Limits...
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.

Show MeSH

Related in: MedlinePlus

Accumulationof fluorocoxibs in the inflamed paw. Carageenan was injected intothe paw at time zero. After 24 h, the fluorocoxib was administeredby intraperitoneal injection.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3375764&req=5

fig23: Accumulationof fluorocoxibs in the inflamed paw. Carageenan was injected intothe paw at time zero. After 24 h, the fluorocoxib was administeredby intraperitoneal injection.

Mentions: The target compounds were evaluated in multiplein vivo models.106 Since COX-2 is an importantinducible component of the inflammatory response, the utility of theCOX-2-targeted imaging agents (termed fluorocoxibs) was examined inthe mouse footpad model of inflammation. Injection of carrageenaninto one footpad of a mouse induces a profound inflammatory response,which is accompanied by the induction of high levels of COX-2 withinapproximately 12 h. Twenty-four hours after carrageenan injection,fluorocoxib A was injected into the peritoneal cavity of the treatedmouse, and optical imaging performed 3–5 h thereafter. As Figure 23 illustrates, compounds selectively accumulatedin the inflamed paw, but not in the noninflamed contralateral paw.


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

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

Accumulationof fluorocoxibs in the inflamed paw. Carageenan was injected intothe paw at time zero. After 24 h, the fluorocoxib was administeredby intraperitoneal injection.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig23: Accumulationof fluorocoxibs in the inflamed paw. Carageenan was injected intothe paw at time zero. After 24 h, the fluorocoxib was administeredby intraperitoneal injection.
Mentions: The target compounds were evaluated in multiplein vivo models.106 Since COX-2 is an importantinducible component of the inflammatory response, the utility of theCOX-2-targeted imaging agents (termed fluorocoxibs) was examined inthe mouse footpad model of inflammation. Injection of carrageenaninto one footpad of a mouse induces a profound inflammatory response,which is accompanied by the induction of high levels of COX-2 withinapproximately 12 h. Twenty-four hours after carrageenan injection,fluorocoxib A was injected into the peritoneal cavity of the treatedmouse, and optical imaging performed 3–5 h thereafter. As Figure 23 illustrates, compounds selectively accumulatedin the inflamed paw, but not in the noninflamed contralateral paw.

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