This project will utilize bioluminescence imaging (BLI) to provide unique insights into the molecular pathogenesis of inflammation-associated cancer, with the human T-cell leukemia virus oncoprotein. Tax. In these studies we will use two different animal models. First, we will analyze Tax transgenic mice with different Tax or NF?B BLI reporters. Second, we will analyze a transplantation model in which a Tax transgenic cell line carrying a click beetle green reporter is grafted onto mice carrying a NF?B firefly luciferase BLI reporter. We will answer the following questions: 1) Does inflammation promote lymphoma through activation ofthe NF?B pathway? For this purpose IkBLuc mice will be used to monitor NF?B activation in transgenic or transplanted mice with or without T cell activation with concanavalin A (con A). Correlation will be perfonned between BLI and IHC of Rel-A and Rel- B NF?B subunits. 2) Which NF?B pathway is most important in the malignant and/or non-malignant cells for lymphoma development? For this purpose IKK1 or IKK2 deleted mice deficient in the alternative or classical NFkB pathways, respectively, will be used in the transgenic and transplantation models for BLI and IHC studies. 3) What is the role in lymphoma development of the NF?B-target gene, IL15, in malignant and/or nonmalignant cells? For this purpose, we will transplant lL15-deleted or IL15-wild type Tax lymphoma cells into IL15-deleted or lL15-wild type animals to determine the role of this critical interieukin in each cellular compartment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
4P50CA094056-16
Application #
8991300
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
2017-12-31
Budget Start
2016-01-01
Budget End
2016-12-31
Support Year
16
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Murali, Bhavna; Ren, Qihao; Luo, Xianmin et al. (2018) Inhibition of the Stromal p38MAPK/MK2 Pathway Limits Breast Cancer Metastases and Chemotherapy-Induced Bone Loss. Cancer Res 78:5618-5630
Miller, Jessica; Wang, Steven T; Orukari, Inema et al. (2018) Perfusion-based fluorescence imaging method delineates diverse organs and identifies multifocal tumors using generic near-infrared molecular probes. J Biophotonics 11:e201700232
Zacharias, Niki; Lee, Jaehyuk; Ramachandran, Sumankalai et al. (2018) Androgen Receptor Signaling in Castration-Resistant Prostate Cancer Alters Hyperpolarized Pyruvate to Lactate Conversion and Lactate Levels In Vivo. Mol Imaging Biol :
Cherian, Mathew A; Olson, Sydney; Sundaramoorthi, Hemalatha et al. (2018) An activating mutation of interferon regulatory factor 4 (IRF4) in adult T-cell leukemia. J Biol Chem 293:6844-6858
Hövener, Jan-Bernd; Pravdivtsev, Andrey N; Kidd, Bryce et al. (2018) Parahydrogen-Based Hyperpolarization for Biomedicine. Angew Chem Int Ed Engl 57:11140-11162
Bauerle, Kevin T; Hutson, Irina; Scheller, Erica L et al. (2018) Glucocorticoid Receptor Signaling Is Not Required for In Vivo Adipogenesis. Endocrinology 159:2050-2061
Prudner, Bethany Cheree; Sun, Fangdi; Kremer, Jeffrey Charles et al. (2018) Amino Acid Uptake Measured by [18F]AFETP Increases in Response to Arginine Starvation in ASS1-Deficient Sarcomas. Theranostics 8:2107-2116
Meinerz, Kelsey; Beeman, Scott C; Duan, Chong et al. (2018) Bayesian Modeling of NMR Data: Quantifying Longitudinal Relaxation in Vivo, and in Vitro with a Tissue-Water-Relaxation Mimic (Crosslinked Bovine Serum Albumin). Appl Magn Reson 49:3-24
Zheleznyak, Alexander; Shokeen, Monica; Achilefu, Samuel (2018) Nanotherapeutics for multiple myeloma. Wiley Interdiscip Rev Nanomed Nanobiotechnol 10:e1526
Choi, Jaebok; Cooper, Matthew L; Staser, Karl et al. (2018) Baricitinib-induced blockade of interferon gamma receptor and interleukin-6 receptor for the prevention and treatment of graft-versus-host disease. Leukemia 32:2483-2494

Showing the most recent 10 out of 283 publications