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dc.contributor.authorBarry, M
dc.contributor.authorCahill, R A
dc.contributor.authorRoche-Nagle, G
dc.contributor.authorNeilan, T G
dc.contributor.authorTreumann, A
dc.contributor.authorHarmey, J H
dc.contributor.authorBouchier-Hayes, D J
dc.date.accessioned2011-04-07T08:33:37Z
dc.date.available2011-04-07T08:33:37Z
dc.date.issued2009-06
dc.identifier.citationNeoplasms escape selective COX-2 inhibition in an animal model of breast cancer. 2009, 178 (2):201-8 Ir J Med Scien
dc.identifier.issn1863-4362
dc.identifier.pmid19340516
dc.identifier.doi10.1007/s11845-009-0335-3
dc.identifier.urihttp://hdl.handle.net/10147/127616
dc.description.abstractCyclo-oxygenase-2 (COX-2) is up-regulated in malignant tumours rendering it an attractive target for cancer therapeutics. However, whether long-term antagonism maintains its initial efficacy on established tumours is unclear.
dc.description.abstract4T1 cells were injected into the mammary fat pad of BALB/c mice (n = 8). Once tumour deposits were established, animals were randomized into two equal groups to receive either a selective COX-2 inhibitor (SC-236) or a drug vehicle. Further animals similarly treated (n = 7) were studied in diuresis cages allowing urine capture and analysis by mass spectrometry to determine Prostaglandin F-1 levels (PGF-1). In addition, both wild-type receiving SC-236 and COX-2 knockout mice receiving either SC 236 or vehicle were subjected to the same studies to determine whether tumour-derived or host-derived (stromal) COX-2 was the critical element. Finally, BALB/c mice with 4T1 tumours (n = 7) were treated with a combination of COX-2 and lipoxygenase (LOX) inhibition to attenuate this escape phenomenon.
dc.description.abstractWhile selective COX-2 inhibition initially retarded tumour growth, a rapid increase in tumour growth rate occurred later (day 9). This escape phenomenon correlated with an increase in urinary PGF-1 levels. An identical trend was also observed whether COX-2 knockout mice received SC-236 or not, suggesting that this effect is due to increased tumour-derived COX-2 production rather than recovery of host COX-2 functional capacity. Finally, dual inhibition of COX and LOX pathways attenuated this escape process.
dc.description.abstractThe anti-neoplastic effects of selective COX-2 inhibition may not be sustained as tumours demonstrate an escape capacity. However, this phenomenon maybe attenuated by a combination of COX/LOX inhibitors.
dc.language.isoenen
dc.subject.meshAnimals
dc.subject.meshBreast Neoplasms
dc.subject.meshCyclooxygenase 2
dc.subject.meshCyclooxygenase 2 Inhibitors
dc.subject.meshDisease Progression
dc.subject.meshFemale
dc.subject.meshLipoxygenase
dc.subject.meshMice
dc.subject.meshMice, Inbred BALB C
dc.subject.meshModels, Animal
dc.subject.meshRandom Allocation
dc.titleNeoplasms escape selective COX-2 inhibition in an animal model of breast cancer.en
dc.typeArticleen
dc.contributor.departmentDepartment of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland. mitchelbarry@hotmail.comen
dc.identifier.journalIrish journal of medical scienceen
dc.description.provinceLeinster
html.description.abstractCyclo-oxygenase-2 (COX-2) is up-regulated in malignant tumours rendering it an attractive target for cancer therapeutics. However, whether long-term antagonism maintains its initial efficacy on established tumours is unclear.
html.description.abstract4T1 cells were injected into the mammary fat pad of BALB/c mice (n = 8). Once tumour deposits were established, animals were randomized into two equal groups to receive either a selective COX-2 inhibitor (SC-236) or a drug vehicle. Further animals similarly treated (n = 7) were studied in diuresis cages allowing urine capture and analysis by mass spectrometry to determine Prostaglandin F-1 levels (PGF-1). In addition, both wild-type receiving SC-236 and COX-2 knockout mice receiving either SC 236 or vehicle were subjected to the same studies to determine whether tumour-derived or host-derived (stromal) COX-2 was the critical element. Finally, BALB/c mice with 4T1 tumours (n = 7) were treated with a combination of COX-2 and lipoxygenase (LOX) inhibition to attenuate this escape phenomenon.
html.description.abstractWhile selective COX-2 inhibition initially retarded tumour growth, a rapid increase in tumour growth rate occurred later (day 9). This escape phenomenon correlated with an increase in urinary PGF-1 levels. An identical trend was also observed whether COX-2 knockout mice received SC-236 or not, suggesting that this effect is due to increased tumour-derived COX-2 production rather than recovery of host COX-2 functional capacity. Finally, dual inhibition of COX and LOX pathways attenuated this escape process.
html.description.abstractThe anti-neoplastic effects of selective COX-2 inhibition may not be sustained as tumours demonstrate an escape capacity. However, this phenomenon maybe attenuated by a combination of COX/LOX inhibitors.


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