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
February-2018 Volume 39 Issue 2

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
February-2018 Volume 39 Issue 2

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 Open Access

P4HB and PDIA3 are associated with tumor progression and therapeutic outcome of diffuse gliomas

  • Authors:
    • Hecun Zou
    • Chunjie Wen
    • Zhigang Peng
    • Ying-Υing Shao
    • Lei Hu
    • Shuang Li
    • Cuilin Li
    • Hong-Hao Zhou
  • View Affiliations / Copyright

    Affiliations: Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, P.R. China, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, P.R. China, Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P.R. China
    Copyright: © Zou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 501-510
    |
    Published online on: December 4, 2017
       https://doi.org/10.3892/or.2017.6134
  • 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

Diffuse gliomas are the most common type of primary brain and central nervous system (CNS) tumors. Protein disulfide isomerases (PDIs) such as P4HB and PDIA3 act as molecular chaperones for reconstructing misfolded proteins, and are involved in endoplasmic reticulum stress and the unfolded protein response. The present study focused on the role of P4HB and PDIA3 in diffuse gliomas. Analysis of GEO and HPA data revealed that the expression levels of P4HB and PDIA3 were upregulated in glioma datasets. their increased expression was then validated in 99 glioma specimens compared with 11 non-tumor tissues. High expression of P4HB and PDIA3 was significantly correlated with high Ki-67 and a high frequency of the TP53 mutation. Kaplan-Meier survival curve and Cox regression analyses showed that glioma patients with high P4HB and PDIA3 expression had a poor survival outcome, P4HB and PDIA3 could be independent prognostic biomarkers for diffuse gliomas. In vitro, knockdown of PDIA3 suppressed cell proliferation, induced cell apoptosis, and decreased the migration of glioma cells. Furthermore, downregulation of P4HB and PDIA3 may contribute to improve the survival of patients who receive chemotherapy and radiotherapy. The data suggest that high expression of P4HB and PDIA3 plays an important role in glioma progression, and could predict the survival outcome and therapeutic response of glioma patients. Therefore, protein disulfide isomerases may be explored as prognostic biomarkers and therapeutic targets for diffuse gliomas.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, Wolinsky Y, Kruchko C and Barnholtz-Sloan JS: CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008–2012. Neuro Oncol. 17 Suppl 4:iv1–iv62. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Reifenberger G, Wirsching HG, Knobbe-Thomsen CB and Weller M: Advances in the molecular genetics of gliomas - implications for classification and therapy. Nat Rev Clin Oncol. 14:434–452. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P and Ellison DW: The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary. Acta Neuropathol. 131:803–820. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Perri E, Parakh S and Atkin J: Protein disulphide isomerases: Emerging roles of PDI and ERp57 in the nervous system and as therapeutic targets for ALS. Expert Opin Ther Targets. 21:37–49. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Zou Q, Yang ZL, Yuan Y, Li JH, Liang LF, Zeng GX and Chen SL: Clinicopathological features and CCT2 and PDIA2 expression in gallbladder squamous/adenosquamous carcinoma and gallbladder adenocarcinoma. World J Surg Oncol. 11:1432013. View Article : Google Scholar : PubMed/NCBI

6 

Choe MH, Min JW, Jeon HB, Cho DH, Oh JS, Lee HG, Hwang SG, An S, Han YH and Kim JS: ERp57 modulates STAT3 activity in radioresistant laryngeal cancer cells and serves as a prognostic marker for laryngeal cancer. Oncotarget. 6:2654–2666. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Chung H, Cho H, Perry C, Song J, Ylaya K, Lee H and Kim JH: Downregulation of ERp57 expression is associated with poor prognosis in early-stage cervical cancer. Biomarkers. 18:573–579. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Takata H, Kudo M, Yamamoto T, Ueda J, Ishino K, Peng WX, Wada R, Taniai N, Yoshida H, Uchida E, et al: Increased expression of PDIA3 and its association with cancer cell proliferation and poor prognosis in hepatocellular carcinoma. Oncol Lett. 12:4896–4904. 2016.PubMed/NCBI

