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Bladder cancer therapy without toxicity—A dose-escalation study of alpha1-oleate

Hien, Tran Thi LU ; Ambite, Ines LU orcid ; Butler, Daniel LU ; Wan, Murphy Lam Yim LU ; Tran, Tuan Hiep LU ; Höglund, Urban ; Babjuk, Marek and Svanborg, Catharina LU (2020) In International Journal of Cancer 147(9). p.2479-2492
Abstract

Potent chemotherapeutic agents are required to counteract the aggressive behavior of cancer cells and patients often experience severe side effects, due to tissue toxicity. Our study addresses if a better balance between efficacy and toxicity can be attained using the tumoricidal complex alpha1-oleate, formed by a synthetic, alpha-helical peptide comprising the N-terminal 39 amino acids of alpha-lactalbumin and the fatty acid oleic acid. Bladder cancer was established, by intravesical instillation of MB49 cells on day 0 and the treatment group received five instillations of alpha1-oleate (1.7-17 mM) on days 3 to 11. A dose-dependent reduction in tumor size, bladder size and bladder weight was recorded in the alpha1-oleate treated group,... (More)

Potent chemotherapeutic agents are required to counteract the aggressive behavior of cancer cells and patients often experience severe side effects, due to tissue toxicity. Our study addresses if a better balance between efficacy and toxicity can be attained using the tumoricidal complex alpha1-oleate, formed by a synthetic, alpha-helical peptide comprising the N-terminal 39 amino acids of alpha-lactalbumin and the fatty acid oleic acid. Bladder cancer was established, by intravesical instillation of MB49 cells on day 0 and the treatment group received five instillations of alpha1-oleate (1.7-17 mM) on days 3 to 11. A dose-dependent reduction in tumor size, bladder size and bladder weight was recorded in the alpha1-oleate treated group, compared to sham-treated mice. Tumor markers Ki-67, Cyclin D1 and VEGF were inhibited in a dose-dependent manner, as was the expression of cancer-related genes. Remarkably, toxicity for healthy tissue was not detected in alpha1-oleate-treated, tumor-bearing mice or healthy mice or rabbits, challenged with increasing doses of the active complex. The results define a dose-dependent therapeutic effect of alpha1-oleate in a murine bladder cancer model.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alpha1-oleate, bladder cancer therapy, dose escalation, lack of toxicity
in
International Journal of Cancer
volume
147
issue
9
pages
14 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:32319672
  • scopus:85084423337
ISSN
0020-7136
DOI
10.1002/ijc.33019
language
English
LU publication?
yes
id
bc232589-a6eb-404d-80e6-681ffa11aca0
date added to LUP
2020-06-15 11:15:08
date last changed
2024-04-17 10:39:22
@article{bc232589-a6eb-404d-80e6-681ffa11aca0,
  abstract     = {{<p>Potent chemotherapeutic agents are required to counteract the aggressive behavior of cancer cells and patients often experience severe side effects, due to tissue toxicity. Our study addresses if a better balance between efficacy and toxicity can be attained using the tumoricidal complex alpha1-oleate, formed by a synthetic, alpha-helical peptide comprising the N-terminal 39 amino acids of alpha-lactalbumin and the fatty acid oleic acid. Bladder cancer was established, by intravesical instillation of MB49 cells on day 0 and the treatment group received five instillations of alpha1-oleate (1.7-17 mM) on days 3 to 11. A dose-dependent reduction in tumor size, bladder size and bladder weight was recorded in the alpha1-oleate treated group, compared to sham-treated mice. Tumor markers Ki-67, Cyclin D1 and VEGF were inhibited in a dose-dependent manner, as was the expression of cancer-related genes. Remarkably, toxicity for healthy tissue was not detected in alpha1-oleate-treated, tumor-bearing mice or healthy mice or rabbits, challenged with increasing doses of the active complex. The results define a dose-dependent therapeutic effect of alpha1-oleate in a murine bladder cancer model.</p>}},
  author       = {{Hien, Tran Thi and Ambite, Ines and Butler, Daniel and Wan, Murphy Lam Yim and Tran, Tuan Hiep and Höglund, Urban and Babjuk, Marek and Svanborg, Catharina}},
  issn         = {{0020-7136}},
  keywords     = {{Alpha1-oleate; bladder cancer therapy; dose escalation; lack of toxicity}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{9}},
  pages        = {{2479--2492}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{International Journal of Cancer}},
  title        = {{Bladder cancer therapy without toxicity—A dose-escalation study of alpha1-oleate}},
  url          = {{http://dx.doi.org/10.1002/ijc.33019}},
  doi          = {{10.1002/ijc.33019}},
  volume       = {{147}},
  year         = {{2020}},
}