Monitoring of Oral Cancer Patients Using Novel Lab-on-a-Chip Ensembles

使用新型芯片实验室整体监测口腔癌患者

• 批准号: 8521443
• 负责人: JOHN T MCDEVITT
• 金额: $ 37.78万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8521443
• 关键词: Algorithms; Award; Biological Markers; Biological Neural Networks; Biopsy; Biopsy Specimen; Cancer Patient; Categories; Cells; Classification; Clinic; Clinical; Computer software; Data; Dentists; Detection; Development; Diagnosis; Diagnostic Procedure; Dysplasia; Elements; Erythroplasia; Health Care Costs; Health Sciences; Hour; Human; Image Analysis; Institution; Keratosis; Lesion; Leukoplakia; Lichen Planus; Logistic Regressions; Malignant - descriptor; Malignant Neoplasms; Measurement; Mechanics; Medical Device; Methodology; Methods; Microfluidics; Modeling; Molecular; Molecular Profiling; Monitor; Mucous Membrane; Myocardial Infarction; Operative Surgical Procedures; Optics; Oral Medicine; Oral Pathology; Oral cavity; Pathology; Patient Monitoring; Patients; Pattern Recognition; Process; Public Health; Receiver Operating Characteristics; Recruitment Activity; Resources; Rice; Risk; Salivary; Sampling; Science; Sensitivity and Specificity; Staging; Statistical Methods; Structure; Survival Rate; Suspension substance; Suspensions; System; Techniques; Technology; Testing; Texas; Time; Training; Translational Research; Translations; Universities; Validation; Visit; advanced disease; anticancer research; base; cancer diagnosis; case control; clinical Diagnosis; clinical application; design; global health; innovation; malignant mouth neoplasm; member; micro-total analysis system; microchip; minimally invasive; model development; molecular marker; mortality; mouth squamous cell carcinoma; nano; novel; novel diagnostics; novel strategies; outcome forecast; point of care; programs; public health relevance; sample collection; scalpel; sensor; standard of care; statistics; tumor progression

DESCRIPTION (provided by applicant): Oral cancer, largely oral squamous cell carcinoma (OSCC), is a global health problem afflicting close to 300,000 people each year. Despite significant advances in surgical procedures and treatment, the long-term prognosis for patients with OSCC remains poor, with a 5-year survival rate at approximately 50% which is among the lowest for all major cancers. High mortality associated with OSCC is often attributed to the advanced disease stage of many OSCCs upon initial identification and surgical biopsy, underscoring the need for new diagnostic methods targeting early tumor progression and malignant transformations. We propose here a broad, innovative, high impact and cross-cutting translational research program that targets development, testing and validation of powerful new microchip sensor systems for the diagnosis, prognosis and monitoring of potentially malignant lesions (PML) and malignant lesions of the oral cavity. This effort pairs the leading group involved in development of nano-bio-chip systems with leading clinicians in pathology and oral cancer research. To support the testing and validation of the new microchip sensor systems, subjects will be recruited that are diagnosed clinically with a suspicious, potentially malignant (provisional clinical diagnosis of leukoplakia or erythroplakia) or oral squamous cell carcinoma, where a conventional biopsy is indicated. The programmable nano-bio-chip (PNBC) to be developed through this program will allow for the analysis of cellular samples obtained from a minimally invasive brush biopsy sample. The cell suspensions collected in this manner will allow for the simultaneous quantification of cell morphometric data and expression of molecular biomarkers of malignant potential in an automated manner using refined image analysis algorithms based on pattern recognition techniques and advanced statistical methods. This novel PNBC approach, which will turn around biopsy results in a matter of minutes as compared to days for traditional pathology methods, has already demonstrated its ability to distinguish between normal mucosa and oral cancer lesions. We propose here to adapt this chip-based platform to include a panel of biomarkers indicative of dysplasia as derived from cytomorphometric and molecular data as well as to assess the capabilities of this approach to function in point of care settings using noninvasive brush biopsy samples. The PNBC approach will be compared to the current standard of care based on biopsy and histopathological assessment of the lesions. The multi-institution, multi-disciplinary team assembled with members from Rice University, the Universities of Texas Health Science Centers in Houston and San Antonio, and the University of Sheffield, offers unique patient based case/control resources, biomarker and pathology proficiency combined with the expertise in integrated microchip sensors that will allow the team to develop new diagnostic aids for oral cancer patients that are desperately needed. PUBLIC HEALTH RELEVANCE: Despite significant advances in surgical procedures and treatment, the long-term prognosis for patients with oral cancer remains among the lowest for all major cancers. In contrast, if detected early, the prognosis for oral cancer patients is excellent with more than 90% five-year survival. We propose the development of a minimally-invasive brush biopsy test for oral cancer diagnosis (no scalpel biopsy would be required) that when combined with a novel microchip can be performed in clinics or dentist's offices with results that are available in a matter of minutes (within visit) versus hours for scalpel biopsies. This "pathology on a chip method" could facilitate regular monitoring of patients at risk of developing oral cancer as well as those receiving treatment. The new methods are projected to benefit greatly both patients and clinicians, while at the same time lowering associated healthcare costs.

