Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/11000
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dc.contributor.authorNeo, Jaclyn H-
dc.contributor.authorAger, Eleanor I-
dc.contributor.authorAngus, Peter W-
dc.contributor.authorZhu, Jin-
dc.contributor.authorHerath, Chandana B-
dc.contributor.authorChristophi, Christopher-
dc.date.accessioned2015-05-16T00:34:44Z
dc.date.available2015-05-16T00:34:44Z
dc.date.issued2010-04-10-
dc.identifier.citationBMC Cancer 2010; 10(): 134en_US
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/11000en
dc.description.abstractBlockade of the renin angiotensin system (RAS) via angiotensin I converting enzyme (ACE) inhibition reduces growth of colorectal cancer (CRC) liver metastases in a mouse model. In this work we defined the expression of the various components of the RAS in both tumor and liver during the progression of this disease.Immunohistochemistry and quantitative RT-PCR was used to examine RAS expression in a mouse CRC liver metastases model. CRC metastases and liver tissue was assessed separately at key stages of CRC liver metastases development in untreated (control) mice and in mice treated with the ACE inhibitor captopril (750 mg/kg/day). Non-tumor induced (sham) mice indicated the effect of tumors on normal liver RAS. The statistical significance of multiple comparisons was determined using one-way analysis of variance followed by Bonferroni adjustment with SAS/STAT software.Reduced volume of CRC liver metastases with captopril treatment was evident. Local RAS of CRC metastases differed from the surrounding liver, with lower angiotensin II type 1 receptor (AT1R) expression but increased ANG-(1-7) receptor (MasR) compared to the liver. The AT1R localised to cancer and stromal infiltrating cells, while other RAS receptors were detected in cancer cells only. Tumor induction led to an initial increase in AT1R and ACE expression while captopril treatment significantly increased ACE expression in the final stages of tumor growth. Conversely, captopril treatment decreased expression of AT1R and angiotensinogen.These results demonstrate significant changes in RAS expression in the tumor-bearing captopril treated liver and in CRC metastases. The data suggests the existence of a tumor-specific RAS that can be independently targeted by RAS blockade.en_US
dc.language.isoenen
dc.subject.otherAngiotensin-Converting Enzyme Inhibitors.pharmacologyen
dc.subject.otherAngiotensinogen.biosynthesisen
dc.subject.otherAnimalsen
dc.subject.otherCaptopril.pharmacologyen
dc.subject.otherColorectal Neoplasms.drug therapy.metabolism.pathologyen
dc.subject.otherLiver Neoplasms, Experimental.metabolism.prevention & control.secondaryen
dc.subject.otherMaleen
dc.subject.otherMiceen
dc.subject.otherMice, Inbred CBAen
dc.subject.otherPeptidyl-Dipeptidase A.biosynthesisen
dc.subject.otherReceptor, Angiotensin, Type 1.biosynthesisen
dc.subject.otherReceptor, Angiotensin, Type 2.biosynthesisen
dc.subject.otherRenin.biosynthesisen
dc.subject.otherRenin-Angiotensin System.drug effects.physiologyen
dc.titleChanges in the renin angiotensin system during the development of colorectal cancer liver metastases.en_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleBMC canceren_US
dc.identifier.affiliationSurgery (University of Melbourne)en_US
dc.identifier.doi10.1186/1471-2407-10-134en_US
dc.description.pages134en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/20380732en
dc.type.contentTexten_US
dc.type.austinJournal Articleen
local.name.researcherAngus, Peter W
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextWith Fulltext-
item.grantfulltextopen-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptVictorian Liver Transplant Unit-
crisitem.author.deptGastroenterology and Hepatology-
crisitem.author.deptSurgery-
crisitem.author.deptHepatopancreatobiliary Surgery-
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