Hume Kelly R, Sylvester Skylar R, Borlle Lucia, Balkman Cheryl E, McCleary-Wheeler Angela L, Pulvino Mary, Casulo Carla, Zhao Jiyong
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Front Vet Sci. 2018 Feb 26;5:25. doi: 10.3389/fvets.2018.00025. eCollection 2018.
Doxycycline has antiproliferative effects in human lymphoma cells and in murine xenografts. We hypothesized that doxycycline would decrease canine lymphoma cell viability and prospectively evaluated its clinical tolerability in client-owned dogs with spontaneous, nodal, multicentric, substage a, B-cell lymphoma, not previously treated with chemotherapy. Treatment duration ranged from 1 to 8 weeks (median and mean, 3 weeks). Dogs were treated with either 10 ( = 6) or 7.5 ( = 7) mg/kg by mouth twice daily. One dog had a stable disease for 6 weeks. No complete or partial tumor responses were observed. Five dogs developed grade 3 and/or 4 metabolic abnormalities suggestive of hepatopathy with elevations in bilirubin, ALT, ALP, and/or AST. To evaluate the absorption of oral doxycycline in our study population, serum concentrations in 10 treated dogs were determined using liquid chromatography tandem mass spectrometry. Serum levels were variable and ranged from 3.6 to 16.6 µg/ml (median, 7.6 µg/ml; mean, 8.8 µg/ml). To evaluate the effect of doxycycline on canine lymphoma cell viability , trypan blue exclusion assay was performed on canine B-cell lymphoma cell lines (17-71 and CLBL) and primary B-cell lymphoma cells from the nodal tissue of four dogs. A doxycycline concentration of 6 µg/ml decreased canine lymphoma cell viability by 80%, compared to matched, untreated, control cells (mixed model analysis, < 0.0001; Wilcoxon signed rank test, = 0.0313). Although the short-term administration of oral doxycycline is not associated with the remission of canine lymphoma, combination therapy may be worthwhile if future research determines that doxycycline can alter cell survival pathways in canine lymphoma cells. Due to the potential for metabolic abnormalities, close monitoring is recommended with the use of this drug in tumor-bearing dogs. Additional research is needed to assess the tolerability of chronic doxycycline therapy.
强力霉素对人淋巴瘤细胞和小鼠异种移植瘤具有抗增殖作用。我们推测强力霉素会降低犬淋巴瘤细胞的活力，并前瞻性评估其在患有自发性、淋巴结性、多中心性、a期、B细胞淋巴瘤且未接受过化疗的宠物犬中的临床耐受性。治疗持续时间为1至8周（中位数和平均值均为3周）。犬只每天口服两次，剂量分别为10（n = 6）或7.5（n = 7）mg/kg。1只犬疾病稳定6周。未观察到完全或部分肿瘤反应。5只犬出现3级和/或4级代谢异常，提示肝病，胆红素、谷丙转氨酶、碱性磷酸酶和/或谷草转氨酶升高。为评估口服强力霉素在我们研究群体中的吸收情况，使用液相色谱串联质谱法测定了10只接受治疗犬的血清浓度。血清水平各不相同，范围为3.6至16.6μg/ml（中位数为7.6μg/ml；平均值为8.8μg/ml）。为评估强力霉素对犬淋巴瘤细胞活力的影响，对犬B细胞淋巴瘤细胞系（17 - 71和CLBL）以及来自4只犬淋巴结组织的原代B细胞淋巴瘤细胞进行了台盼蓝排斥试验。与配对的未处理对照细胞相比，6μg/ml的强力霉素浓度使犬淋巴瘤细胞活力降低了80%（混合模型分析P < 0.0001；Wilcoxon符号秩检验P = 0.0313）。虽然短期口服强力霉素与犬淋巴瘤的缓解无关，但如果未来研究确定强力霉素可改变犬淋巴瘤细胞的细胞存活途径，联合治疗可能是值得的。由于存在代谢异常的可能性，建议在荷瘤犬使用该药物时进行密切监测。需要进一步研究来评估长期使用强力霉素治疗的耐受性。
