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
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
July-2016 Volume 36 Issue 1

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
July-2016 Volume 36 Issue 1

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

T-box transcription factor brachyury promotes tumor cell invasion and metastasis in non-small cell lung cancer via upregulation of matrix metalloproteinase 12

  • Authors:
    • Zongmiao Wan
    • Dongjie Jiang
    • Su Chen
    • Jian Jiao
    • Lei Ji
    • Abdus Saboor Shah
    • Haifeng Wei
    • Xinghai Yang
    • Xiaotao Li
    • Ying Wang
    • Jianru Xiao
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai 200241, P.R. China, The Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 310036, P.R. China
  • Pages: 306-314
    |
    Published online on: May 9, 2016
       https://doi.org/10.3892/or.2016.4792
  • 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

T-box transcription factor brachyury and matrix metalloproteinases (MMPs) play important roles in non-small cell lung cancer (NSCLC) cell invasion and metastasis. However, the association between Brachyury and the MMP family has not yet been fully investigated. The present study aimed to assess the influence of Brachyury on the expression of 23 MMP members and to further explore the mechanisms involved in the promotion of NSCLC cell invasion by Brachyury and MMPs in the H460 and H1299 stable cell lines. The protein expression levels and correlations between the brachyury transcription factor and the targeted MMPs were also validated in 52 NSCLC patient tissue samples. We observed that brachyury significantly upregulated MMP12 expression to promote NSCLC cell invasion. We also found a potential binding site for the brachyury transcription factor in the MMP12 promoter.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Kispert A, Koschorz B and Herrmann BG: The T protein encoded by Brachyury is a tissue-specific transcription factor. EMBO J. 14:4763–4772. 1995.PubMed/NCBI

2 

Haro A, Yano T, Kohno M, Yoshida T, Koga T, Okamoto T, Takenoyama M and Maehara Y: Expression of Brachyury gene is a significant prognostic factor for primary lung carcinoma. Ann Surg Oncol. 20(Suppl 3): S509–S516. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Imajyo I, Sugiura T, Kobayashi Y, Shimoda M, Ishii K, Akimoto N, Yoshihama N, Kobayashi I and Mori Y: T-box transcription factor Brachyury expression is correlated with epithelial-mesenchymal transition and lymph node metastasis in oral squamous cell carcinoma. Int J Oncol. 41:1985–1995. 2012.PubMed/NCBI

4 

Kilic N, Feldhaus S, Kilic E, Tennstedt P, Wicklein D, Wasielewski R, Viebahn C, Kreipe H and Schumacher U: Brachyury expression predicts poor prognosis at early stages of colorectal cancer. Eur J Cancer. 47:1080–1085. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Roselli M, Fernando RI, Guadagni F, Spila A, Alessandroni J, Palmirotta R, Costarelli L, Litzinger M, Hamilton D, Huang B, et al: Brachyury, a driver of the epithelial-mesenchymal transition, is overexpressed in human lung tumors: An opportunity for novel interventions against lung cancer. Clin Cancer Res. 18:3868–3879. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Fernando RI, Litzinger M, Trono P, Hamilton DH, Schlom J and Palena C: The T-box transcription factor Brachyury promotes epithelial-mesenchymal transition in human tumor cells. J Clin Invest. 120:533–544. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Xu K, Liu B and Liu Y: Impact of Brachyury on epithelial-mesenchymal transitions and chemosensitivity in non-small cell lung cancer. Mol Med Rep. 12:995–1001. 2015.PubMed/NCBI

8 

Kleiner DE and Stetler-Stevenson WG: Matrix metalloproteinases and metastasis. Cancer Chemother Pharmacol. 43(Suppl): S42–S51. 1999. View Article : Google Scholar : PubMed/NCBI

9 

Sternlicht MD and Werb Z: How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol. 17:463–516. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Wang R, Ke ZF, Wang F, Zhang WH, Wang YF, Li SH and Wang LT: GOLPH3 overexpression is closely correlated with poor prognosis in human non-small cell lung cancer and mediates its metastasis through upregulating MMP-2 and MMP-9. Cell Physiol Biochem. 35:969–982. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Ali-Labib R, Louka ML, Galal IH and Tarek M: Evaluation of matrix metalloproteinase-2 in lung cancer. Proteomics Clin Appl. 8:251–257. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Zhang J, Luo J, Ni J, Tang L, Zhang HP, Zhang L, Xu JF and Zheng D: MMP-7 is upregulated by COX-2 and promotes proliferation and invasion of lung adenocarcinoma cells. Eur J Histochem. 58:22622014. View Article : Google Scholar : PubMed/NCBI

13 

Liang Y, Guo S and Zhou Q: Prognostic value of matrix metalloproteinase-7 expression in patients with non-small cell lung cancer. Tumour Biol. 35:3717–3724. 2014. View Article : Google Scholar

