9 results on '"Backlund, Michael G"'
Search Results
2. Mechanisms for the Prevention of Gastrointestinal Cancer: The Role of Prostaglandin E2.
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Backlund, Michael G., Mann, Jason R., and DuBois, Raymond N.
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COLON cancer , *RECTAL cancer , *NONSTEROIDAL anti-inflammatory agents , *CYCLOOXYGENASES , *CYCLOOXYGENASE 2 , *TUMORS - Abstract
Carcinoma of the colon or rectum represents one of the most common malignancies worldwide with a higher prevalence in industrialized regions. Epidemiologic studies of individuals taking non-steroidal anti-inflammatory drugs (NSAIDs) have shown a significant reduction in colorectal cancer (CRC) mortality compared to those individuals not receiving these agents. NSAIDs inhibit the enzymatic activity of both isoforms of cyclooxygenase (COX-1 and COX-2), while COX-2-selective inhibitors have shown some efficacy in reducing polyp formation. COX-2-derived bioactive lipids, including the primary prostaglandin (PG) generated in colorectal tumors, PGE2, are known to stimulate cell migration, proliferation and tumor-associated neovascularization while inhibiting cell death. Here we briefly review the role of NSAIDs in preventing CRC, as well as the proposed mechanism by which a COX-2-derived PG, PGE2, promotes colon cancer. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
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- 2005
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3. Mechanisms for the Prevention of Gastrointestinal Cancer: The Role of Prostaglandin E2.
- Author
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Backlund, Michael G., Mann, Jason R., and DuBois, Raymond N.
- Subjects
COLON cancer ,RECTAL cancer ,NONSTEROIDAL anti-inflammatory agents ,CYCLOOXYGENASES ,CYCLOOXYGENASE 2 ,TUMORS - Abstract
Carcinoma of the colon or rectum represents one of the most common malignancies worldwide with a higher prevalence in industrialized regions. Epidemiologic studies of individuals taking non-steroidal anti-inflammatory drugs (NSAIDs) have shown a significant reduction in colorectal cancer (CRC) mortality compared to those individuals not receiving these agents. NSAIDs inhibit the enzymatic activity of both isoforms of cyclooxygenase (COX-1 and COX-2), while COX-2-selective inhibitors have shown some efficacy in reducing polyp formation. COX-2-derived bioactive lipids, including the primary prostaglandin (PG) generated in colorectal tumors, PGE
2 , are known to stimulate cell migration, proliferation and tumor-associated neovascularization while inhibiting cell death. Here we briefly review the role of NSAIDs in preventing CRC, as well as the proposed mechanism by which a COX-2-derived PG, PGE2 , promotes colon cancer. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]- Published
- 2005
- Full Text
- View/download PDF
4. 15-Hydroxyprostaglandin Dehydrogenase Is Down-regulated in Colorectal Cancer.
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Backlund, Michael G., Mann, Jason R., Holla, Vijaykumar R., Buchanan, F. Gregory, Hsin-Hhsiung Tai, Musiek, Erik S., Milne, Ginger L., Katkuri, Sharada, and DuBois, Raymond N.
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PROSTAGLANDINS , *PROSTANOIDS , *INFLAMMATORY mediators , *DEHYDROGENASES , *COLON cancer , *CANCER invasiveness - Abstract
Prostaglandin E2 (PGE2) can stimulate tumor progression by modulating several proneoplastic pathways, including proliferation, angiogenesis, cell migration, invasion, and apoptosis. Although steady-state tissue levels of PGE2 stem from relative rates of biosynthesis and breakdown, most reports examining PGE2 have focused solely on the cyclooxygenase-dependent formation of this bioactive lipid. Enzymatic degradation of PGE2 involves the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). The present study examined a range of normal tissues in the human and mouse and found high levels of 15-PGDH in the large intestine. By contrast, the expression of 15-PGDH is decreased in several colorectal carcinoma cell lines and in other human malignancies such as breast and lung carcinomas. Consistent with these findings, we observe diminished 15-Pgdh expression in ApcMin+/- mouse adenomas. Enzymatic activity of 15-PGDH correlates with expression levels and the genetic disruption of 15-Pgdh completely blocks production of the urinary PGE2 metabolite. Finally, 15-PGDH expression and activity are significantly down-regulated in human colorectal carcinomas relative to matched normal tissue. In summary, these results suggest a novel tumor suppressive role for 15-PGDH due to loss of expression during colorectal tumor progression. [ABSTRACT FROM AUTHOR]
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- 2005
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5. Novel strategies for the treatment of lung cancer: modulation of eicosanoids.
