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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
May-2014 Volume 9 Issue 5

Full Size Image

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
May-2014 Volume 9 Issue 5

Full Size Image

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
Article

Telbivudine decreases proportion of peripheral blood CD4+CD25+CD127low T cells in parallel with inhibiting hepatitis B virus DNA

  • Authors:
    • Zehui Yan
    • Jijun Zhou
    • Mengjun Zhang
    • Xiaolan Fu
    • Yuzhang Wu
    • Yuming Wang
  • View Affiliations / Copyright

    Affiliations: Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China, Institute of Immunology, Third Military Medical University, Chongqing 400038, P.R. China
  • Pages: 2024-2030
    |
    Published online on: March 12, 2014
       https://doi.org/10.3892/mmr.2014.2042
  • 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

Regulatory T cells (Treg) have significant roles in the immunopathology of patients with chronic hepatitis B (CHB) and exhibit an evident correlation with antiviral immunity when antiviral therapy is applied. In order to investigate how circulating Tregs are affected by telbivudine treatment and its significance in patients with CHB, peripheral blood mononuclear cells (PBMCs) were isolated and the proportions of circulating cluster of differentiation (CD)4+CD25+CD127low and CD8+CD25+ T cells of CHB patients prior to and during the three or six months of treatment were assessed and detected by flow cytometric analysis. The levels of forkhead/winged helix transcription factor (Foxp3) mRNA were also quantified using quantitative polymerase chain reaction. A significantly higher percentage of CD4+CD25+CD127low and CD8+CD25+ T cells in the PBMCs of patients with CHB were identified compared with that of healthy individuals. Patients with CHB also demonstrated significantly higher levels of Foxp3 mRNA compared with that of healthy individuals. Following six months of telbivudine treatment, the proportion of circulating CD4+CD25+CD127low and CD8+CD25+ T cells and the relative levels of Foxp3 mRNA in patients with CHB was comparable to the proportion in healthy individuals. The proportions of circulating peripheral blood CD4+CD25+CD127low T cells were paralleled with its HBV DNA inhibition. The results of the present study indicate that telbivudine treatment reduces HBV DNA levels rapidly and indirectly affects the immune system by downregulating the proportion of circulating Treg markedly, which may be beneficial to restore the antiviral immune response.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Lai CL, Ratziu V, Yuen MF and Poynard T: Viral hepatitis B. Lancet. 362:2089–2094. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Guidotti LG and Chisari FV: Immunobiology and pathogenesis of viral hepatitis. Annu Rev Pathol. 1:23–61. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Rehermann B, Fowler P, Sidney J, et al: The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis. J Exp Med. 181:1047–1058. 1995. View Article : Google Scholar : PubMed/NCBI

4 

Bertoletti A and Naoumov NV: Translation of immunological knowledge into better treatments of chronic hepatitis B. J Hepatol. 39:115–124. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Bertoletti A, D’Elios MM, Boni C, et al: Different cytokine profiles of intraphepatic T cells in chronic hepatitis B and hepatitis C virus infections. Gastroenterology. 112:193–199. 1997. View Article : Google Scholar : PubMed/NCBI

6 

Zhang Z, Zhang JY, Wang LF and Wang FS: Immunopathogenesis and prognostic immune markers of chronic hepatitis B virus infection. J Gastroenterol Hepatol. 27:223–230. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Sakaguchi S, Yamaguchi T, Nomura T and Ono M: Regulatory T cells and immune tolerance. Cell. 133:775–787. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Miyara M and Sakaguchi S: Natural regulatory T cells: mechanisms of suppression. Trends Mol Med. 13:108–116. 2007. View Article : Google Scholar

9 

Xu D, Fu J, Jin L, et al: Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B. J Immunol. 177:739–747. 2006.

10 

Stoop JN, van der Molen RG, Baan CC, et al: Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. Hepatology. 41:771–778. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Franzese O, Kennedy PT, Gehring AJ, et al: Modulation of the CD8+-T-cell response by CD4+ CD25+ regulatory T cells in patients with hepatitis B virus infection. J Virol. 79:3322–3328. 2005.

12 

Feng IC, Koay LB, Sheu MJ, et al: HBcAg-specific CD4+CD25+ regulatory T cells modulate immune tolerance and acute exacerbation on the natural history of chronic hepatitis B virus infection. J Biomed Sci. 14:43–57. 2007.

13 

Taams LS, Vukmanovic-Stejic M, Smith J, et al: Antigen-specific T cell suppression by human CD4+CD25+ regulatory T cells. Eur J Immunol. 32:1621–1630. 2002.

