度准确的手段，用于鉴定现场癌作用，从而用作非影响力的CRC筛查测试。我们的方法是基于一种新型生物素技术，部分波光谱显微镜（PWS）的组合，它具有独特的能力，能够对细胞纳米级组织的统计数据进行成像和量化，并以实用方式获得高质量的非凋亡粪便结肠。在临床前和临床模型中，PWS和microRNA的性能特征非常出色，因此为筛查测试提供了希望。在未来的确定临床验证之前，有几个必要的步骤。我们将开发高通量PWS技术，并确定纳米结构改变的细胞位置。我们将制定并前瞻性测试一个结合纳米结构和分子改变的预测规则。该项目将确认纳米结构/分子粪便分析可能会提供敏感的，无创的风险分层工具，从而预示着个性化医学时代的CRC人群筛查时代。

项目成果

Measuring the Autocorrelation Function of Nanoscale Three-Dimensional Density Distribution in Individual Cells Using Scanning Transmission Electron Microscopy, Atomic Force Microscopy, and a New Deconvolution Algorithm.

• DOI: 10.1017/s1431927617000447
• 发表时间: 2017-06
• 期刊: Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada
• 作者: Li Y;Zhang D;Capoglu I;Hujsak KA;Damania D;Cherkezyan L;Roth E;Bleher R;Wu JS;Subramanian H;Dravid VP;Backman V
• 通讯作者: Backman V

Preservation of cellular nano-architecture by the process of chemical fixation for nanopathology

通过纳米病理学化学固定过程保存细胞纳米结构

• DOI: 10.1371/journal.pone.0219006
• 发表时间: 2019
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Zhou, Xiang;Gladstein, Scott;Almassalha, Luay M.;Li, Yue;Eshein, Adam;Cherkezyan, Lusik;Viswanathan, Parvathi;Subramanian, Hariharan;Szleifer, Igal;Backman, Vadim
• 通讯作者: Backman, Vadim

Spectroscopic microscopy can quantify the statistics of subdiffractional refractive-index fluctuations in media with random rough surfaces.

• DOI: 10.1364/ol.40.004931
• 发表时间: 2015-11-01
• 期刊: Optics letters
• 影响因子: 3.6
• 作者: Zhang D;Cherkezyan L;Capoglu I;Subramanian H;Chandler J;Thompson S;Taflove A;Backman V
• 通讯作者: Backman V

Correction: Biophotonic detection of high order chromatin alterations in field carcinogenesis predicts risk of future hepatocellular carcinoma: A pilot study.

更正：现场致癌过程中高阶染色质改变的生物光子检测可预测未来肝细胞癌的风险：一项试点研究。

• DOI: 10.1371/journal.pone.0201500
• 发表时间: 2018
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kalman,RichardS;Stawarz,Andrew;Nunes,David;Zhang,Di;DelaCruz,MartA;Mohanty,Arpan;Subramanian,Hariharan;Backman,Vadim;Roy,HemantK
• 通讯作者: Roy,HemantK

Early increase in blood supply (EIBS) is associated with tumor risk in the Azoxymethane model of colon cancer.

• DOI: 10.1186/s12885-018-4709-7
• 发表时间: 2018-08-13
• 期刊: BMC cancer
• 影响因子: 3.8
• 作者: Ruderman S;Eshein A;Valuckaite V;Dougherty U;Almoghrabi A;Gomes A;Singh A;Pabla B;Roy HK;Hart J;Bissonnette M;Konda V;Backman V
• 通讯作者: Backman V