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• W2909606969 abstract "Objectives Desmoplastic changes of extracellular matrix (ECM) containing large amounts of hyaluronan (HA) are of interest in chemo- and immunoresistance of pancreatic ductal adenocarcinoma (PDAC). The goal of this study was to evaluate the effects of 4-methylumbelliferone (MU), a selective inhibitor of HA, on ECM and to examine how MU affects adoptive immunotherapy. Methods The effect of MU on cell proliferation, HA synthesis and formation of ECM were investigated in four PDAC cell lines. In addition, the cytotoxicity of γδ T-cell-rich peripheral blood mononuclear cells (PBMCs) collected from healthy donors and stimulated with zoledronate and interleukin-2 was examined in the presence of MU. The amount of HA and tumor-infiltrating lymphocytes were also investigated in mice xenograft models. Results In vitro , 1.0 mM MU inhibited cell proliferation by 45–70% and HA synthesis by 55–80% in all four PDAC cell lines, and enhanced γδ T-cell-rich PBMC-mediated cytotoxicity against PDAC cells. In vivo , MU reduced intratumoral HA and promoted infiltration of inoculated γδ T-cells into tumor tissue, and consequently suppressed tumor growth. Conclusions 4-methylumbelliferone may be an effective immunosensitizer against PDAC through induction of structural changes in the ECM." @default.
• W2909606969 created "2019-01-25" @default.
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• W2909606969 date "2019-02-01" @default.
• W2909606969 modified "2023-09-29" @default.
• W2909606969 title "Increase of Tumor Infiltrating γδ T-cells in Pancreatic Ductal Adenocarcinoma Through Remodeling of the Extracellular Matrix by a Hyaluronan Synthesis Suppressor, 4-Methylumbelliferone" @default.
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• W2909606969 doi "https://doi.org/10.1097/mpa.0000000000001211" @default.
• W2909606969 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30589828" @default.
• W2909606969 hasPublicationYear "2019" @default.
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