ArticleOncotarget2015
The heparan sulfate mimetic PG545 interferes with Wnt/β-catenin signaling and significantly suppresses pancreatic tumorigenesis alone and in combination with gemcitabine.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 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
- Article
- PG545 sensitizes ovarian cancer cells to PARP inhibitors through modulation of RAD51-DEK interaction.Oncogene · 2023Article
- Heparan sulfate proteoglycans in cancer: Pathogenesis and therapeutic potential.Advances in cancer research · 2023Article
- Phase Ib open-label, multicenter study of pixatimod, an activator of TLR9, in combination with nivolumab in subjects with microsatellite-stable metastatic colorectal cancer, metastatic pancreatic ductal adenocarcinoma and other solid tumors.Journal for immunotherapy of cancer · 2023Article
- Characterization of a novel bispecific antibody targeting tissue factor-positive tumors with T cell engagement.Acta pharmaceutica Sinica. B · 2022Article
- Article
- Identification of tumor antigens and immune subtypes of pancreatic adenocarcinoma for mRNA vaccine development.Molecular cancer · 2021Article
- Inhibition of PFKFB3 induces cell death and synergistically enhances chemosensitivity in endometrial cancer.Oncogene · 2021Article
- Expression and Role of Heparan Sulfated Proteoglycans in Pancreatic Cancer.Frontiers in oncology · 2021Review
- Wnt7a inhibits transformed cell proliferation while promoting migration and invasion in non-small cell lung cancer.Translational cancer research · 2020Article
- Sulfated glycolipid PG545 induces endoplasmic reticulum stress and augments autophagic flux by enhancing anticancer chemotherapy efficacy in endometrial cancer.Biochemical pharmacology · 2020Article
- The Heparan Sulfate Mimetic PG545 Modulates T Cell Responses and Prevents Delayed-Type Hypersensitivity.Frontiers in immunology · 2020Article
- Wnt/β-Catenin Signaling: The Culprit in Pancreatic Carcinogenesis and Therapeutic Resistance.International journal of molecular sciences · 2019Review
- Targeting Heparanase in Cancer: Inhibition by Synthetic, Chemically Modified, and Natural Compounds.iScience · 2019Review
- Leukocyte Heparanase: A Double-Edged Sword in Tumor Progression.Frontiers in oncology · 2019Review
- Heparan Sulfate Mimetics in Cancer Therapy: The Challenge to Define Structural Determinants and the Relevance of Targets for Optimal Activity.Molecules (Basel, Switzerland) · 2018Review
- Immunomodulatory activities of pixatimod: emerging nonclinical and clinical data, and its potential utility in combination with PD-1 inhibitors.Journal for immunotherapy of cancer · 2018Article
- Wnt7a activates canonical Wnt signaling, promotes bladder cancer cell invasion, and is suppressed by miR-370-3p.The Journal of biological chemistry · 2018Article
- Patient derived xenografts (PDX) predict an effective heparanase-based therapy for lung cancer.Oncotarget · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The heparan sulfate mimetic PG545 has been shown to exert anti-angiogenic and anti-metastatic activity in vitro and in vivo cancer models. Although much of this activity has been attributed to inhibition of heparanase and heparan sulfate-binding growth factors, it was hypothesized that PG545 may additionally disrupt Wnt signaling, an important pathway underlying the malignancy of pancreatic cancer. We show that PG545, by directly interacting with Wnt3a and Wnt7a, inhibits Wnt/β-catenin signaling leading to inhibition of proliferation in pancreatic tumor cell lines. Additionally, we demonstrate for the first time that the combination of PG545 with gemcitabine has strong synergistic effects on viability, motility and apoptosis induction in several pancreatic cell lines. In an orthotopic xenograft mouse model, combination of PG545 with gemcitabine efficiently inhibited tumor growth and metastasis compared to single treatment alone. Also, PG545 treatment alone decreased the levels of β-catenin and its downstream targets, cyclin D1, MMP-7 and VEGF which is consistent with our in vitro data. Collectively, our findings suggest that PG545 exerts anti-tumor activity by disrupting Wnt/β-catenin signaling and combination with gemcitabine should be considered as a novel therapeutic strategy for pancreatic cancer 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.