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Electrogene therapy with interleukin-12 in canine mast cell tumors

机译:白细胞介素12的电基因治疗犬肥大细胞肿瘤

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Background. Mast cell tumors (MCT) are the most common malignant cutaneous tumors in dogs with extremely variable biological behaviour. Different treatment approaches can be used in canine cutaneous MCT, with surgical excision being the treatment of choice. In this study, electrogene therapy (EGT) as a new therapeutic approach to canine MCTs, was established.Materials and methods. Eight dogs with a total of eleven cutaneous MCTs were treated with intratumoral EGT using DNA plasmid encoding human interleukin-12 (IL-12). The local response to the therapy was evaluated by repeated measurements of tumor size and histological examination of treated tumors. A possible systemic response was assessed by determination of IL-12 and interferon- ?3 (IFN-?3) in patients' sera. The occurence of side effects was monitored with weekly clinical examinations of treated animals and by performing basic bloodwork, consisting of the complete bloodcount and determination of selected biochemistry parameters.Results. Intratumoral EGT with IL-12 elicits significant reduction of treated tumors' size, ranging from 13% to 83% (median 50%) of the initial tumor volume. Additionally, a change in the histological structure of treated nodules was seen. There was a reduction in number of malignant mast cells and inflammatory cell infiltration of treated tumors. Systemic release of IL-12 in four patients was detected, without any noticeable local or systemic side effects.Conclusions. These data suggest that intratumoral EGT with plasmid encoding IL-12 may be useful in the treatment of canine MCTs, exerting a local antitumor effect.
机译:背景。肥大细胞肿瘤(MCT)是生物学行为极为不同的犬中最常见的恶性皮肤肿瘤。犬皮肤MCT可以使用不同的治疗方法,手术切除是首选的治疗方法。在这项研究中,建立了电基因疗法(EGT)作为犬MCT的新治疗方法。材料和方法。使用编码人白介素12(IL-12)的DNA质粒,用肿瘤内EGT治疗总共有11个皮肤MCT的8只狗。通过重复测量肿瘤大小和治疗肿瘤的组织学检查评估对治疗的局部反应。通过测定患者血清中的IL-12和干扰素-α3(IFN-α3)评估可能的全身反应。通过每周对治疗的动物进行临床检查并通过进行基本的血液检查来监测副作用的发生,该检查包括全血细胞计数和所选生化参数的确定。带有IL-12的肿瘤内EGT引起治疗后肿瘤大小的显着减少,范围从初始肿瘤体积的13%到83%(中值50%)。另外,观察到治疗结节的组织学结构发生了变化。所治疗的肿瘤的恶性肥大细胞数量减少和炎性细胞浸润减少。在四名患者中检测到IL-12的全身释放,没有任何明显的局部或全身性副作用。这些数据表明,带有编码IL-12的质粒的肿瘤内EGT可用于犬MCT的治疗,发挥局部抗肿瘤作用。

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