Dectection of occult mediastinal lymph node mestastases

隐匿性纵隔淋巴结转移的检测

• 批准号: 7172287
• 负责人: MICHAEL Bradley WALLACE
• 金额: $ 31.74万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7172287
• 关键词: Applications Grants; Biological Assay; Cancer Etiology; Cessation of life; Clinical; Combination Chemotherapy; Data; Detection; Development; Diagnostic; Diagnostic Neoplasm Staging; Disease; Fine needle aspiration biopsy; General Anesthesia; Genes; Invasive; Malignant neoplasm of lung; Mediastinal lymph node group; Mediastinoscopy; Messenger RNA; Methods; Molecular; Molecular Biology; Non-Small-Cell Lung Carcinoma; Operative Surgical Procedures; Outcome; Patients; Positron-Emission Tomography; Protein Overexpression; Radiation therapy; Research; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Specimen; Test Result; Therapeutic; Thoracoscopy; Time; Ultrasonography; United States; Validation; X-Ray Computed Tomography; cancer cell; cohort; improved; prognostic

DESCRIPTION (provided by applicant): Non-small cell lung carcinoma (NSCLC) is the most common cause of cancer death in the United States. The presence of metastatic disease in the mediastinal lymph nodes of NSCLC patients has profound prognostic and therapeutic implications. For instance, patients with documented disease in mediastinal lymph nodes are typically not candidates for surgical treatment, and are often treated with a combination of chemotherapy and radiotherapy. Current methods for detection of disease in mediastinal lymph nodes either lack sensitivity (computed tomography, positron emission tomography), or are invasive requiring general anesthesia (mediastinoscopy, thoracoscopy). We believe that endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of mediastinal lymph nodes in combination with real-time RT-PCR has the potential to dramatically improve lung cancer staging. One limitation of EUS-FNA is that it currently relies on cytologic analysis of the specimen. Such an analysis is dependent on a skilled cytopathologist and lacks sensitivity. The identification of genes overexpressed in lung cancer combined with recent advances in molecular biology provides the opportunity to establish a more sensitive, and specific way to analyze EUS-FNA samples. In Section 6c. Preliminary Studies, we present preliminary data that real-time RT-PCR provides the ability to precisely determine the expression levels of lung cancer-associated mRNA, facilitating the sensitive detection of NSCLC. Furthermore, we present evidence of lung cancer-associated gene overexpression in EUS-FNA samples from patients with presumed NSCLC. The hypothesis of the proposed research is that real-time RT-PCR detection of lung cancer cells in EUS-FNA specimens of mediastinal lymph nodes in NSCLC patients is associated with clinical outcome. The successful development and validation of such a molecular diagnostic assay is likely to have a significant clinical impact. In the R21 component of this grant application we will analyze a preliminary cohort of patients and controls so that criteria for the interpretation of test results can be established. In the R33 component of the grant application these criteria will be prospectively evaluated and correlated with clinical outcome in a second, larger cohort of patients.

描述（由申请人提供）： 非小细胞肺癌（NSCLC）是癌症死亡的最常见原因 在美国。纵隔存在转移性疾病 NSCLC患者的淋巴结具有深远的预后和治疗作用 影响。例如，有纵隔疾病记录的患者 淋巴结通常不适合手术治疗，并且通常是 联合化疗和放疗进行治疗。目前的方法 检测纵隔淋巴结疾病要么缺乏敏感性 （计算机断层扫描、正电子发射断层扫描），或者是侵入性的 全身麻醉（纵隔镜检查、胸腔镜检查）。我们相信内窥镜 超声引导下纵隔淋巴结细针抽吸活检 (EUS-FNA) 与实时 RT-PCR 相结合有可能显着改善 肺癌分期。 EUS-FNA 的一个局限性是它目前依赖于 标本的细胞学分析。这种分析依赖于熟练的 细胞病理学家缺乏敏感性。肺癌中过表达基因的鉴定结合分子生物学的最新进展 生物学提供了建立更敏感、更具体的方法的机会 分析 EUS-FNA 样本的方法。在第 6c 节中。初步研究，我们提出 初步数据表明，实时 RT-PCR 能够精确地 确定肺癌相关 mRNA 的表达水平，促进 NSCLC 的灵敏检测。此外，我们还提供了肺 患有以下疾病的患者的 EUS-FNA 样本中癌症相关基因过度表达 推测为非小细胞肺癌。本研究的假设是实时 RT-PCR检测纵隔EUS-FNA标本中肺癌细胞 NSCLC 患者的淋巴结与临床结果相关。这 这种分子诊断测定的成功开发和验证是 可能会产生重大的临床影响。在这个的R21组件中 我们将分析初步的患者队列和拨款申请 控制，以便可以解释测试结果的标准 已确立的。在拨款申请的 R33 部分中，这些标准将 立即进行前瞻性评估并与临床结果相关联， 更大的患者群体。

项目成果

Detection of telomerase expression in mediastinal lymph nodes of patients with lung cancer.

肺癌患者纵隔淋巴结端粒酶表达检测

• DOI: 10.1164/rccm.200211-1297oc
• 发表时间: 2003
• 期刊: American journal of respiratory and critical care medicine
• 影响因子: 24.7
• 作者: Wallace,MichaelB;Block,Mark;Hoffman,BrendaJ;Hawes,RobertH;Silvestri,Gerard;Reed,CarolynE;Mitas,Michael;Ravenel,James;Fraig,Mostafa;Miller,Scott;Jones,EdwardT;Boylan,Alice
• 通讯作者: Boylan,Alice