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肿瘤局部化疗热疗用多西紫杉醇嵌入磁脂体:化疗与热疗的相互作用。

Tumor local chemohyperthermia using docetaxel-embedded magnetoliposomes: Interaction of chemotherapy and hyperthermia.

机构信息

Department of Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

出版信息

J Gastroenterol Hepatol. 2012 Feb;27(2):406-11. doi: 10.1111/j.1440-1746.2011.06972.x.

Abstract

BACKGROUND AND AIM

We have studied and reported the usefulness of tumor local chemohyperthermia at a low-grade temperature below 43°C with docetaxel-embedded magnetoliposome (DML) and an applied alternating current magnetic field. However, the mechanisms of this treatment and the dynamics of the injected docetaxel were not investigated in our previous study. Thus, we investigated the interaction of chemotherapy and hyperthermia in the treated tumor.

METHODS

Human MKN45 gastric cancer cells were implanted in the hind limbs of Balb-c/nu/nu mice. DML, magnetite-loaded liposome, and docetaxel were injected into the tumors with or without being exposed to an alternating current magnetic field. Docetaxel and tumor necrosis factor-α concentrations, the cell cycle, and cell death rates in the tumor were examined.

RESULTS

Docetaxel concentrations were significantly higher in the DML-injected group than in the docetaxel-injected group 3 days after injection. A G2/M peak was observed 1 day after treatment in the DML-injected and exposed group and the docetaxel-injected group, while it was observed 3 days after treatment in the DML-injected without heating group and the magnetite-loaded liposome group. The tumor cell death rate gradually increased in the DML-injected group, with or without being exposed, while it gradually decreased after its peak in other groups. The tumor necrosis factor-α concentration in the tumor treated with DML with heating remained at a high level on the 7th day after treatment, while it decreased after its peak in other groups.

CONCLUSION

The antitumor effect of this treatment derives from a combination of hyperthermia and chemotherapy locally in the tumor.

摘要

背景与目的

我们已经研究并报道了使用载有多西紫杉醇的磁脂质体(DML)和外加交流磁场在 43°C 以下的低温度下进行肿瘤局部化学热疗的有效性。然而,在我们之前的研究中,没有研究这种治疗的机制和注射的多西紫杉醇的动力学。因此,我们研究了治疗肿瘤中化疗和热疗的相互作用。

方法

将人 MKN45 胃癌细胞植入 Balb-c/nu/nu 小鼠的后肢。将 DML、载磁铁矿脂质体和多西紫杉醇注入肿瘤,同时或不暴露于交流磁场。检查肿瘤中的多西紫杉醇和肿瘤坏死因子-α浓度、细胞周期和细胞死亡率。

结果

与注射多西紫杉醇组相比,注射 DML 组的多西紫杉醇浓度在注射后 3 天显著升高。在 DML 注射和暴露组以及多西紫杉醇注射组中,处理后 1 天观察到 G2/M 峰,而在 DML 未加热注射组和载磁铁矿脂质体组中观察到处理后 3 天观察到 G2/M 峰。在有或没有加热的 DML 注射组中,肿瘤细胞死亡率逐渐增加,而在其他组中,在达到峰值后逐渐降低。在接受加热的 DML 治疗的肿瘤中,肿瘤坏死因子-α浓度在治疗后第 7 天仍保持高水平,而在其他组中则在达到峰值后降低。

结论

这种治疗的抗肿瘤作用源于肿瘤内局部热疗和化疗的联合作用。

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