ArticleUnited European gastroenterology journal2013
Hedgehog inhibition reduces angiogenesis by downregulation of tumoral VEGF-A expression in hepatocellular carcinoma.
Article in United European gastroenterology journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Targeted Therapy and Immunotherapies in Hepatocellular Carcinoma: Mechanisms and Clinical Studies.MedComm · 2026Review
- Reappraisal of the Roles of the Sonic Hedgehog Signaling Pathway in Hepatocellular Carcinoma.Cancers · 2024Review
- Review
- ARL13B promotes angiogenesis and glioma growth by activating VEGFA-VEGFR2 signaling.Neuro-oncology · 2023Article
- Critical signaling pathways governing hepatocellular carcinoma behavior; small molecule-based approaches.Cancer cell international · 2021Review
- Article
- The hedgehog pathway in nonalcoholic fatty liver disease.Critical reviews in biochemistry and molecular biology · 2018Review
- Hedgehog signalling in liver pathophysiology.Journal of hepatology · 2018Review
- Expression and significance of the Hedgehog signal transduction pathway in oxygen-induced retinal neovascularization in mice.Drug design, development and therapy · 2018Article
- Sonic hedgehog (SHH) signaling improves the angiogenic potential of Wharton's jelly-derived mesenchymal stem cells (WJ-MSC).Stem cell research & therapy · 2017Article
- Implication of the Hedgehog pathway in hepatocellular carcinoma.World journal of gastroenterology · 2017Review
- Bcl-2 degradation is an additional pro-apoptotic effect of polo-like kinase inhibition in cholangiocarcinoma cells.World journal of gastroenterology · 2017Article
- Macrophages and endothelial cells orchestrate tumor-associated angiogenesis in oral cancer via hedgehog pathway activation.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Intravenous Administration Is an Effective and Safe Route for Cancer Gene Therapy Using the Bifidobacterium-Mediated Recombinant HSV-1 Thymidine Kinase and Ganciclovir.International journal of molecular sciences · 2016Article
- Hedgehog signaling: modulation of cancer properies and tumor mircroenvironment.Molecular cancer · 2016Review
- BRD4 induces cell migration and invasion in HCC cells through MMP-2 and MMP-9 activation mediated by the Sonic hedgehog signaling pathway.Oncology letters · 2015Article
- Statins activate the canonical hedgehog-signaling and aggravate non-cirrhotic portal hypertension, but inhibit the non-canonical hedgehog signaling and cirrhotic portal hypertension.Scientific reports · 2015Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDysregulation and activation of Hedgehog (Hh) signalling may contribute to tumorigenesis, angiogenesis, and metastatic seeding in several solid tumours.
objectiveWe investigated the impact of Hh inhibition on tumour growth and angiogenesis using in-vitro and in-vivo models of hepatocellular carcinoma (HCC).
methodsThe effect of the Hh pathway inhibitor GDC-0449 on tumour growth was investigated using an orthotopic rat model. Effects on angiogenesis were determined by immunohistochemical staining of von Willebrand factor antigen and by assessing the mRNA expression of several angiogenic factors. In vitro, HCC cell lines were treated with GDC-0449 and evaluated for viability and expression of vascular endothelial growth factor (VEGF). Endothelial cells were evaluated for viability, migration, and tube formation.
resultsIn the orthotopic HCC model, GDC-0449 significantly decreased tumoral VEGF expression which was accompanied by a significant reduction of microvessel density and tumour growth. In HCC cells, GDC-0449 had no effect on cell growth but significantly reduced target gene regulation and VEGF expression while having no direct effect on endothelial cell viability, migration, and tube formation.
conclusionsHh inhibition with GDC-0449 downregulates tumoral VEGF production in vitro and reduces tumoral VEGF expression, angiogenesis, and tumour growth in an orthotopic HCC model.
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