Autoinflammatory Reaction in Dogs Treated for Cancer via G6PD Inhibition
Author
Source
Case Reports in Veterinary Medicine
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-4, 4 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-08-08
Country of Publication
Egypt
No. of Pages
4
Main Subjects
Abstract EN
Glucose-6-phosphate dehydrogenase (G6PD) is an oncoprotein that is overexpressed in cancer cells to provide the NADPH required for their increased anabolism.
NADPH, sourced from G6PD fuels nucleotide biosynthesis, maintains redox potential of thioredoxin and glutathione and drives the mevalonate pathway that powers many of the basic mechanisms by which cancer cells escape host control.
G6PD is thus a target for cancer treatment being addressed by many groups around the world.
We have discovered that systemic inhibition of G6PD by high dose dehydroepiandrosterone (DHEA) causes a severe autoinflammatory response in dogs, which does not occur in mice or rats.
Since dogs more closely model the human adrenal androgen system than do common laboratory animals, this finding is relevant to the design of G6PD-inhibiting drugs for humans.
The autoinflammatory reaction observed closely resembles mevalonate kinase deficiency (MKD), a rare autosomal recessive disease in humans characterized by recurrent febrile attacks, arthralgia, skin rash, and aphthous ulcers of mucocutaneous tissues.
In a manner comparable to animal models of MKD, the reconstitution of protein geranylgeranylation blocked the autoinflammatory reaction caused by systemic G6PD inhibition.
This autoinflammatory response to systemic G6PD inhibition represents an unexpected result that must be taken into consideration when targeting this oncoprotein.
American Psychological Association (APA)
Nyce, Jonathan W.. 2017. Autoinflammatory Reaction in Dogs Treated for Cancer via G6PD Inhibition. Case Reports in Veterinary Medicine،Vol. 2017, no. 2017, pp.1-4.
https://search.emarefa.net/detail/BIM-1150731
Modern Language Association (MLA)
Nyce, Jonathan W.. Autoinflammatory Reaction in Dogs Treated for Cancer via G6PD Inhibition. Case Reports in Veterinary Medicine No. 2017 (2017), pp.1-4.
https://search.emarefa.net/detail/BIM-1150731
American Medical Association (AMA)
Nyce, Jonathan W.. Autoinflammatory Reaction in Dogs Treated for Cancer via G6PD Inhibition. Case Reports in Veterinary Medicine. 2017. Vol. 2017, no. 2017, pp.1-4.
https://search.emarefa.net/detail/BIM-1150731
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1150731