(PQC2) Optical Hallmarks of Aggressive Clones Within Oral Field Cancerization

(PQC2) 口腔癌化中侵袭性克隆的光学标志

• 批准号: 9319642
• 负责人: Ann M Gillenwater
• 金额: $ 64.06万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9319642
• 关键词: Address; Algorithms; Animal Model; Area; Biological Markers; Biopsy; Cancer Detection; Cancerous; Carcinoma; Cells; Chemopreventive Agent; Cicatrix; Classification; Clinical; Clinical Research; Clone Cells; Complex; Data; Development; Diagnosis; Diagnostic; Dimensions; Dysplasia; Early Diagnosis; Fluorescence; Goals; Histology; Image; Imaging Device; Individual; Inflammation; Lesion; Light; Lighting; Link; Longitudinal Studies; Loss of Heterozygosity; Malignant - descriptor; Malignant Neoplasms; Measures; Methods; Microscopy; Modality; Molecular; Molecular Analysis; Molecular Carcinogenesis; Monitor; Mouth Neoplasms; Multi-modal optical imaging; Multimodal Imaging; Mutation; Neoplasm Metastasis; Neoplasms; Newly Diagnosed; Nuclear; Optics; Oral; Oral cavity; Oral mucous membrane structure; Organ; Outcome; Pathologic; Patients; Performance; Permeability; Phenotype; Premalignant; Process; Property; Recurrent disease; Regimen; Research; Resolution; Risk; Risk Assessment; Screening for Oral Cancer; Sensitivity and Specificity; Severe dysplasia; Site; Specificity; Stem cells; Surface; Survival Rate; Techniques; Technology; Time; Tissues; Translations; Tumor Initiators; Unnecessary Surgery; Visual; alcohol exposure; base; cancer stem cell; carcinogenesis; cost; high resolution imaging; high risk; imaging biomarker; imaging system; improved; in vivo; insight; malignant mouth neoplasm; microendoscopy; molecular marker; morphometry; neoplastic; novel; nuclear imaging; optical imaging; oral carcinogenesis; oral lesion; oral premalignancy; outcome forecast; physical property; point of care; predictive marker; predictive modeling; preneoplastic cell; public health relevance; response; screening; spatial relationship; tissue preparation; tobacco exposure; tool; treatment response; tumor progression

DESCRIPTION (provided by applicant): Oral cancer is the 6th most common cancer worldwide. Despite the easy accessibility of the oral cavity for screening, oral cancer has one of the lowest 5-year survival rates of all cancers. Oral cancer is thought to arise as a result of fied cancerization, where, often in response to tobacco and alcohol exposure, wide areas of the mucosal surface develop subclinical carcinogenetic changes. The poor outcomes of oral cancer arise primarily because: (1) most patients are diagnosed at a late stage since the molecular changes that put patients at risk of neoplasia often do not give rise to clinically visible lesions and (2) a large fraction of patients treated for oral cancer develop subsequent cancers because areas of field cancerization persist following treatment and are not clinically visible. The development and progression of oral cancer is ultimately a molecular process, reflecting a complex succession of genetic changes within the field-at-risk. Ultimately tumor-initiating stem cells give rise to aggressive clones within a mucosal field-at-risk, resulting in malignant progression. While much progress has been made to understand the molecular alterations associated with oral cancer progression, this research has not yet led to improvements in early detection mainly because molecular analysis methods are costly and can only be carried out with tissues obtained from invasive biopsies. There is increasing evidence to suggest that key molecular alterations result in phenotypic changes that can be measured clinically at the point-of-care. Recent studies by our group and others suggest that multi-modal optical imaging can image changes in tissue fluorescence and nuclear morphometry to identify high grade oral precancer and early cancer with significantly improved sensitivity and specificity compared to visual examination; moreover, changes in optical properties correlate strongly with molecular markers associated with neoplastic progression. The goal of this proposal is to validate the ability of multimodal optical imaging to improve early detection and to determine whether risk-related optical markers (RROMs) can be used to predict the likelihood of malignant progression. We will perform longitudinal studies in patients with oral lesions using cutting edge autofluorescence and microendoscopy technology with automated diagnostic algorithms. In an animal model of oral cancer, we will combine optical imaging and novel tissue preparation techniques, which render tissue optically transparent and macromolecular permeable, to assess the temporal and spatial correlations of molecular alterations to phenotypic changes during development and progression of oral cancer. With this data, we propose to develop and validate predictive models relating RROMs to malignant transformation.

描述（由申请人提供）：口腔癌是全球第六大常见癌症。尽管口腔筛查很容易，但口腔癌是所有癌症中 5 ​​年生存率最低的癌症之一。口腔癌被认为是由现场癌化引起的，通常由于暴露于烟草和酒精，粘膜表面的大面积区域发生亚临床致癌变化。口腔癌的不良预后主要是因为：（1）大多数患者在晚期才被诊断出来，因为使患者面临肿瘤风险的分子变化通常不会引起临床上可见的病变，（2）大部分患者口腔癌治疗后会发展为后续癌症，因为局部癌化区域在治疗后持续存在并且在临床上不可见。口腔癌的发生和进展最终是一个分子过程，反映了危险领域内一系列复杂的遗传变化。最终，肿瘤起始干细胞在危险的粘膜区域内产生攻击性克隆，导致恶性进展。虽然在了解与口腔癌进展相关的分子改变方面已经取得了很大进展，但这项研究尚未改善早期检测，主要是因为分子分析方法成本高昂，而且只能对从侵入性活检获得的组织进行分析。越来越多的证据表明，关键分子改变会导致表型变化，这些变化可以在护理点进行临床测量。我们小组和其他人最近的研究表明，多模态光学成像可以对组织荧光和核形态测量的变化进行成像，以识别高级别口腔癌前病变和早期癌症，与目视检查相比，其灵敏度和特异性显着提高；此外，光学特性的变化与肿瘤进展相关的分子标记密切相关。该提案的目标是验证多模态光学成像改善早期检测的能力，并确定风险相关光学标记（RROM）是否可用于预测恶性进展的可能性。我们将使用尖端的自发荧光和显微内窥镜技术以及自动诊断算法对口腔病变患者进行纵向研究。在口腔癌动物模型中，我们将结合光学成像和新颖的组织制备技术，使组织光学透明且大分子可渗透，以评估口腔癌发生和进展过程中分子改变与表型变化的时间和空间相关性。利用这些数据，我们建议开发和验证 RROM 与恶性转化相关的预测模型。