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1
Subcutaneous or intrahepatic injection of suicide gene modified tumour cells induces a systemic antitumour response in a metastatic model of colon carcinoma in rats.皮下或肝内注射自杀基因修饰的肿瘤细胞可在大鼠结肠癌转移模型中诱导全身性抗肿瘤反应。
Gut. 2002 Mar;50(3):387-91. doi: 10.1136/gut.50.3.387.
2
Cytosine deaminase/5-fluorocytosine-based vaccination against liver tumors: evidence of distant bystander effect.基于胞嘧啶脱氨酶/5-氟胞嘧啶的肝癌疫苗接种：远处旁观者效应的证据。
J Natl Cancer Inst. 1999 Dec 1;91(23):2014-9. doi: 10.1093/jnci/91.23.2014.
3
[Vaccination by suicide gene therapy against a model of hepatic metastasis from colon cancer in the rat].[自杀基因疗法对大鼠结肠癌肝转移模型的疫苗接种]
Ann Chir. 2000 Jul;125(6):552-9. doi: 10.1016/s0003-3944(00)00240-6.
4
Regression of experimental liver tumor after distant intra-hepatic injection of cytosine deaminase-expressing tumor cells and 5-fluorocytosine treatment.在肝内远处注射表达胞嘧啶脱氨酶的肿瘤细胞并进行5-氟胞嘧啶治疗后实验性肝肿瘤的消退
Int J Mol Med. 2000 Mar;5(3):275-8. doi: 10.3892/ijmm.5.3.275.
5
Re: Cytosine deaminase/5-fluorocytosine-based vaccination against liver tumors: evidence of distant bystander effect.回复：基于胞嘧啶脱氨酶/5-氟胞嘧啶的肝癌疫苗接种：远处旁观者效应的证据
J Natl Cancer Inst. 2000 Mar 15;92(6):494-5. doi: 10.1093/jnci/92.6.494.
6
Regional delivery and selective expression of a high-activity yeast cytosine deaminase in an intrahepatic colon cancer model.高活性酵母胞嘧啶脱氨酶在肝内结肠癌模型中的区域递送和选择性表达
Cancer Res. 2003 Feb 1;63(3):658-63.
7
Regional 'pro-drug' gene therapy: intravenous administration of an adenoviral vector expressing the E. coli cytosine deaminase gene and systemic administration of 5-fluorocytosine suppresses growth of hepatic metastasis of colon carcinoma.区域性“前药”基因治疗：静脉注射表达大肠杆菌胞嘧啶脱氨酶基因的腺病毒载体并全身给予5-氟胞嘧啶可抑制结肠癌肝转移灶的生长。
Gene Ther. 1998 Apr;5(4):507-13. doi: 10.1038/sj.gt.3300611.
8
Systemic administration of a recombinant vaccinia virus expressing the cytosine deaminase gene and subsequent treatment with 5-fluorocytosine leads to tumor-specific gene expression and prolongation of survival in mice.全身性给予表达胞嘧啶脱氨酶基因的重组痘苗病毒，随后用5-氟胞嘧啶进行治疗，可导致肿瘤特异性基因表达并延长小鼠的生存期。
Cancer Res. 1999 Jul 15;59(14):3396-403.
9
The potential of 5-fluorocytosine/cytosine deaminase enzyme prodrug gene therapy in an intrahepatic colon cancer model.5-氟胞嘧啶/胞嘧啶脱氨酶前药基因疗法在肝内结肠癌模型中的潜力。
Gene Ther. 2002 Jul;9(13):844-9. doi: 10.1038/sj.gt.3301706.
10
Hepatic intra-arterial delivery of a retroviral vector expressing the cytosine deaminase gene, controlled by the CEA promoter and intraperitoneal treatment with 5-fluorocytosine suppresses growth of colorectal liver metastases.通过肝动脉内递送由癌胚抗原（CEA）启动子控制的表达胞嘧啶脱氨酶基因的逆转录病毒载体，并腹腔注射5-氟胞嘧啶，可抑制结直肠癌肝转移灶的生长。
Gene Ther. 2001 Aug;8(16):1241-7. doi: 10.1038/sj.gt.3301518.

