Molecular Target for Liver Cancer Diagnosis and Therapy

肝癌是世界上最常见的恶性肿瘤之一。的 肝癌的发病率在美国正在上升。大多数肝癌是 长期发展，常伴有慢性肝病。这提供了一个窗口， 有机会根除或至少减缓肝癌的进展。当务之急是 确定可用于早期诊断和治疗干预的分子靶点。新 可用的适体和纳米颗粒技术为此目的提供了独特的机会。在 与基因组学和蛋白质组学方法相比，适体技术可以识别 使用完整肿瘤细胞的标记物，其将通过密切反映肿瘤细胞的生长而具有显著优势。 癌症的生理状态。我们的研究计划的总体目标是应用这一点， 用于人肝癌早期的癌症特异性适体的选择和表征技术 诊断和治疗。我们之前的工作已经验证了几种癌症特异性适体， 包括鼠肝癌。我们已经建立了一个可靠的系统来分离和培养人类 原代肝细胞和肝癌细胞。我们还验证了人类的动物模型 肝癌在这项提案中，我们将产生和测试人类肝癌特异性适体， 验证其在肿瘤诊断和靶向治疗中的应用。该目标将通过以下方式实现： 三个具体目的：目的1：鉴定和表征人肝癌细胞特异性适体; 目标2.将核酸适体和纳米粒子应用于人肝癌的诊断;目的3.发展 使用适体-纳米颗粒-化疗剂的新型且有效的靶向癌症治疗 配合物我们的研究将确定肝癌的适体和生物标志物， 完整的癌细胞适体和纳米颗粒的结合将为生物医学领域提供一种强有力的工具。 癌症早期诊断和靶向治疗。我们所获得的经验将不仅有助于 用于后续的临床试验，而且对其他固体的生物标志物的发现也有重大影响。 肿瘤的

Liver cancer is among the most common and malignant human cancers in the world. The incidence of liver cancer is increasing in the United States. The majority of liver cancers are developed over long period of time, often with chronic liver disease. This offers a window of opportunity to eradicate or at least slow the progression of liver cancer. The urgent issue is to identify molecular targets that can be used for early diagnosis and therapeutic intervention. Newly available aptamer and nanoparticle technology provides a unique opportunity for this purpose. In comparison with genomic and proteomic approaches, the aptamer technology can identify markers using intact tumor cells, which will have significant advantages by closely reflecting the physiological state of cancer. The overall objective of our research program is to apply this technology to select and characterize cancer-specific aptamers for human liver cancer early diagnosis and therapy. Our previous work has validated several cancer-specific aptamers, including murine liver cancer. We have established a reliable system to isolate and culture human primary hepatocytes and liver cancer cells. We have also validated an animal model for human liver cancer. In this proposal, we will generate and test human liver cancer-specific aptamers, and validate their application in cancer diagnosis and target therapy. The goal will be achieved through three specific aims: Aim 1: To identify and characterize human liver cancer cell-specific aptamers; Aim 2. To apply aptamers and nanoparticles for human liver cancer diagnosis; Aim 3. To develop novel and effective target cancer therapy using aptamers-nanoparticle-chemotherapy agent complexes. Our investigation will identify aptamers and biomarkers for liver caner in the context of intact cancer cells. The combination of aptamer and nanoparticles will provide a powerful tool for cancer early diagnosis and targeting therapy. The experience we gain will not only be instrumental for subsequent clinical trails but also have significant impact on biomarker discovery of other solid tumors.