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.

项目总结/摘要 口腔癌是全球第六大最常见的癌症，约有350，000例新发病例，夺去约180，000人的生命。 每年。常见的风险因素包括吸烟和饮酒。然而，当地的其他习惯，如 咀嚼阿拉伯茶，可导致区域性的高发病率（在一些国家，所有癌症病例中高达40 亚洲国家）。目前，口腔癌的识别和诊断依赖于肉眼检查，然后进行活检 和组织病理学分析。这一程序冗长、昂贵，而且往往容易出错。因此，口腔癌 今天，通常在晚期诊断，预后不良，5年生存率徘徊在 50%，几十年来。即使是那些已经治愈的人，他们也经常面临严重的疾病，比如毁容， 言语和吞咽困难。然而，如果口腔癌可以早期诊断并允许早期干预， 成活率可提高到90%左右。唾液生物标志物的检测是一种很有前途的方法， 更早地筛查和诊断口腔癌，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）唾液是最接近的肿瘤发展的主要部位，其中可以包含 指示恶性转化的分子。因此，通过适当的生物标志物，一个简单的唾液测试可以 在护理点（POC，例如，牙科诊所）进行快速筛查和早期 口腔癌的诊断 最近，从全球范围内的一些临床研究来看，促炎细胞因子已成为有希望的 用于筛选和诊断口腔癌的生物标志物具有良好的灵敏度和特异性。在这些细胞因子中， IL-6和IL-8显示出对口腔癌的最佳预测能力。目前，IL-6和IL-8的测量， 以及其它细胞因子，通常需要繁琐的人工测定或精密的自动化系统， 既耗时又昂贵。因此，目前，通过唾液检测来筛查口腔癌是不切实际的。 POC的生物标志物。根据需求和临床价值，GlucoSentient（GSI）建议开发一种POC 通过测量相关促炎细胞因子的唾液水平筛选口腔癌的系统。的POC 该系统将基于现有的血糖仪（BGM）硬件和一次性微流控盒。 今天的BGM是几十年研发的结晶，设计的POC操作简单，成本低，规模大 生产利用BGM技术，我们可以大大减少与 设备开发和规模化生产。在这个拟议的第一阶段项目中，我们将证明 通过开发用于IL-6和IL-8的基于BGM的POC测试， 在相关标本中的表现。