The long term objective of this Program is to develop a mechanistic understanding of the causal relationship of inflammation to cancer. A specific objective is to determine the role of Nitric Oxide (NO) in the process of inflammation-induced carcinogenesis and in the maintenance of the melanoma cancer cell. The results of these investigations will be applied in a translational manner to human cancers and pre-cancerous states, including inflammatory bowel disease (IBD), colon cancer, and melanoma. The research will utilize cells in culture and animal models. The animal models will be used to develop biomarkers of inflammation chemistry that can be applied to archived human tissue to determine whether the animal model represents the human case. The biomarkers can then be used to develop a therapeutic approach to cancer prevention. This Program has already demonstrated that NO-synthase inhibitors can ameliorate the early stages of tissue changes in IBD and colon cancer in our animal models.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA026731-31
Application #
7796738
Study Section
Special Emphasis Panel (ZCA1-GRB-P (M1))
Program Officer
Blair, Donald G
Project Start
1997-01-15
Project End
2013-12-31
Budget Start
2010-01-01
Budget End
2010-12-31
Support Year
31
Fiscal Year
2010
Total Cost
$1,804,658
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Townsend, Todd A; Parrish, Marcus C; Engelward, Bevin P et al. (2017) The development and validation of EpiComet-Chip, a modified high-throughput comet assay for the assessment of DNA methylation status. Environ Mol Mutagen 58:508-521
Fedeles, Bogdan I (2017) G-quadruplex-forming promoter sequences enable transcriptional activation in response to oxidative stress. Proc Natl Acad Sci U S A 114:2788-2790
Chang, Shiou-Chi; Seneviratne, Uthpala I; Wu, Jie et al. (2017) 1,3-Butadiene-Induced Adenine DNA Adducts Are Genotoxic but Only Weakly Mutagenic When Replicated in Escherichia coli of Various Repair and Replication Backgrounds. Chem Res Toxicol 30:1230-1239
Chen, Fangyi; Bian, Ke; Tang, Qi et al. (2017) Oncometabolites d- and l-2-Hydroxyglutarate Inhibit the AlkB Family DNA Repair Enzymes under Physiological Conditions. Chem Res Toxicol 30:1102-1110
Kimoto, Takafumi; Kay, Jennifer E; Li, Na et al. (2017) Recombinant cells in the lung increase with age via de novo recombination events and clonal expansion. Environ Mol Mutagen 58:135-145
Wang, C; Gong, G; Sheh, A et al. (2017) Interleukin-22 drives nitric oxide-dependent DNA damage and dysplasia in a murine model of colitis-associated cancer. Mucosal Immunol 10:1504-1517
Iverson, Nicole M; Bisker, Gili; Farias, Edgardo et al. (2016) Quantitative Tissue Spectroscopy of Near Infrared Fluorescent Nanosensor Implants. J Biomed Nanotechnol 12:1035-47
Chen, Fangyi; Tang, Qi; Bian, Ke et al. (2016) Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA. Chem Res Toxicol 29:687-93
Seneviratne, Uthpala; Nott, Alexi; Bhat, Vadiraja B et al. (2016) S-nitrosation of proteins relevant to Alzheimer's disease during early stages of neurodegeneration. Proc Natl Acad Sci U S A 113:4152-7
Peng, Chunte Sam; Fedeles, Bogdan I; Singh, Vipender et al. (2015) Two-dimensional IR spectroscopy of the anti-HIV agent KP1212 reveals protonated and neutral tautomers that influence pH-dependent mutagenicity. Proc Natl Acad Sci U S A 112:3229-34

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