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 口腔癌是全球第六大常见癌症，新增病例约35万例，夺走了约18万人的生命 每年一次。常见的危险因素包括吸烟和饮酒。然而，当地的其他习惯，如 嚼阿拉伯茶，会导致显著更高的地区性更高的患病率(在某些情况下，高达所有癌症病例的40% 亚洲国家)。目前，口腔癌的识别和诊断依赖于目视检查和活检。 并进行组织病理学分析。这一过程冗长、昂贵，而且经常容易出错。结果，口腔癌 如今的患者通常被诊断为晚期，预后不佳，五年存活率徘徊不前。 50%，持续几十年。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， 口齿不清，吞咽困难。然而，如果口腔癌能够被早期诊断并允许早期干预， 存活率可提高到~90%。唾液生物标记物检测是一种很有希望的方法 更早地筛查和诊断口腔癌，因为1)唾液采集方便，甚至可以进行 在牙医办公室，2)唾液最接近肿瘤发生的主要部位，这可能包含 代表恶变的分子。因此，有了适当的生物标志物，简单的唾液测试就可以 在护理地点(POC，例如牙医办公室)开发和部署，用于快速筛查和早期 口腔癌的鉴定。 最近，全球多项临床研究显示，促炎细胞因子前景看好。 筛选和诊断口腔癌的生物标志物具有良好的敏感性和特异性。在这些细胞因子中， IL-6和IL-8对口腔癌的预测能力最强。目前，IL-6和IL-8的检测， 与其他细胞因子一样，通常需要繁琐的手动化验或精密的自动化系统，这可能是 既耗时又昂贵。因此，目前通过唾液筛查口腔癌是不切实际的。 POC的生物标志物。基于需求和临床价值，GLucoSentient(GSI)正在提议开发一种POC 口腔癌筛查系统，通过测量唾液中相关促炎细胞因子的水平。PoC 该系统将基于现有的血糖仪(BGM)硬件和一次性微流控墨盒。 今天的BGM是几十年来研发的顶峰，设计的POC操作简单，成本低，规模大 制作。利用BGM技术，我们可以显著减少以下方面的时间和成本 设备开发和扩大生产。在这项拟议的第一期工程中，我们将论证其可行性 通过建立基于BGM的白介素6和白介素8的白介素6和白介素8的白介素6和白介素8的白介素6和白介素8的白介素C检测，建立口腔癌的白介素C筛查试验，并验证其有效性。 在相关样品中的表现。