• 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

头颈部鳞状细胞癌对西妥昔单抗治疗的反应取决于极光激酶A多态性。

The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism.

作者信息

Pickhard Anja, Siegl Michael, Baumann Alexander, Huhn Maximilian, Wirth Markus, Reiter Rudolf, Rudelius Martina, Piontek Guido, Brockhoff Gero

机构信息

Department of Otolaryngology Head and Neck Surgery, Technical University of Munich, Muenchen, Germany. Equal contribution.

Department of Otolaryngology Head and Neck Surgery, Technical University of Munich, Muenchen, Germany.

出版信息

Oncotarget. 2014 Jul 30;5(14):5428-38. doi: 10.18632/oncotarget.2117.

DOI:10.18632/oncotarget.2117
PMID:24980817
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4170642/
Abstract

OBJECTIVES

The aim of this study was to evaluate the efficiency of cetuximab-based anti-EGFR treatment and Aurora kinase A / B knockdown as a function of Aurora kinase polymorphism in HNSCC cell lines.

MATERIALS AND METHODS

First, protein expression of Aurora kinase A / B and EGFR and Aurora kinase A polymorphism were studied in tumour samples. The survival and proliferation of Aurora kinase A homo- (Cal27) and heterozygous (HN) HNSCC cell lines was evaluated using a colony formation assay and a flow cytometric assay. Also, aneuploidy was determined. EGFR signalling pathway were visualised by western blotting.

RESULTS

Immunohistochemistry revealed the overexpression of Aurora kinase A / B in HNSCC. The knockdown of each kinase caused a significant decrease in clonogenic survival, independent of Aurora kinase A polymorphism. In contrast, cetuximab treatment impaired clonogenic survival only in the Aurora kinase A-homozygous cell line (Cal27).

CONCLUSION

This study provides in vitro evidence for the predictive value of Aurora kinase A polymorphism in the efficiency of cetuximab treatment. Resistance to cetuximab treatment can be overcome by simultaneous Aurora kinase A/B knockdown.

摘要

目的

本研究旨在评估基于西妥昔单抗的抗表皮生长因子受体（EGFR）治疗以及极光激酶A/B基因敲低对头颈部鳞状细胞癌（HNSCC）细胞系中极光激酶多态性的影响。

材料与方法

首先，研究肿瘤样本中极光激酶A/B、EGFR的蛋白表达以及极光激酶A多态性。使用集落形成试验和流式细胞术评估极光激酶A纯合（Cal27）和杂合（HN）HNSCC细胞系的存活和增殖情况。此外，还测定了非整倍体情况。通过蛋白质印迹法观察EGFR信号通路。

结果

免疫组织化学显示HNSCC中极光激酶A/B过表达。每种激酶的基因敲低均导致克隆形成存活率显著降低，且与极光激酶A多态性无关。相比之下，西妥昔单抗治疗仅在极光激酶A纯合细胞系（Cal27）中损害克隆形成存活率。

结论

本研究为极光激酶A多态性对西妥昔单抗治疗效果的预测价值提供了体外证据。同时敲低极光激酶A/B可克服对西妥昔单抗治疗的耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afb/4170642/6d551affb0e5/oncotarget-05-5428-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afb/4170642/d486a210a444/oncotarget-05-5428-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afb/4170642/4cd44317fab2/oncotarget-05-5428-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afb/4170642/b702c7300b24/oncotarget-05-5428-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afb/4170642/269cf21cfbf7/oncotarget-05-5428-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afb/4170642/f65f3f848867/oncotarget-05-5428-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afb/4170642/6d551affb0e5/oncotarget-05-5428-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afb/4170642/d486a210a444/oncotarget-05-5428-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afb/4170642/4cd44317fab2/oncotarget-05-5428-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afb/4170642/b702c7300b24/oncotarget-05-5428-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afb/4170642/269cf21cfbf7/oncotarget-05-5428-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afb/4170642/f65f3f848867/oncotarget-05-5428-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afb/4170642/6d551affb0e5/oncotarget-05-5428-g006.jpg

