• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

Survivin 反应型、条件复制型腺病毒在成人 T 细胞白血病/淋巴瘤中诱导强烈的细胞毒性作用。

A survivin-responsive, conditionally replicating adenovirus induces potent cytocidal effects in adult T-cell leukemia/lymphoma.

机构信息

Department of Clinical Oncology, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.

Department of Hematology and Rheumatology, Kagoshima University Hospital, Kagoshima, Japan.

出版信息

BMC Cancer. 2019 May 29;19(1):516. doi: 10.1186/s12885-019-5730-1.

DOI:10.1186/s12885-019-5730-1
PMID:31142289
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6542078/
Abstract

BACKGROUND

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by long-term human T-cell leukemia virus type I (HTLV-1) infection. Survivin-responsive, conditionally replicating adenoviruses regulated by multiple tumor-specific factors (Surv.m-CRAs), in which the expression of the adenoviral early region 1A gene is regulated by the survivin (BIRC5) promoter, can be used to treat several cancers. As survivin is overexpressed in ATL, we examined the effects of Surv.m-CRAs on ATL-selective replication and survival.

METHODS

We tested two ATL cell lines and four HTLV-1-infected T-cell lines. The cells were subjected to infection with either E1-deleted, replication-defective adenoviruses or Surv.m-CRAs at various multiplicities of infection.

RESULTS

Strong activation of survivin promoter was observed in all six cell lines. Moreover, the expression of the coxsackie and adenovirus receptor (CAR), which is important for adenoviral infection, was high in the cell lines. In contrast, we observed the absence of survivin promoter activity and a low expression of CAR in activated peripheral blood lymphocytes (PBLs) from healthy subjects. Surv.m-CRAs actively replicated and induced cytocidal effects in five out of six cell lines; conversely, we observed minimal viral replication and no marked cytotoxicity in normal activated PBLs.

CONCLUSIONS

This is the first report demonstrating that Surv.m-CRAs constitute attractive potential anti-ATL agents.

摘要

背景

成人 T 细胞白血病/淋巴瘤（ATL）是一种由长期人类 T 细胞白血病病毒 I 型（HTLV-1）感染引起的外周 T 细胞恶性肿瘤。受生存素调控、多肿瘤特异性因子调控的条件复制腺病毒（Surv.m-CRAs），其中腺病毒早期区域 1A 基因的表达受生存素（BIRC5）启动子调控，可用于治疗多种癌症。由于生存素在 ATL 中过度表达，我们研究了 Surv.m-CRAs 对 ATL 选择性复制和存活的影响。

方法

我们检测了两种 ATL 细胞系和四种 HTLV-1 感染的 T 细胞系。细胞以不同的感染复数接受 E1 缺失、复制缺陷型腺病毒或 surv.m-CRAs 的感染。

结果

在所有六种细胞系中均观察到生存素启动子的强烈激活。此外，细胞系中细胞表面 Coxsackie 和腺病毒受体（CAR）的表达水平较高，CAR 对腺病毒感染很重要。相反，我们观察到健康供体的激活外周血淋巴细胞（PBLs）中生存素启动子活性缺失和 CAR 表达水平低。Surv.m-CRAs 在五种细胞系中的六种细胞系中均可积极复制并诱导细胞毒性作用；相反，我们观察到在正常激活的 PBLs 中病毒复制很少且无明显细胞毒性。

结论

这是第一个报道表明 Surv.m-CRAs 构成有吸引力的潜在抗 ATL 药物的报告。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8623/6542078/72dff7f88c7a/12885_2019_5730_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8623/6542078/a28697517ca3/12885_2019_5730_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8623/6542078/3af1bd57ef33/12885_2019_5730_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8623/6542078/e6f53b7c0577/12885_2019_5730_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8623/6542078/f0eb1612e207/12885_2019_5730_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8623/6542078/72dff7f88c7a/12885_2019_5730_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8623/6542078/a28697517ca3/12885_2019_5730_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8623/6542078/3af1bd57ef33/12885_2019_5730_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8623/6542078/e6f53b7c0577/12885_2019_5730_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8623/6542078/f0eb1612e207/12885_2019_5730_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8623/6542078/72dff7f88c7a/12885_2019_5730_Fig5_HTML.jpg

