Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Ft. Collins, CO 80523, USA.
Vet Comp Oncol. 2013 Dec;11(4):296-305. doi: 10.1111/j.1476-5829.2012.00319.x. Epub 2012 Apr 27.
Increased numbers of tumour-associated macrophages correlate with rapid tumour growth and metastasis in tumours. Thus, macrophage depletion has potential as a novel cancer therapy and positive responses have been reported in rodent tumour models. To investigate the effectiveness of this approach in dogs with cancer, we evaluated the effects of the macrophage-depleting agent liposomal clodronate (LC) in dogs with soft-tissue sarcoma (STS). To this end, we conducted a clinical trial of LC therapy in 13 dogs with STS. Repeated LC administration was well tolerated clinically. Preliminary examination of tumour biopsy sets from 5 of the 13 dogs demonstrated that the density of CD11b(+) macrophages was significantly decreased after LC treatment. Circulating concentrations of interleukin-8 were also significantly reduced. These preliminary studies are the first to suggest that LC can be used as a systemic macrophage-depleting agent in dogs to reduce numbers of tumour-associated macrophages.
肿瘤相关巨噬细胞数量的增加与肿瘤的快速生长和转移相关。因此，巨噬细胞耗竭具有作为一种新的癌症治疗方法的潜力，并且在啮齿动物肿瘤模型中已经报道了阳性反应。为了研究这种方法在患有癌症的狗中的有效性，我们评估了巨噬细胞耗竭剂脂质体氯膦酸（LC）在患有软组织肉瘤（STS）的狗中的作用。为此，我们对 13 只患有 STS 的狗进行了 LC 治疗的临床试验。重复给予 LC 在临床上耐受良好。对 13 只狗中的 5 只的肿瘤活检样本进行的初步检查表明，LC 治疗后 CD11b（+）巨噬细胞的密度显着降低。循环白细胞介素-8 的浓度也显着降低。这些初步研究首次表明，LC 可作为一种全身性巨噬细胞耗竭剂用于狗，以减少肿瘤相关巨噬细胞的数量。
