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磁阳离子脂质体热疗强力抑制新型大鼠模型前列腺癌骨转移。

Thermotherapy using magnetic cationic liposomes powerfully suppresses prostate cancer bone metastasis in a novel rat model.

机构信息

Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan.

出版信息

Prostate. 2013 Jun;73(9):913-22. doi: 10.1002/pros.22637. Epub 2013 Jan 17.

DOI:10.1002/pros.22637
PMID:23334935
Abstract

BACKGROUND

Bone metastasis is a serious problem for individuals with prostate cancer, and the effects of the anticancer drug docetaxel (DTX) are insufficient. We therefore examined the therapeutic potential of magnetic cationic liposomes (MCL) in a novel rat model that allows the evaluation of tumor immunity. The effects of MCL thermotherapy were compared with those of DTX as a conventional therapy for the treatment of bone metastatic prostate cancer.

METHODS

Prostate tumor tissues were transplanted into the femurs of model rats divided into four groups: control, MCL, DTX, and MCL + DTX. Tumors were injected with MCL, and alternating magnetic field (AMF) irradiation was performed three times a week. Tumor proliferation and bone destruction were evaluated by proliferating cell nuclear antigen positivity, computed tomography, and CD68-positive cell number, while tumor immunity was evaluated by heat shock protein (HSP) 70 expression and CD8-positive lymphocyte number.

RESULTS

We successfully established a novel femur metastasis model of prostate cancer, and demonstrated that tumor proliferation and bone destruction in the MCL and MCL + DTX groups were significantly suppressed compared with control and DTX groups. MCL thermotherapy concurrently induced necrosis and apoptosis. The expression of HSP70 in the MCL and MCL + DTX groups was also significantly increased, and tumor immunity was enhanced through the induction of CD8-positive lymphocytes.

CONCLUSION

MCL thermotherapy was clearly more effective than DTX in treating bone metastatic prostate cancer. A combination of MCL thermotherapy and DTX therefore deserves consideration as a novel treatment for this disease.

摘要

背景

骨转移是前列腺癌患者的严重问题,抗癌药物多西紫杉醇(DTX)的疗效不足。因此,我们在一种新型大鼠模型中研究了磁性阳离子脂质体(MCL)的治疗潜力,该模型允许评估肿瘤免疫。将 MCL 热疗的效果与 DTX 作为常规疗法治疗骨转移前列腺癌的效果进行了比较。

方法

将前列腺肿瘤组织移植到模型大鼠的股骨中,分为四组:对照组、MCL 组、DTX 组和 MCL+DTX 组。肿瘤内注射 MCL,并每周进行三次交变磁场(AMF)照射。通过增殖细胞核抗原阳性、计算机断层扫描和 CD68 阳性细胞数评估肿瘤增殖和骨破坏,通过热休克蛋白(HSP)70 表达和 CD8 阳性淋巴细胞数评估肿瘤免疫。

结果

我们成功建立了一种新型的前列腺癌股骨转移模型,并证明 MCL 和 MCL+DTX 组的肿瘤增殖和骨破坏明显低于对照组和 DTX 组。MCL 热疗同时诱导了坏死和凋亡。MCL 和 MCL+DTX 组 HSP70 的表达也显著增加,通过诱导 CD8 阳性淋巴细胞增强了肿瘤免疫。

结论

MCL 热疗在治疗骨转移前列腺癌方面明显优于 DTX。因此,MCL 热疗联合 DTX 值得考虑作为治疗这种疾病的新方法。

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