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Development of prednisone resistance in naïve canine lymphoma: Longitudinal evaluation of NR3C1α, ABCB1, and 11β-HSD mRNA expression.
Journal of Veterinary Pharmacology and Therapeutics ( IF 1.3 ) Pub Date : 2020-01-14 , DOI: 10.1111/jvp.12837
Camille C Hanot 1, 2 , Katrina L Mealey 1, 3 , Janean L Fidel 1 , Neal S Burke 3 , Laura A White 4 , Rance K Sellon 1
Affiliation  

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 naïve 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.

中文翻译:

初次犬淋巴瘤中泼尼松耐药的发展:NR3C1α,ABCB1和11β-HSDmRNA表达的纵向评估。

用皮质类固醇治疗患有淋巴瘤的狗时,泼尼松耐药性会迅速发展,并且基本上会普遍发展。我们调查了口服泼尼松治疗的七只幼稚多中心淋巴瘤狗对泼尼松耐药的自然发生机制。四只狗同时进行细胞毒性化疗。NR3C1α,ABCB1(以前称为MDR1),11β-HSD1和11β-HSD2mRNA的表达通过实时RT-PCR在肿瘤淋巴结中评估。使用Wilcoxon秩和检验纵向比较诊断和临床对泼尼松耐药时的表达水平变化。开始治疗后中位数为68天(范围:7-348天),观察到对泼尼松的临床耐药性。相对于预处理样品,泼尼松抵抗与所有高级别淋巴瘤犬(6只,p = .031)的活检组织中NR3C1α表达的降低有关;一只患有惰性T区淋巴瘤的狗的NR3C1α表达增加。抗药性并不总是与ABCB1、11β-HSD1或11β-HSD2表达的变化相关。糖皮质激素受体(NR3C1α)的表达降低可能在赋予淋巴瘤犬对泼尼松的抗性中起作用。结果表明,在荷瘤犬的泼尼松耐药中,ABCB1、11β-HSD1和11β-HSD2表达的变化没有广泛的作用。糖皮质激素受体(NR3C1α)的表达降低可能在赋予淋巴瘤犬对泼尼松的抗性中起作用。结果表明,在荷瘤犬的泼尼松耐药中,ABCB1、11β-HSD1和11β-HSD2表达的变化没有广泛的作用。糖皮质激素受体(NR3C1α)的表达降低可能在赋予淋巴瘤犬对泼尼松的抗性中起作用。结果表明,在荷瘤犬的泼尼松耐药中,ABCB1、11β-HSD1和11β-HSD2表达的变化没有广泛的作用。
更新日期:2020-01-14
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