Development of prednisone resistance in naïve canine lymphoma: Longitudinal evaluation of NR3C1α, ABCB1, and 11β-HSD mRNA expression
| Autor: | Neal S. Burke, Rance K. Sellon, Janean Fidel, Camille C. Hanot, Laura A. White, Katrina L. Mealey |
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| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty Antineoplastic Agents Hormonal Lymphoma 040301 veterinary sciences Mrna expression Drug resistance Gastroenterology Drug Administration Schedule 0403 veterinary science Cohort Studies 03 medical and health sciences 0302 clinical medicine Glucocorticoid receptor Dogs Receptors Glucocorticoid Prednisone Internal medicine 11-beta-Hydroxysteroid Dehydrogenase Type 2 11-beta-Hydroxysteroid Dehydrogenase Type 1 medicine Animals ATP Binding Cassette Transporter Subfamily B Member 1 Dog Diseases RNA Messenger Pharmacology Messenger RNA Canine Lymphoma General Veterinary business.industry 04 agricultural and veterinary sciences medicine.disease Gene Expression Regulation Drug Resistance Neoplasm 030220 oncology & carcinogenesis Female Lymph business medicine.drug |
| Zdroj: | Journal of veterinary pharmacology and therapeuticsREFERENCES. 43(2) |
| ISSN: | 1365-2885 |
| Popis: | Prednisone resistance develops rapidly and essentially universally when dogs with lymphoma are treated with corticosteroids. We investigated naturally occurring mechanisms of prednisone resistance in seven dogs with naive multicentric lymphoma, treated with oral prednisone; four dogs were administered concurrent cytotoxic chemotherapy. Expression of NR3C1α, ABCB1 (formerly MDR1), 11β-HSD1, and 11β-HSD2 mRNA was evaluated in neoplastic lymph nodes by real-time RT-PCR. Changes of expression levels at diagnosis and at time of clinical resistance to prednisone were compared longitudinally using a Wilcoxon signed-rank test. Clinical resistance to prednisone was observed after a median of 68 days (range: 7-348 days) after initiation of treatment. Relative to pretreatment samples, prednisone resistance was associated with decreased NR3C1α expression in biopsies of all dogs with high-grade lymphoma (six dogs, p=.031); one dog with indolent T-zone lymphoma had increased expression of NR3C1α. Resistance was not consistently associated with changes in ABCB1, 11β-HSD1, or 11β-HSD2 expression. Decreased expression of the glucocorticoid receptor (NR3C1α) may play a role in conferring resistance to prednisone in dogs with lymphoma. Results do not indicate a broad role for changes in expression of ABCB1, 11β-HSD1, and 11β-HSD2 in the emergence of prednisone resistance in lymphoma-bearing dogs. |
| Databáze: | OpenAIRE |
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