Publications by authors named "Jason M Dey"

3 Publications

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Mol Pharmacol 2021 Jul 30. Epub 2021 Jul 30.

School of Pharmacy, University of Buffalo, United States

Cisplatin is a platinum-based drug which remains among the most efficacious anticancer treatment options. Unfortunately, use of cisplatin is hindered by dose-limiting toxicities, including irreversible hearing loss, which can grossly affect patient quality of life. Cisplatin-induced ototoxicity is the result of cochlear hair cell damage through a mechanism that is poorly understood. However, cisplatin cytotoxicity is reliant on intracellular accumulation, a process that is largely dependent on the presence of particular membrane transporters. This review will provide an update on our current understanding of the various transporters known to be involved in the disposition and cytotoxicity of platinum drugs or their metabolites, as well as their role in mediating cisplatin-induced hearing loss. We also provide a summary of the successes and opportunities in therapeutically targeting membrane transporters to alleviate platinum-induced hearing loss. Moreover, we describe how this approach could be used to reduce the severity or onset of other adverse events associated with exposure to various forms of platinum drugs, without diminishing anti-tumor efficacy. Cisplatin-induced hearing loss is a dose limiting and irreversible adverse event with no current preventative or curative treatment measures. Pharmacological targeting of membrane transporters that regulate platinum uptake into cochlear hair cells, if conducted appropriately, may alleviate this devastating side effect and could be applied to alleviate other platinum-induced toxicities.
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http://dx.doi.org/10.1124/molpharm.121.000274DOI Listing
July 2021

Antibody-mediated inhibition of EGFR reduces phosphate excretion and induces hyperphosphatemia and mild hypomagnesemia in mice.

Physiol Rep 2017 Mar;5(5)

Department of Biology, The College at Brockport State University of New York, Brockport, New York.

Monoclonal antibody therapies targeting the EGF receptor (EGFR) frequently result in hypomagnesemia in human patients. In contrast, EGFR tyrosine kinase inhibitors do not affect Mg balance in patients and only have a mild effect on Mg homeostasis in rodents at elevated doses. EGF has also been shown to affect phosphate (P) transport in rat and rabbit proximal convoluted tubules (PCT), but evidence from studies targeting EGFR and looking at P excretion in whole animals is still missing. Thus, the role of EGF in regulating reabsorption of Mg and/or P in the kidney remains controversial. Here, we inject mice with the anti-EGFR monoclonal antibody ME-1 for 2 weeks and observe a significant increase in serum P and mild hypomagnesemia, but no changes in P or Mg excretion. In contrast, a single injection of ME-1 resulted in hyperphosphatemia and a significant reduction in P excretion 2 days after treatment, while no changes in serum Mg or Mg excretion were observed. Dietary Mg deprivation is known to trigger a rapid Mg conservation response in addition to hyperphosphatemia and hyperphosphaturia. Interestingly, one dose of ME-1 did not significantly modify the response of mice to 2 days of Mg deprivation. These data show that EGFR plays a significant role in regulating P reabsorption in the kidney PCT, but suggest only a minor role in long-term regulation of Mg transport in the distal convoluted tubule.
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http://dx.doi.org/10.14814/phy2.13176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350180PMC
March 2017

Hyperphosphatemia, hypocalcemia and increased serum potassium concentration as distinctive features of early hypomagnesemia in magnesium-deprived mice.

Magnes Res 2015 Dec;28(4):126-35

Department of Biology, The College at Brockport, State University of New York, 350 New Campus Drive, Brockport, NY 14420, USA.

Magnesium-deficient patients show dysfunctional calcium (Ca(2+)) metabolism due to defective parathyroid hormone (PTH) secretion. In mice and rats, long-term magnesium (Mg(2+)) deprivation causes hyperphosphaturia and increases fibroblast growth factor 23 (FGF23) secretion, despite normal serum phosphate (Pi) and Ca(2+). Electrolyte disturbances during early hypomagnesemia may explain the response of mice to long-term Mg(2+) deprivation, but our knowledge of electrolyte homeostasis during this stage is limited. This study compares the effect of both short- and long-term Mg(2+) restriction on the electrolyte balance in mice. Mice were fed control or Mg(2+)-deficient diets for one to three days, one week, or three weeks. Prior to killing the mice, urine was collected over 24 h using metabolic cages. Within 24 h of Mg(2+) deprivation, hypomagnesemia, hypocalcemia and hyperphosphatemia developed, and after three days of Mg(2+) deprivation, serum potassium (K(+)) was increased. These changes were accompanied by a reduction in urinary volume, hyperphosphaturia, hypocalciuria and decreased Mg(2+), sodium (Na(+)) and K(+) excretion. Surprisingly, after one week of Mg(2+) deprivation, serum K(+), Pi and Ca(2+) had normalized, showing that mineral homeostasis is most affected during early hypomagnesemia. Serum Pi and K(+) are known to stimulate secretion of FGF23 and aldosterone, which are usually elevated during Mg(2+) deficiency. Thus, the hyperphosphatemia and increased serum K(+) concentration observed during short-term Mg(2+) deprivation may help our understanding of adaptation to chronic Mg(2+) deficiency.
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http://dx.doi.org/10.1684/mrh.2015.0394DOI Listing
December 2015
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