M-HIFU inhibits tumor growth, suppresses STAT3 activity and enhances tumor specific immunity in a transplant tumor model of prostate cancer.
M-HIFU inhibits tumor growth, suppresses STAT3 activity and enhances tumor specific immunity in a transplant tumor model of prostate cancer.
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DOI：
10.1371/journal.pone.0041632
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zhong P
中科院分区：
文献类型：
--
作者：
Huang X;Yuan F;Liang M;Lo HW;Shinohara ML;Robertson C;Zhong P
在这项研究中，我们探讨了使用机械高强度聚焦超声（M-HIFU）作为新辅助治疗手术切除原发性肿瘤之前。我们还利用前列腺癌移植瘤模型研究了信号转导子和转录激活子3（STAT 3）在M-HIFU诱导抗肿瘤免疫应答中的作用。将具有组成性激活的STAT 3的小鼠前列腺癌细胞系RM-9皮下接种在C57 BL/6 J小鼠中。在手术切除原发性肿瘤前两天，通过M-HIFU或假暴露治疗荷瘤小鼠（最大肿瘤直径为5 × 6 mm）。恢复后，如果在30天内未观察到肿瘤复发，则进行肿瘤再激发。观察再攻击肿瘤的生长情况、动物的存活率和抗肿瘤免疫应答。在采用M-HIFU +手术和单独手术的两个治疗组中均未观察到肿瘤复发和远处转移。然而，与单独手术相比，M-HIFU联合手术被发现显著抑制再攻击肿瘤的生长，下调肿瘤内STAT 3活性，增加脾脏和肿瘤引流淋巴结（TDLN）中的细胞毒性T细胞，并改善宿主存活。此外，M-HIFU结合手术被发现显着降低免疫抑制的水平，同时增加树突状细胞的数量和活动，相比单独手术。我们的研究结果表明，M-HIFU可以抑制STAT 3的活动，并与手术协同结合时，可能会提供一个新的和有前途的策略，用于治疗前列腺癌。
In this study, we explored the use of mechanical high intensity focused ultrasound (M-HIFU) as a neo-adjuvant therapy prior to surgical resection of the primary tumor. We also investigated the role of signal transducer and activator of transcription 3 (STAT3) in M-HIFU elicited anti-tumor immune response using a transplant tumor model of prostate cancer. RM-9, a mouse prostate cancer cell line with constitutively activated STAT3, was inoculated subcutaneously in C57BL/6J mice. The tumor-bearing mice (with a maximum tumor diameter of 5∼6 mm) were treated by M-HIFU or sham exposure two days before surgical resection of the primary tumor. Following recovery, if no tumor recurrence was observed in 30 days, tumor rechallenge was performed. The growth of the rechallenged tumor, survival rate and anti-tumor immune response of the animal were evaluated. No tumor recurrence and distant metastasis were observed in both treatment groups employing M-HIFU + surgery and surgery alone. However, compared to surgery alone, M-HIFU combined with surgery were found to significantly inhibit the growth of rechallenged tumors, down-regulate intra-tumoral STAT3 activities, increase cytotoxic T cells in spleens and tumor draining lymph nodes (TDLNs), and improve the host survival. Furthermore, M-HIFU combined with surgery was found to significantly decrease the level of immunosuppression with concomitantly increased number and activities of dendritic cells, compared to surgery alone. Our results demonstrate that M-HIFU can inhibit STAT3 activities, and when combined synergistically with surgery, may provide a novel and promising strategy for the treatment of prostate cancers.
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影响因子：
11.2
作者：
Bai, JR;Sui, JH;Callery, MP
通讯作者：
Callery, MP
影响因子：
5.2
作者：
Kim, Jeong Kyu;Jung, Kwang Hwa;Nam, Suk Woo
通讯作者：
Nam, Suk Woo
影响因子：
4.4
作者：
Pallandre, Jean-Rene;Brillard, Emilie;Borg, Christophe
通讯作者：
Borg, Christophe
影响因子：
3.6
作者：
Selvendiran, Karuppaiyah;Kuppusamy, M. Lakshmi;Kuppusamy, Periannan
通讯作者：
Kuppusamy, Periannan
影响因子：
8
作者：
Martin, SS;Ridgeway, AG;Leder, P
通讯作者：
Leder, P