The overall objective of the Program is to understand how chronic inflammation contributes to tumor promotion and progression. The current program will address several aspects of injury/pathogen-initiated signaling pathways focusing upon TLRs, the involvement of altered transcriptional and post-transcriptional control, and the causal links between inflammatory signaling and neoplasia. A major component that links three of the projects involves much expanded utilization of mouse genetics and mouse models of inflammatory disease and carcinogenesis. In each of project 1, 3 and 4, new transgenic mice will be generated, characterized and tested in several models of in vivo inflammatory response. A central focus of these studies will be the use of the mouse model of DSS colitis and its linkage with colon tumorigenesis. This central activity will be coordinated by the newly propose Core B (Mouse Colitis and Colitis-associated Cancer Analysis Core). The colitis analysis portion ofthis Core's primary objective is to set up a colitis model induced by DSS, TNBS or adoptive transfer and provide technical assistance in the analysis of the colitis symptoms, states of homeostasis and inflammation induced in transgenic mice produced by projects. The colitis-associated cancer portion ofthis core's primary objective is to set up the AOM+DSS-indueed CAC model and provide specific technical assistance in phenotype analyses (including tumor number, tumor size, histology analysis and other assays). Standardization of the protocols, evaluation and quantitative assays of colitis and tumorigenesis will facilitate inter-laboratory collaboration and data comparisons.

Public Health Relevance

This activity will standardize the protocols, evaluation and quantification assays for colitis and colitis- associated cancer models, so that consistent results will be obtained across the projects.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA062220-18
Application #
8434247
Study Section
Special Emphasis Panel (ZCA1-RPRB-0)
Project Start
Project End
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
18
Fiscal Year
2013
Total Cost
$219,448
Indirect Cost
$79,672
Name
Cleveland Clinic Lerner
Department
Type
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195
Dermawan, Josephine Kam Tai; Hitomi, Masahiro; Silver, Daniel J et al. (2016) Pharmacological Targeting of the Histone Chaperone Complex FACT Preferentially Eliminates Glioblastoma Stem Cells and Prolongs Survival in Preclinical Models. Cancer Res 76:2432-42
Zhou, Hao; Yu, Minjia; Zhao, Junjie et al. (2016) IRAKM-Mincle axis links cell death to inflammation: Pathophysiological implications for chronic alcoholic liver disease. Hepatology 64:1978-1993
Wang, Xin; Majumdar, Tanmay; Kessler, Patricia et al. (2016) STING Requires the Adaptor TRIF to Trigger Innate Immune Responses to Microbial Infection. Cell Host Microbe 20:329-41
Chattopadhyay, Saurabh; Kuzmanovic, Teodora; Zhang, Ying et al. (2016) Ubiquitination of the Transcription Factor IRF-3 Activates RIPA, the Apoptotic Pathway that Protects Mice from Viral Pathogenesis. Immunity 44:1151-61
White, Christine L; Kessler, Patricia M; Dickerman, Benjamin K et al. (2016) Interferon Regulatory Factor 8 (IRF8) Impairs Induction of Interferon Induced with Tetratricopeptide Repeat Motif (IFIT) Gene Family Members. J Biol Chem 291:13535-45
Lu, Tao; Stark, George R (2015) Using sequential immunoprecipitation and mass spectrometry to identify methylation of NF-κB. Methods Mol Biol 1280:383-93
Lu, Tao; Stark, George R (2015) NF-κB: Regulation by Methylation. Cancer Res 75:3692-5
Dasgupta, Maupali; Dermawan, Josephine Kam Tai; Willard, Belinda et al. (2015) STAT3-driven transcription depends upon the dimethylation of K49 by EZH2. Proc Natl Acad Sci U S A 112:3985-90
Zhao, Junjie; Bulek, Katarzyna; Gulen, Muhammet F et al. (2015) Human Colon Tumors Express a Dominant-Negative Form of SIGIRR That Promotes Inflammation and Colitis-Associated Colon Cancer in Mice. Gastroenterology 149:1860-1871.e8
De, Sarmishtha; Zhou, Hao; DeSantis, David et al. (2015) Erlotinib protects against LPS-induced endotoxicity because TLR4 needs EGFR to signal. Proc Natl Acad Sci U S A 112:9680-5

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