14 

Ruiz-Morales JM, Dorantes-Heredia R, Arrieta O, Chavez-Tapia NC and Motola-Kuba D: Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) prognostic value in lung adenocarcinoma. Tumour Biol. 36:3601–3610. 2015. View Article : Google Scholar

15 

Gill JH, Kirwan IG, Seargent JM, Martin SW, Tijani S, Anikin VA, Mearns AJ, Bibby MC, Anthoney A and Loadman PM: MMP-10 is overexpressed, proteolytically active, and a potential target for therapeutic intervention in human lung carcinomas. Neoplasia. 6:777–785. 2004. View Article : Google Scholar

16 

Kettunen E, Anttila S, Seppänen JK, Karjalainen A, Edgren H, Lindström I, Salovaara R, Nissén AM, Salo J, Mattson K, et al: Differentially expressed genes in nonsmall cell lung cancer: Expression profiling of cancer-related genes in squamous cell lung cancer. Cancer Genet Cytogenet. 149:98–106. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Cho NH, Hong KP, Hong SH, Kang S, Chung KY and Cho SH: MMP expression profiling in recurred stage IB lung cancer. Oncogene. 23:845–851. 2004. View Article : Google Scholar

18 

Wang YZ, Wu KP, Wu AB, Yang ZC, Li JM, Mo YL, Xu M, Wu B and Yang ZX: MMP-14 overexpression correlates with poor prognosis in non-small cell lung cancer. Tumour Biol. 35:9815–9821. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Zhou H, Wu A, Fu W, Lv Z and Zhang Z: Significance of semaphorin-3A and MMP-14 protein expression in non-small cell lung cancer. Oncol Lett. 7:1395–1400. 2014.PubMed/NCBI

20 

Yu G, Herazo-Maya JD, Nukui T, Romkes M, Parwani A, Juan-Guardela BM, Robertson J, Gauldie J, Siegfried JM, Kaminski N, et al: Matrix metalloproteinase-19 promotes metastatic behavior in vitro and is associated with increased mortality in non-small cell lung cancer. Am J Respir Crit Care Med. 190:780–790. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Zhang Y, Zhao H, Wang Y, Lin Y, Tan Y, Fang X and Zheng L: Non-small cell lung cancer invasion and metastasis promoted by MMP-26. Mol Med Rep. 4:1201–1209. 2011.PubMed/NCBI

22 

Li J, Zhu L, Qu X, Li J, Lin R, Liao L, Wang J, Wang S, Xu Q and Zhao RC: Stepwise differentiation of human adipose-derived mesenchymal stem cells toward definitive endoderm and pancreatic progenitor cells by mimicking pancreatic development in vivo. Stem Cells Dev. 22:1576–1587. 2013. View Article : Google Scholar

23 

Wang HZ, He YX, Yang CJ, Zhou W and Zou CG: Hepcidin is regulated during blood-stage malaria and plays a protective role in malaria infection. J Immunol. 187:6410–6416. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Sarkar S, Nuttall RK, Liu S, Edwards DR and Yong VW: Tenascin-C stimulates glioma cell invasion through matrix metalloproteinase-12. Cancer Res. 66:11771–11780. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Edwards YH, Putt W, Lekoape KM, Stott D, Fox M, Hopkinson DA and Sowden J: The human homolog T of the mouse T(Brachyury) gene; Gene structure, cDNA sequence, and assignment to chromosome 6q27. Genome Res. 6:226–233. 1996. View Article : Google Scholar : PubMed/NCBI

26 

Ali A, Wang Z, Fu J, Ji L, Liu J, Li L, Wang H, Chen J, Caulin C, Myers JN, Zhang P, Xiao J, Zhang B and Li X: Differential regulation of the REGγ-proteasome pathway by p53/TGF-β signalling and mutant p53 in cancer cells. Nat Commun. 4:26672013. View Article : Google Scholar

27 

Krukovskaia LL, Polev DE, Nosova Iu K, Baranova AV, Koliubaeva SN and Kozlov AP: Investigation of transcription factor Brachyury (T) expression in human normal and tumor tissues. Vopr Onkol. 54:739–743. 2008.In Russian.

28 

Palena C, Fernando RI, Hamilton DH, Huang B and Schlom J: Brachyury, a driver of tumor invasiveness and resistance to multiple therapies, is a novel immunotherapy target. J Immunother Cancer. 1(Suppl 1): P2302013. View Article : Google Scholar

29 

Kobayashi Y, Sugiura T, Imajyo I, Shimoda M, Ishii K, Akimoto N, Yoshihama N and Mori Y: Knockdown of the T-box transcription factor Brachyury increases sensitivity of adenoid cystic carcinoma cells to chemotherapy and radiation in vitro: Implications for a new therapeutic principle. Int J Oncol. 44:1107–1117. 2014.PubMed/NCBI

