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:Immunotherapeutic potential of ethanolic olive leaves extract (EOLE) and IL-28B combination therapy in ENU induced animal model of leukemia.
Immunotherapeutic potential of ethanolic olive leaves extract (EOLE) and IL-28B combination therapy in ENU induced animal model of leukemia.
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细胞因子疗法已显示出抗癌潜力。细胞因子由人体不同细胞自然分泌;与化疗和放疗相比,其副作用较少、特异性较高。在白血病中,正常造血改变和白细胞生成缺陷会减少功能性免疫细胞数量,从而限制免疫治疗疗效。
因此,白血病治疗需要能够靶向多种维持癌症生长机制的先进疗法。联合治疗采用两种不同治疗药物,可从多个方面影响癌症生长,有时还会产生协同效应。
本研究考察乙醇橄榄叶提取物(EOLE)与 IL-28B 联合治疗的效果。研究者以 N-N′-乙基亚硝基脲(ENU)在瑞士白化小鼠中诱导白血病,确认白血病形成后给予 EOLE 治疗 4 周,并给予 IL-28B 治疗 1 周。联合治疗显著降低外周血原始细胞和白细胞总数,改变血浆中多种细胞因子水平,并增强白血病小鼠 NK 细胞的功能活性。NK 活性增强与通过实时 PCR 检测到的穿孔素和颗粒酶基因表达升高相关。联合治疗还提高了血清 IL-10 和 IFN-γ 水平,并降低血清 TGF-β,提示整体免疫功能改善。
总体而言,EOLE 与 IL-28B 联合治疗对白血病显示出显著治疗活性。
Cytokine therapies have shown promising results against cancers. Cytokines are secreted naturally from different bodily cells. These have fewer side effects but higher specificity than chemotherapy and radiation therapy. In leukemia, changes in normal hematopoiesis and defective leukocyte production limit the efficacy of immunotherapy by reducing the count of functional immune cells.
Therefore, the treatment of leukemia needs advanced therapeutics that can target multiple cancer sustaining mechanisms. In combination therapy, using two different therapeutic agents affect cancer growth in many ways and sometimes gives synergistic effects.
Here, we examined the effect of the ethanolic olive leaf extract (EOLE) and IL-28B in combination. N-N' Ethyl-nitrosourea (ENU) induced leukemia in Swiss albino mice was treated with EOLE for four weeks and IL-28B for one week after confirming the development of leukemia. The combination of EOLE and IL-28B significantly reduced the blast cell and total WBC counts in the peripheral blood, altered the levels of various cytokines in plasma, and induced the functional activity of NK cells in leukemic mice.
The induced NK activity correlates with increased expression of perforin and granzyme studied at the gene level through real-time (RT)-PCR. The treatment of leukemic mice with combined EOLE and IL-28B has also caused an increased serum IL-10 and IFN- level, and reduced serum TGF- indicates improved overall immunity. Altogether, the combination of EOLE and IL-28B has given substantial therapeutic activity against leukemia.
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