ArticleNature communications2019
Relaxin gene delivery mitigates liver metastasis and synergizes with check point therapy.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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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
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Who cites it
65 citing papers in PubMed, 128 citations in OpenAlex.
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- Circular RNA encoding relaxin-2 as a potential therapy for liver fibrosis.Molecular therapy. Nucleic acids · 2026Article
- Integrating transcriptomics and Mendelian randomisation identifies immune-related genes causally linked to prostate cancer lymph node metastasis.Discover oncology · 2026Article
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- Dual-functional nanovesicles simultaneously inhibit stromal fibrosis and angiogenesis to suppress cholangiocarcinoma progression.Journal of nanobiotechnology · 2025Article
- The role of relaxins in blood cell modulation: interactions with relaxin family peptide receptor 1 (RXFP1) and glucocorticoid receptor (GR).Clinical science (London, England : 1979) · 2025Review
- Hydrogel Loaded with Aminoethyl Anisamide-Modified Exosomes Attenuates Hepatic Fibrosis by Targeting Activated Hepatic Stellate Cells.ACS nano · 2025Article
- Developments in nanotechnology approaches for the treatment of solid tumors.Experimental hematology & oncology · 2025Review
- Vasomics of the liver.Gut · 2025Review
- The lncRNA MIR181A1HG in extracellular vesicles derived from highly metastatic colorectal cancer cells promotes liver metastasis by remodeling the extracellular matrix and recruiting myeloid-derived suppressor cells.Cell & bioscience · 2025Article
- Relaxin-2 Exhibits a Beneficial Role in Energy Metabolism to Alleviate Atrial Fibrillation Susceptibility.ACS pharmacology & translational science · 2025Article
- Relaxin-2-secreting CAR-T cells exhibit enhanced efficacy in stromal-rich xenograft tumors.Frontiers in immunology · 2025Article
- Smart Nanobiomaterials for Gene Delivery in Localized Cancer Therapy: An Overview from Emerging Materials and Devices to Clinical Applications.Current cancer drug targets · 2025Review
- A Review on Nanotechnologically Derived Phytomedicines for the Treatment of Hepatocellular Carcinoma: Recent Advances in Molecular Mechanism and Drug Targeting.Current drug targets · 2025Review
- Role of Relaxin Signaling in Cancer: A Review.Biochemical pharmacology · 2024Review
- Inhibition of heme-thiolate monooxygenase CYP1B1 prevents hepatic stellate cell activation and liver fibrosis by accumulating trehalose.Science translational medicine · 2024Article
- Current landscape of mRNA technologies and delivery systems for new modality therapeutics.Journal of biomedical science · 2024Review
- Consideration on immunotherapy of liver metastases of malignant tumors.World journal of gastrointestinal surgery · 2024Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
Activated hepatic stellate cell (aHSC)-mediated liver fibrosis is essential to the development of liver metastasis. Here, we discover intra-hepatic scale-up of relaxin (RLN, an anti-fibrotic peptide) in response to fibrosis along with the upregulation of its primary receptor (RXFP1) on aHSCs. The elevated expression of RLN serves as a natural regulator to deactivate aHSCs and resolve liver fibrosis. Therefore, we hypothesize this endogenous liver fibrosis repair mechanism can be leveraged for liver metastasis treatment via enforced RLN expression. To validate the therapeutic potential, we utilize aminoethyl anisamide-conjugated lipid-calcium-phosphate nanoparticles to deliver plasmid DNA encoding RLN. The nanoparticles preferentially target metastatic tumor cells and aHSCs within the metastatic lesion and convert them as an in situ RLN depot. Expressed RLN reverses the stromal microenvironment, which makes it unfavorable for established liver metastasis to grow. In colorectal, pancreatic, and breast cancer liver metastasis models, we confirm the RLN gene therapy results in significant inhibition of metastatic progression and prolongs survival. In addition, enforced RLN expression reactivates intra-metastasis immune milieu. The combination of the RLN gene therapy with PD-L1 blockade immunotherapy further produces a synergistic anti-metastatic efficacy. Collectively, the targeted RLN gene therapy represents a highly efficient, safe, and versatile anti-metastatic modality, and is promising for clinical translation.
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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.