Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
March-2020 Volume 56 Issue 3

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2020 Volume 56 Issue 3

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

A novel loop‑mediated isothermal amplification method for efficient and robust detection of EGFR mutations

  • Authors:
    • Sho Horiuchi
    • Yuichi Saito
    • Atsuka Matsui
    • Nobumasa Takahashi
    • Tomohiko Ikeya
    • Eishin Hoshi
    • Yoshihiko Shimizu
    • Masanori Yasuda
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Saitama Medical University International Medical Center, Hidaka 350‑1298, Japan, Department of Thoracic Surgery, Saitama Cardiovascular and Respiratory Center, Kumagaya, Saitama 360‑0197, Japan, Fundamental Research Laboratory, Fundamental Technology Research Department, Eiken Chemical Co., Ltd., Otawara, Tochigi 324‑0036, Japan, Department of Surgery, Teikyo University School of Medicine, Tokyo 173‑8605, Japan, Department of Pathology, Saitama Cardiovascular and Respiratory Center, Kumagaya, Saitama 360‑0197, Japan
    Copyright: © Horiuchi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 743-749
    |
    Published online on: January 14, 2020
       https://doi.org/10.3892/ijo.2020.4961
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The activation of somatic mutations conferring sensitivity to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors has been widely used in the development of advanced or metastatic primary lung cancer therapy. Therefore, identification of EGFR mutations is essential. In the present study, a loop‑mediated isothermal amplification (LAMP) method was used to identify EGFR mutations, and its efficiency was compared with the Therascreen quantitative PCR assay. Using LAMP and Therascreen to analyze surgically resected tissue samples from patients with pulmonary adenocarcinoma, EGFR mutations were observed in 32/59 tumor samples (LAMP) and 33/59 tumor samples (Therascreen). Notably, the LAMP assay identified one tumor as wild‑type, which had previously been identified as a deletion mutation in exon 19 via the Therascreen assay (Case X). However, the direct sequencing to confirm the EGFR status of the Case X adhered to the results of the LAMP assay. Further experiments using Case X DNA identified this exon 19 deletion mutation using both methods. In addition, a novel deletion mutation in exon 19 of the EGFR was identified. Overall, the present study shows that the LAMP method may serve as a valuable alternative for the identification oncogene mutations.
View Figures

Figure 1

Figure 2

View References

1 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Siegel R, Naishadham D and Jemal A: Cancer statics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Travis WD, Brambilla E, Burke AP, Marx A and Nicholson AG: Introduction to the 2015 world health organization classification of tumors of the lung, pleura, thymus, and heart. J Thorac Oncol. 10:1240–1242. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Lin JJ, Cardarella S, Lydon CA, Dahlberg SE, Jackman DM, Jänne PA and Johnson BE: Five-year survival in EGFR-mutant metastatic lung adenocarcinoma treated with EGFR-TKIs. J Thorac Oncol. 11:556–565. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, et al: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 350:2129–2139. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Kohno T, Tsuta K, Tsuchihara K, Nakaoku T, Yoh K and Goto K: RET fusion gene: Translation to personalized lung cancer therapy. Cancer Sci. 104:1396–1400. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Pao W and Hutchinson KE: Chipping away at the lung cancer genome. Nat Med. 18:349–351. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Li T, Kung HJ, Mack PC and Gandara DR: Genotyping and genomic profiling of non-small-cell lung cancer: Implications for current and future therapies. J Clin Oncol. 31:1039–1049. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, et al: EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science. 304:1497–1500. 2004. View Article : Google Scholar : PubMed/NCBI

10 

De Pas T, Toffalorio F, Manzotti M, Fumagalli C, Spitaleri G, Catania C, Delmonte A, Giovannini M, Spaggiari L, de Braud F and Barberis M: Activity of epidermal growth factor receptor-tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring rare epidermal growth factor receptor mutations. J Thorac Oncol. 6:1895–1901. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, et al: First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: Analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 26:1883–1889. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, et al: Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): Analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 16:141–151. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Garinet S, Laurent-Puig P, Blons H and Oudart JB: Current and future molecular testing in NSCLC, what can we expect from new sequencing technologies? J Clin Med. 7:E1442018. View Article : Google Scholar : PubMed/NCBI

