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Inflammation and cancer: chemical approaches to mechanisms, imaging, and treatment.

Marnett LJ - J. Org. Chem. (2012)

Bottom Line: Chronic inflammation contributes to the etiology of multiple diseases, especially those associated with aging, such as cancer and cardiovascular disease.The current perspective summarizes our research on unsaturated fatty acid oxidation in the context of inflammation and cancer.In addition to understanding the consequences of DNA and protein modification by lipid electrophiles, our research has focused on the development of molecularly targeted agents to image and treat cancer.

View Article: PubMed Central - PubMed

Affiliation: A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA. larry.marnett@vanderbilt.edu

ABSTRACT
The inflammatory response represents a first line of defense against invading pathogens and is important to human health. Chronic inflammation contributes to the etiology of multiple diseases, especially those associated with aging, such as cancer and cardiovascular disease. The chemistry of the inflammatory response is complex and involves the generation of highly reactive oxidants and electrophiles designed to kill the pathogen as well as the release of small molecule and protein mediators of intercellular signaling, chemotaxis, vasoconstriction, and wound-healing. Oxidation of unsaturated fatty acids--either nonenzymatic or enzymatic--contributes to the inflammatory response and associated cellular pathologies. The current perspective summarizes our research on unsaturated fatty acid oxidation in the context of inflammation and cancer. In addition to understanding the consequences of DNA and protein modification by lipid electrophiles, our research has focused on the development of molecularly targeted agents to image and treat cancer.

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COX-2 is expressed at the earliest detected premalignant phase ofcolon cancer. Reproduced with permission from ref (97). 1999. Nature PublishingGroup.
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fig19: COX-2 is expressed at the earliest detected premalignant phase ofcolon cancer. Reproduced with permission from ref (97). 1999. Nature PublishingGroup.

Mentions: COX-2 is not expressed in most untransformed epithelial cells,but early in transformation to malignancy it is expressed at a highlevel (Figure 19).93 In fact, the earliest premalignant lesions that lead to most solidtumors display COX-2 expression.94,95 As progressionto malignancy occurs, COX-2 enzyme levels increase. The prostaglandinproducts of COX-2 action contribute to the cancer progression process,and COX-2 selective inhibitors prevent tumor development in animalmodels. These discoveries were initially made in the colon, but similarobservations have been reported in most solid tumors except ovariancancer where COX-1 appears to be induced.96


Inflammation and cancer: chemical approaches to mechanisms, imaging, and treatment.

Marnett LJ - J. Org. Chem. (2012)

COX-2 is expressed at the earliest detected premalignant phase ofcolon cancer. Reproduced with permission from ref (97). 1999. Nature PublishingGroup.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3375764&req=5

fig19: COX-2 is expressed at the earliest detected premalignant phase ofcolon cancer. Reproduced with permission from ref (97). 1999. Nature PublishingGroup.
Mentions: COX-2 is not expressed in most untransformed epithelial cells,but early in transformation to malignancy it is expressed at a highlevel (Figure 19).93 In fact, the earliest premalignant lesions that lead to most solidtumors display COX-2 expression.94,95 As progressionto malignancy occurs, COX-2 enzyme levels increase. The prostaglandinproducts of COX-2 action contribute to the cancer progression process,and COX-2 selective inhibitors prevent tumor development in animalmodels. These discoveries were initially made in the colon, but similarobservations have been reported in most solid tumors except ovariancancer where COX-1 appears to be induced.96

Bottom Line: Chronic inflammation contributes to the etiology of multiple diseases, especially those associated with aging, such as cancer and cardiovascular disease.The current perspective summarizes our research on unsaturated fatty acid oxidation in the context of inflammation and cancer.In addition to understanding the consequences of DNA and protein modification by lipid electrophiles, our research has focused on the development of molecularly targeted agents to image and treat cancer.

View Article: PubMed Central - PubMed

Affiliation: A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA. larry.marnett@vanderbilt.edu

ABSTRACT
The inflammatory response represents a first line of defense against invading pathogens and is important to human health. Chronic inflammation contributes to the etiology of multiple diseases, especially those associated with aging, such as cancer and cardiovascular disease. The chemistry of the inflammatory response is complex and involves the generation of highly reactive oxidants and electrophiles designed to kill the pathogen as well as the release of small molecule and protein mediators of intercellular signaling, chemotaxis, vasoconstriction, and wound-healing. Oxidation of unsaturated fatty acids--either nonenzymatic or enzymatic--contributes to the inflammatory response and associated cellular pathologies. The current perspective summarizes our research on unsaturated fatty acid oxidation in the context of inflammation and cancer. In addition to understanding the consequences of DNA and protein modification by lipid electrophiles, our research has focused on the development of molecularly targeted agents to image and treat cancer.

Show MeSH
Related in: MedlinePlus