RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:In vivo evaluation of oxidized multiwalled-carbon nanotubes-mediated hyperthermia treatment for breast cancer.
In vivo evaluation of oxidized multiwalled-carbon nanotubes-mediated hyperthermia treatment for breast cancer.
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乳腺癌是全球范围内导致高死亡率的最常见癌症类型之一。热疗(HT)曾被引入作为治疗乳腺癌的替代疗法之一,但其主要缺点是会损伤邻近正常细胞。
本研究探讨了多壁碳纳米管(MWCNTs)与热疗联合应用于乳腺癌治疗方案中的整合效应。在本研究中,采用H2SO4/HNO3(98%/68%)以3:1(ν/ν)比例通过酸洗法制备了酸功能化MWCNTs(ox-MWCNTs),并通过胶体分散性测试、FTIR、TGA、XRD、FESEM和EDX分析进行了表征。对荷EMT6肿瘤小鼠给予ox-MWCNTs联合43 °C局部HT治疗。监测肿瘤进展并评估免疫应答的影响。
本研究结果表明,ox-MWCNTs联合局部HT治疗组小鼠实现了完全肿瘤根除,并伴随中位生存期的显著延长。肿瘤组织的组织学和免疫组织化学分析显示,联合治疗处理的肿瘤发生细胞坏死,且与未处理肿瘤相比,增殖细胞显著减少。这一观察结果还伴随HT处理肿瘤中Hsp70表达的升高。引流淋巴结的流式细胞术分析显示,联合治疗小鼠中树突状细胞浸润和成熟增加。
此外,在联合治疗处理的肿瘤中观察到肿瘤浸润性CD8+和CD4+ T细胞以及巨噬细胞和NK 细胞显著增加。总之,本研究呈现的结果表明ox-MWCNTs介导的HT作为抗癌治疗剂的潜力,因此可能在未来乳腺癌治疗中具有益处。
Breast cancer is one of the most common types of cancer that contribute to high mortality worldwide. Hyperthermia (HT) was introduced as one of the alternative treatments to treat breast cancer but has major drawback of damaging normal adjacent cells.
This study explores the integration effect of multiwalled‑carbon nanotubes (MWCNTs) in combination with hyperthermia treatment for breast cancer therapy regimes. In this study, acid-functionalized MWCNTs (ox-MWCNTs) were prepared by acid washing methods using H 2 SO 4 /HNO 3 (98%/68%) with the ratio of 3:1 (ν/ν) and characterized by colloidal dispersibility test, FTIR, TGA, XRD, FESEM and EDX analysis. EMT6 tumor-bearing mice were treated with ox-MWCNTs in combination with local HT at 43 °C. The tumor progression was monitored and the influence of immune response was evaluated.
Results from this study demonstrated that mice from ox-MWCNTs in combination with local HT treatment group experienced complete tumor eradication, accompanied by a significant increase in median survival of the mice. Histological and immunohistochemical analysis of tumor tissues revealed that tumor treated with combined treatment underwent cell necrosis and there was a significant reduction of proliferating cells when compared to the untreated tumor.
This observation is also accompanied with an increase in Hsp70 expression in tumor treated with HT. Flow cytometry analysis of the draining lymph nodes showed an increase in dendritic cells infiltration and maturation in mice treated with combined treatment.
In addition, a significant increase of tumor-infiltrated CD8 + and CD4 + T cells along with macrophages and natural killer cells was observed in tumor treated with combined treatment. Altogether, results presented in this study suggested the potential of ox-MWCNTs-mediated HT as an anticancer therapeutic agent, hence might be beneficial in the future of breast cancer treatment.
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