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在微泡存在的情况下进行超声照射,可能会增强化疗药物对膀胱癌的抗肿瘤作用。

Ultrasound irradiation in the presence of microbubbles may enhance the antitumor effect of chemotherapeutic agents against bladder cancer.

作者信息

Suzuki Takehiro, Sato Takuma, Sukhbaatar Ariunbuyan, Sakamoto Maya, Mori Shiro, Kodama Tetsuya, Ito Akihiro

机构信息

Department of Urology, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.

Graduate School of Biomedical Engineering, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.

出版信息

J Cancer. 2025 Jan 1;16(2):368-381. doi: 10.7150/jca.100846. eCollection 2025.

Abstract

Intravesical instillation of chemotherapy has been performed to reduce the risk of intravesical recurrence of bladder cancer. However, its antitumor effect is not necessarily sufficient, which may be partially due to inadequate delivery of intravesically administered chemotherapeutic agents to bladder tumors. Ultrasound irradiation to target tissues in the presence of microbubbles is a technique to transiently enhance cell membrane permeability and achieve efficient drug delivery to the desired sites without damage to non-target areas; this technique has been used in chemotherapy, immunotherapy, gene therapy, and radiotherapy for the treatment of various cancers. However, the effectiveness of combining intravesical instillation of chemotherapy and this strategy for the treatment of bladder cancer has not been fully investigated. This report shows that mitomycin C combined with ultrasound and microbubbles has a higher antitumor effect than mitomycin C alone against mouse bladder cancer cells. Next, the antitumor effect of intravesical instillation of chemotherapy combined with ultrasound and microbubbles was demonstrated using an orthotopic mouse bladder cancer model. experiments showed that ultrasound irradiation in the presence of microbubbles enhanced the local delivery of fluorescent molecules and had the potential to enhance the antitumor effect of intravesical instillation of chemotherapy without visible damage to the surrounding normal tissues. The results of the present study demonstrate that intravesical chemotherapy combined with ultrasound and microbubbles is potentially a safe and effective treatment for bladder cancer.

摘要

膀胱内灌注化疗已被用于降低膀胱癌膀胱内复发的风险。然而,其抗肿瘤效果不一定足够,这可能部分归因于膀胱内给予的化疗药物向膀胱肿瘤的递送不足。在微泡存在下对靶组织进行超声照射是一种可瞬时增强细胞膜通透性并在不损伤非靶区域的情况下实现向所需部位有效递送药物的技术;该技术已用于化疗、免疫治疗、基因治疗和放射治疗以治疗各种癌症。然而,膀胱内灌注化疗与该策略联合用于治疗膀胱癌的有效性尚未得到充分研究。本报告表明,丝裂霉素C联合超声和微泡对小鼠膀胱癌细胞的抗肿瘤作用高于单独使用丝裂霉素C。接下来,使用原位小鼠膀胱癌模型证明了膀胱内灌注化疗联合超声和微泡的抗肿瘤作用。实验表明,在微泡存在下进行超声照射可增强荧光分子的局部递送,并有可能增强膀胱内灌注化疗的抗肿瘤作用,而对周围正常组织无明显损伤。本研究结果表明,膀胱内化疗联合超声和微泡可能是一种安全有效的膀胱癌治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5f/11685697/9c8b41c37db1/jcav16p0368g001.jpg

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