Halofuginone: a novel oral and intravesical agent for the treatment of non-muscle invasive bladder cancer

Nativ Omri, Dalal Eilata, S. Edmond, Aronson Moshe, H. Guy, Nativ Ofer
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引用次数: 2

Abstract

Background: Non-muscle invasive form (NMIBC) is a chronic disease with a high recurrence rate and requires lifelong surveillance. Various intravesical agents were shown to reduce tumor recurrence but unfortunately, none of these agents proved to be of benefit in long-term prevention of local recurrence or disease progression. Aim of Research: Previous studies have shown that Halofuginone (HF), an antiprotozoal agent, exerts anti-neoplastic activity in various cancer models. Our aim was to evaluate the in vivo activity of oral and intravesical HF treatment in an experimental mouse model harboring NMIBC. Methods: Initially, 60 mice were divided into six treatment groups to evaluate the toxicity of this anti-parasitic agent on the bladder mucosa. The second stage included 126 mice which underwent intravesical implantation with Mouse Bladder Tumor cells (MBT-2): Group 1 (n = 30) received no treatment, group 2 (n = 32) received 6 intravesical instillations of PBS, group 3 (n = 32) received 6 doses of 250 μg oral HF, whereas group 4 (n = 32) received 6 intravesical instillations of 250 μg HF. Results: The average weight of bladders, which reflects the anti-neoplastic activity, differed significantly between the control and treated groups: 88.8 mg ± 15.58 SEM and 81.2 mg ± 13.79 SEM for untreated and PBS-treated mice, respectively, versus 38.0 mg ± 4.02 SEM and 39.6 mg ± 5.97 SEM for animals treated with oral and intravesical HF, respectively. Conclusions: HF exerted a significant anti-neoplastic activity in mice bearing NMIBC upon oral as well as intravesical administration. These results may constitute the basis for the maintenance of oral treatment with HF in patients with NMIBC. Submitted: November 12, 2018; Revised: November 24, 2018; Accepted: November 25, 2018
Halofuginone:一种治疗非肌肉浸润性膀胱癌的新型口服和膀胱内药物
背景:非肌肉浸润型(NMIBC)是一种复发率高的慢性疾病,需要终身监测。各种膀胱内药物被证明可以减少肿瘤复发,但不幸的是,这些药物中没有一种被证明对长期预防局部复发或疾病进展有益。研究目的:已有研究表明,Halofuginone (HF)是一种抗原虫药物,在多种肿瘤模型中具有抗肿瘤活性。我们的目的是在一个携带NMIBC的实验性小鼠模型中评估口服和膀胱内HF治疗的体内活性。方法:将60只小鼠分为6个治疗组,观察该抗寄生虫剂对膀胱黏膜的毒性作用。第二阶段采用小鼠膀胱肿瘤细胞(MBT-2)膀胱内植入126只小鼠:1组(n = 30)不治疗,2组(n = 32)腹腔注射6次PBS, 3组(n = 32)腹腔注射6次250 μg HF, 4组(n = 32)腹腔注射6次250 μg HF。结果:反映抗肿瘤活性的膀胱平均重量在对照组和治疗组之间差异显著:未治疗组和pbs治疗组小鼠的膀胱平均重量分别为88.8 mg±15.58 SEM和81.2 mg±13.79 SEM,而口服和膀胱内HF治疗组小鼠的膀胱平均重量分别为38.0 mg±4.02 SEM和39.6 mg±5.97 SEM。结论:经口服和经体内给药,HF对NMIBC小鼠具有显著的抗肿瘤活性。这些结果可能构成维持NMIBC患者HF口服治疗的基础。提交日期:2018年11月12日;修订日期:2018年11月24日;录用日期:2018年11月25日
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