相似文献

1
The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism.头颈部鳞状细胞癌对西妥昔单抗治疗的反应取决于极光激酶A多态性。
Oncotarget. 2014 Jul 30;5(14):5428-38. doi: 10.18632/oncotarget.2117.
2
Overcoming cetuximab resistance in HNSCC: the role of AURKB and DUSP proteins.克服头颈部鳞状细胞癌中西妥昔单抗的耐药性：AURKB 和 DUSP 蛋白的作用。
Cancer Lett. 2014 Nov 28;354(2):365-77. doi: 10.1016/j.canlet.2014.08.039. Epub 2014 Sep 2.
3
Aurora kinase inhibition overcomes cetuximab resistance in squamous cell cancer of the head and neck.极光激酶抑制可克服头颈部鳞状细胞癌对西妥昔单抗的耐药性。
Oncotarget. 2011 Aug;2(8):599-609. doi: 10.18632/oncotarget.311.
4
Dacomitinib, an irreversible Pan-ErbB inhibitor significantly abrogates growth in head and neck cancer models that exhibit low response to cetuximab.达可替尼，一种不可逆的泛 ErbB 抑制剂，可显著抑制对西妥昔单抗反应较低的头颈部癌症模型的生长。
PLoS One. 2013;8(2):e56112. doi: 10.1371/journal.pone.0056112. Epub 2013 Feb 6.
5
AXL mediates resistance to cetuximab therapy.AXL介导对西妥昔单抗治疗的耐药性。
Cancer Res. 2014 Sep 15;74(18):5152-64. doi: 10.1158/0008-5472.CAN-14-0294. Epub 2014 Aug 18.
6
Signaling via ErbB2 and ErbB3 associates with resistance and epidermal growth factor receptor (EGFR) amplification with sensitivity to EGFR inhibitor gefitinib in head and neck squamous cell carcinoma cells.通过ErbB2和ErbB3的信号传导与头颈部鳞状细胞癌细胞中的耐药性以及表皮生长因子受体（EGFR）扩增相关，且对EGFR抑制剂吉非替尼敏感。
Clin Cancer Res. 2006 Jul 1;12(13):4103-11. doi: 10.1158/1078-0432.CCR-05-2404.
7
Cetuximab Resistance in Head and Neck Cancer Is Mediated by EGFR-K Polymorphism.头颈部癌症中的西妥昔单抗耐药性由 EGFR-K 多态性介导。
Cancer Res. 2017 Mar 1;77(5):1188-1199. doi: 10.1158/0008-5472.CAN-16-0754. Epub 2016 Dec 28.
8
Combination of anti-HER3 antibody MM-121/SAR256212 and cetuximab inhibits tumor growth in preclinical models of head and neck squamous cell carcinoma.抗HER3抗体MM-121/SAR256212与西妥昔单抗联合使用可抑制头颈部鳞状细胞癌临床前模型中的肿瘤生长。
Mol Cancer Ther. 2014 Jul;13(7):1826-36. doi: 10.1158/1535-7163.MCT-13-1093. Epub 2014 Apr 18.
9
The dual PI3K/mTOR inhibitor PKI-587 enhances sensitivity to cetuximab in EGFR-resistant human head and neck cancer models.双重 PI3K/mTOR 抑制剂 PKI-587 增强了 EGFR 耐药性人类头颈部癌细胞模型对西妥昔单抗的敏感性。
Br J Cancer. 2014 Jun 10;110(12):2887-95. doi: 10.1038/bjc.2014.241. Epub 2014 May 13.
10
Antitumor mechanisms of targeting the PDK1 pathway in head and neck cancer.针对头颈部癌症中 PDK1 通路的抗肿瘤机制。
Mol Cancer Ther. 2012 Jun;11(6):1236-46. doi: 10.1158/1535-7163.MCT-11-0936. Epub 2012 Apr 5.

引用本文的文献

1
Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines.抗表皮生长因子受体（EGFR）单克隆抗体西妥昔单抗在猫口腔鳞状细胞癌细胞系中显示出潜在的抗癌活性。
Front Vet Sci. 2022 Nov 17;9:1040552. doi: 10.3389/fvets.2022.1040552. eCollection 2022.
2
Major Molecular Signaling Pathways in Oral Cancer Associated With Therapeutic Resistance.与治疗耐药相关的口腔癌主要分子信号通路
Front Oral Health. 2021 Jan 25;1:603160. doi: 10.3389/froh.2020.603160. eCollection 2020.
3
Precision Medicine Approaches to Overcome Resistance to Therapy in Head and Neck Cancers.