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Flavokawain C inhibits glucose metabolism and tumor angiogenesis in nasopharyngeal carcinoma by targeting the HSP90B1/STAT3/HK2 signaling axis.黄樟素C通过靶向HSP90B1/STAT3/HK2信号轴抑制鼻咽癌的葡萄糖代谢和肿瘤血管生成。
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EGFR-PKM2 signaling promotes the metastatic potential of nasopharyngeal carcinoma through induction of FOSL1 and ANTXR2.EGFR-PKM2 信号通过诱导 FOSL1 和 ANTXR2 促进鼻咽癌的转移潜能。
Carcinogenesis. 2020 Jul 10;41(6):723-733. doi: 10.1093/carcin/bgz180.
3
Progress and problems with the use of suicide genes for targeted cancer therapy.用于靶向癌症治疗的自杀基因的进展与问题
Adv Drug Deliv Rev. 2016 Apr 1;99(Pt A):113-128. doi: 10.1016/j.addr.2015.05.009. Epub 2015 May 22.
4
A systemic antitumor immune response prevents outgrowth of lung tumors after i.v. rechallenge but is not able to prevent growth of experimental liver tumors.全身性抗肿瘤免疫反应可在静脉内再次激发后阻止肺肿瘤生长，但无法阻止实验性肝肿瘤的生长。
Clin Exp Metastasis. 2004;21(1):13-8. doi: 10.1023/b:clin.0000017162.35708.73.
5
Adenovirus-mediated prodrug-enzyme therapy for CEA-producing colorectal cancer cells.腺病毒介导的前药-酶疗法用于产生癌胚抗原的结肠直肠癌细胞
J Cancer Res Clin Oncol. 2003 Jun;129(6):367-73. doi: 10.1007/s00432-003-0444-8. Epub 2003 Jun 3.

本文引用的文献

1
Antitumoral vaccination with granulocyte-macrophage colony-stimulating factor or interleukin-12-expressing DHD/K12 colon adenocarcinoma cells.用粒细胞巨噬细胞集落刺激因子或表达白细胞介素-12的DHD/K12结肠腺癌细胞进行抗肿瘤疫苗接种。
Cancer Gene Ther. 2000 May;7(5):676-82. doi: 10.1038/sj.cgt.7700152.
2
Re: Cytosine deaminase/5-fluorocytosine-based vaccination against liver tumors: evidence of distant bystander effect.回复：基于胞嘧啶脱氨酶/5-氟胞嘧啶的肝癌疫苗接种：远处旁观者效应的证据
J Natl Cancer Inst. 2000 Mar 15;92(6):494-5. doi: 10.1093/jnci/92.6.494.
3
Regression of experimental liver tumor after distant intra-hepatic injection of cytosine deaminase-expressing tumor cells and 5-fluorocytosine treatment.在肝内远处注射表达胞嘧啶脱氨酶的肿瘤细胞并进行5-氟胞嘧啶治疗后实验性肝肿瘤的消退
Int J Mol Med. 2000 Mar;5(3):275-8. doi: 10.3892/ijmm.5.3.275.
4
Cytosine deaminase/5-fluorocytosine-based vaccination against liver tumors: evidence of distant bystander effect.基于胞嘧啶脱氨酶/5-氟胞嘧啶的肝癌疫苗接种：远处旁观者效应的证据。
J Natl Cancer Inst. 1999 Dec 1;91(23):2014-9. doi: 10.1093/jnci/91.23.2014.
5
Suicide gene therapy of chemically induced mammary tumor in rat: efficacy and distant bystander effect.大鼠化学诱导乳腺肿瘤的自杀基因治疗：疗效及远距离旁观者效应
Cancer Res. 1998 Aug 15;58(16):3529-32.
6
Induction of potent antitumor natural killer cell activity by herpes simplex virus-thymidine kinase and ganciclovir therapy in an orthotopic mouse model of prostate cancer.在前列腺癌原位小鼠模型中，单纯疱疹病毒胸苷激酶和更昔洛韦疗法诱导强效抗肿瘤自然杀伤细胞活性。
Cancer Res. 1998 Aug 1;58(15):3221-5.
7
The immune response elicited by mammary adenocarcinoma cells transduced with interferon-gamma and cytosine deaminase genes cures lung metastases by parental cells.用干扰素-γ和胞嘧啶脱氨酶基因转导的乳腺腺癌细胞引发的免疫反应可治愈亲本细胞的肺转移。
Hum Gene Ther. 1998 Jan 20;9(2):217-24. doi: 10.1089/hum.1998.9.2-217.
8
Local and systemic antitumor response after combined therapy of mouse metastatic tumors with tumor cells expressing IFN-alpha and HSVtk: perspectives for the generation of cancer vaccines.用表达干扰素-α和单纯疱疹病毒胸苷激酶的肿瘤细胞联合治疗小鼠转移性肿瘤后的局部和全身抗肿瘤反应：癌症疫苗生成的前景
Gene Ther. 1997 Nov;4(11):1246-55. doi: 10.1038/sj.gt.3300518.
9
A "distant" bystander effect of suicide gene therapy: regression of nontransduced tumors together with a distant transduced tumor.自杀基因治疗的“远距离”旁观者效应：未转导肿瘤与远距离转导肿瘤一同消退。
Hum Gene Ther. 1997 Oct 10;8(15):1807-14. doi: 10.1089/hum.1997.8.15-1807.
10
An HSVtk-mediated local and distant antitumor bystander effect in tumors of head and neck origin in athymic mice.在无胸腺小鼠头颈部原发肿瘤中，单纯疱疹病毒胸苷激酶介导的局部及远处抗肿瘤旁观者效应。
Cancer Gene Ther. 1997 Jul-Aug;4(4):246-52.

