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An orally active ga...
An orally active galectin-3 antagonist inhibits lung adenocarcinoma growth and augments response to PD-L1 blockade
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- Vuong, Lynda (författare)
- King's College London
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- Kouverianou, Eleni (författare)
- University of Edinburgh
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- Rooney, Claire M. (författare)
- King's College London
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visa fler...
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- McHugh, Brian J. (författare)
- University of Edinburgh
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- Howie, Sarah E.M. (författare)
- University of Edinburgh
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- Gregory, Christopher D. (författare)
- University of Edinburgh
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- Forbes, Stuart J. (författare)
- University of Edinburgh
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- Henderson, Neil C. (författare)
- University of Edinburgh
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- Zetterberg, Fredrik R. (författare)
- Galecto Biotech ApS, Denmark
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- Nilsson, Ulf J. (författare)
- Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Leffler, Hakon (författare)
- Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine
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- Ford, Paul (författare)
- Galecto Biotech ApS, Denmark
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- Pedersen, Anders (författare)
- Galecto Biotech ApS, Denmark
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- Gravelle, Lise (författare)
- Galecto Biotech ApS, Denmark
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- Tantawi, Susan (författare)
- Galecto Biotech ApS, Denmark
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- Schambye, Hans (författare)
- Galecto Biotech ApS, Denmark
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- Sethi, Tariq (författare)
- King's College London
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- MacKinnon, Alison C. (författare)
- University of Edinburgh
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(creator_code:org_t)
- 2019
- 2019
- Engelska 13 s.
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Ingår i: Cancer Research. - 0008-5472. ; 79:7, s. 1480-1492
- Relaterad länk:
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https://aacrjournals...
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- A combination therapy approach is required to improve tumor immune infiltration and patient response to immune checkpoint inhibitors that target negative regulatory receptors. Galectin-3 is a β-galactoside-binding lectin that is highly expressed within the tumor microenvironment of aggressive cancers and whose expression correlates with poor survival particularly in patients with non-small cell lung cancer (NSCLC). To examine the role of galectin-3 inhibition in NSCLC, we tested the effects of galectin-3 depletion using genetic and pharmacologic approaches on syngeneic mouse lung adenocarcinoma and human lung adenocarcinoma xenografts. Galectin-3-/- mice developed significantly smaller and fewer tumors and metastases than syngeneic C57/ Bl6 wild-type mice. Macrophage ablation retarded tumor growth, whereas reconstitution with galectin-3-positive bone marrow restored tumor growth in galectin-3-/- mice, indicating that macrophages were a major driver of the antitumor response. Oral administration of a novel small molecule galectin-3 inhibitor GB1107 reduced human and mouse lung adenocarcinoma growth and blocked metastasis in the syngeneic model. Treatment with GB1107 increased tumor M1 macrophage polarization and CD8 + T-cell infiltration. Moreover, GB1107 potentiated the effects of a PD-L1 immune checkpoint inhibitor to increase expression of cytotoxic (IFNγ, granzyme B, perforin-1, Fas ligand) and apoptotic (cleaved caspase-3) effector molecules. In summary, galectin-3 is an important regulator of lung adenocarcinoma progression. The novel galectin-3 inhibitor presented could provide an effective, nontoxic monotherapy or be used in combination with immune checkpoint inhibitors to boost immune infiltration and responses in lung adenocarcinoma and potentially other aggressive cancers. Significance: A novel and orally active galectin-3 antagonist inhibits lung adenocarcinoma growth and metastasis and augments response to PD-L1 blockade.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
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Till lärosätets databas
- Av författaren/redakt...
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Vuong, Lynda
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Kouverianou, Ele ...
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Rooney, Claire M ...
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McHugh, Brian J.
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Howie, Sarah E.M ...
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Gregory, Christo ...
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visa fler...
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Forbes, Stuart J ...
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Henderson, Neil ...
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Zetterberg, Fred ...
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Nilsson, Ulf J.
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Leffler, Hakon
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Ford, Paul
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Pedersen, Anders
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Gravelle, Lise
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Tantawi, Susan
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Schambye, Hans
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Sethi, Tariq
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MacKinnon, Aliso ...
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visa färre...
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Cancer Research
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Lunds universitet