本文引用的文献

1
Aurora kinase inhibitors: Potential molecular-targeted drugs for gynecologic malignant tumors.极光激酶抑制剂：用于妇科恶性肿瘤的潜在分子靶向药物。
Biomed Rep. 2013 May;1(3):335-340. doi: 10.3892/br.2013.91. Epub 2013 Mar 27.
2
Aurora kinases in head and neck cancer.头颈部癌中的极光激酶。
Lancet Oncol. 2013 Sep;14(10):e425-35. doi: 10.1016/S1470-2045(13)70128-1.
3
Identification of aurora kinase B and Wee1-like protein kinase as downstream targets of (V600E)B-RAF in melanoma.鉴定出极光激酶 B 和 Wee1 样蛋白激酶是黑色素瘤中（V600E）B-RAF 的下游靶标。
克服头颈癌治疗耐药性的精准医学方法
Front Oncol. 2021 Feb 25;11:614332. doi: 10.3389/fonc.2021.614332. eCollection 2021.
4
AURKA rs2273535 T>A Polymorphism Associated With Cancer Risk: A Systematic Review With Meta-Analysis.AURKA基因rs2273535位点T>A多态性与癌症风险的关联：一项荟萃分析的系统评价
Front Oncol. 2020 Jun 30;10:1040. doi: 10.3389/fonc.2020.01040. eCollection 2020.
5
A Novel AURKA Mutant-Induced Early-Onset Severe Hepatocarcinogenesis Greater than Wild-Type via Activating Different Pathways in Zebrafish.一种新型AURKA突变体通过激活斑马鱼中的不同途径诱导早发性严重肝癌发生，且比野生型更严重。
Cancers (Basel). 2019 Jul 2;11(7):927. doi: 10.3390/cancers11070927.
6
Synergistic inhibitory effects of cetuximab and curcumin on human cisplatin-resistant oral cancer CAR cells through intrinsic apoptotic process.西妥昔单抗和姜黄素通过内源性凋亡过程对人顺铂耐药口腔癌CAR细胞的协同抑制作用。
Oncol Lett. 2018 Nov;16(5):6323-6330. doi: 10.3892/ol.2018.9418. Epub 2018 Sep 7.
7
A Prognostic 5-lncRNA Expression Signature for Head and Neck Squamous Cell Carcinoma.用于头颈部鳞状细胞癌的预后 5-长链非编码 RNA 表达特征。
Sci Rep. 2018 Oct 15;8(1):15250. doi: 10.1038/s41598-018-33642-1.
8
Molecular Markers of Anticancer Drug Resistance in Head and Neck Squamous Cell Carcinoma: A Literature Review.头颈部鳞状细胞癌中抗癌药物耐药性的分子标志物：文献综述
Cancers (Basel). 2018 Oct 10;10(10):376. doi: 10.3390/cancers10100376.
9
The Aurora-Kinase A Phe31-Ile polymorphism as possible predictor of response to treatment in head and neck squamous cell carcinoma.极光激酶A Phe31-Ile多态性作为头颈部鳞状细胞癌治疗反应的可能预测指标。
Oncotarget. 2018 Jan 30;9(16):12769-12780. doi: 10.18632/oncotarget.24355. eCollection 2018 Feb 27.
10
Epidermal growth factor receptor variant III in head and neck squamous cell carcinoma is not relevant for targeted therapy and irradiation.头颈部鳞状细胞癌中的表皮生长因子受体III型变异体与靶向治疗和放疗无关。
Oncotarget. 2017 May 16;8(20):32668-32682. doi: 10.18632/oncotarget.15949.
Am J Pathol. 2013 Apr;182(4):1151-62. doi: 10.1016/j.ajpath.2012.12.019. Epub 2013 Feb 12.
4
Association of Aurora-A (STK15) kinase polymorphisms with clinical outcome of esophageal cancer treated with preoperative chemoradiation.Aurora-A（STK15）激酶多态性与术前放化疗治疗食管癌的临床结局的相关性。
Cancer. 2012 Sep 1;118(17):4346-53. doi: 10.1002/cncr.26581. Epub 2011 Dec 27.
5
Aurora kinase inhibition overcomes cetuximab resistance in squamous cell cancer of the head and neck.极光激酶抑制可克服头颈部鳞状细胞癌对西妥昔单抗的耐药性。
Oncotarget. 2011 Aug;2(8):599-609. doi: 10.18632/oncotarget.311.
6
Inhibition of mitotic kinase Aurora suppresses Akt-1 activation and induces apoptotic cell death in all-trans retinoid acid-resistant acute promyelocytic leukemia cells.抑制有丝分裂激酶 Aurora 可抑制 Akt-1 的激活，并诱导全反式视黄酸耐药急性早幼粒细胞白血病细胞发生凋亡性细胞死亡。
J Transl Med. 2011 May 21;9:74. doi: 10.1186/1479-5876-9-74.
7
Aurora B expression as a prognostic indicator and possible therapeutic target in oral squamous cell carcinoma.Aurora B 表达作为口腔鳞状细胞癌的预后指标和可能的治疗靶点。
Int J Immunopathol Pharmacol. 2011 Jan-Mar;24(1):79-88. doi: 10.1177/039463201102400110.
8
Evaluation of Aurora-A gene polymorphism and esophageal cancer risk in a South Indian population.南印度人群中极光激酶A基因多态性与食管癌风险的评估。
Genet Test Mol Biomarkers. 2011 Mar;15(3):185-9. doi: 10.1089/gtmb.2010.0143. Epub 2011 Jan 3.
9
Aurora-A overexpression and aneuploidy predict poor outcome in serous ovarian carcinoma.Aurora-A 过表达和非整倍体预示浆液性卵巢癌不良预后。
Gynecol Oncol. 2011 Jan;120(1):11-7. doi: 10.1016/j.ygyno.2010.09.003.
10
Cetuximab: a review of its use in squamous cell carcinoma of the head and neck.西妥昔单抗：在头颈部鳞状细胞癌中的应用综述。
Drugs. 2010 Oct 22;70(15):1987-2010. doi: 10.2165/11205010-000000000-00000.