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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 ...

  • 2021-06-08
  • Springer Science and Business Media LLC,2021

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:704fa103-122d-4946-8180-e13a9f6ddf23
  • https://lup.lub.lu.se/record/704fa103-122d-4946-8180-e13a9f6ddf23URI
  • https://doi.org/10.1038/s41467-021-23748-yDOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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)
  • Kandiyal, Pancham S.Trinity College Dublin (author)
  • Ng, Justin T.Y.School of Biological Sciences, Singapore (author)
  • 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)
  • 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)
  • Háček, JaromirUniversity Hospital Motol (author)
  • 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)
  • 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)
  • 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)
  • Tran, Tuan HiepLund University (author)
  • Hastings, AnnaTrinity College Dublin (author)
  • 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)
  • Fortunati, Daniel L.Trinity College Dublin (author)
  • 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)
  • Novotna, HanaUniversity Hospital Motol (author)
  • Horňák, JakubUniversity Hospital Motol (author)
  • Mu, Y. G.School of Biological Sciences, Singapore (author)
  • Mok, K. H.Trinity College Dublin(Swepub:lu)med-kem (author)
  • Babjuk, MarekUniversity Hospital Motol (author)
  • 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)
  • 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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