14 

Marino P, Touzani R, Perrier L, Rouleau E, Kossi DS, Zhaomin Z, Charrier N, Goardon N, Preudhomme C, Durand-Zaleski I, et al: Cost of cancer diagnosis using next-generation sequencing targeted gene panels in routine practice: A nationwide French study. Eur J Hum Genet. 26:314–323. 2018. View Article : Google Scholar : PubMed/NCBI

15 

Notomi T, Okayama H, Masubuchi H, Yonekawa T, Watanabe K, Amino N and Hase T: Loop-mediated isothermal amplification of DNA. Nucleic Acids Res. 28:E632000. View Article : Google Scholar : PubMed/NCBI

16 

Yoshino M, Annaka T, Kojima T and Ikedo M: Sensitive and rapid detection of mycoplasma pneumoniae by loop-mediated isothermal amplification. Kansenshogaku Zasshi. 82:168–176. 2008.In Japanese. View Article : Google Scholar : PubMed/NCBI

17 

Poon LL, Leung CS, Tashiro M, Chan KH, Wong BW, Yuen KY, Guan Y and Peiris JS: Rapid detection of the severe acute respiratory syndrome (SARS) coronavirus by a loop-mediated isothermal amplification assay. Clin Chem. 50:1050–1052. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Imai M, Ninomiya A, Minekawa H, Notomi T, Ishizaki T, Van Tu P, Tien NT, Tashiro M and Odagiri T: Rapid diagnosis of H5N1 avian influenza virus infection by newly developed influenza H5 hemagglutinin gene-specific loop-mediated isothermal amplification method. J Virol Methods. 141:173–180. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WE, Nicholson AG, Groome P, Mitchell A, Bolejack V, et al: The IASLC lung cancer staging project: Proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM Classification for lung cancer. J Thorac Oncol. 11:39–51. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Angulo B, García-García E, Martínez R, Suárez-Gauthier A, Conde E, Hidalgo M and López-Ríos F: A commercial real-time PCR kit provides greater sensitivity than direct sequencing to detect KRAS mutations: A morphology-based approach in colorectal carcinoma. J Mol Diagn. 12:292–299. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Vallée A, Le Loupp AG and Denis MG: Efficiency of the Therascreen® RGQ PCR kit for the detection of EGFR mutations in non-small cell lung carcinomas. Clin Chim Acta. 429:8–11. 2014. View Article : Google Scholar

22 

Kimura H, Kasahara K, Kawaishi M, Kunitoh H, Tamura T, Holloway B and Nishio K: Detection of epidermal growth factor receptor mutations in serum as a predictor of the response to gefitinib in patients with non-small-cell lung cancer. Clin Cancer Res. 12:3915–3921. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Hall JG, Eis PS, Law SM, Reynaldo LP, Prudent JR, Marshall DJ, Allawi HT, Mast AL, Dahlberg JE, Kwiatkowski RW, et al: Sensitive detection of DNA polymorphisms by the serial invasive signal amplification reaction. Proc Natl Acad Sci USA. 97:8272–8277. 2002. View Article : Google Scholar

24 

Nagai Y, Miyazawa H, Huqun, Tanaka T, Udagawa K, Kato M, Fukuyama S, Yokote A, Kobayashi K, Kanazawa M and Hagiwara K: Genetic heterogeneity of the epidermal growth factor receptor in non-small cell lung cancer cell lines revealed by a rapid and sensitive detection system, the peptide nucleic acid-locked nucleic acid PCR clamp. Cancer Res. 65:7276–7282. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Yatabe Y, Hida T, Horio Y, Kosaka T, Takahashi T and Mitsudomi T: A rapid, sensitive assay to detect EGFR mutation in small biopsy specimens from lung cancer. J Mol Diagn. 8:335–341. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Tanaka T, Nagai Y, Miyazawa H, Koyama N, Matsuoka S, Sutani A, Huqun, Udagawa K, Murayama Y, Nagata M, et al Reliability of the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp-based test for epidermal growth factor receptor mutations integrated into the clinical practice for non-small cell lung cancers. Cancer Sci. 98:246–252. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Nakamura H, Koizumi H, Sakai H, Kimura H, Miyazawa T, Marushima H, Saji H and Takagi M: Accuracy of the cobas EGFR mutation assay in non-small-cell lung cancer compared with three laboratory-developed tests. Clin Lung Cancer. 19:170–174. 2018. View Article : Google Scholar

