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

Construction of vectors containing a single defined DNA adduct.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Construction of vectors containing a single defined DNA adduct.

Mentions: This mutation spectrum was consistent with thechemistry of DNA modification if one made the assumption that mutationsat particular nucleosides resulted from the replication of an adductformed at that nucleoside. To test this, a more direct method forrelating adduct structure to mutation was employed. Site-specificmutagenesis is a technique in which a chemical adduct of known structureis built into a single position of a DNA molecule that is capableof being replicated in a bacterial or mammalian cell. Since the vectorstypically used contain 5000–7000 nucleotides, this would appearto be a formidable synthetic challenge. In fact, a combination oforganic synthesis and genetic engineering makes singly adducted vectorconstruction relatively straightforward (Figure 6).


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

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

Construction of vectors containing a single defined DNA adduct.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Construction of vectors containing a single defined DNA adduct.
Mentions: This mutation spectrum was consistent with thechemistry of DNA modification if one made the assumption that mutationsat particular nucleosides resulted from the replication of an adductformed at that nucleoside. To test this, a more direct method forrelating adduct structure to mutation was employed. Site-specificmutagenesis is a technique in which a chemical adduct of known structureis built into a single position of a DNA molecule that is capableof being replicated in a bacterial or mammalian cell. Since the vectorstypically used contain 5000–7000 nucleotides, this would appearto be a formidable synthetic challenge. In fact, a combination oforganic synthesis and genetic engineering makes singly adducted vectorconstruction relatively straightforward (Figure 6).

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