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Veterinary and comparative oncology2017; 15(4); 1543-1552; doi: 10.1111/vco.12299

Glycolysis inhibition improves photodynamic therapy response rates for equine sarcoids.

Abstract: Photodynamic therapy (PDT) holds great promise in treating veterinary and human dermatological neoplasms, including equine sarcoids, but is currently hindered by the amount of photosensitiser and light that can be delivered to lesions thicker than around 2 mm, and by the intrinsic antioxidant defences of tumour cells. We have developed a new PDT technique that combines an efficient transdermal penetration enhancer solution, for topical delivery of 5-aminolevulinic acid (ALA) photosensitiser, with acute topical post-PDT application of the glycolysis inhibitor lonidamine. We show that the new PDT combination treatment selectively kills sarcoid cells in vitro, with repeated rounds of treatment increasing sarcoid sensitisation to PDT. In vivo, ALA PDT followed by 600 μM lonidamine substantially improves treatment outcomes for occult, verrucous, nodular and fibroblastic sarcoids after 1 month (93% treatment response in 27 sarcoids), compared with PDT using only ALA (14% treatment response in 7 sarcoids).
Publication Date: 2017-01-27 PubMed ID: 28127949DOI: 10.1111/vco.12299Google Scholar: Lookup
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  • Clinical Trial
  • Journal Article

Summary

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The research article presents a new Photodynamic therapy (PDT) technique for treating equine sarcoids that significantly improves treatment outcomes by combining topical application of 5-aminolevulinic acid (ALA) photosensitiser with glycolysis inhibitor lonidamine.

Background and Objectives

  • The study is based on the application of Photodynamic therapy (PDT) as a potential treatment for both veterinary and human dermatological neoplasms, including equine sarcoids. The limitation of PDT lies in the delivery capacity for photosensitiser and light towards lesions that are thicker than 2mm, and antioxidant defenses of tumor cells.

Methodology

  • The researchers devised a new PDT method that included a proficient transdermal penetration enhancer solution for 5-aminolevulinic acid (ALA) photosensitiser delivery along with acute topical post-PDT application of glycolysis inhibitor lonidamine.
  • This method was tested in vitro, showing significant cell death in sarcoid cells, with an increase in the sensitization of these cells to PDT with each round of treatment.

Results

  • In in vivo studies, the combination of ALA PDT followed by a 600 μM dosage of lonidamine produced significant improvements in the treatment outcomes for various types of sarcoids (occult, verrucous, nodular, and fibroblastic), showing a 93% treatment response in 27 sarcoids after one month.
  • This was in contrast to PDT using only the ALA, which showed a significantly lower 14% treatment response in 7 sarcoids.

Conclusion

  • The study concludes that inhibition of glycolysis can substantially improve PDT response rates for treating equine sarcoids. The results show the potential of the combined use of a glycolysis inhibitor with ALA-PDT to provide a more efficacious treatment option for these conditions.

Cite This Article

APA
Golding JP, Kemp-Symonds JG, Dobson JM. (2017). Glycolysis inhibition improves photodynamic therapy response rates for equine sarcoids. Vet Comp Oncol, 15(4), 1543-1552. https://doi.org/10.1111/vco.12299

Publication

ISSN: 1476-5829
NlmUniqueID: 101185242
Country: England
Language: English
Volume: 15
Issue: 4
Pages: 1543-1552

Researcher Affiliations

Golding, J P
  • School of Life, Health and Chemical Sciences, The Open University, Milton Keynes, UK.
Kemp-Symonds, J G
  • School of Animal, Rural and Environmental Sciences, Nottingham Trent University, Southwell, UK.
Dobson, J M
  • Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.

MeSH Terms

  • Aminolevulinic Acid / therapeutic use
  • Animals
  • Cell Line, Tumor
  • Glycolysis
  • Horse Diseases / drug therapy
  • Horses
  • Photochemotherapy / methods
  • Photochemotherapy / veterinary
  • Photosensitizing Agents / therapeutic use
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / veterinary

Citations

This article has been cited 3 times.
  1. Bollinger L, Bartel A, Weber C, Gehlen H. Pre-Ride Biomarkers and Endurance Horse Welfare: Analyzing the Impact of the Elimination of Superoxide Dismutase, δ-Aminolevulinic-Dehydratase, Thiobarbituric Acid Reactive Substances, Iron, and Serum Amyloid A Levels in Elite 160 km Endurance Rides. Animals (Basel) 2023 May 17;13(10).
    doi: 10.3390/ani13101670pubmed: 37238102google scholar: lookup
  2. Han W, Shi J, Cao J, Dong B, Guan W. Emerging Roles and Therapeutic Interventions of Aerobic Glycolysis in Glioma. Onco Targets Ther 2020;13:6937-6955.
    doi: 10.2147/OTT.S260376pubmed: 32764985google scholar: lookup
  3. Sun J, Kormakov S, Liu Y, Huang Y, Wu D, Yang Z. Recent Progress in Metal-Based Nanoparticles Mediated Photodynamic Therapy. Molecules 2018 Jul 12;23(7).
    doi: 10.3390/molecules23071704pubmed: 30002333google scholar: lookup