皮下或肝内注射自杀基因修饰的肿瘤细胞可在大鼠结肠癌转移模型中诱导全身性抗肿瘤反应。

Subcutaneous or intrahepatic injection of suicide gene modified tumour cells induces a systemic antitumour response in a metastatic model of colon carcinoma in rats.

作者信息

Pierrefite-Carle V, Baqué P, Gavelli A, Brossette N, Benchimol D, Bourgeon A, Saint Paul M C, Staccini P, Rossi B

机构信息

Unité INSERM 364, IFR 50, Faculté de Médecine, Avenue de Valombrose, 06107 Nice cedex 2, France.

出版信息

Gut. 2002 Mar;50(3):387-91. doi: 10.1136/gut.50.3.387.

DOI:10.1136/gut.50.3.387
PMID:11839720
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1773127/
Abstract

BACKGROUND

Suicide gene therapy consists of the transfer into tumour cells of a "suicide" gene that can convert a non-toxic compound into a lethal drug. Expression of the cytosine deaminase gene leads to the conversion of the non-toxic compound 5-fluorocytosine to 5-fluorouracil. We have recently shown that "suicide cell based vaccination" consisting of intrahepatic injection of cytosine deaminase expressing colon cancer cells followed by 5-fluorocytosine treatment induces regression of a distant wild-type liver tumour in rats.

AIMS

This study was conducted to test if (i) a distant bystander effect on a liver tumour can be induced after subcutaneous suicide cell based vaccination and (ii) suicide cell based vaccination is efficient in limiting tumour dissemination to extrahepatic compartments.

METHODS

An aggressive variant of rat colon carcinoma cells was selected after successive passages in vitro. Rats carrying an experimental liver "metastasis" generated by injection of these cells were vaccinated by subcapsular or subcutaneous injection of cytosine deaminase expressing cells followed by 5-fluorocytosine treatment.

RESULTS

Subcutaneous and subcapsular vaccination induced 70% regression in the median volume of the pre-established liver tumour (p=0.001) and abolished tumour dissemination compared with control animals.

CONCLUSIONS

This study has compared for the first time the efficiency of subcutaneous and intrahepatic suicide cell based vaccination in a metastatic colorectal carcinoma model in rats. The results indicate that both modes of vaccination are equally efficient in inducing a systemic antitumour response, suggesting that this strategy is a powerful approach against the development and dissemination of metastatic colon carcinoma.

摘要

背景

自杀基因疗法是将一种“自杀”基因导入肿瘤细胞，该基因可将无毒化合物转化为致死性药物。胞嘧啶脱氨酶基因的表达可导致无毒化合物5-氟胞嘧啶转化为5-氟尿嘧啶。我们最近发现，“基于自杀细胞的疫苗接种”，即肝内注射表达胞嘧啶脱氨酶的结肠癌细胞，随后进行5-氟胞嘧啶治疗，可诱导大鼠远处野生型肝肿瘤消退。

目的

本研究旨在测试（i）皮下基于自杀细胞的疫苗接种后是否能诱导对肝肿瘤的远处旁观者效应，以及（ii）基于自杀细胞的疫苗接种在限制肿瘤向肝外区域扩散方面是否有效。

方法

在体外连续传代后筛选出大鼠结肠癌细胞的侵袭性变体。通过包膜下或皮下注射表达胞嘧啶脱氨酶的细胞，随后进行5-氟胞嘧啶治疗，对携带由注射这些细胞产生的实验性肝“转移瘤”的大鼠进行疫苗接种。

结果

与对照动物相比，皮下和包膜下疫苗接种使预先建立的肝肿瘤中位体积缩小了70%（p = 0.001），并消除了肿瘤扩散。

结论

本研究首次比较了皮下和肝内基于自杀细胞的疫苗接种在大鼠转移性结直肠癌模型中的效率。结果表明，两种疫苗接种方式在诱导全身抗肿瘤反应方面同样有效，表明该策略是对抗转移性结肠癌发生和扩散的有力方法。