A point-of-care salivary cytokine test for early detection of oral cancer

用于早期发现口腔癌的即时唾液细胞因子检测

• 批准号: 10760626
• 负责人: Tian Lan
• 金额: $ 26.9万
• 依托单位: GLUCOSENTIENT, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-17 至 2024-08-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10760626
• 关键词: Alcohol consumption; American; Amino Acids; Annual Reports; Antibodies; Area; Areca; Asian; Attention; Biological; Biological Assay; Biological Markers; Biopsy; Blood Glucose; Cancer Patient; Case Study; Cessation of life; Clinical; Clinical Research; Collection; Complex; Consumption; Country; Data; Deglutition; Dental; Dentists; Development; Device or Instrument Development; Diagnosis; Diagnostic; Diagnostic tests; Early Diagnosis; Early Intervention; Early identification; Enzyme-Linked Immunosorbent Assay; Habits; Health; Healthcare; High Prevalence; IL8 gene; Immunoassay; Individual; Inflammatory; Interleukin-6; Laboratories; Lesion; Location; Malignant - descriptor; Malignant Neoplasms; Manuals; Mastication; Measurement; Measures; Methods; Microfluidics; Molecular Diagnostic Testing; Morbidity - disease rate; Nuts; Oral Diagnosis; Oral cavity; Outcome; Performance; Pharmaceutical Preparations; Phase; Predictive Value; Prevalence; Procedures; Prognosis; ROC Curve; Rapid screening; Renal function; Reporting; Risk; Risk Factors; Saliva; Salivary; Sampling; Sampling Biases; Screening for Oral Cancer; Sensitivity and Specificity; Site; Smoking; Specificity; Specimen; Speech; Survival Rate; System; TNF gene; Technology; Testing; Time; Tissues; Validation; Visual; assay development; cohort; cost; cytokine; design; detection limit; follow-up; glucose monitor; improved; instrument; interest; khat; large scale production; malignant mouth neoplasm; manufacturing scale-up; meter; operation; point of care; prototype; research and development; salivary assay; screening; smokeless tobacco use; success; tumor; tumorigenesis; viral DNA

Project Summary / Abstract Oral cancer is the 6th most common cancer globally with ~ 350,000 new cases and claiming ~ 180,000 lives annually. Common risk factors include smoking and alcohol consumption. However, other local habits, such as khat chewing, can cause significantly higher regional higher prevalence (up to 40% of all cancer cases in some Asian countries). Currently, identification and diagnosis of oral cancer rely on visual inspection followed by biopsy and histopathological analysis. This procedure is lengthy, costly and often prone to error. As a result, oral cancer today is often diagnosed at advanced stages that have poor prognosis with a 5-year survival rate hovering around 50% for decades. Even for those who have been cured, they often face severe morbidities, such as disfigurement, speech and swallowing difficulties. However, if oral cancer can be diagnosed early and allowing early intervention, survival rate can improve to ~ 90%. Testing for salivary biomarkers represents a promising approach for screening and diagnosing oral cancer earlier, since 1) saliva collection is convenient and can be performed even at the dentist’s office, and 2) saliva is closest to the primary site of tumor development which can contain molecules indicative of malignant transformation. Hence, with appropriate biomarkers, a simple saliva test can be developed and deployed at the point-of-care (POC, e.g., dentist’s office) for rapid screening and early identification of oral cancer. Recently, from a number of clinical studies globally, pro-inflammatory cytokines have emerged as promising biomarkers for screening and diagnosing oral cancer with good sensitivity and specificity. Among these cytokines, IL-6 and IL-8 have shown the best predictive power for oral cancer. Currently, measurement for IL-6 and IL-8, as well as other cytokines, often require tedious manual assays or delicate automated systems which can be both time consuming and costly. As a result, currently, it is impractical to screen for oral cancer via salivary biomarkers at the POC. Based on need and clinical values, GlucoSentient (GSI) is proposing to develop a POC system for screening oral cancer by measuring salivary levels of relevant pro-inflammatory cytokines. The POC system will be based on the existing blood glucose meter (BGM) hardware and a disposable microfluidic cartridge. Today’s BGM is the culmination of decades of R&D, designed POC simple operation, low cost and large-scale production. Leveraging on the BGM technology, we can significantly reduce the time and cost associated with device development and scale-up production. In this proposed Phase I project, we will demonstrate the feasibility of a POC screening test for oral cancer by developing BGM based POC tests for IL-6 and IL-8 and validate their performance in relevant specimen.

项目摘要 /摘要 口腔癌是全球第六个最常见的癌症，新病例约为350,000例 总是。常见的危险因素包括吸烟和饮酒。但是，其他当地习惯，例如 Khat咀嚼，可能导致区域较高的患病率更高（在某些癌症病例中，最多40％ 亚洲国家）。目前，口腔癌的识别和诊断依赖于视觉检查，然后进行活检 和组织病理学分析。此过程冗长，昂贵且通常容易出错。结果，口腔癌 如今，通常在预后较差的高级阶段被诊断出来，生存率徘徊了5年 数十年来50％。即使对于那些已经治愈的人，他们也经常面临严重的病态，例如毁容， 言语和吞咽困难。但是，如果可以尽早诊断出口腔癌并允许早期干预，则 生存率可以提高到〜90％。唾液生物标志物的测试代表了一种有希望的方法 较早的筛查和诊断口腔癌，因为1）唾液收集很方便，甚至可以进行 在牙医的办公室和2）唾液不受肿瘤发育的主要地点，其中可能包含 分子指示恶性转化。因此，使用适当的生物标志物，一个简单的唾液测试可以 可以在护理点（例如牙医办公室）进行开发和部署，以进行快速筛查和早期筛查 口腔癌的鉴定。 最近，从全球的许多临床研究中，促炎性细胞因子已成为有前途的 具有良好敏感性和特异性的筛查和诊断口腔癌的生物标志物。在这些细胞因子中， IL-6和IL-8显示了口腔癌的最佳预测能力。目前，IL-6和IL-8的测量， 以及其他细胞因子，通常需要乏味的手动测定或精致的自动化系统 耗时且昂贵。结果，目前，通过唾液筛选口腔癌是不切实际的 POC的生物标志物。基于需求和临床值，葡萄糖剂（GSI）提议开发POC 通过测量相关促炎细胞因子的唾液水平来筛查口腔癌的系统。 POC 系统将基于现有的血糖计（BGM）硬件和一次性微流体弹药筒。 当今的BGM是数十年的研发，设计的POC简单操作，低成本和大规模的高潮 生产。利用BGM技术，我们可以大大降低与 设备开发和扩大生产。在这个拟议的I期项目中，我们将证明可行性 通过为IL-6和IL-8开发基于BGM的POC测试的POC筛查测试，并验证其 相关标本的性能。