9 

Negroni L, Taouji S, Arma D, Pallares-Lupon N, Leong K, Beausang LA, Latterich M, Bossé R, Balabaud C, Schmitter JM, et al: Integrative quantitative proteomics unveils proteostasis imbalance in human hepatocellular carcinoma developed on nonfibrotic livers. Mol Cell Proteomics. 13:3473–3483. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Shen H, Huang J, Pei H, Zeng S, Tao Y, Shen L, Zeng L and Zhu H: Comparative proteomic study for profiling differentially expressed proteins between Chinese left- and right-sided colon cancers. Cancer Sci. 104:135–141. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Xia W, Zhuang J, Wang G, Ni J, Wang J and Ye Y: P4HB promotes HCC tumorigenesis through downregulation of GRP78 and subsequent upregulation of epithelial-to-mesenchymal transition. Oncotarget. 8:8512–8521. 2017.PubMed/NCBI

12 

Da Costa GG, Gomig TH, Kaviski R, Santos Sousa K, Kukolj C, De Lima RS, De Andrade Urban C, Cavalli IJ and Ribeiro EM: Comparative proteomics of tumor and paired normal breast tissue highlights potential biomarkers in breast cancer. Cancer Genomics Proteomics. 12:251–261. 2015.PubMed/NCBI

13 

Gromov P, Gromova I, Bunkenborg J, Cabezon T, Moreira JM, Timmermans-Wielenga V, Roepstorff P, Rank F and Celis JE: Up-regulated proteins in the fluid bathing the tumour cell microenvironment as potential serological markers for early detection of cancer of the breast. Mol Oncol. 4:65–89. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Sun L, Hui AM, Su Q, Vortmeyer A, Kotliarov Y, Pastorino S, Passaniti A, Menon J, Walling J, Bailey R, et al: Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain. Cancer Cell. 9:287–300. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Costa BM, Smith JS, Chen Y, Chen J, Phillips HS, Aldape KD, Zardo G, Nigro J, James CD, Fridlyand J, et al: Reversing HOXA9 oncogene activation by PI3K inhibition: Epigenetic mechanism and prognostic significance in human glioblastoma. Cancer Res. 70:453–462. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Freije WA, Castro-Vargas FE, Fang Z, Horvath S, Cloughesy T, Liau LM, Mischel PS and Nelson SF: Gene expression profiling of gliomas strongly predicts survival. Cancer Res. 64:6503–6510. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Kawaguchi A, Yajima N, Tsuchiya N, Homma J, Sano M, Natsumeda M, Takahashi H, Fujii Y, Kakuma T and Yamanaka R: Gene expression signature-based prognostic risk score in patients with glioblastoma. Cancer Sci. 104:1205–1210. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, et al: NCBI GEO: Archive for functional genomics data sets - update. Nucleic Acids Res. 41(D1): D991–D995. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E, Asplund A, et al: Proteomics. Tissue-based map of the human proteome. Science. 347:12604192015. View Article : Google Scholar : PubMed/NCBI

20 

Zeng A, Hu Q, Liu Y, Wang Z, Cui X, Li R, Yan W and You Y: IDH1/2 mutation status combined with Ki-67 labeling index defines distinct prognostic groups in glioma. Oncotarget. 6:30232–30238. 2015. View Article : Google Scholar : PubMed/NCBI

21 

England B, Huang T and Karsy M: Current understanding of the role and targeting of tumor suppressor p53 in glioblastoma multiforme. Tumour Biol. 34:2063–2074. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Sun S, Lee D, Ho AS, Pu JK, Zhang XQ, Lee NP, Day PJ, Lui WM, Fung CF and Leung GK: Inhibition of prolyl 4-hydroxylase, beta polypeptide (P4HB) attenuates temozolomide resistance in malignant glioma via the endoplasmic reticulum stress response (ERSR) pathways. Neuro Oncol. 15:562–577. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Li S, Li C, Ryu HH, Lim SH, Jang WY and Jung S: Bacitracin inhibits the migration of U87-MG glioma cells via interferences of the integrin outside-in signaling pathway. J Korean Neurosurg Soc. 59:106–116. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Binet F and Sapieha P: ER Stress and Angiogenesis. Cell Metab. 22:560–575. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Bechtel TJ and Weerapana E: From structure to redox: The diverse functional roles of disulfides and implications in disease. Proteomics. 17:16003912017. View Article : Google Scholar

26 

Xu S, Sankar S and Neamati N: Protein disulfide isomerase: A promising target for cancer therapy. Drug Discov Today. 19:222–240. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Na KS, Park BC, Jang M, Cho S, Lee DH, Kang S, Lee CK, Bae KH and Park SG: Protein disulfide isomerase is cleaved by caspase-3 and −7 during apoptosis. Mol Cells. 24:261–267. 2007.PubMed/NCBI

