Bladder cancer therapy without toxicity-A dose-escalation study of alpha1-oleate
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
32319672
DOI
10.1002/ijc.33019
Knihovny.cz E-zdroje
- Klíčová slova
- Alpha1-oleate, bladder cancer therapy, dose escalation, lack of toxicity,
- MeSH
- antitumorózní látky aplikace a dávkování chemie toxicita MeSH
- aplikace intravezikální MeSH
- králíci MeSH
- kyselina olejová aplikace a dávkování chemie toxicita MeSH
- laktalbumin aplikace a dávkování chemie toxicita MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- močový měchýř účinky léků patologie MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nádorové buněčné linie transplantace MeSH
- nádory močového měchýře farmakoterapie patologie MeSH
- testy subchronické toxicity MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antitumorózní látky MeSH
- kyselina olejová MeSH
- laktalbumin MeSH
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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Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252-264.
Chari RV. Targeted cancer therapy: conferring specificity to cytotoxic drugs. Acc Chem Res. 2007;41:98-107.
Hu Q, Sun W, Wang C, Gu Z. Recent advances of cocktail chemotherapy by combination drug delivery systems. Adv Drug Deliv Rev. 2016;98:19-34.
Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161:205-214.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5-29.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424.
Jalilian H, Ziaei M, Weiderpass E, Rueegg CS, Khosravi Y, Kjaerheim K. Cancer incidence and mortality among firefighters. Int J Cancer. 2019;145:2639-2646.
Soloway MS, Sofer M, Vaidya A. Contemporary management of stage T1 transitional cell carcinoma of the bladder. J Urol. 2002;167:1573-1583.
Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol. 2001;19:666-675.
Kang M, Jeong CW, Kwak C, et al. Single, immediate postoperative instillation of chemotherapy in non-muscle invasive bladder cancer: a systematic review and network meta-analysis of randomized clinical trials using different drugs. Oncotarget. 2016;7:45479.
Sylvester RJ, Oosterlinck W, Holmang S, et al. Systematic review and individual patient data meta-analysis of randomized trials comparing a single immediate instillation of chemotherapy after transurethral resection with transurethral resection alone in patients with stage pTa-pT1 urothelial carcinoma of the bladder: which patients benefit from the instillation? Eur Urol. 2016;69:231-244.
Kamat AM, Hahn NM, Efstathiou JA, et al. Bladder cancer. Lancet. 2016;388:2796-2810.
Malmström P-U, Sylvester RJ, Crawford DE, et al. An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guérin for non-muscle-invasive bladder cancer. Eur Urol. 2009;56:247-256.
Mok KH, Nagashima T, Day IJ, Hore PJ, Dobson CM. Multiple subsets of side-chain packing in partially folded states of α-lactalbumins. Proc Natl Acad Sci U S A. 2005;102:8899-8904.
Nadeem A, Sanborn J, Gettel DL, et al. Protein receptor-independent plasma membrane remodeling by HAMLET: a tumoricidal protein-lipid complex. Sci Rep. 2015;5:16432.
Mossberg A-K, Hou Y, Svensson M, Holmqvist B, Svanborg C. HAMLET treatment delays bladder cancer development. J Urol. 2010;183:1590-1597.
Ho J, Rydstrom A, Manimekalai MSS, et al. Low resolution solution structure of HAMLET and the importance of its alpha-domains in tumoricidal activity. PLoS One. 2012;7:e53051.
Hien TT, Garcia-Vaz E, Stenkula KG, et al. MicroRNA-dependent regulation of KLF4 by glucose in vascular smooth muscle. J Cell Physiol. 2018;233:7195-7205.
Shariat SF, Youssef RF, Gupta A, et al. Association of angiogenesis related markers with bladder cancer outcomes and other molecular markers. J Urol. 2010;183:1744-1750.
Dovedi SJ, Davies BR. Emerging targeted therapies for bladder cancer: a disease waiting for a drug. Cancer Metastasis Rev. 2009;28:355-367.
Mossberg AK, Wullt B, Gustafsson L, Månsson W, Ljunggren E, Svanborg C. Bladder cancers respond to intravesical instillation of (HAMLET human α-lactalbumin made lethal to tumor cells). Int J Cancer. 2007;121:1352-1359.
Storm P, Klausen TK, Trulsson M, et al. A unifying mechanism for cancer cell death through ion channel activation by HAMLET. PLoS One. 2013;8:e58578.
Düringer C, Hamiche A, Gustafsson L, Kimura H, Svanborg C. HAMLET interacts with histones and chromatin in tumor cell nuclei. J Biol Chem. 2003;278:42131-42135.
Ho J, Sielaff H, Nadeem A, Svanborg C, Grüber G. The molecular motor F-ATP synthase is targeted by the tumoricidal protein HAMLET. J Mol Biol. 2015;427:1866-1874.
Gustafsson L, Aits S, Önnerfjord P, Trulsson M, Storm P, Svanborg C. Changes in proteasome structure and function caused by HAMLET in tumor cells. PLoS One. 2009;4:e5229.
Köhler C, Gogvadze V, Håkansson A, Svanborg C, Orrenius S, Zhivotovsky B. A folding variant of human α-lactalbumin induces mitochondrial permeability transition in isolated mitochondria. Eur J Biochem. 2001;268:186-191.
Colomer AG, Martínez RR, Castillo CP, et al. Dermatological side effects of intravesical Mitomycin C: delayed hypersensitivity. Arch Esp Urol. 2016;69:89-91.
Chou R, Selph S, Buckley DI, et al. Intravesical therapy for the treatment of nonmuscle invasive bladder cancer: a systematic review and meta-analysis. J Urol. 2017;197:1189-1199.
Clinical and molecular response to alpha1-oleate treatment in patients with bladder cancer
Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex
