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:Dual-Protein Intervention in CT26 Tumor-Bearing Mice: A Preliminary Evaluation of Its Effects on Anti-Tumor Efficacy of 5-Fluorouracil and Immune Responses.
Dual-Protein Intervention in CT26 Tumor-Bearing Mice: A Preliminary Evaluation of Its Effects on Anti-Tumor Efficacy of 5-Fluorouracil and Immune Responses.
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中等剂量(0.67 g/kg)的 DP 具有最有利的趋势,且干预前模式更为有效。本研究还提供了 DP 在降低化疗相关毒性方面潜力的探索性数据。这些发现将为结直肠癌患者的营养治疗,以及特殊医学用途双蛋白食品的研发和应用提供初步的科学支持。
结直肠癌是一种常见的恶性肿瘤,尽管5-氟尿嘧啶(FU)具有毒性,但它仍然是化疗的主要药物。作为肿瘤综合治疗的重要组成部分,双蛋白(DP)营养干预正受到越来越多的关注。
本研究初步评价了DP干预对CT26荷瘤小鼠结直肠细胞的调节作用,考察了DP的剂量和给药方式,以及FU单用或联合DP的抗肿瘤效果。
结果显示,低剂量和中剂量DP在数值上提高了脾脏指数,并显示出减轻FU诱导的胸腺萎缩、脾脏损伤、肾毒性和心肌损伤的趋势。它还在一定程度上缓解了肌肉消耗,防止了FU诱导的结直肠缩短,并减少了肠道损伤。此外,DP与淋巴细胞、单核细胞和血小板计数增加以及粒细胞减少相关,提示可能减轻化疗诱导的骨髓抑制,并对造血功能具有潜在影响。流式细胞术结果提示DP可能影响CD4 + T和CD8 + T细胞的增殖或凋亡,调节效应和记忆表型,降低脾脏中性粒细胞水平,平衡B细胞功能,并维持NK 细胞活性。此外,DP干预还显示出调节肝脏脂质代谢以及部分缓解FU诱导的血脂异常和肌肉损伤的趋势。此外,DP和FU可增加IL-2、IL-10、GM-CSF和IFN-γ,并降低IL-6和TNF-α。
Colorectal cancer is a common malignancy and 5-fluorouracil (FU) remains a mainstay of chemotherapy despite its toxicity. As an important part of comprehensive tumor treatment, dual-protein (DP) nutritional intervention is attracting more and more attention.
This study preliminarily evaluated the regulatory effects of DP intervention on colorectal cells of CT26 tumor-bearing mice, examining the dosage and administration methods of DP, as well as the anti-tumor effects of FU alone or in combination with DP.
The results showed that low- and medium-dose DP numerically increased spleen index and showed trends toward alleviating FU-induced thymic atrophy, splenic damage, nephrotoxicity, and myocardial injury. It also partly mitigated muscle wasting, prevented FU-induced shortening of the colorectal tract, and reduced intestinal injury. In addition, DP was associated with increased lymphocyte, monocyte, and platelet counts and decreased granulocytes, suggesting possible alleviation of chemotherapy-induced bone marrow suppression and a potential effect on hematopoietic function. Flow cytometry results indicated possible effects of DP on CD4 + T and CD8 + T cell proliferation or apoptosis, modulation of effector and memory phenotypes, reduced splenic neutrophil levels, balanced B cell function, and maintained natural killer cell activity. In addition, DP intervention also showed trends toward regulating hepatic lipid metabolism and partially alleviating FU-induced dyslipidemia and muscle damage. In addition, DP and FU could increase IL-2, IL-10, GM-CSF and IFN-γ and decrease IL-6 and TNF-α.
In conclusion, a moderate dose (0.67 g/kg) of DP had the most favorable trends, and the pre-intervention mode was more effective. This study also provided exploratory data on the potential of DP in reducing chemotherapy-related toxicity. These findings will provide preliminary scientific support for nutritional therapy in colorectal cancer patients, as well as for the research, development, and application of dual-protein foods for special medical purposes.
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