描述（由申请人提供）：口腔癌，主要是口腔鳞状细胞癌（OSCC），是一个全球性的健康问题，每年困扰近30万人。尽管在外科手术和治疗方面取得了重大进展，但OSCC患者的长期预后仍然很差，5年生存率约为50%，是所有主要癌症中最低的。与OSCC相关的高死亡率通常归因于许多OSCC在初始识别和手术活检时的晚期疾病阶段，强调需要针对早期肿瘤进展和恶性转化的新诊断方法。我们在这里提出了一个广泛的，创新的，高影响力和跨领域的转化研究计划，目标是开发，测试和验证功能强大的新型微芯片传感器系统，用于诊断，预后和监测潜在的恶性病变（PML）和口腔恶性病变。这项工作将参与纳米生物芯片系统开发的领导小组与病理学和口腔癌研究的领先临床医生配对。 为了支持新的微芯片传感器系统的测试和验证，将招募临床诊断为可疑、潜在恶性（白斑或红斑的临时临床诊断）或口腔鳞状细胞癌的受试者，其中需要进行常规活检。通过该计划开发的可编程纳米生物芯片（PNBC）将允许分析从微创刷检样本中获得的细胞样本。以这种方式收集的细胞悬液将允许使用基于模式识别技术和高级统计方法的精细图像分析算法以自动方式同时定量细胞形态测量数据和恶性潜能的分子生物标志物的表达。与传统病理学方法的几天相比，这种新型PNBC方法将在几分钟内改变活检结果，已经证明了其区分正常粘膜和口腔癌病变的能力。我们在这里建议调整这个基于芯片的平台，包括一组来自细胞形态学和分子数据的指示发育异常的生物标志物，以及评估这种方法在使用非侵入性刷检样本的护理点设置中发挥作用的能力。将根据病变的活检和组织病理学评估，将PNBC方法与当前标准治疗进行比较。这个多机构、多学科的团队由来自莱斯大学、休斯顿和圣安东尼奥的德克萨斯大学健康科学中心以及谢菲尔德大学的成员组成，提供独特的基于患者的病例/对照资源、生物标志物和病理学熟练程度以及集成微芯片传感器的专业知识，这将使该团队能够为迫切需要的口腔癌患者开发新的诊断辅助工具。 公共卫生相关性：尽管在外科手术和治疗方面取得了重大进展，但口腔癌患者的长期预后仍然是所有主要癌症中最低的。相反，如果早期发现，口腔癌患者的预后非常好，五年生存率超过90%。我们建议开发一种用于口腔癌诊断的微创刷检检测（不需要手术刀活检），当与新型微芯片结合时，可以在诊所或牙医办公室进行，结果在几分钟内（访问内）即可获得，而手术刀活检则需要几个小时。这种“芯片病理学方法”可以促进对有患口腔癌风险的患者以及接受治疗的患者进行定期监测。新方法预计将大大有利于患者和临床医生，同时降低相关的医疗成本。

项目成果

Interobserver agreement in dysplasia grading: toward an enhanced gold standard for clinical pathology trials.

• DOI: 10.1016/j.oooo.2015.05.023
• 发表时间: 2015-10
• 期刊: Oral surgery, oral medicine, oral pathology and oral radiology
• 作者: Speight PM;Abram TJ;Floriano PN;James R;Vick J;Thornhill MH;Murdoch C;Freeman C;Hegarty AM;D'Apice K;Kerr AR;Phelan J;Corby P;Khouly I;Vigneswaran N;Bouquot J;Demian NM;Weinstock YE;Redding SW;Rowan S;Yeh CK;McGuff HS;Miller FR;McDevitt JT
• 通讯作者: McDevitt JT