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3,4-Difluorobenzocu...
3,4-Difluorobenzocurcumin Inhibits Vegfc-Vegfr3-Erk Signalling to Block Developmental Lymphangiogenesis in Zebrafish
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- Okuda, Kazuhide S. (author)
- Peter MacCallum Canc Ctr, Organogenesis & Canc Program, Melbourne, Vic 3000, Australia.;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic 3000, Australia.;Univ Melbourne, Dept Anat & Physiol, Melbourne, Vic 3000, Australia.;Univ Queensland, Div Genom Dev & Dis, Inst Mol Biosci, St Lucia, Qld 4072, Australia.;Canc Res Malaysia, Subang Jaya 47500, Selangor, Malaysia.
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- Ng, Mei Fong (author)
- Canc Res Malaysia, Subang Jaya 47500, Selangor, Malaysia.
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- Ruslan, Nur Faizah (author)
- Canc Res Malaysia, Subang Jaya 47500, Selangor, Malaysia.
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- Bower, Neil, I (author)
- Univ Queensland, Div Genom Dev & Dis, Inst Mol Biosci, St Lucia, Qld 4072, Australia.
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- Song, Dedrick Soon Seng (author)
- Canc Res Malaysia, Subang Jaya 47500, Selangor, Malaysia.
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- Chen, Huijun (author)
- Univ Queensland, Div Genom Dev & Dis, Inst Mol Biosci, St Lucia, Qld 4072, Australia.
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- Baek, Sungmin (author)
- Univ Queensland, Div Genom Dev & Dis, Inst Mol Biosci, St Lucia, Qld 4072, Australia.;Stowers Inst Med Res, Kansas City, MO 64110 USA.
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- Crosier, Philip S. (author)
- Univ Auckland, Dept Mol Med & Pathol, Sch Med Sci, Auckland 1010, New Zealand.
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- Koltowska, Katarzyna (author)
- Uppsala universitet,Vaskulärbiologi,Univ Queensland, Div Genom Dev & Dis, Inst Mol Biosci, St Lucia, Qld 4072, Australia.
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- Astin, Jonathan W. (author)
- Univ Auckland, Dept Mol Med & Pathol, Sch Med Sci, Auckland 1010, New Zealand.
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- Tan, Pei Jean (author)
- Canc Res Malaysia, Subang Jaya 47500, Selangor, Malaysia.
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- Hogan, Benjamin M. (author)
- Peter MacCallum Canc Ctr, Organogenesis & Canc Program, Melbourne, Vic 3000, Australia.;Univ Melbourne, Dept Anat & Physiol, Melbourne, Vic 3000, Australia.;Univ Queensland, Div Genom Dev & Dis, Inst Mol Biosci, St Lucia, Qld 4072, Australia.
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- Patel, Vyomesh (author)
- Canc Res Malaysia, Subang Jaya 47500, Selangor, Malaysia.
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Peter MacCallum Canc Ctr, Organogenesis & Canc Program, Melbourne, Vic 3000, Australia;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic 3000, Australia.;Univ Melbourne, Dept Anat & Physiol, Melbourne, Vic 3000, Australia.;Univ Queensland, Div Genom Dev & Dis, Inst Mol Biosci, St Lucia, Qld 4072, Australia.;Canc Res Malaysia, Subang Jaya 47500, Selangor, Malaysia. Canc Res Malaysia, Subang Jaya 47500, Selangor, Malaysia. (creator_code:org_t)
- 2021-06-26
- 2021
- English.
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In: Pharmaceuticals. - : MDPI. - 1424-8247. ; 14:7
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https://doi.org/10.3...
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Abstract
Subject headings
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- Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing vasculature, plays critical roles in disease, including in cancer metastasis and chronic inflammation. Preclinical and recent clinical studies have now demonstrated therapeutic utility for several anti-lymphangiogenic agents, but optimal agents and efficacy in different settings remain to be determined. We tested the anti-lymphangiogenic property of 3,4-Difluorobenzocurcumin (CDF), which has previously been implicated as an anti-cancer agent, using zebrafish embryos and cultured vascular endothelial cells. We used transgenic zebrafish labelling the lymphatic system and found that CDF potently inhibits lymphangiogenesis during embryonic development. We also found that the parent compound, Curcumin, does not inhibit lymphangiogenesis. CDF blocked lymphatic and venous sprouting, and lymphatic migration in the head and trunk of the embryo. Mechanistically, CDF impaired VEGFC-VEGFR3-ERK signalling in vitro and in vivo. In an in vivo pathological model of Vegfc-overexpression, treatment with CDF rescued endothelial cell hyperplasia. CDF did not inhibit the kinase activity of VEGFR3 yet displayed more prolonged activity in vivo than previously reported kinase inhibitors. These findings warrant further assessment of CDF and its mode of action as a candidate for use in metastasis and diseases of aberrant lymphangiogenesis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- 3
- 4-Difluorobenzocurcumin
- zebrafish
- lymphatic
- Vegfc
- Vegfr3
- Erk
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Okuda, Kazuhide ...
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Ng, Mei Fong
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Ruslan, Nur Faiz ...
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Bower, Neil, I
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Song, Dedrick So ...
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Chen, Huijun
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Baek, Sungmin
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Crosier, Philip ...
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Koltowska, Katar ...
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Astin, Jonathan ...
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Tan, Pei Jean
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Hogan, Benjamin ...
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Patel, Vyomesh
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Pharmaceuticals
- By the university
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Uppsala University