Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/11294
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dc.contributor.authorAger, Eleanor Ien
dc.contributor.authorWen, Shu Wenen
dc.contributor.authorChan, Joynaen
dc.contributor.authorChong, Way Wen
dc.contributor.authorNeo, Jaclyn Hen
dc.contributor.authorChristophi, Christopheren
dc.date.accessioned2015-05-16T00:53:00Z
dc.date.available2015-05-16T00:53:00Z
dc.date.issued2011-06-26en
dc.identifier.citationBmc Cancer 2011; 11(): 274en
dc.identifier.govdoc21703011en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/11294en
dc.description.abstractTargeting of the renin angiotensin system (RAS) reduces tumour growth in experimental models of cancer. We aimed to establish if combined targeting of the 'classical' and 'alternative' arms of the RAS could result in synergistic inhibition of colorectal cancer (CRC) liver metastases.Immediately following induction of CRC liver metastases through intrasplenic injection of murine CRC cells, treatment with irbesartan (AT1R blocker; 50 mg/kg/day s.c.), captopril (ACE inhibitor; 750 mg/kg/day i.p.), CGP42112A (AT2R agonist; 0.6 μg/kg/hr i.p.), and/or ANG-(1-7) (24 μg/kg/hr i.p.) began and continued for 21 days. Liver to body weight ratio and/or stereology were used as a measure of tumour burden. Immunohistochemistry was used to determine AT1R and VEGF expression as well as proliferation (Ki67), apoptosis (active caspase 3) and angiogenesis (CD34).Combined RAS therapies failed to improve upon single arm therapies. However, while irbesartan previously inhibited tumour growth in this model, in the current experiments irbesartan failed to affect tumour burden. Subsequent analysis showed a cancer-cell specific upregulation of the angiotensin II type I receptor (AT1R) in irbesartan-insensitive compared to irbesartan-sensitive tumours. The upregulation of AT1R was associated with an increase in proliferation and VEGF expression by cancer cells. While animals bearing irbesartan-sensitive tumours showed a marked decrease in the number of proliferating cells in the liver and VEGF-expressing infiltrating cells in the tumour following AT1R treatment, these were unchanged by treatment in animals bearing irbesartan-insensitive (high AT1R expressing) tumours.Although the results do not support increased efficacy of combined treatment, they provide intriguing evidence of the importance of RAS expression in determining patient response and tumour growth potential and suggest that components of the RAS could be used as biomarkers to aid in patient selection.en
dc.language.isoenen
dc.subject.otherAdenocarcinoma.drug therapy.genetics.metabolism.secondaryen
dc.subject.otherAngiotensin I.pharmacology.therapeutic useen
dc.subject.otherAngiotensin II Type 1 Receptor Blockers.pharmacology.therapeutic useen
dc.subject.otherAngiotensin-Converting Enzyme Inhibitors.pharmacology.therapeutic useen
dc.subject.otherAnimalsen
dc.subject.otherBiphenyl Compounds.pharmacology.therapeutic useen
dc.subject.otherCaptopril.pharmacology.therapeutic useen
dc.subject.otherColorectal Neoplasms.drug therapy.genetics.metabolismen
dc.subject.otherDrug Resistance, Neoplasmen
dc.subject.otherDrug Screening Assays, Antitumoren
dc.subject.otherDrug Synergismen
dc.subject.otherGene Expression Regulation, Neoplasticen
dc.subject.otherLiver Neoplasms, Experimental.drug therapy.genetics.metabolismen
dc.subject.otherMiceen
dc.subject.otherMice, Inbred CBAen
dc.subject.otherMolecular Targeted Therapyen
dc.subject.otherNeoplasm Proteins.antagonists & inhibitors.physiologyen
dc.subject.otherNeovascularization, Pathologic.drug therapyen
dc.subject.otherOligopeptides.pharmacologyen
dc.subject.otherPeptide Fragments.pharmacology.therapeutic useen
dc.subject.otherReceptor, Angiotensin, Type 1.biosynthesis.drug effects.geneticsen
dc.subject.otherReceptor, Angiotensin, Type 2.agonistsen
dc.subject.otherRenin-Angiotensin System.physiologyen
dc.subject.otherTetrazoles.pharmacology.therapeutic useen
dc.subject.otherTumor Burdenen
dc.subject.otherTumor Markers, Biologicalen
dc.subject.otherUp-Regulationen
dc.subject.otherVascular Endothelial Growth Factor A.biosynthesis.geneticsen
dc.titleAltered efficacy of AT1R-targeted treatment after spontaneous cancer cell-AT1R upregulation.en
dc.typeJournal Articleen
dc.identifier.journaltitleBMC canceren
dc.identifier.affiliationThe Department of Surgery, Austin Health, The University of Melbourne, Heidelberg, VIC, Australiaen
dc.identifier.doi10.1186/1471-2407-11-274en
dc.description.pages274en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/21703011en
dc.type.austinJournal Articleen
local.name.researcherChristophi, Christopher
item.languageiso639-1en-
item.fulltextWith Fulltext-
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.openairetypeJournal Article-
crisitem.author.deptSurgery-
crisitem.author.deptHepatopancreatobiliary Surgery-
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