28 

Zhao G, Lu H and Li C: Proapoptotic activities of protein disulfide isomerase (PDI) and PDIA3 protein, a role of the Bcl-2 protein Bak. J Biol Chem. 290:8949–8963. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Lwin ZM, Yip GW, Chew FT and Bay BH: Downregulation of ER60 protease inhibits cellular proliferation by inducing G1/S arrest in breast cancer cells in vitro. Anat Rec (Hoboken). 295:410–416. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Thongwatchara P, Promwikorn W, Srisomsap C, Chokchaichamnankit D, Boonyaphiphat P and Thongsuksai P: Differential protein expression in primary breast cancer and matched axillary node metastasis. Oncol Rep. 26:185–191. 2011.PubMed/NCBI

31 

Khan MM, Simizu S, Suzuki T, Masuda A, Kawatani M, Muroi M, Dohmae N and Osada H: Protein disulfide isomerase-mediated disulfide bonds regulate the gelatinolytic activity and secretion of matrix metalloproteinase-9. Exp Cell Res. 318:904–914. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Kullmann M, Kalayda GV, Hellwig M, Kotz S, Hilger RA, Metzger S and Jaehde U: Assessing the contribution of the two protein disulfide isomerases PDIA1 and PDIA3 to cisplatin resistance. J Inorg Biochem. 153:247–252. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Xu S, Butkevich AN, Yamada R, Zhou Y, Debnath B, Duncan R, Zandi E, Petasis NA and Neamati N: Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment. Proc Natl Acad Sci USA. 109:pp. 16348–16353. 2012; View Article : Google Scholar : PubMed/NCBI

34 

Caorsi C, Niccolai E, Capello M, Vallone R, Chattaragada MS, Alushi B, Castiglione A, Ciccone G, Mautino A, Cassoni P, et al: Protein disulfide isomerase A3-specific Th1 effector cells infiltrate colon cancer tissue of patients with circulating anti-protein disulfide isomerase A3 autoantibodies. Transl Res. 171:17–28 e11-12. 2016. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zou H, Wen C, Peng Z, Shao Y, Hu L, Li S, Li C and Zhou H: P4HB and PDIA3 are associated with tumor progression and therapeutic outcome of diffuse gliomas. Oncol Rep 39: 501-510, 2018.
APA
Zou, H., Wen, C., Peng, Z., Shao, Y., Hu, L., Li, S. ... Zhou, H. (2018). P4HB and PDIA3 are associated with tumor progression and therapeutic outcome of diffuse gliomas. Oncology Reports, 39, 501-510. https://doi.org/10.3892/or.2017.6134
MLA
Zou, H., Wen, C., Peng, Z., Shao, Y., Hu, L., Li, S., Li, C., Zhou, H."P4HB and PDIA3 are associated with tumor progression and therapeutic outcome of diffuse gliomas". Oncology Reports 39.2 (2018): 501-510.
Chicago
Zou, H., Wen, C., Peng, Z., Shao, Y., Hu, L., Li, S., Li, C., Zhou, H."P4HB and PDIA3 are associated with tumor progression and therapeutic outcome of diffuse gliomas". Oncology Reports 39, no. 2 (2018): 501-510. https://doi.org/10.3892/or.2017.6134
Copy and paste a formatted citation
x
Spandidos Publications style
Zou H, Wen C, Peng Z, Shao Y, Hu L, Li S, Li C and Zhou H: P4HB and PDIA3 are associated with tumor progression and therapeutic outcome of diffuse gliomas. Oncol Rep 39: 501-510, 2018.
APA
Zou, H., Wen, C., Peng, Z., Shao, Y., Hu, L., Li, S. ... Zhou, H. (2018). P4HB and PDIA3 are associated with tumor progression and therapeutic outcome of diffuse gliomas. Oncology Reports, 39, 501-510. https://doi.org/10.3892/or.2017.6134
MLA
Zou, H., Wen, C., Peng, Z., Shao, Y., Hu, L., Li, S., Li, C., Zhou, H."P4HB and PDIA3 are associated with tumor progression and therapeutic outcome of diffuse gliomas". Oncology Reports 39.2 (2018): 501-510.
Chicago
Zou, H., Wen, C., Peng, Z., Shao, Y., Hu, L., Li, S., Li, C., Zhou, H."P4HB and PDIA3 are associated with tumor progression and therapeutic outcome of diffuse gliomas". Oncology Reports 39, no. 2 (2018): 501-510. https://doi.org/10.3892/or.2017.6134
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