相似文献

1
A survivin-responsive, conditionally replicating adenovirus induces potent cytocidal effects in adult T-cell leukemia/lymphoma.Survivin 反应型、条件复制型腺病毒在成人 T 细胞白血病/淋巴瘤中诱导强烈的细胞毒性作用。
BMC Cancer. 2019 May 29;19(1):516. doi: 10.1186/s12885-019-5730-1.
2
Survivin-responsive conditionally replicating adenovirus exhibits cancer-specific and efficient viral replication.生存素反应性条件复制腺病毒表现出癌症特异性且高效的病毒复制。
Cancer Res. 2005 Jun 15;65(12):5284-91. doi: 10.1158/0008-5472.CAN-04-2657.
3
Survivin-responsive conditionally replicating adenovirus kills rhabdomyosarcoma stem cells more efficiently than their progeny.Survivin 反应性条件复制腺病毒比其后代更有效地杀死横纹肌肉瘤干细胞。
J Transl Med. 2014 Jan 27;12:27. doi: 10.1186/1479-5876-12-27.
4
Adenovirus Biology, Recombinant Adenovirus, and Adenovirus Usage in Gene Therapy.腺病毒生物学、重组腺病毒和腺病毒在基因治疗中的应用。
Viruses. 2021 Dec 14;13(12):2502. doi: 10.3390/v13122502.
5
Assessment of an altered E1B promoter on the specificity and potency of triple-regulated conditionally replicating adenoviruses: implications for the generation of ideal m-CRAs.评估 E1B 启动子改变对三重调节条件复制腺病毒特异性和效力的影响：对理想 m-CRA 产生的意义。
Cancer Gene Ther. 2011 Oct;18(10):724-33. doi: 10.1038/cgt.2011.44. Epub 2011 Aug 12.
6
A survivin-mediated oncolytic adenovirus induces non-apoptotic cell death in lung cancer cells and shows antitumoral potential in vivo.一种survivin介导的溶瘤腺病毒可诱导肺癌细胞发生非凋亡性细胞死亡，并在体内显示出抗肿瘤潜力。
J Gene Med. 2006 Oct;8(10):1232-42. doi: 10.1002/jgm.953.
7
Development of replication-competent adenovirus for bladder cancer by controlling adenovirus E1a and E4 gene expression with the survivin promoter.通过使用生存素启动子控制腺病毒E1a和E4基因表达来开发用于膀胱癌的具有复制能力的腺病毒。
Oncotarget. 2014 Jul 30;5(14):5615-23. doi: 10.18632/oncotarget.2151.
8
Conditionally replicating adenovirus prevents pluripotent stem cell-derived teratoma by specifically eliminating undifferentiated cells.条件复制型腺病毒通过特异性消除未分化细胞来预防多能干细胞源性畸胎瘤。
Mol Ther Methods Clin Dev. 2015 Aug 12;2:15026. doi: 10.1038/mtm.2015.26. eCollection 2015.
9
Incorporating the survivin promoter in an infectivity enhanced CRAd-analysis of oncolysis and anti-tumor effects in vitro and in vivo.将生存素启动子整合到一种感染性增强的条件复制腺病毒中，用于体外和体内的溶瘤及抗肿瘤作用分析。
Int J Oncol. 2005 Jul;27(1):237-46.
10
Etoposide enhances antitumor efficacy of MDR1-driven oncolytic adenovirus through autoupregulation of the MDR1 promoter activity.依托泊苷通过自上调多药耐药蛋白1（MDR1）启动子活性增强MDR1驱动的溶瘤腺病毒的抗肿瘤疗效。
Oncotarget. 2015 Nov 10;6(35):38308-26. doi: 10.18632/oncotarget.5702.

引用本文的文献

1
Tat-dependent conditionally replicating adenoviruses expressing diphtheria toxin A for specifically killing HIV-1-infected cells.依赖 Tat 的条件复制型腺病毒表达白喉毒素 A 特异性杀伤 HIV-1 感染细胞。
Mol Ther. 2024 Jul 3;32(7):2316-2327. doi: 10.1016/j.ymthe.2024.05.015. Epub 2024 May 11.
2
Correlation analysis of survivin, ING4, CXCL8 and VEGF expression in prostate cancer tissue.前列腺癌组织中生存素、ING4、CXCL8和血管内皮生长因子表达的相关性分析
Am J Transl Res. 2021 Dec 15;13(12):13784-13790. eCollection 2021.
3
Adenovirus Biology, Recombinant Adenovirus, and Adenovirus Usage in Gene Therapy.

