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首页> 外文期刊>Human gene therapy. Clinical development >lnterleukin-27 Gene Delivery for Modifying Malignant Interactions Between Prostate Tumor and Bone
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lnterleukin-27 Gene Delivery for Modifying Malignant Interactions Between Prostate Tumor and Bone

机译：白细胞介素27基因传递修改前列腺肿瘤和骨之间的恶性相互作用。

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We have examined the role of a novel cytokine, interleukin-27 (IL-27), in mediating interactions between prostate cancer and bone. IL-27 is the most recently characterized member of the family of heterodimeric IL-12-related cytokines and has shown promise in halting tumor growth and mediating tumor regression in several cancer models, including prostate cancer. Prostate cancer is frequently associated with metastases to the bone, where the tumor induces a vicious cycle of communication with osteoblasts and osteoclasts to induce bone lesions, which are a significant cause of pain and skeletal-related events for patients, including a high fracture risk. We describe our findings in the effects of IL-27 gene delivery on prostate cancer cells, osteoblasts, and osteoclasts at different stages of differentiation. We applied the IL-27 gene delivery protocol in vivo utilizing sonoporation (sonodelivery) with the goal of treating and reducing the growth of prostate cancer at a bone metastatic site in vivo. We used a new model of immune-competent prostate adenocarcinoma and characterized the tumor growth reduction, gene expression, and effector cellular profiles. Our results suggest that IL-27 can be effective in reducing tumor growth, can help normalize bone structure, and can promote enhanced accumulation of effector cells in prostate tumors. These results are promising, because they are relevant to developing a novel IL-27-based strategy that can treat both the tumor and the bone, by using this simple and effective sonodelivery method for treating prostate tumor bone metastases.
机译：我们已经研究了新型细胞因子白介素27（IL-27）在介导前列腺癌和骨骼之间的相互作用中的作用。 IL-27是异二聚体IL-12相关细胞因子家族中最新鉴定的成员，并且在包括前列腺癌在内的多种癌症模型中显示了在阻止肿瘤生长和介导肿瘤消退方面的前景。前列腺癌通常与骨转移有关，在该处，肿瘤诱发与成骨细胞和破骨细胞的恶性交流，从而诱发骨病变，这是造成患者疼痛和骨骼相关事件的重要原因，包括高骨折风险。我们描述我们的发现在分化的不同阶段对前列腺癌细胞，成骨细胞和破骨细胞的IL-27基因传递的影响。我们在体内利用声波穿孔（sonodelivery）应用了IL-27基因递送方案，目的是在体内骨转移部位治疗和减少前列腺癌的生长。我们使用了一种具有免疫功能的前列腺腺癌的新模型，并对肿瘤的生长减少，基因表达和效应细胞谱进行了表征。我们的结果表明，IL-27可以有效减少肿瘤的生长，有助于骨骼结构正常化，并可以促进前列腺癌细胞中效应细胞的积累。这些结果令人鼓舞，因为它们与通过使用这种简单而有效的超声递送法治疗前列腺肿瘤的骨转移而开发出可以治疗肿瘤和骨骼的新型基于IL-27的策略有关。

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