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纳米脂质体紫杉醇化疗联合表达凋亡诱导蛋白的基因治疗对自发性犬乳腺肿瘤的疗效评估

Evaluation of chemotherapy with nanosomal paclitaxel and gene therapy expressing apoptosis-inducing proteins in the management of spontaneous canine mammary neoplasm.

作者信息

Divya Mohan, Maiti Swapan Kumar, Sangeetha Palakkara, Shivaraju Shivaramu, Kumar Naveen, Tiwari Ashok Kumar, Hescheler Jurgen

机构信息

Ph. D Scholars, Surgery Division, ICAR-Indian Veterinary Research Institute, Izatnagar, 243 122, Uttar Pradesh, India.

Principal Scientist, Surgery Division, ICAR-Indian Veterinary Research Institute, Izatnagar, 243 122, Uttar Pradesh, India.

出版信息

J Stem Cells Regen Med. 2019 Dec 24;15(2):24-34. doi: 10.46582/jsrm.1502007. eCollection 2019.

Abstract

Mammary gland tumours are the second most common neoplasm representing about 40-50% of all neoplasm after skin tumour, but the majority of these tumours occur in intact/ non spaying female dogs. Surgical excision of the benign tumour is the standard treatment of canine mammary tumours. Chemotherapy is the choice of treatment if the tumour is malignant or shows evidence of invasion into lymph or blood vessels, however, they showed different side effects and their success rate is varied. Taxanes are now the most promising anti-cancer drugs with little side effects. Gene therapy expressing apoptosis-inducing proteins have ability to kill cancer cells while sparing normal cells. The present study was conducted for exploring the oncolytic effect of viral gene therapy expressing apoptosis-inducing proteins construct (ns1 +vp3), nanosomal paclitaxel as chemotherapeutic agent and surgical therapy in the management of spontaneous canine mammary tumours. Chemotherapy (nanosomal paclitaxel) (n=10), viral gene construct (ns1 +vp3) (n=10) and surgical therapy (n=10) were used in 30 female dogs of different breeds having different types of spontaneous mammary tumours. Chemotherapeutic drug and viral gene construct (ns1 +vp3) induced apoptosis in canine mammary neoplasms were studied using fluorescent activated cell sorting analysis. However, apoptotic percentage was significantly higher in chemotherapeutic group than viral gene construct therapy. No major side effects were observed in any groups. Matrix metalloproteinase-2 was found as an important prognostic tool in the management of canine mammary tumours. In conclusion, chemotherapy with nanosomal paclitaxel proved better than viral gene construct (ns1 +vp3) in the treatment of canine mammary neoplasm.

摘要

乳腺肿瘤是第二常见的肿瘤,约占皮肤肿瘤后所有肿瘤的40%-50%,但这些肿瘤大多发生在未绝育的雌性犬中。良性肿瘤的手术切除是犬乳腺肿瘤的标准治疗方法。如果肿瘤是恶性的或有侵犯淋巴管或血管的迹象,化疗是治疗的选择,然而,它们显示出不同的副作用且成功率各不相同。紫杉烷类现在是最有前景的抗癌药物,副作用很小。表达凋亡诱导蛋白的基因疗法有能力杀死癌细胞而不损伤正常细胞。本研究旨在探讨表达凋亡诱导蛋白构建体(ns1+vp3)的病毒基因疗法、纳米脂质体紫杉醇作为化疗药物以及手术疗法对自发性犬乳腺肿瘤的治疗效果。对30只患有不同类型自发性乳腺肿瘤的不同品种雌性犬使用了化疗(纳米脂质体紫杉醇)(n=10)、病毒基因构建体(ns1+vp3)(n=10)和手术疗法(n=10)。使用荧光激活细胞分选分析研究了化疗药物和病毒基因构建体(ns1+vp3)诱导犬乳腺肿瘤细胞凋亡的情况。然而,化疗组的凋亡百分比显著高于病毒基因构建体治疗组。任何组均未观察到重大副作用。基质金属蛋白酶-2被发现是犬乳腺肿瘤治疗中的一种重要预后工具。总之,在犬乳腺肿瘤的治疗中,纳米脂质体紫杉醇化疗比病毒基因构建体(ns1+vp3)效果更好。

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