DEVELOPMENT OF A BABOON MODEL OF LIVER CANCER

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这是一项创建肝癌研究和治疗新模式的试点计划。我们将使用先进的诊断和治疗技术，利用先进的成像技术对肿瘤进行可视化和治疗，从而创造出一种用于新技术的狒狒肝癌模型。目前还没有大的肝癌动物模型可用于发展和完善这些方法。肝癌是全球第四大癌症死亡原因。因为它是一种生长迅速的肿瘤，很少在早期阶段被诊断出来，所以肝癌通常在确诊后一年内就会致命。在这个节目中，我们将从狒狒身上克隆与肝癌相关的基因，这样所有涉及的基因都与宿主同源。我们将引入基因修饰，将这些基因转化为致癌基因或癌基因。我们将使用基因治疗载体(慢病毒载体)将多个修饰基因导入生长在我们成熟的狒狒肝细胞培养系统中的肝细胞(肝细胞)。具有致瘤特性的细胞将首先在SCID小鼠模型中被选择，然后被引入作为细胞的原始捐赠者的狒狒的肝脏中(自体细胞移植)。一旦完善，该模型将被用于推进肝癌的新疗法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This is a pilot program to create a new model for liver cancer research and therapy. We will create a baboon model of liver cancer for use in new technologies involving advanced diagnostics and therapies using sophisticated imaging techniques to visualize and treat the tumor. Currently no large animal model of liver cancer is available to develop and perfect these methods. Liver cancer is the 4th leading cause of cancer death worldwide. Because it is a fast-growing tumor that is rarely diagnosed in the early stages, liver cancer is typically fatal within a year of diagnosis. In this program we will clone the genes involved in liver cancer from the baboon, such that all genes involved are homologous to the host. We will introduce genetic modifications to convert the genes into cancer inducing genes or oncogenes. We will use gene therapy vectors (Lentivirus vectors) to introduce multiple modified genes into liver cells (hepatocytes) growing in our well established hepatocyte culture system for baboon hepatocytes. Cells with tumorigenic properties will first be selected in the SCID mouse model and then introduced into the liver of baboon that was the original donor of the cells (autologous cell transplant). Once perfected, the model will be used to advance new therapies for liver cancer.