14 

Liaw YF and Chu CM: Hepatitis B virus infection. Lancet. 373:582–592. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Dienstag JL: Hepatitis B virus infection. N Engl J Med. 359:1486–1500. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Sprengers D, Stoop JN, Binda RS, et al: Induction of regulatory T-cells and interleukin-10-producing cells in non-responders to pegylated interferon-alpha therapy for chronic hepatitis B. Antivir Ther. 12:1087–1096. 2007.PubMed/NCBI

17 

Rico MA, Quiroga JA, Subirá D, et al: Hepatitis B virus-specific T-cell proliferation and cytokine secretion in chronic hepatitis B e antibody-positive patients treated with ribavirin and interferon alpha. Hepatology. 33:295–300. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Maini MK, Reignat S, Boni C, et al: T cell receptor usage of virus-specific CD8 cells and recognition of viral mutations during acute and persistent hepatitis B virus infection. Eur J Immunol. 30:3067–3078. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Boni C, Penna A, Bertoletti A, et al: Transient restoration of anti-viral T cell responses induced by lamivudine therapy in chronic hepatitis B. J Hepatol. 39:595–605. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Tsai SL, Sheen IS, Chien RN, et al: Activation of Th1 immunity is a common immune mechanism for the successful treatment of hepatitis B and C: tetramer assay and therapeutic implications. J Biomed Sci. 10:120–135. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Stoop JN, van der Molen RG, Kuipers EJ, Kusters JG and Janssen HL: Inhibition of viral replication reduces regulatory T cells and enhances the antiviral immune response in chronic hepatitis B. Virology. 361:141–148. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Chen Y, Li X, Ye B, et al: Effect of telbivudine therapy on the cellular immune response in chronic hepatitis B. Antiviral Res. 91:23–31. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Koay LB, Feng IC, Sheu MJ, et al: Hepatitis B virus (HBV) core antigen-specific regulatory T cells confer sustained remission to anti-HBV therapy in chronic hepatitis B with acute exacerbation. Hum Immunol. 72:687–698. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Nash K: Telbivudine in the treatment of chronic hepatitis B. Adv Ther. 26:155–169. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Lai CL, Gane E, Liaw YF, et al: Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med. 357:2576–2588. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Lai CL, Leung N, Teo EK, et al: A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B. Gastroenterology. 129:528–536. 2005.PubMed/NCBI

27 

Lai CL, Gane E, Hsu CW, et al: Two-year results from the GLOBE trial in patients with hepatitis B: greater clinical and antiviral efficacy for telbivudine (LdT) vs. lamivudine Hepatology. 44(Suppl 1): 222A2006.

28 

Liaw YF, Gane E, Leung N, et al: 2-Year GLOBE trial results: telbivudine Is superior to lamivudine in patients with chronic hepatitis B. Gastroenterology. 136:486–495. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Chinese Society of Hepatology, Chinese Medical Association; Chinese Society for Infectious Diseases, Chinese Medical Association. Guideline on prevention and treatment of chronic hepatitis B in China (2005). Chin Med J (Engl). 120:2159–2173. 2007.PubMed/NCBI

30 

Shaik GM, Dráberová L and Dráber P, Boubelík M and Dráber P: Tetraalkylammonium derivatives as real-time PCR enhancers and stabilizers of the qPCR mixtures containing SYBR Green I. Nucleic Acids Res. 36:e932008. View Article : Google Scholar : PubMed/NCBI

31 

Lan RY, Cheng C, Lian ZX, et al: Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis. Hepatology. 43:729–737. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Li S, Gowans EJ, Chougnet C, Plebanski M and Dittmer U: Natural regulatory T cells and persistent viral infection. J Virol. 82:21–30. 2008. View Article : Google Scholar

33 

Fontenot JD and Rudensky AY: A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol. 6:331–337. 2005. View Article : Google Scholar : PubMed/NCBI

34 

Fontenot JD, Gavin MA and Rudensky AY: Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 4:330–336. 2003.

35 

Hori S, Nomura T and Sakaguchi S: Control of regulatory T cell development by the transcription factor Foxp3. Science. 299:1057–1061. 2003. View Article : Google Scholar : PubMed/NCBI

36 

Yang G, Liu A, Xie Q, et al: Association of CD4+CD25+Foxp3+ regulatory T cells with chronic activity and viral clearance in patients with hepatitis B. Int Immunol. 19:133–140. 2007.