- Author
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Backlund MG, Amann JM, Johnson DH, Backlund, Michael G, Amann, Joseph M, and Johnson, David H
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- 2008
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6. Ras Up-Regulation of Cyclooxygenase-2.
- Author
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Backlund, Michael G., Mann, Jason R., Dingzhi Wang, and DuBois, Raymond N.
- Abstract
An abstract of the article "Ras Up-Regulation of Cyclooxygenase-2," by Michael G. Backlund and colleagues is presented.
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- 2006
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7. Deployment of the 1st Area Medical Laboratory in a Split-Based Configuration During the Largest Ebola Outbreak in History.
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Cardile, Anthony P., Littell, Christopher T., Backlund, Michael G., Heipertz, Richard A., Brammer, Jerod A., Palmer, Sean M., Vento, Todd J., Ortiz, Felix A., Rosa, William R., Major, Michael J., and Garman, Patrick M.
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GASTROENTERITIS , *EBOLA virus disease , *DEPLOYMENT (Military strategy) , *PUBLIC health , *DIAGNOSIS ,TREATMENT of Ebola virus diseases - Abstract
Background: The U.S. Army 1st Area Medical Laboratory (1st AML) is currently the only deployable medical CBRNE (Chemical, Biological, Radiological, Nuclear, and Explosives) laboratory in the Army's Forces Command. In support of the United States Agency for International Development Ebola response, the U.S. military initiated Operation United Assistance (OUA), and deployed approximately 2,500 service members to support the Government of Liberia's Ebola control efforts. Due to its unique molecular diagnostic and expeditionary capabilities, the 1st AML was ordered to deploy in October of 2014 in support of OUA via establishment of Ebola testing laboratories. To meet the unique mission requirements of OUA, the unit was re-organized to operate in a split-based configuration and sustain four separate Ebola testing laboratories.Methods: This article is a review of the 1st AML's OUA participation in a split-based configuration. Topics highlighted include pre-deployment planning/training, operational/logistical considerations in fielding/withdrawing laboratories, laboratory testing results, disease and non-battle injuries, and lessons learned.Findings: Fielding the 1st AML in a split-based configuration required careful pre-deployment planning, additional training, optimal use of personnel, and the acquisition of additional laboratory equipment. Challenges in establishing and sustaining remote laboratories in Liberia included: difficulties in transportation of equipment due to poor road infrastructure, heavy equipment unloading, and equipment damage during transit. Between November 26, 2014 and February 18, 2015 the four 1st AML labs successfully tested blood samples from patients and oral swabs collected by burial teams in rural Liberia. The most significant equipment malfunction during laboratory operations was generators powering the labs, with the same problem impacting headquarters. Generator failures delayed laboratory operations/result reporting, and put temperature sensitive reagents at risk. None of the 22 1st AML soldiers (at remote labs or headquarters) had an Ebola exposure, none were infected with malaria or other tropical diseases, and none required evacuation from the time deployed to remote sites. The primary medical condition encountered was acute gastroenteritis, and within the first week of arrival to Liberia, 19 (86%) soldiers were affected.Discussion/impact/recommendations: With proper planning and training, the 1st AML can successfully conduct split-based operations in an outbreak setting, and this capability can be utilized in future operations. The performance of the 1st AML during the current Ebola outbreak highlights the value of this asset, and the need to continue its evolution to support U.S. military operations. [ABSTRACT FROM AUTHOR]- Published
- 2016
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8. Microsomal prostaglandin E synthase-2 is not essential for in vivo prostaglandin E2 biosynthesis
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Jania, Leigh A., Chandrasekharan, Subhashini, Backlund, Michael G., Foley, Nicholas A., Snouwaert, John, Wang, I-Ming, Clark, Patsy, Audoly, Laurent P., and Koller, Beverly H.
