ArticleHepatology (Baltimore, Md.)2014
Differential effects of sorafenib on liver versus tumor fibrosis mediated by stromal-derived factor 1 alpha/C-X-C receptor type 4 axis and myeloid differentiation antigen-positive myeloid cell infiltration in mice.
Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
122 citing papers in PubMed, 2 syntheses or guidelines pooled it, 211 citations in OpenAlex.
- Collagenase-mediated extracellular matrix targeting for enhanced drug penetration and therapeutic efficacy in nanoscale delivery systems for cancer therapy.Journal of nanobiotechnology · 2025Pooled it
- Impact of Bevacizumab on parenchymal damage and functional recovery of the liver in patients with colorectal liver metastases.BMC cancer · 2016Pooled it
- Liver fibrosis: Pathogenesis and innovative nanoparticle-based therapeutic strategies.International journal of pharmaceutics: X · 2026Review
- CXCR4-Targeted Nanotherapeutics: A Promising Approach for Liver Fibrosis and Hepatocellular Carcinoma Management.International journal of nanomedicine · 2026Review
- Nanomaterial-based strategies to overcome sorafenib resistance in hepatocellular carcinoma: from mechanistic insights to translational applications.Frontiers in oncology · 2026Article
- Inhibiting B cells enhances the efficacy of STING agonism or immune checkpoint blockade in hepatocellular carcinoma.Nature communications · 2025Article
- Research Trends of Hepatic Stellate Cells in Hepatoma: A Bibliometric Analysis.Journal of cellular and molecular medicine · 2025Review
- A metal-drug self-delivery nanomedicine alleviates tumor immunosuppression to potentiate synergistic chemo/chemodynamic therapy against hepatocellular carcinoma.Fundamental research · 2025Article
- Preoperative TACE with PD-1 inhibitors and TKIs in beyond "up-to-seven" hepatocellular carcinoma: a propensity score matched analysis.Frontiers in immunology · 2025Article
- Immune Microenvironment and the Effect of Vascular Endothelial Growth Factor Inhibition in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- Present and prospect of transarterial chemoembolization combined with tyrosine kinase inhibitor and PD-1 inhibitor for unresectable hepatocellular carcinoma.World journal of gastrointestinal oncology · 2024Article
- Type I MET inhibitors cooperate with PD-1 blockade to promote rejection of hepatocellular carcinoma.Journal for immunotherapy of cancer · 2024Article
- Multiomic analysis of monocyte-derived alveolar macrophages in idiopathic pulmonary fibrosis.Journal of translational medicine · 2024Article
- Tramadol suppresses growth of orthotopic liver tumors via promoting M1 macrophage polarization in the tumor microenvironment.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Efficacy of Sorafenib-Based Therapies for Non-Small Cell Lung Cancer.Medical sciences (Basel, Switzerland) · 2024Review
- Targeting the lipid metabolic reprogramming of tumor-associated macrophages: A novel insight into cancer immunotherapy.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Tumor-associated macrophages in anti-PD-1/PD-L1 immunotherapy for hepatocellular carcinoma: recent research progress.Frontiers in pharmacology · 2024Review
- The Combination of R848 with Sorafenib Enhances Antitumor Effects by Reprogramming the Tumor Immune Microenvironment and Facilitating Vascular Normalization in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The role of myeloid-derived suppressor cells in liver cancer.Discover oncology · 2023Review
- Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.Journal of hematology & oncology · 2023Review
62 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledSorafenib--a broad kinase inhibitor--is a standard therapy for advanced hepatocellular carcinoma (HCC) and has been shown to exert antifibrotic effects in liver cirrhosis, a precursor of HCC. However, the effects of sorafenib on tumor desmoplasia--and its consequences on treatment resistance--remain unknown. We demonstrate that sorafenib has differential effects on tumor fibrosis versus liver fibrosis in orthotopic models of HCC in mice. Sorafenib intensifies tumor hypoxia, which increases stromal-derived factor 1 alpha (SDF-1α) expression in cancer and stromal cells and, subsequently, myeloid differentiation antigen-positive (Gr-1(+)) myeloid cell infiltration. The SDF-1α/C-X-C receptor type 4 (CXCR4) pathway directly promotes hepatic stellate cell (HSC) differentiation and activation through the mitogen-activated protein kinase pathway. This is consistent with the association between SDF-1α expression with fibrotic septa in cirrhotic liver tissues as well as with desmoplastic regions of human HCC samples. We demonstrate that after treatment with sorafenib, SDF-1α increased the survival of HSCs and their alpha-smooth muscle actin and collagen I expression, thus increasing tumor fibrosis. Finally, we show that Gr-1(+) myeloid cells mediate HSC differentiation and activation in a paracrine manner. CXCR4 inhibition, using AMD3100 in combination with sorafenib treatment, prevents the increase in tumor fibrosis--despite persistently elevated hypoxia--in part by reducing Gr-1(+) myeloid cell infiltration and inhibits HCC growth. Similarly, antibody blockade of Gr-1 reduces tumor fibrosis and inhibits HCC growth when combined with sorafenib treatment.
conclusionBlocking SDF-1α/CXCR4 or Gr-1(+) myeloid cell infiltration may reduce hypoxia-mediated HCC desmoplasia and increase the efficacy of sorafenib treatment.
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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.