37 

Belkaid Y: Regulatory T cells and infection: a dangerous necessity. Nat Rev Immunol. 7:875–888. 2007. View Article : Google Scholar : PubMed/NCBI

38 

Belkaid Y and Rouse BT: Natural regulatory T cells in infectious disease. Nat Immunol. 6:353–360. 2005. View Article : Google Scholar : PubMed/NCBI

39 

Alatrakchi N and Koziel M: Regulatory T cells and viral liver disease. J Viral Hepat. 16:223–229. 2009. View Article : Google Scholar : PubMed/NCBI

40 

Rushbrook SM, Hoare M and Alexander GJ: T-regulatory lymphocytes and chronic viral hepatitis. Expert Opin Biol Ther. 7:1689–1703. 2007. View Article : Google Scholar : PubMed/NCBI

41 

Billerbeck E, Bottler T and Thimme R: Regulatory T cells in viral hepatitis. World J Gastroenterol. 13:4858–4864. 2007.PubMed/NCBI

42 

Aandahl EM, Michaëlsson J, Moretto WJ, Hecht FM and Nixon DF: Human CD4+ CD25+ regulatory T cells control T-cell responses to human immunodeficiency virus and cytomegalovirus antigens. J Virol. 78:2454–2459. 2004.

43 

Cabrera R, Tu Z, Xu Y, et al: An immunomodulatory role for CD4(+)CD25(+) regulatory T lymphocytes in hepatitis C virus infection. Hepatology. 40:1062–1071. 2004.

44 

Lau GK, Cooksley H, Ribeiro RM, et al: Impact of early viral kinetics on T-cell reactivity during antiviral therapy in chronic hepatitis B. Antivir Ther. 12:705–718. 2007.PubMed/NCBI

45 

Peng G, Li S, Wu W, Sun Z, Chen Y and Chen Z: Circulating CD4+ CD25+ regulatory T cells correlate with chronic hepatitis B infection. Immunology. 123:57–65. 2008.

46 

Cao D, Malmström V, Baecher-Allan C, Hafler D, Klareskog L and Trollmo C: Isolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritis. Eur J Immunol. 33:215–223. 2003.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yan Z, Zhou J, Zhang M, Fu X, Wu Y and Wang Y: Telbivudine decreases proportion of peripheral blood CD4+CD25+CD127low T cells in parallel with inhibiting hepatitis B virus DNA. Mol Med Rep 9: 2024-2030, 2014.
APA
Yan, Z., Zhou, J., Zhang, M., Fu, X., Wu, Y., & Wang, Y. (2014). Telbivudine decreases proportion of peripheral blood CD4+CD25+CD127low T cells in parallel with inhibiting hepatitis B virus DNA. Molecular Medicine Reports, 9, 2024-2030. https://doi.org/10.3892/mmr.2014.2042
MLA
Yan, Z., Zhou, J., Zhang, M., Fu, X., Wu, Y., Wang, Y."Telbivudine decreases proportion of peripheral blood CD4+CD25+CD127low T cells in parallel with inhibiting hepatitis B virus DNA". Molecular Medicine Reports 9.5 (2014): 2024-2030.
Chicago
Yan, Z., Zhou, J., Zhang, M., Fu, X., Wu, Y., Wang, Y."Telbivudine decreases proportion of peripheral blood CD4+CD25+CD127low T cells in parallel with inhibiting hepatitis B virus DNA". Molecular Medicine Reports 9, no. 5 (2014): 2024-2030. https://doi.org/10.3892/mmr.2014.2042
Copy and paste a formatted citation
x
Spandidos Publications style
Yan Z, Zhou J, Zhang M, Fu X, Wu Y and Wang Y: Telbivudine decreases proportion of peripheral blood CD4+CD25+CD127low T cells in parallel with inhibiting hepatitis B virus DNA. Mol Med Rep 9: 2024-2030, 2014.
APA
Yan, Z., Zhou, J., Zhang, M., Fu, X., Wu, Y., & Wang, Y. (2014). Telbivudine decreases proportion of peripheral blood CD4+CD25+CD127low T cells in parallel with inhibiting hepatitis B virus DNA. Molecular Medicine Reports, 9, 2024-2030. https://doi.org/10.3892/mmr.2014.2042
MLA
Yan, Z., Zhou, J., Zhang, M., Fu, X., Wu, Y., Wang, Y."Telbivudine decreases proportion of peripheral blood CD4+CD25+CD127low T cells in parallel with inhibiting hepatitis B virus DNA". Molecular Medicine Reports 9.5 (2014): 2024-2030.
Chicago
Yan, Z., Zhou, J., Zhang, M., Fu, X., Wu, Y., Wang, Y."Telbivudine decreases proportion of peripheral blood CD4+CD25+CD127low T cells in parallel with inhibiting hepatitis B virus DNA". Molecular Medicine Reports 9, no. 5 (2014): 2024-2030. https://doi.org/10.3892/mmr.2014.2042
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