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:Antitumor Effect of 5-Aminolevulinic Acid Methyl Ester-Mediated Photodynamic Therapy on Local Skin Melanoma and Its Metastasized Tumor, in Relation with Antitumor Immunity.
Antitumor Effect of 5-Aminolevulinic Acid Methyl Ester-Mediated Photodynamic Therapy on Local Skin Melanoma and Its Metastasized Tumor, in Relation with Antitumor Immunity.
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ALA-Me-PDT 对黑色素瘤的局部肿瘤生长和远处肺转移均有显著抑制作用。ALA-Me-PDT 也引起了显著的抗肿瘤免疫。本研究结果为 ALA-Me-PDT 治疗皮肤黑色素瘤及其转移提供了潜在的可能性。
建立了一个非色素性黑色素瘤小鼠模型,用36只裸鼠接种人原代黑色素瘤细胞WM266-4进行攻击。当黑色素瘤生长至(0.4 ȕ 0.4) cm2大小时,将36只小鼠随机分为4组,即ALA-Me静脉(i.v.)注射-PDT组、ALA-Me腹腔(i.p.)注射-PDT组、ALA-Me局部应用-PDT组和未接受任何治疗的对照组。ALA-Me全身给药(i.v.和i.p.)的剂量为250 mg/kg。对于ALA-Me局部应用,将25 mg/cm2的乳膏涂抹于肿瘤组织上。肿瘤部位用LED灯发出的红光照射,注量率为90 mW/cm2,能量率为50 J/cm2。
上述三种处理后均观察到对肿瘤生长和转移的抑制作用。在抑制肿瘤生长方面,治疗组与对照组肿瘤体积差异有统计学意义(P < 0.05)。此外,三种处理后均发现对肿瘤肺转移有非常显著的抑制作用(P < 0.01)。同时,通过T细胞缺陷裸鼠脾脏中免疫细胞NK细胞的增加,也观察到了ALA-Me-PDT诱导的免疫反应。
A non-pigmented melanoma mouse model, which was challenged with human primary melanoma cells WM266-4, was established in 36 nude mice. When the melanoma grew to size of (0.4 ȕ 0.4) cm2, the 36 mice were randomly divided into 4 groups, i.e., ALA-Me intravenous (i.v.) injection-PDT, ALA-Me intraperitoneal (i.p.) injection-PDT, ALA-Me topical application-PDT and control group without any treatment. The dose for systemic administration (i.v. and i.p.) of ALA-Me was 250 mg/kg. For topical application of ALA-Me, a cream with 25 mg/cm2 was smeared on the tumor tissue. The tumor site was irradiated by the red light from LEDs lamp with fluence rate 90 mW/cm2 and energy rate 50 J/cm2.
The inhibitory effects on both tumor growth and metastasis were observed after all three treatments mentioned above. In terms of inhibiting tumor growth, there was a significant difference in the volume of tumor between the treatment groups and the control group (P < 0.05). Furthermore, a very significant (P < 0.01) inhibitory effect on tumor lung metastasis was found after the three treatments. Moreover, the ALA-Me-PDT-induced immune response was also observed by means of increase of immune cells NK cells in the spleen of the T cell-deficient nude mice.
ALA-Me-PDT had significant inhibitory effects both on local tumor growth and distant lung metastasis of melanoma. There was also significant antitumor immunity caused by ALA-Me-PDT. Results of the present study provide a potential possibility for ALA-Me-PDT in the treatment of skin melanoma and its metastasis.
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