ArticleBMC cancer2012
Reverse translation of phase I biomarker findings links the activity of angiotensin-(1-7) to repression of hypoxia inducible factor-1α in vascular sarcomas.
Article in BMC cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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The trial behind it
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- The potential role of renin angiotensin system in acute leukemia: a narrative review.Molecular biology reports · 2024Review
- Exogenous Ang-(1-7) inhibits autophagy via HIF-1α/THBS1/BECN1 axis to alleviate chronic intermittent hypoxia-enhanced airway remodelling of asthma.Cell death discovery · 2023Article
- Review
- HIF-hypoxia signaling in skeletal muscle physiology and fibrosis.Journal of cell communication and signaling · 2020Review
- Stabilization of Angiotensin-(1-7) by key substitution with a cyclic non-natural amino acid.Amino acids · 2017Article
- Phase II Trial of Angiotensin-(1-7) for the Treatment of Patients with Metastatic Sarcoma.Sarcoma · 2016Article
- Angiotensin-(1-7) Suppresses Hepatocellular Carcinoma Growth and Angiogenesis via Complex Interactions of Angiotensin II Type 1 Receptor, Angiotensin II Type 2 Receptor and Mas Receptor.Molecular medicine (Cambridge, Mass.) · 2015Article
- Angiotensin-(1-7) prevents radiation-induced inflammation in rat primary astrocytes through regulation of MAP kinase signaling.Free radical biology & medicine · 2013Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIn 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.
methodsPlasma 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.
resultsTests 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 1α (HIF-1α) expression (P < .001).
conclusionsAng-(1-7) has clinical and pre-clinical activity for vascular sarcomas that is linked to reduced HIF-1α and PlGF expression.
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