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:Intratumoral Treatment with 5-Androstene-3β, 17α-Diol Reduces Tumor Size and Lung Metastasis in a Triple-Negative Experimental Model of Breast Cancer.
Intratumoral Treatment with 5-Androstene-3β, 17α-Diol Reduces Tumor Size and Lung Metastasis in a Triple-Negative Experimental Model of Breast Cancer.
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乳腺癌治疗失败与低缓解率、高成本和长期毒性相关。因此,有必要寻找毒性更低、更便宜且更有效的治疗方法。原位给药确保药物递送至肿瘤细胞并减少全身毒性效应。雄甾烯-3β, 17α-二醇(α-AED)可减少乳腺肿瘤细胞增殖,是治疗乳腺肿瘤的理想候选药物。
本研究旨在确定α-AED对三阴性乳腺肿瘤模型的体外和体内效应。在用α-AED处理的小鼠和人乳腺肿瘤细胞中观察到体外双相类固醇效应。
在此意义上,用较高剂量(100和200 μM)处理的细胞显示出抗增殖效应。瘤内给药的α-AED降低了小鼠肿瘤的平均肿瘤重量,并增加了NK 细胞、浆细胞和浆母细胞细胞的百分比。
值得注意的是,所有α-AED处理的肿瘤中VEGF水平均低于对照组和载体组。肿瘤原位反应增强在全身反映为α-AED处理小鼠血清中抗4T1 IgG浓度更高,但未检测到其他相关的全身变化。局部注射α-AED使肿瘤大小减小与该类固醇的抗增殖效应相关,而较低的局部VEGF水平可能与α-AED处理小鼠中不可察觉的宏观转移有关。上述表明,α-AED可用于临床研究,以证明其作为替代乳腺肿瘤治疗或与已确立疗法联合使用的疗效。
Breast cancer treatment failure is related to low response rates, high costs, and long-term toxicities.
Thus, it is necessary to find less toxic, cheaper, and more effective treatments. In situ administration ensures drug delivery to tumor cells and decreases systemic toxic effects. The androstene-3β, 17α-diol (α-AED) reduces breast tumor cell proliferation and is an ideal candidate to treat mammary tumors.
This study aims to identify the in vitro and in vivo effects of α-AED on a triple-negative mammary tumor model. An in vitro biphasic steroid effect was observed in mouse and human mammary tumor cells treated with α-AED. In this sense, cells treated with higher doses (100 and 200 μM) showed an antiproliferative effect. The α-AED administrated intratumorally reduced average tumor weight and increased the percentage of natural killer cells (NK), plasmatic, and plasmablast cells in mice tumors. Of note, VEGF levels in all α-AED-treated tumors was lower than in the control and vehicle groups.
The tumor in situ increased response was reflected systemically by higher anti-4T1 IgG concentration in serum from α-AED-treated mice, but no other associated systemic changes were detected.
The reduction in tumor size for the local injection of α-AED is associated with the anti-proliferative effect of this steroid, and the lower local levels of VEGF may be related to the imperceptible macroscopic metastasis in α-AED-treated mice. The above suggests that α-AED may be used in clinical studies to prove its efficacy as an alternative breast tumor treatment or in conjunction with already established therapies.
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