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白细胞介素-2联合CD80免疫基因疗法对胃癌腹膜转移的协同抗肿瘤作用。

A synergistic antitumor effect of interleukin-2 addition with CD80 immunogene therapy for peritoneal metastasis of gastric carcinoma.

作者信息

Kosaka Kinshi, Yashiro Masakazu, Sakate Yoji, Hirakawa Kosei

机构信息

Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.

出版信息

Dig Dis Sci. 2007 Aug;52(8):1946-53. doi: 10.1007/s10620-006-9637-8. Epub 2007 Apr 3.

DOI:10.1007/s10620-006-9637-8
PMID:17404853
Abstract

The co-stimulatory molecule CD80 is a ligand of CD28, which plays a key role in the induction of cell-mediated immune responses. Many tumors, including gastric cancer, decrease the expression of CD80, which results in the failure of immune recognition. We evaluated the effect of interleukin-2 addition combined with CD80 infection on the peritoneal metastasis in gastric cancer. CD80 infection combined with interleukin-2 addition significantly increased the activated cytotoxicity of mononuclear cells compared to CD80 gene infection and compared to the lacZ control group. In vivo, the survival of animals with intraperitoneal tumor was longest in those given CD80 infection with interleukin-2 addition (median survival, 46 days), followed by those given interleukin-2 (39 days), those given CD80 infection (37 days), and those given lacZ (29 days). These results suggest that interleukin-2 addition might contribute to improving the observed outcome of CD80 immunogene therapy in peritoneal metastasis of gastric carcinoma.

摘要

共刺激分子CD80是CD28的配体,在诱导细胞介导的免疫反应中起关键作用。包括胃癌在内的许多肿瘤会降低CD80的表达,从而导致免疫识别失败。我们评估了添加白细胞介素-2联合CD80感染对胃癌腹膜转移的影响。与CD80基因感染相比以及与lacZ对照组相比,添加白细胞介素-2联合CD80感染显著增加了单核细胞的活化细胞毒性。在体内,腹腔内有肿瘤的动物中,接受CD80感染并添加白细胞介素-2的动物存活时间最长(中位生存期为46天),其次是接受白细胞介素-2的动物(39天)、接受CD80感染的动物(37天)和接受lacZ的动物(29天)。这些结果表明,添加白细胞介素-2可能有助于改善CD80免疫基因疗法在胃癌腹膜转移中的观察结果。

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引用本文的文献

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Molecular biology and immunology of gastric cancer peritoneal metastasis.胃癌腹膜转移的分子生物学与免疫学
Transl Gastroenterol Hepatol. 2020 Oct 5;5:57. doi: 10.21037/tgh.2020.02.08. eCollection 2020.
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Gastric cancer cell supernatant causes apoptosis and fibrosis in the peritoneal tissues and results in an environment favorable to peritoneal metastases, in vitro and in vivo.胃癌细胞上清液在体外和体内引起腹膜组织细胞凋亡和纤维化,导致有利于腹膜转移的环境。
BMC Gastroenterol. 2012 Apr 20;12:34. doi: 10.1186/1471-230X-12-34.
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Destruction of gastric cancer cells to mesothelial cells by apoptosis in the early peritoneal metastasis.

本文引用的文献

1
ICAM-2 gene therapy for peritoneal dissemination of scirrhous gastric carcinoma.ICAM - 2基因疗法治疗硬癌型胃癌腹膜播散
Clin Cancer Res. 2004 Jul 15;10(14):4885-92. doi: 10.1158/1078-0432.CCR-0393-03.
2
Suppression of peritoneal metastasis in human gastric carcinoma by enhanced immunogenicity of B7-1 transfection.通过增强B7-1转染的免疫原性抑制人胃癌腹膜转移
Oncol Rep. 2004 Jul;12(1):53-7.
3
Molecular therapy for peritoneal dissemination of xenotransplanted human MKN-45 gastric cancer cells with adenovirus mediated Bax gene transfer.
早期腹膜转移中胃癌细胞通过凋亡对间皮细胞的破坏。
J Huazhong Univ Sci Technolog Med Sci. 2009 Apr;29(2):163-8. doi: 10.1007/s11596-009-0205-2. Epub 2009 Apr 28.
腺病毒介导Bax基因转移对人异种移植MKN-45胃癌细胞腹膜播散的分子治疗
Gut. 2004 Apr;53(4):554-60. doi: 10.1136/gut.2003.021683.
4
Oestradiol enhances tumour regression induced by B7-1/IL-2 adenoviral gene transfer in a murine model of breast cancer.在小鼠乳腺癌模型中,雌二醇可增强由B7-1/IL-2腺病毒基因转移诱导的肿瘤消退。
Br J Cancer. 2003 Jul 21;89(2):385-90. doi: 10.1038/sj.bjc.6601099.
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Recombinant adenovirus vector activates and protects human monocyte-derived dendritic cells from apoptosis.重组腺病毒载体激活并保护人单核细胞衍生的树突状细胞免于凋亡。
Hum Gene Ther. 2002 Sep 1;13(13):1541-9. doi: 10.1089/10430340260201635.
6
Phase I trial of a B7-1 (CD80) gene modified autologous tumor cell vaccine in combination with systemic interleukin-2 in patients with metastatic renal cell carcinoma.一项B7-1(CD80)基因修饰的自体肿瘤细胞疫苗联合全身应用白细胞介素-2治疗转移性肾细胞癌患者的I期试验。
J Urol. 2002 May;167(5):1995-2000.
7
CD80-mediated induction of immunostimulation in two ocular melanoma cell lines is augmented by interferon-gamma.干扰素-γ增强了CD80介导的两种眼黑色素瘤细胞系的免疫刺激诱导作用。
Melanoma Res. 2002 Apr;12(2):129-38. doi: 10.1097/00008390-200204000-00005.
8
Efficacy of intraperitoneal adenovirus-mediated p53 gene therapy in ovarian cancer.腹腔内腺病毒介导的p53基因治疗在卵巢癌中的疗效
Int J Gynecol Cancer. 1999 Sep;9(5):365-372. doi: 10.1046/j.1525-1438.1999.99040.x.
9
ICAM-1 (intercellular adhesion molecule-1) gene transfection inhibits lymph node metastasis by human gastric cancer cells.细胞间黏附分子-1(ICAM-1)基因转染抑制人胃癌细胞的淋巴结转移。
Jpn J Cancer Res. 2000 Sep;91(9):925-33. doi: 10.1111/j.1349-7006.2000.tb01036.x.
10
Effectiveness of combined interleukin 2 and B7.1 vaccination strategy is dependent on the sequence and order: a liposome-mediated gene therapy treatment for bladder cancer.白细胞介素2与B7.1联合疫苗接种策略的有效性取决于顺序和次序:一种用于膀胱癌的脂质体介导基因治疗方法
Clin Cancer Res. 2000 Jul;6(7):2913-20.