{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Petty WJ"],"funding":["FDA HHS","NCI NIH HHS"],"pagination":["404"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3495013"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12"],"pubmed_abstract":["In a phase I study of angiotensin-(1-7) [Ang-(1-7)], clinical benefit was associated with reduction in plasma placental growth factor (PlGF) concentrations. The current study examines Ang-(1-7) induced changes in biomarkers according to cancer type and investigates mechanisms of action engaged in vitro.Plasma biomarkers were measured prior to Ang-(1-7) administration as well as 1, 2, 3, 4, and 6?hours after treatment. Tests for interaction were performed to determine the impact of cancer type on angiogenic hormone levels. If a positive interaction was detected, treatment-induced biomarker changes for individual cancer types were assessed. To investigate mechanisms of action, in vitro growth assays were performed using a murine endothelioma cell line (EOMA). PCR arrays were performed to identify and statistically validate genes that were altered by Ang-(1-7) treatment in these cells.Tests for interaction controlled for dose cohort and clinical response indicated a significant impact of cancer type on post-treatment VEGF and PlGF levels. Following treatment, PlGF levels decreased over time in patients with sarcoma (P?=?.007). Treatment of EOMA cells with increasing doses of Ang-(1-7) led to significant growth suppression at doses as low as 100 nM. PCR arrays identified 18 genes that appeared to have altered expression after Ang-(1-7) treatment. Replicate analyses confirmed significant changes in 8 genes including reduction in PlGF (P?=?.04) and hypoxia inducible factor 1? (HIF-1?) expression (P?<?.001).Ang-(1-7) has clinical and pre-clinical activity for vascular sarcomas that is linked to reduced HIF-1? and PlGF expression."],"journal":["BMC cancer"],"pubmed_title":["Reverse translation of phase I biomarker findings links the activity of angiotensin-(1-7) to repression of hypoxia inducible factor-1? in vascular sarcomas."],"pmcid":["PMC3495013"],"funding_grant_id":["P30-CA012197","R01-FD003936"],"pubmed_authors":["Petty WJ","Aklilu M","Varela VA","Lovato J","Miller AA","Savage PD"],"additional_accession":[]},"is_claimable":false,"name":"Reverse translation of phase I biomarker findings links the activity of angiotensin-(1-7) to repression of hypoxia inducible factor-1? in vascular sarcomas.","description":"In a phase I study of angiotensin-(1-7) [Ang-(1-7)], clinical benefit was associated with reduction in plasma placental growth factor (PlGF) concentrations. The current study examines Ang-(1-7) induced changes in biomarkers according to cancer type and investigates mechanisms of action engaged in vitro.Plasma biomarkers were measured prior to Ang-(1-7) administration as well as 1, 2, 3, 4, and 6?hours after treatment. Tests for interaction were performed to determine the impact of cancer type on angiogenic hormone levels. If a positive interaction was detected, treatment-induced biomarker changes for individual cancer types were assessed. To investigate mechanisms of action, in vitro growth assays were performed using a murine endothelioma cell line (EOMA). PCR arrays were performed to identify and statistically validate genes that were altered by Ang-(1-7) treatment in these cells.Tests for interaction controlled for dose cohort and clinical response indicated a significant impact of cancer type on post-treatment VEGF and PlGF levels. Following treatment, PlGF levels decreased over time in patients with sarcoma (P?=?.007). Treatment of EOMA cells with increasing doses of Ang-(1-7) led to significant growth suppression at doses as low as 100 nM. PCR arrays identified 18 genes that appeared to have altered expression after Ang-(1-7) treatment. Replicate analyses confirmed significant changes in 8 genes including reduction in PlGF (P?=?.04) and hypoxia inducible factor 1? (HIF-1?) expression (P?<?.001).Ang-(1-7) has clinical and pre-clinical activity for vascular sarcomas that is linked to reduced HIF-1? and PlGF expression.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Sep","modification":"2021-02-20T04:37:04Z","creation":"2019-03-27T01:00:18Z"},"accession":"S-EPMC3495013","cross_references":{"pubmed":["22963500"],"doi":["10.1186/1471-2407-12-404"]}}