30 

Pinto F, Pértega-Gomes N, Pereira MS, Vizcaíno JR, Monteiro P, Henrique RM, Baltazar F, Andrade RP and Reis RM: T-box transcription factor brachyury is associated with prostate cancer progression and aggressiveness. Clin Cancer Res. 20:4949–4961. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Hofmann HS, Hansen G, Richter G, Taege C, Simm A, Silber RE and Burdach S: Matrix metalloproteinase-12 expression correlates with local recurrence and metastatic disease in non-small cell lung cancer patients. Clin Cancer Res. 11:1086–1092. 2005.PubMed/NCBI

32 

Weigelt B, Glas AM, Wessels LF, Witteveen AT, Peterse JL and van't Veer LJ: Gene expression profiles of primary breast tumors maintained in distant metastases. Proc Natl Acad Sci USA. 100:15901–15905. 2003. View Article : Google Scholar : PubMed/NCBI

33 

Gomez-Roca C, Raynaud CM, Penault-Llorca F, Mercier O, Commo F, Morat L, Sabatier L, Dartevelle P, Taranchon E, Besse B, et al: Differential expression of biomarkers in primary non-small cell lung cancer and metastatic sites. J Thorac Oncol. 4:1212–1220. 2009. View Article : Google Scholar : PubMed/NCBI

34 

Sarkar D, Shields B, Davies ML, Muller J and Wakeman JA: Brachyury confers cancer stem cell characteristics on colorectal cancer cells. Int J Cancer. 130:328–337. 2012. View Article : Google Scholar

35 

Palena C, Roselli M, Litzinger MT, Ferroni P, Costarelli L, Spila A, Cavaliere F, Huang B, Fernando RI, Hamilton DH, et al: Overexpression of the EMT driver brachyury in breast carcinomas: Association with poor prognosis. J Natl Cancer Inst. 106:piidju054. 2014. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wan Z, Jiang D, Chen S, Jiao J, Ji L, Shah AS, Wei H, Yang X, Li X, Wang Y, Wang Y, et al: T-box transcription factor brachyury promotes tumor cell invasion and metastasis in non-small cell lung cancer via upregulation of matrix metalloproteinase 12. Oncol Rep 36: 306-314, 2016.
APA
Wan, Z., Jiang, D., Chen, S., Jiao, J., Ji, L., Shah, A.S. ... Xiao, J. (2016). T-box transcription factor brachyury promotes tumor cell invasion and metastasis in non-small cell lung cancer via upregulation of matrix metalloproteinase 12. Oncology Reports, 36, 306-314. https://doi.org/10.3892/or.2016.4792
MLA
Wan, Z., Jiang, D., Chen, S., Jiao, J., Ji, L., Shah, A. S., Wei, H., Yang, X., Li, X., Wang, Y., Xiao, J."T-box transcription factor brachyury promotes tumor cell invasion and metastasis in non-small cell lung cancer via upregulation of matrix metalloproteinase 12". Oncology Reports 36.1 (2016): 306-314.
Chicago
Wan, Z., Jiang, D., Chen, S., Jiao, J., Ji, L., Shah, A. S., Wei, H., Yang, X., Li, X., Wang, Y., Xiao, J."T-box transcription factor brachyury promotes tumor cell invasion and metastasis in non-small cell lung cancer via upregulation of matrix metalloproteinase 12". Oncology Reports 36, no. 1 (2016): 306-314. https://doi.org/10.3892/or.2016.4792
Copy and paste a formatted citation
x
Spandidos Publications style
Wan Z, Jiang D, Chen S, Jiao J, Ji L, Shah AS, Wei H, Yang X, Li X, Wang Y, Wang Y, et al: T-box transcription factor brachyury promotes tumor cell invasion and metastasis in non-small cell lung cancer via upregulation of matrix metalloproteinase 12. Oncol Rep 36: 306-314, 2016.
APA
Wan, Z., Jiang, D., Chen, S., Jiao, J., Ji, L., Shah, A.S. ... Xiao, J. (2016). T-box transcription factor brachyury promotes tumor cell invasion and metastasis in non-small cell lung cancer via upregulation of matrix metalloproteinase 12. Oncology Reports, 36, 306-314. https://doi.org/10.3892/or.2016.4792
MLA
Wan, Z., Jiang, D., Chen, S., Jiao, J., Ji, L., Shah, A. S., Wei, H., Yang, X., Li, X., Wang, Y., Xiao, J."T-box transcription factor brachyury promotes tumor cell invasion and metastasis in non-small cell lung cancer via upregulation of matrix metalloproteinase 12". Oncology Reports 36.1 (2016): 306-314.
Chicago
Wan, Z., Jiang, D., Chen, S., Jiao, J., Ji, L., Shah, A. S., Wei, H., Yang, X., Li, X., Wang, Y., Xiao, J."T-box transcription factor brachyury promotes tumor cell invasion and metastasis in non-small cell lung cancer via upregulation of matrix metalloproteinase 12". Oncology Reports 36, no. 1 (2016): 306-314. https://doi.org/10.3892/or.2016.4792
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