The goal of the Intravital Microscope (IVM) Core is to provide a unique animal model. Our model in awake mice, uses fluorescence video-microscopy and permits the evaluation of various physiological parameters. Under high magnification, the underlying mechanisms behind tumor regression such as cell cycle arrest, mitotic catastrophe, or apoptosis can be distinguished. Temporal and spatial relation of vessel density to cell death allows detailed quantitative evaluation of regimen effectiveness. Our model thus provides a unique means to acquire real time data of micro tumor biological events in the context of the host, and allows repeated measurements of a variety of physiological parameters from one and the same animal, making it extremely cost effective compared to obtaining similar data from numerous histological specimens. We have combined the transparent chamber technique, with spontaneously fluorescent proteins (H2B-GFP), intensified video cameras, and elaborate image analysis software, and this has made it possible for us to generate reliable quantitative data. Our model allows repeated evaluation of: a) Tumor growth, b) Tumor cell invasiveness, c) Tumor angiogenesis, as well as d) Mitotic and apoptotic indices. The system is also well suited for evaluation of homing of fluorescently labeled probes to the vasculature of prostate tissue as well as prostate tumors. Our syngeneic """"""""pseudo-orthotopic"""""""" micro metastasis model progression, based on these technologies, is unique and not available in any other laboratory. The IVM Core will be utilized in all five projects. In Project 1 our """"""""pseudo-orthotopic"""""""" model will be extremely useful to analyze TE3 expression and quantify efficacy of the TE-3 antibody in a variety of murine tumor models. In project 2, peptides derived through peptide library-based vascular targeting developed in the laboratory of Dr. Ruoslahti will be evaluated using IVM. In Project 3 the IVM Core will be used to optimize the dose, schedule and optimal mode of delivery of the icon for therapy. Finally, in Project 4 we will use IVM to evaluate the effects of alpha-v-beta3-targeted NP/raf-mu treatment. The PI for the intravital microscope core has more than 30 years of experience of microcirculatory physiology, and has developed the unique """"""""pseudo-orthotopic"""""""" intravital microscopic models to be utilized in this core.
| Oh, Phil; Testa, Jacqueline E; Borgstrom, Per et al. (2014) In vivo proteomic imaging analysis of caveolae reveals pumping system to penetrate solid tumors. Nat Med 20:1062-8 |
| Sawada, Junko; Urakami, Takeo; Li, Fangfei et al. (2012) Small GTPase R-Ras regulates integrity and functionality of tumor blood vessels. Cancer Cell 22:235-49 |
| Chrastina, Adrian; Schnitzer, Jan E (2012) Laser-targeted photosensitizer-induced lung injury: noninvasive rat model of pulmonary infarction. Exp Lung Res 38:1-8 |
| Weis, Sara M; Cheresh, David A (2011) ?V integrins in angiogenesis and cancer. Cold Spring Harb Perspect Med 1:a006478 |
| Shields, D J; Murphy, E A; Desgrosellier, J S et al. (2011) Oncogenic Ras/Src cooperativity in pancreatic neoplasia. Oncogene 30:2123-34 |
| Murphy, Eric A; Majeti, Bharat K; Mukthavaram, Rajesh et al. (2011) Targeted nanogels: a versatile platform for drug delivery to tumors. Mol Cancer Ther 10:972-82 |
| Chrastina, Adrian; Massey, Kerri A; Schnitzer, Jan E (2011) Overcoming in vivo barriers to targeted nanodelivery. Wiley Interdiscip Rev Nanomed Nanobiotechnol 3:421-37 |
| Mielgo, Ainhoa; Seguin, Laetitia; Huang, Miller et al. (2011) A MEK-independent role for CRAF in mitosis and tumor progression. Nat Med 17:1641-5 |
| Griffin, Noelle M; Yu, Jingyi; Long, Fred et al. (2010) Label-free, normalized quantification of complex mass spectrometry data for proteomic analysis. Nat Biotechnol 28:83-9 |
| Li, Pingchuan; Liu, Yanzheng; Maynard, Jonathan et al. (2010) Use of adenoviral vectors to target chemotherapy to tumor vascular endothelial cells suppresses growth of breast cancer and melanoma. Mol Ther 18:921-8 |
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