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In Vivo Laser Capture Microdissection

体内激光捕获显微切割

基本信息

批准号：
9207464
负责人：
Adam Joel Bass
金额：
$ 64.74万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-01 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9207464
关键词：
Address Barrett Esophagus Bass Biopsy Cells Choristoma Clinical Clinical Research DNA DNA Sequence Alteration Deglutition Detection Devices Diagnostic Disease Disease Management Disease Progression Dysplasia Encapsulated Endoscopic Biopsy Endoscopy Engineering Esophageal Adenocarcinoma Esophageal Intraepithelial Neoplasia Esophagus Excision Excision biopsy Family suidae Genetic Genetic Markers Genetic Screening Genome Genomic medicine Genomics Genotype Grant Human Image Institutional Review Boards Laboratories Lasers Malignant Neoplasms Maps Mechanics Medical Device Medicine Methods Microscopic Microscopy Molecular Molecular Analysis Molecular Medicine Morphology Mutation Onset of illness Operative Surgical Procedures Organ Patient Care Patient Isolators Patients Pharmacology Population Porifera Precancerous Conditions Precision therapeutics Process Property RNA Research Resolution Risk Sampling Sampling Errors Sensitivity and Specificity Site Slide Somatic Mutation Specificity Specimen Surface System Techniques Technology Testing Time Tissue Adhesives Tissue Extracts Tissue Procurements Tissue Sample Tissues Validation Work base blind capsule clinical application clinical practice compare effectiveness design genetic information improved in vivo innovation laser capture microdissection microendoscopy microscopic imaging minimally invasive new technology next generation sequencing novel personalized care pill precision medicine public health relevance safety and feasibility screening technology development tool

项目摘要

DESCRIPTION (provided by applicant): Our ability to characterize somatic DNA alterations promises to revolutionize medicine, allowing us to predict disease onset/progression and craft individualized pharmacologic therapies with an unprecedented level of precision. This transformative potential of genomics has elevated the importance of identifying and isolating the most diagnostically useful tissue from the body. Today, most tissues are extracted via surgery or standard biopsy. Unfortunately, these methods are invasive, expensive, time-consuming, and imprecise. Because macroscopic inspection cannot identify microscopic tissue features and excision is crude, both sensitivity and specificity are lacking. Current excisional approaches either fail to sample critical microscopic disease or extract a composite of normal and diseased tissues, complicating downstream genomic analysis. In this proposal, we will address this key barrier in the field by developing a new technology termed in vivo laser capture microdissection (IVLCM). IVLCM uses a minimally invasive device to at once conduct comprehensive microscopy in the living patient, identify tissue with microscopic evidence of disease, and laser capture the targeted tissues onto the device. After the device is removed from the body, the tissues are processed for subsequent genetic, molecular and histopathologic analysis. By making tissue procurement more accurate and accessible, IVLCM will allow genomic diagnostics to be used routinely in clinical practice, expanding the reach of precision medicine. The clinical focus of this grant is Barrett's esophagus (BE), a precancerous condition with unmet clinical needs in screening and surveillance that can be addressed by an improved tool for precise isolation and genotyping of aberrant tissues. Our proposed solution for BE is a tethered IVLCM pill that can be swallowed by unsedated subjects, making it much easier and less expensive to administer than standard endoscopic biopsy. Following development of the technology, we will validate the capabilities of capsule IVLCM for BE surveillance and screening in clinical studies that compare genomic analysis of IVLCM-extracted tissues to that of conventional biopsies and cells acquired using a blind-sampling screening device.

描述（由申请人提供）：我们表征体细胞DNA改变的能力有望彻底改变医学，使我们能够预测疾病的发作/进展，并以前所未有的精确度制定个性化的药物治疗。基因组学的这种变革潜力提高了从身体中识别和分离最具诊断价值的组织的重要性。今天，大多数组织通过手术或标准活检提取。不幸的是，这些方法是侵入性的，昂贵的，耗时的，和不精确的。由于肉眼检查无法识别微观组织特征，且切除方法粗糙，因此缺乏敏感性和特异性。目前的切除方法要么无法对关键的微观疾病进行采样，要么无法提取正常组织和患病组织的复合物，从而使下游基因组分析复杂化。在本提案中，我们将通过开发一种称为体内激光捕获显微切割（IVLCM）的新技术来解决该领域的这一关键障碍。IVLCM使用微创设备立即在活体患者中进行全面的显微镜检查，识别具有疾病显微证据的组织，并将目标组织激光捕获到设备上。在从体内取出该装置后，对组织进行处理以用于随后的遗传、分子和组织病理学分析。通过使组织获取更加准确和可访问，IVLCM将允许基因组诊断在临床实践中常规使用，扩大精准医学的范围。该补助金的临床重点是巴雷特食管（BE），这是一种在筛查和监测方面临床需求未得到满足的癌前疾病，可以通过改进的异常组织精确分离和基因分型工具来解决。我们提出的BE解决方案是一种栓系IVLCM药丸，可由未服用镇静剂的受试者吞咽，使其比标准内镜活检更容易和更便宜。在技术开发之后，我们将在临床研究中验证胶囊IVLCM用于BE监测和筛查的能力，这些临床研究将IVLCM提取的组织的基因组分析与使用盲样筛选装置获得的常规活检和细胞的基因组分析进行比较。