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.
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