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PROSTAGLANDINS E , *CYCLOOXYGENASES , *GENE frequency , *GENE expression , *LABORATORY mice - Abstract
Abstract: Prostaglandin E2 (PGE2) plays an important role in the normal physiology of many organ systems. Increased levels of this lipid mediator are associated with many disease states, and it potently regulates inflammatory responses. Three enzymes capable of in vitro synthesis of PGE2 from the cyclooxygenase metabolite PGH2 have been described. Here, we examine the contribution of one of these enzymes to PGE2 production, mPges-2, which encodes microsomal prostaglandin synthase-2 (mPGES-2), by generating mice homozygous for the null allele of this gene. Loss of mPges-2 expression did not result in a measurable decrease in PGE2 levels in any tissue or cell type examined from healthy mice. Taken together, analysis of the mPGES-2 deficient mouse lines does not substantiate the contention that mPGES-2 is a PGE2 synthase. [Copyright &y& Elsevier]
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- 2009
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9. Cyclopentenone Isoprostanes Inhibit the Inflammatory Response in Màcrophages.
- Author
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Musiek, Erik S., Ling Gao, Milne, Ginger L., Wei Han, Everhart, M. Brett, Dingzhi Wang, Backlund, Michael G., DuBois, Raymond N., Zanoni, Giuseppe, Vidari, Giovanni, Blackwell, Timothy S., and Morrow, Jason D.
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INFLAMMATORY mediators , *MACROPHAGES , *TRANSCRIPTION factors , *ANTIGEN presenting cells , *CONNECTIVE tissue cells , *NITRIC-oxide synthases , *CELL receptors , *OXIDATIVE stress - Abstract
Although both inflammation and oxidative stress contribute to the pathogenesis of many disease states, the interaction between the two is poorly understood. Cyclopentenone isoprostanes (IsoPs), highly reactive structural isomers of the bioactive cyclopentenone prostaglandins PGA2 and PGJ2, are formed non-enzymatically as products of oxidative stress in vivo. We have, for the first time, examined the effects of synthetic 15-A2- and 15-J2-IsoPs, two groups of endogenous cyclopentenone IsoPs, on the inflammatory response in RAW264.7 and primary murine macrophages. Cyclopentenone IsoPs potently inhibited lipopolysaccharide-stimulated IΚBα degradation and subsequent NF-ΚB nuclear translocation and transcriptional activity. Expression of inducible nitric-oxide synthase and cyclooxygenase-2 were also inhibited by cyclopentenone IsoPs as was nitrite and prostaglandin production (IC50 ∼ 360 and 210 mM, respectively), 15-J2-IsoPs potently activated peroxisome proliferator-activated receptor γ (PPARγ) nuclear receptors, whereas 15-A2-IsoP did not, although the anti-inflammatory effects of both molecules were PPARγ-independent. Interestingly 15-A2- IsoPs induced oxidative stress in RAW cells that was blocked by the antioxidant 4-hydroxy-TEMPO (TEMPOL) or the mitochondrial uncoupler carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone. TEMPOL also abrogated the inhibitory effect of 15-A2-IsoPs on lipopolysaccharide-induced NF-ΚB activation, inducible nitricoxide synthase expression, and nitrite production, suggesting that 15-A2-IsoPs inhibit the NF-ΚB pathway at least partially via a redoxdependent mechanism. 15-J2-IsoP, but not 15-A2-IsoP, also potently induced RAW cell apoptosis again via a PPARγ-independent mechanism. These findings suggest that cyclopentenone IsoPs may serve as negative feedback regulators of inflammation and have important implications for defining the role of oxidative stress in the inflammatory response. [ABSTRACT FROM AUTHOR]
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- 2005
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