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[白细胞介素-2基因疗法联合放疗对头颈部鳞状细胞癌的抗肿瘤研究]

[Antitumour study with combined IL-2 gene therapy and radiation for head and neck squamous cell carcinoma].

作者信息

Liu Shixi, Yang Huan, Tang Zhiquan, Liang Chuanyu

机构信息

Department of Otolaryngology, West China Hospital, Sichuan University, Chengdu 610041.

出版信息

Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2003 Feb;17(2):105-7.

Abstract

OBJECTIVE

To assess the efficacy of combination therapy with IL-2 gene transfer and radiation in an immunocompetent murine model that parallel more closely the clinical therapy of head and neck Squamous cell carcinoma(HNSCC).

METHOD

Tumors were established in the floor of mouth in C3H/HeJ mice with SCC VII cell line. Lipid-DNA complexed (lipoplexes) by using polycationic liposome-Mediated transduction for HNSCC were transducted in tumor-bearing mouse by direct intratumoral gene transfer. The local tumor radiation with 2 Gy were done in second day. Tumor size were measured before and after the treatment as compared to different single treatment groups and the controls. After tumors were subcultured, the supernatants were collected for IL-2 expression by enzyme-linked immunosorbent assay (ELISA). Natural killer (NK) cell activity and cytotoxic T-lymphocyte (CTL) activity were also assayed by LDH method. CD4+ and CD8+ T-lymphcyte in tumour tissues were examined by immunohistochemistry.

RESULT

HNSCC tumor growth was significantly inhibited after a combined IL-2 gene and radiation therapy as compared to the controls. Increased secreted levels of IL-2 protein expression were found in combined and single IL-2 gene treated groups. The combination and IL-2 gene treated groups produced greater activation of CTL and NK than the other groups. The significant CD4+ and CD8+ T lymphocyte infiltration was distributed in tumor tissues after IL-2 gene therapy.

CONCLUSION

Combined IL-2 gene therapy and radiation could significantly inhibited HNSCC tumor growth in the murine model and efficiently induced antitumor immunity of the host.

摘要

目的

在更接近头颈部鳞状细胞癌(HNSCC)临床治疗的免疫活性小鼠模型中,评估白细胞介素-2(IL-2)基因转移与放疗联合治疗的疗效。

方法

用SCC VII细胞系在C3H/HeJ小鼠的口腔底部建立肿瘤。通过聚阳离子脂质体介导的转导将脂质-DNA复合物(脂质体)用于HNSCC,通过直接瘤内基因转移将其转导至荷瘤小鼠体内。在第二天进行2 Gy的局部肿瘤放疗。与不同的单一治疗组和对照组相比,在治疗前后测量肿瘤大小。肿瘤传代培养后,收集上清液,通过酶联免疫吸附测定(ELISA)检测IL-2表达。还用乳酸脱氢酶(LDH)法检测自然杀伤(NK)细胞活性和细胞毒性T淋巴细胞(CTL)活性。通过免疫组织化学检查肿瘤组织中的CD4+和CD8+ T淋巴细胞。

结果

与对照组相比,IL-2基因与放疗联合治疗后HNSCC肿瘤生长受到显著抑制。在联合治疗组和单一IL-2基因治疗组中发现IL-2蛋白表达的分泌水平增加。联合治疗组和IL-2基因治疗组比其他组产生了更强的CTL和NK激活。IL-2基因治疗后,肿瘤组织中有显著的CD4+和CD8+ T淋巴细胞浸润。

结论

IL-2基因治疗与放疗联合可显著抑制小鼠模型中HNSCC肿瘤生长,并有效诱导宿主的抗肿瘤免疫。

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