ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
PI-88 inhibits postoperative recurrence of hepatocellular carcinoma via disrupting the surge of heparanase after liver resection.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Elevated heparanase expression is associated with poor prognosis in breast cancer: a study based on systematic review and TCGA data.Oncotarget · 2017Pooled it
- Targeting the heparan sulfate proteoglycan/heparanase axis as a novel therapeutic strategy to drive adipogenesis and block tumor growth of dedifferentiated liposarcoma.International journal of biological sciences · 2026Article
- Advances in postoperative adjuvant therapy for primary liver cancer.World journal of gastrointestinal oncology · 2022Review
- Upregulation of ERK-EGR1-heparanase axis by HDAC inhibitors provides targets for rational therapeutic intervention in synovial sarcoma.Journal of experimental & clinical cancer research : CR · 2021Article
- Metastasis Prevention: Focus on Metastatic Circulating Tumor Cells.Molecular diagnosis & therapy · 2021Review
- Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management.Biomolecules · 2021Review
- The Role and Therapeutic Value of Syndecan-1 in Cancer Metastasis and Drug Resistance.Frontiers in cell and developmental biology · 2021Review
- New classes of potent heparanase inhibitors from ligand-based virtual screening.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Heparan sulfate proteoglycans as targets for cancer therapy: a review.Cancer biology & therapy · 2020Review
- Tumor‑suppressive miR‑299‑3p inhibits gastric cancer cell invasion by targeting heparanase.Molecular medicine reports · 2019Article
- Heparan Sulfate Mimetics in Cancer Therapy: The Challenge to Define Structural Determinants and the Relevance of Targets for Optimal Activity.Molecules (Basel, Switzerland) · 2018Review
- Low-Molecular-Weight Heparins: Reduced Size Particulate Systems for Improved Therapeutic Outcomes.Molecules (Basel, Switzerland) · 2018Review
- Cellular and molecular targets for the immunotherapy of hepatocellular carcinoma.Molecular and cellular biochemistry · 2018Review
- Heparin Mimetics: Their Therapeutic Potential.Pharmaceuticals (Basel, Switzerland) · 2017Review
- The progress of early growth response factor 1 and leukemia.Intractable & rare diseases research · 2016Review
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9 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Phosphomannopentaose sulfate (PI-88), an effective inhibitor of heparanase (HPSE), exhibited anti-recurrence and anti-metastasis activity in preliminary clinical trials of hepatocellular carcinoma (HCC); however, the underlying mechanisms remain uncertain. Our aim was to reveal the mechanism by which PI-88 inhibits recurrence and intrahepatic metastasis. A tissue microarray containing samples from 352 HCC patients was used to determine HPSE expression. We performed enzyme-linked immunosorbent assay (ELISA) to detect plasma levels of HPSE in 40 HCC patients. We also used quantitative polymerase chain reaction, western blot analysis, and immunohistochemical staining to assess HPSE expression of HCC cell lines and tissues. The in vitro effects of PI-88 were examined by cell proliferation and migration assays. In vivo PI-88 activity was assessed using murine orthotopic HCC models. Intratumoral HPSE was an independent prognostic marker for postsurgical overall survival (P = 0.001) and time to recurrence (P < 0.001) of HCC patients with hepatectomy. Elevated levels of HPSE were detected both in postsurgical plasma of HCC patients and an orthotopic mouse model after hepatectomy. PI-88 inhibited tumor recurrence and metastasis after liver resection in the mouse model. In vitro expression of HPSE was up-regulated by overexpression of early growth response 1 (EGR1), which is induced after hepatectomy. Up-regulation of HPSE enhanced the sensitivity of HCC cells to PI-88 and the inhibitive effect of PI-88 on cell proliferation and migration. Our data show that PI-88 effectively inhibits postoperative recurrence and intrahepatic metastasis of HCC, providing an experimental basis for the clinical application of PI-88 in HCC patients who have undergone hepatectomy.
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