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Bladder cancer ther...
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Brisuda, AntonínUniversity Hospital Motol
(author)
Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2021-06-08
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Springer Science and Business Media LLC,2021
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:704fa103-122d-4946-8180-e13a9f6ddf23
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https://lup.lub.lu.se/record/704fa103-122d-4946-8180-e13a9f6ddf23URI
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https://doi.org/10.1038/s41467-021-23748-yDOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Partially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). Nuclear magnetic resonance measurements and computational simulations reveal a lipid core surrounded by conformationally fluid, alpha-helical peptide motifs. In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.
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Ho, James C.S.Lund University
(author)
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Kandiyal, Pancham S.Trinity College Dublin
(author)
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Ng, Justin T.Y.School of Biological Sciences, Singapore
(author)
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Ambite, InesLund 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(Swepub:lu)med-iam
(author)
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Butler, Daniel S.C.Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancerinfektion,Forskargrupper vid Lunds universitet,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Cancer Infection,Lund University Research Groups(Swepub:lu)da3085bu
(author)
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Háček, JaromirUniversity Hospital Motol
(author)
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Wan, Murphy Lam YimLund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancerinfektion,Forskargrupper vid Lunds universitet,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Cancer Infection,Lund University Research Groups(Swepub:lu)la4748wa
(author)
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Tran, Thi HienLund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancerinfektion,Forskargrupper vid Lunds universitet,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Cancer Infection,Lund University Research Groups(Swepub:lu)med-thr
(author)
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Nadeem, AftabLund 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(Swepub:lu)med-afa
(author)
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Tran, Tuan HiepLund University
(author)
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Hastings, AnnaTrinity College Dublin
(author)
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Storm, PetterLund 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(Swepub:lu)med-psm
(author)
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Fortunati, Daniel L.Trinity College Dublin
(author)
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Esmaeili, ParisaLund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancerinfektion,Forskargrupper vid Lunds universitet,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Cancer Infection,Lund University Research Groups(Swepub:lu)pa1724es
(author)
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Novotna, HanaUniversity Hospital Motol
(author)
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Horňák, JakubUniversity Hospital Motol
(author)
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Mu, Y. G.School of Biological Sciences, Singapore
(author)
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Mok, K. H.Trinity College Dublin(Swepub:lu)med-kem
(author)
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Babjuk, MarekUniversity Hospital Motol
(author)
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Svanborg, CatharinaLund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancerinfektion,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Cancer Infection,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)mmb-csv
(author)
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University Hospital MotolLund University
(creator_code:org_t)
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In:Nature Communications: Springer Science and Business Media LLC122041-1723
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Brisuda, Antonín
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Ho, James C.S.
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Kandiyal, Pancha ...
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Ng, Justin T.Y.
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Ambite, Ines
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Butler, Daniel S ...
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Háček, Jaromir
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Wan, Murphy Lam ...
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Tran, Thi Hien
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Nadeem, Aftab
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Tran, Tuan Hiep
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Hastings, Anna
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Storm, Petter
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Fortunati, Danie ...
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Esmaeili, Parisa
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Novotna, Hana
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Horňák, Jakub
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Mu, Y. G.
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Mok, K. H.
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Babjuk, Marek
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