本文引用的文献

1
Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial.纳武利尤单抗对比研究者选择的标准单药疗法用于复发性或转移性头颈部鳞状细胞癌（CheckMate 141）：一项随机3期试验的健康相关生活质量结果
Lancet Oncol. 2017 Aug;18(8):1104-1115. doi: 10.1016/S1470-2045(17)30421-7. Epub 2017 Jun 23.
2
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer.帕博利珠单抗对比化疗用于 PD-L1 阳性非小细胞肺癌。
N Engl J Med. 2016 Nov 10;375(19):1823-1833. doi: 10.1056/NEJMoa1606774. Epub 2016 Oct 8.
3
腺病毒生物学、重组腺病毒和腺病毒在基因治疗中的应用。
Viruses. 2021 Dec 14;13(12):2502. doi: 10.3390/v13122502.
4
Hitting the Target but Missing the Point: Recent Progress towards Adenovirus-Based Precision Virotherapies.击中目标却未抓住重点：基于腺病毒的精准病毒疗法的最新进展
Cancers (Basel). 2020 Nov 11;12(11):3327. doi: 10.3390/cancers12113327.
5
Emerging Importance of Survivin in Stem Cells and Cancer: the Development of New Cancer Therapeutics.**新兴的** **Survivin** **在干细胞和癌症中的重要性：新癌症治疗方法的发展**。
Stem Cell Rev Rep. 2020 Oct;16(5):828-852. doi: 10.1007/s12015-020-09995-4.
6
Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity.溶瘤腺病毒：提高靶向性和特异性的策略
Cancers (Basel). 2020 Jun 9;12(6):1504. doi: 10.3390/cancers12061504.
Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002.
来那度胺治疗复发或难治性成人 T 细胞白血病/淋巴瘤的多中心 II 期研究：ATLL-002。
J Clin Oncol. 2016 Dec;34(34):4086-4093. doi: 10.1200/JCO.2016.67.7732. Epub 2016 Sep 30.
4
Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers.多种癌症中通过 3'-UTR 破坏导致的异常 PD-L1 表达。
Nature. 2016 Jun 16;534(7607):402-6. doi: 10.1038/nature18294. Epub 2016 May 23.
5
Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.纳武单抗与依维莫司治疗晚期肾细胞癌的比较
N Engl J Med. 2015 Nov 5;373(19):1803-13. doi: 10.1056/NEJMoa1510665. Epub 2015 Sep 25.
6
Conditionally replicating adenovirus prevents pluripotent stem cell-derived teratoma by specifically eliminating undifferentiated cells.条件复制型腺病毒通过特异性消除未分化细胞来预防多能干细胞源性畸胎瘤。
Mol Ther Methods Clin Dev. 2015 Aug 12;2:15026. doi: 10.1038/mtm.2015.26. eCollection 2015.
7
Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma.替莫唑胺胶丸联合放疗治疗恶性脑胶质瘤的疗效观察
J Clin Oncol. 2015 Sep 1;33(25):2780-8. doi: 10.1200/JCO.2014.58.3377. Epub 2015 May 26.
8
Molecular and genetic properties of tumors associated with local immune cytolytic activity.与局部免疫细胞溶解活性相关的肿瘤的分子和遗传特性。
Cell. 2015 Jan 15;160(1-2):48-61. doi: 10.1016/j.cell.2014.12.033.
9
Nivolumab in previously untreated melanoma without BRAF mutation.纳武利尤单抗治疗未经 BRAF 突变检测的初治黑色素瘤。
N Engl J Med. 2015 Jan 22;372(4):320-30. doi: 10.1056/NEJMoa1412082. Epub 2014 Nov 16.
10
Human T-cell leukaemia virus type I and adult T-cell leukaemia-lymphoma.人类 T 细胞白血病病毒 I 型与成人 T 细胞白血病/淋巴瘤。
Lancet Oncol. 2014 Oct;15(11):e517-26. doi: 10.1016/S1470-2045(14)70202-5.