VECTOR CORE

细胞和组织成像核心(核心C)。 这项计划的重点是细胞因子的局部区域表达的影响，以及它们对 肿瘤微环境。这就需要研究转导细胞的传递效率，以及多个 对这些细胞对肿瘤影响的不同分析。项目中的核心问题是：1)效率如何 传递给肿瘤的细胞？2)这些细胞表达的蛋白质产物是不是合适的？3) 有什么疗效吗？后者包括对细胞渗透、血管新生、肿瘤的研究 衰老，以及细胞对肿瘤环境的募集。在每种情况下，这些研究都将严重依赖于 定量光学方法学。将在其中执行这项核心服务的Biolo_c成像中心， 就是考虑到这一功能而设计的。它配备了一系列连续的光学方法，包括所有类型 对这个项目至关重要的光学和电子显微镜。在本项目的范围内，委托人 核心的目标将是多种多样的。例如，我们将量化和表征肿瘤中的细胞浸润物。 微环境。我们将确定外源转基因细胞是否达到肿瘤靶点，量化它们的 确定这些细胞是否表达转导的细胞因子，并检查结构变化 产生于这些细胞因子的表达。为了执行这些功能，我们将使用不同的 显微技术。在光镜水平上，这些包括：组织学、免疫组织学、原位 杂交、激光共聚焦、双光子和活细胞技术。此外，我们在这方面的丰富经验 计算机化的图像处理和形态测量将允许对观察到的现象进行定量分析 佐证了更早的，可能是相当微妙的质变。这个核心将被所有项目广泛使用， 尽管所使用的成像工具会因项目而异。在以前提交的提案中，这 CORE被评为卓越，很好地融入了该计划，并提供了基本和集成的服务 这个项目。因此，本申请中的更改很少，并在引言中进行了描述。

Cell and tissue imaging core (Core C). This program project focuses on the effects of locoregional expression ofcytokines, and their effect on the tumor microenvironment. This demands study of the efficiency of delivery of tranduced cells, and multiple different analyses of the effects of these cells on the tumor. Central questions in projects are: 1) how effectively are cells delivered to the tumor? 2) Is the appropriate message and the protein product expressed by these cells? 3) is any therapeutic effect seen? This latter component includes study of cellular infiltration, angiogcnesis, tumor senescence, and cellular recruitment to the tumor environment. In each case these studies will rely critically on quantitative optical methodologies. The Center for Biolo_c lmaging, in which this core service will be performed, is designed with this function in mind. It is equipped to perform a continuum of optical methods including all types of light and electron microscopy essential to this program project. Within the scope of this project the principal goals of the core will be various. For example we will quantify and characterize cellular infiltrates into the tumor micro-environment. We will determine whether exogenously transfected cells reach tumor targets, quantify their abundance, determine whether these cells are expressing the transduced cytokines, and examine structural changes resulting from the expression of these cytokines. To perform these functions we will use a diverse array of microscopy technologies. At the light microscopic level these include: histological, immuno-histological, in situ hybridization, laser confocal, 2 photon and live cell technologies. Furthermore, our considerable experience in computerized image processing and morphometry will allow quantitative analysis of observed phenomena to corroborate earlier, possibly quite subtle qualitative changes. This core will be used extensively by all projects, though the imaging tools used will vary from project to project. In previous submissions of the proposal, this core was rated as superior, well integrated into the program and offering essential and integrated services to the program. As such the changes in this application are few, and are described in the introduction.