Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA026731-33
Application #
8210885
Study Section
Special Emphasis Panel (ZCA1-GRB-P (M1))
Program Officer
Johnson, Ronald L
Project Start
1997-01-15
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
33
Fiscal Year
2012
Total Cost
$1,748,209
Indirect Cost
$703,309

  Institution

Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Tajai, Preechaya; Fedeles, Bogdan I; Suriyo, Tawit et al. (2018) An engineered cell line lacking OGG1 and MUTYH glycosylases implicates the accumulation of genomic 8-oxoguanine as the basis for paraquat mutagenicity. Free Radic Biol Med 116:64-72
Rothenberg, Daniel A; Taliaferro, J Matthew; Huber, Sabrina M et al. (2018) A Proteomics Approach to Profiling the Temporal Translational Response to Stress and Growth. iScience 9:367-381
Wang, Xin; Garcia, Carlos T; Gong, Guanyu et al. (2018) Automated Online Solid-Phase Derivatization for Sensitive Quantification of Endogenous S-Nitrosoglutathione and Rapid Capture of Other Low-Molecular-Mass S-Nitrosothiols. Anal Chem 90:1967-1975
Chan, Cheryl; Pham, Phuong; Dedon, Peter C et al. (2018) Lifestyle modifications: coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses. Genome Biol 19:228
Gu, Chen; Ramos, Jillian; Begley, Ulrike et al. (2018) Phosphorylation of human TRM9L integrates multiple stress-signaling pathways for tumor growth suppression. Sci Adv 4:eaas9184
Wadduwage, Dushan N; Kay, Jennifer; Singh, Vijay Raj et al. (2018) Automated fluorescence intensity and gradient analysis enables detection of rare fluorescent mutant cells deep within the tissue of RaDR mice. Sci Rep 8:12108
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
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
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
Edrissi, Bahar; Taghizadeh, Koli; Moeller, Benjamin C et al. (2017) N6-Formyllysine as a Biomarker of Formaldehyde Exposure: Formation and Loss of N6-Formyllysine in Nasal Epithelium in Long-Term, Low-Dose Inhalation Studies in Rats. Chem Res Toxicol 30:1572-1576

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