28 

Waites KB, Xiao L, Liu Y, Balish MF and Atlinson TP: Mycoplasma pneumoniae from the respiratory tract and beyond. Clin Microbiol Rev. 30:747–809. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Dinh DT, Le MT, Vuong CD, Hasebe F and Morita K: An updated loop-mediated isothermal amplification method for rapid diagnosis of H5N1 avian influenza viruses. Trop Med Health. 39:3–7. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Ikeda S, Takabe K, Inagaki M, Funakoshi N and Suzuki K: Detection of gene point mutation in paraffin sections using in situ loop-mediated isothermal amplification. Pathol Int. 57:594–599. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Fan X, Furnari FB, Cavenee WK and Castresana JS: Non-isotopic silver-stained SSCP is more sensitive than automated direct sequencing for the detection of PTEN mutations in a mixture of DNA extracted from normal and tumor cells. Int J Oncol. 18:1023–1026. 2001.PubMed/NCBI

32 

Endo K, Konishi A, Sasaki H, Takada M, Tanaka H, Okumura M, Kawahara M, Sugiura H, Kuwabara Y, Fukai I, et al: Epidermal growth factor receptor gene mutation in non-small cell lung cancer using highly sensitive and fast TaqMan PCR assay. Lung Cancer. 50:375–384. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Horiuchi S, Saito Y, Matsui A, Takahashi N, Ikeya T, Hoshi E, Shimizu Y and Yasuda M: A novel loop‑mediated isothermal amplification method for efficient and robust detection of EGFR mutations. Int J Oncol 56: 743-749, 2020.
APA
Horiuchi, S., Saito, Y., Matsui, A., Takahashi, N., Ikeya, T., Hoshi, E. ... Yasuda, M. (2020). A novel loop‑mediated isothermal amplification method for efficient and robust detection of EGFR mutations. International Journal of Oncology, 56, 743-749. https://doi.org/10.3892/ijo.2020.4961
MLA
Horiuchi, S., Saito, Y., Matsui, A., Takahashi, N., Ikeya, T., Hoshi, E., Shimizu, Y., Yasuda, M."A novel loop‑mediated isothermal amplification method for efficient and robust detection of EGFR mutations". International Journal of Oncology 56.3 (2020): 743-749.
Chicago
Horiuchi, S., Saito, Y., Matsui, A., Takahashi, N., Ikeya, T., Hoshi, E., Shimizu, Y., Yasuda, M."A novel loop‑mediated isothermal amplification method for efficient and robust detection of EGFR mutations". International Journal of Oncology 56, no. 3 (2020): 743-749. https://doi.org/10.3892/ijo.2020.4961
Copy and paste a formatted citation
x
Spandidos Publications style
Horiuchi S, Saito Y, Matsui A, Takahashi N, Ikeya T, Hoshi E, Shimizu Y and Yasuda M: A novel loop‑mediated isothermal amplification method for efficient and robust detection of EGFR mutations. Int J Oncol 56: 743-749, 2020.
APA
Horiuchi, S., Saito, Y., Matsui, A., Takahashi, N., Ikeya, T., Hoshi, E. ... Yasuda, M. (2020). A novel loop‑mediated isothermal amplification method for efficient and robust detection of EGFR mutations. International Journal of Oncology, 56, 743-749. https://doi.org/10.3892/ijo.2020.4961
MLA
Horiuchi, S., Saito, Y., Matsui, A., Takahashi, N., Ikeya, T., Hoshi, E., Shimizu, Y., Yasuda, M."A novel loop‑mediated isothermal amplification method for efficient and robust detection of EGFR mutations". International Journal of Oncology 56.3 (2020): 743-749.
Chicago
Horiuchi, S., Saito, Y., Matsui, A., Takahashi, N., Ikeya, T., Hoshi, E., Shimizu, Y., Yasuda, M."A novel loop‑mediated isothermal amplification method for efficient and robust detection of EGFR mutations". International Journal of Oncology 56, no. 3 (2020): 743-749. https://doi.org/10.3892/ijo.2020.4961
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team