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徒步者(HIKESHI)在去势抵抗性前列腺癌热疗中的作用以及一种新型碳纳米角磁性纳米颗粒在磁热疗中的应用。

Role of HIKESHI on Hyperthermia for Castration-Resistant Prostate Cancer and Application of a Novel Magnetic Nanoparticle with Carbon Nanohorn for Magnetic Hyperthermia.

作者信息

Nagai Takashi, Kawai Noriyasu, Gonda Masakazu, Iida Keitaro, Etani Toshiki, Kobayashi Daichi, Naiki Taku, Naiki-Ito Aya, Ando Ryosuke, Yamaguchi Sataro, Sugahara Yuto, Ueno Sakyo, Tsutsumiuchi Kaname, Imae Toyoko, Yasui Takahiro

机构信息

Department of Nephron-Urology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Aichi, Japan.

Experimental Pathology and Tumor Biology, Nagoya City University, Nagoya 467-8601, Aichi, Japan.

出版信息

Pharmaceutics. 2023 Feb 13;15(2):626. doi: 10.3390/pharmaceutics15020626.

Abstract

The prognosis of castration-resistant prostate cancer (CRPC) is technically scarce; therefore, a novel treatment for CRPC remains warranted. To this end, hyperthermia (HT) was investigated as an alternative therapy. In this study, the analysis focused on the association between CRPC and heat shock protein nuclear import factor "hikeshi (HIKESHI)", a factor of heat tolerance. Silencing the HIKESHI expression of 22Rv1 cells (human CRPC cell line) treated with siRNAs inhibited the translocation of heat shock protein 70 from the cytoplasm to the nucleus under heat shock and enhanced the effect of hyperthermia. Moreover, a novel magnetic nanoparticle was developed via binding carbon nanohorn (CNH) and iron oxide nanoparticle (IONP) with 3-aminopropylsilyl (APS). Tumor-bearing model mice implanted with 22 Rv1 cells were examined to determine the effect of magnetic HT (mHT). We locally injected CNH-APS-IONP into the tumor, which was set under an alternative magnetic field and showed that tumor growth in the treatment group was significantly suppressed compared with other groups. This study suggests that HIKESHI silencing enhances the sensitivity of 22Rv1 cells to HT, and CNH-APTES-IONP deserves consideration for mHT.

摘要

去势抵抗性前列腺癌(CRPC)的预后在技术上缺乏相关研究;因此,仍需要一种针对CRPC的新疗法。为此,对热疗(HT)作为一种替代疗法进行了研究。在本研究中,分析聚焦于CRPC与热耐受因子热休克蛋白核输入因子“徒步者(HIKESHI)”之间的关联。用小干扰RNA(siRNAs)处理22Rv1细胞(人CRPC细胞系)使其HIKESHI表达沉默,抑制了热休克下热休克蛋白70从细胞质向细胞核的转运,并增强了热疗效果。此外,通过将碳纳米角(CNH)和氧化铁纳米颗粒(IONP)与3-氨丙基硅烷基(APS)结合,开发了一种新型磁性纳米颗粒。对植入22Rv1细胞的荷瘤模型小鼠进行检查,以确定磁性热疗(mHT)的效果。我们将CNH-APS-IONP局部注射到置于交变磁场下的肿瘤中,结果显示治疗组的肿瘤生长与其他组相比受到显著抑制。本研究表明,HIKESHI沉默增强了22Rv1细胞对热疗的敏感性,并且CNH-APTES-IONP值得考虑用于磁性热疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/958c/9967786/a625b3d2aaf0/pharmaceutics-15-00626-g001.jpg

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