(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: 8912436
• 负责人: Ann M Gillenwater
• 金额: $ 64.07万
• 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 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8912436
• 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; Mutation; Neoplasm Metastasis; Neoplasms; Newly Diagnosed; Nuclear; Optics; Oral; Oral cavity; Oral mucous membrane structure; Organ; Outcome; Pathologic; Patients; Performance; Premalignant; Process; Property; Recurrent disease; Regimen; Research; Resolution; Risk; Risk Assessment; Screening for Oral Cancer; Sensitivity and Specificity; Severe dysplasia; Site; Specificity; Staging; Stem cells; Surface; Survival Rate; Techniques; Technology; Time; Tissues; Translations; Unnecessary Surgery; Visual; alcohol exposure; base; cancer stem cell; carcinogenesis; high risk; imaging system; improved; in vivo; insight; malignant mouth neoplasm; molecular imaging; molecular marker; morphometry; neoplastic; novel; optical imaging; oral carcinogenesis; oral lesion; oral premalignancy; outcome forecast; physical property; point of care; predictive marker; predictive modeling; public health relevance; response; screening; spatial relationship; tissue preparation; tobacco exposure; tool; tumor; 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）：口腔癌是全球第六个最常见的癌症。尽管口腔进行筛查容易获得，但口腔癌的占所有癌症的5年生存率之一。人们认为口腔癌是由于癌症癌化而引起的，通常，粘液表面的广泛区域会响应烟草和酒精暴露，会产生亚临床的致癌变化。口腔癌的不良结局主要是因为：（1）大多数患者在后期被诊断出来，因为使患者处于肿瘤风险的分子变化通常不会引起临床可见的病变，并且（2）大部分患者接受口腔癌治疗的患者随后会发生癌症，因为治疗后癌症的治疗持续不断，并且在临床上持续存在临床可见。口腔癌的发展和进展最终是一个分子过程，反映了风险野外风险中遗传变化的复杂连续。最终，肿瘤发射干细胞会在粘膜危险中产生侵略性克隆，导致恶性进展。尽管已经取得了很大的进步来了解与口腔癌进展相关的分子改变，但这项研究尚未导致早期检测的改善，主要是因为分子分析方法昂贵，并且只能使用从侵入性活检获得的组织进行。越来越多的证据表明，关键的分子改变会导致表型变化，可以在护理点进行临床测量。我们小组和其他人的最新研究表明，与视觉检查相比，多模式光学成像可以对组织荧光和核形态计量学的变化进行图像变化，以鉴定高级口服前癌和早期癌症，并显着提高敏感性和特异性。此外，光学性质的变化与与肿瘤进展相关的分子标记密切相关。该建议的目的是验证多模式光学成像改善早期检测的能力，并确定是否可以使用与风险相关的光学标记（RROM）来预测恶性进展的可能性。我们将使用自动诊断算法的尖端自动荧光和微观镜检查技术对口腔病变的患者进行纵向研究。在口腔癌的动物模型中，我们将结合光学成像和新型的组织制备技术，这些技术使组织具有光学透明和大分子渗透性，以评估分子改变与口腔癌发育过程中表型变化的时间和空间相关性。通过这些数据，我们建议开发和验证将RROM与恶性转化相关的预测模型。