ArticleThe American journal of pathology2010
Small interfering RNAs induce target-independent inhibition of tumor growth and vasculature remodeling in a mouse model of hepatocellular carcinoma.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Neuropilins as potential biomarkers in hepatocellular carcinoma: a systematic review of basic and clinical implications.Clinical and molecular hepatology · 2023Pooled it
- Toll-like receptors: versatile players in tumor.Frontiers in immunology · 2026Review
- Polymeric Nanomedicines for siRNA Delivery in Hepatocellular Carcinoma: Emerging Therapeutic Strategies, Combination Approaches, and Translational Perspectives.International journal of nanomedicine · 2026Review
- Neuropilin-1: A Multifaceted Target for Cancer Therapy.Current oncology (Toronto, Ont.) · 2025Review
- Advances in Lipid-Based Nanomedicine: Pathway Specific siRNA Therapy and Optimizing Delivery for Hepatocellular Carcinoma.International journal of nanomedicine · 2025Review
- Prediction and therapeutic targeting of the tumor microenvironment-associated gene CTSK in gastric cancer.Discover oncology · 2023Article
- Toll-like receptor-targeted anti-tumor therapies: Advances and challenges.Frontiers in immunology · 2022Review
- Blood Flow and Shear Stress Allow Monitoring of Progression and Prognosis of Tumor Diseases.Frontiers in physiology · 2021Article
- Roles of Toll-Like Receptor 3 in Human Tumors.Frontiers in immunology · 2021Review
- Article
- Toll-like Receptor 3 Is a Therapeutic Target for Pulmonary Hypertension.American journal of respiratory and critical care medicine · 2019Article
- Anti-neuropilin-1 monoclonal antibody suppresses the migration and invasion of human gastric cancer cells via Akt dephosphorylation.Experimental and therapeutic medicine · 2018Article
- Type I Interferons Impede Short Hairpin RNA-Mediated RNAi via Inhibition of Dicer-Mediated Processing to Small Interfering RNA.Molecular therapy. Nucleic acids · 2017Article
- Innate immunity and hepatocarcinoma: Can toll-like receptors open the door to oncogenesis?World journal of hepatology · 2016Review
- Neuropilins and liver.World journal of gastroenterology · 2015Review
- TLR3 engagement induces IRF-3-dependent apoptosis in androgen-sensitive prostate cancer cells and inhibits tumour growth in vivo.Journal of cellular and molecular medicine · 2015Article
- The role of death receptor 3 in the biological behavior of hepatocellular carcinoma cells.Molecular medicine reports · 2015Article
- Neuropilin-1 as Therapeutic Target for Malignant Melanoma.Frontiers in oncology · 2015Review
- Neuropilin 1: function and therapeutic potential in cancer.Cancer immunology, immunotherapy : CII · 2014Review
- Use of rodents as models of human diseases.Journal of pharmacy & bioallied sciences · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA interference mediated by small interfering RNAs (siRNAs) has emerged as a potential therapeutic approach to treat various diseases, including cancer. Recent studies with several animal models of posttraumatic revascularization demonstrated that synthetic siRNAs may produce therapeutic effects in a target-independent manner through the stimulation of the toll-like receptor-3 (TLR3)/interferon pathway and suppression of angiogenesis. To analyze the impact of siRNAs on tumor angiogenesis, we injected transgenic mice developing hepatocellular carcinoma (HCC) with either control siRNAs or siRNA targeting neuropilin-1. We found that treatment with these siRNAs led to a comparable reduction in tumor liver volume and to inhibition of tumor vasculature remodeling. We further determined that TLR3, which recognizes double-stranded siRNA, was up-regulated in mouse HCC. Treatment of HCC mice with polyinosinic-polycytidylic acid [poly(I:C)], a TLR3 agonist, led to both a reduction of tumor liver enlargement and a decrease in hepatic arterial blood flow, indicating that TLR3 is functional and may mediate both anti-angiogenic and anti-tumor responses. We also demonstrated that siRNAs increased interferon-γ levels in the liver. In vitro, interferon-γ inhibited proliferation of endothelial cells. In addition, we found that siRNAs inhibited endothelial cell proliferation and morphogenesis in an interferon-γ-independent manner. Our results suggest that synthetic siRNAs inhibit target-independently HCC growth and angiogenesis through the activation of the innate interferon response and by directly inhibiting endothelial cell function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.