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
December-2015 Volume 12 Issue 6

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
December-2015 Volume 12 Issue 6

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

Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19

  • Authors:
    • Minghe Li
    • Zhihong Li
    • Jia Li
    • Liou Jin
    • Chengxue Jin
    • Chengmin Han
    • Xin Ji
    • Fei Sun
  • View Affiliations / Copyright

    Affiliations: Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130022, P.R. China, Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Oral and Maxillofacial Surgery, School of Stomatology Hospital of Jilin University, Changchun, Jilin 130000, P.R. China
  • Pages: 8185-8192
    |
    Published online on: October 9, 2015
       https://doi.org/10.3892/mmr.2015.4423
  • 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

Gene associated with retinoid‑interferon‑induced mortality 19 (GRIM‑19) is a novel candidate tumor suppressor gene located on the human chromosome 19p13.1 region. Our previous study demonstrated that the upregulation of GRIM‑19 in human oral squamous cell carcinoma (OSCC) cells significantly inhibited tumor cell growth in vitro and in vivo. In the present study, the combined effects of cationic liposome (LP)‑mediated GRIM‑19 gene (LP‑pGRIM‑19) and the low‑dose chemotherapeutic drug, cisplatin (CDDP), on tumor cell growth in vitro and in vivo were examined, and the molecular mechanism of their mutual action was investigated by cell proliferation, colony formation, apoptosis, migration, invasion and western blotting assays in vitro, and a node nude tumor model. It was demonstrated that cationic LP‑pGRIM‑19 gene therapy sensitized the response of breast cancer cells to CDDP, and that LP‑pGRIM‑19 in combination with CDDP significantly induced apoptosis and inhibited proliferation, colony formation, migration and invasion of the cells, compared with CDDP treatment alone. In addition, systemic treatment with a combination of intravenous injection of LP‑pGRIM‑19 and intraperitoneal injection of low‑dose CDDP into subcutaneous HSC3 human OSCC xenograft mice resulted in a significant inhibition of tumor growth (P<0.05). Further investigations indicated that the enhancement of CPPP‑mediated antitumor effects by GRIM‑19 may be associated with the upregulation of phosphorylated p53 and the downregulation of B cell lymphoma‑2, cyclin D1, vascular endothelial growth factor, matrix metalloproteinase (MMP)‑2 and MMP‑9, the proteins of which are involved in the activation of signal transducer and activator of transcription 3. The results of the present study suggested that the combination of GRIM‑19 gene therapy with low‑dose CPPP‑based chemotherapy may be a potent therapeutic strategy for the treatment of OSCC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Warnakulasuriya S: Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 45:309–316. 2009. View Article : Google Scholar

2 

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

3 

Jerjes W, Upile T, Petrie A, Riskalla A, Hamdoon Z, Vourvachis M, Karavidas K, Jay A, Sandison A, Thomas GJ, et al: Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients. Head Neck Oncol. 2:92010. View Article : Google Scholar : PubMed/NCBI

4 

Forastiere A, Koch W, Trotti A and Sidransky D: Head and neck cancer. New Engl J Med. 345:1890–1900. 2001. View Article : Google Scholar

5 

O'Dwyer PJ, Stevenson JP and Johnson SW: Clinical pharmacokinetics and administration of established platinum drugs. Drugs. 59(Suppl 4): 19–27. 2000. View Article : Google Scholar : PubMed/NCBI

6 

Baruah H, Barry CG and Bierbach U: Platinum-intercalator conjugates: From DNA-targeted cisplatin derivatives to adenine binding complexes as potential modulators of gene regulation. Curr Top Med Chem. 4:1537–1549. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Shimanishi M, Ogi K, Sogabe Y, Kaneko T, Dehari H, Miyazaki A and Hiratsuka H: Silencing of GLUT-1 inhibits sensitization of oral cancer cells to cisplatin during hypoxia. J Oral Pathol Med. 42:382–388. 2013. View Article : Google Scholar

8 

Perez RP: Cellular and molecular determinants of cisplatin resistance. Eur J Cancer. 34:1535–1542. 1998. View Article : Google Scholar

9 

Rabik CA and Dolan ME: Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev. 33:9–23. 2007. View Article : Google Scholar :

10 

Cohen SM and Lippard SJ: Cisplatin: From DNA damage to cancer chemotherapy. Prog Nucleic Acid Res Mol Biol. 67:93–130. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Johnson DH: Evolution of cisplatin-based chemotherapy in non-small cell lung cancer: A historical perspective and the eastern cooperative oncology group experience. Chest. 117(Suppl 1): S133–S137. 2000. View Article : Google Scholar

12 

Maitra A, Wistuba II, Washington C, Virmani AK, Ashfaq R, Milchgrub S, Gazdar AF and Minna JD: High-resolution chromosome 3p allelotyping of breast carcinomas and precursor lesions demonstrates frequent loss of heterozygosity and a discontinuous pattern of allele loss. Am J Pathol. 159:119–130. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Zabarovsky ER, Lerman MI and Minna JD: Tumor suppressor genes on chromosome 3p involved in the pathogenesis of lung and other cancers. Oncogene. 21:6915–6935. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Lerman MI and Minna JD: The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: Identification and evaluation of the resident candidate tumor suppressor genes. The international lung cancer chromosome 3p213 tumor suppressor gene consortium. Cancer Res. 60:6116–6133. 2000.PubMed/NCBI

15 

Angell JE, Lindner DJ, Shapiro PS, Hofmann ER and Kalvakolanu DV: Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach. J Biol Chem. 275:33416–33426. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Li M, Li Z, Liang C, Han C, Huang W and Sun F: Upregulation of GRIM-19 suppresses the growth of oral squamous cell carcinoma in vitro and in vivo. Oncolo Rep. 32:2183–2190. 2014.

17 

Ou W, Ye S, Yang W, Wang Y, Ma Q, Yu C, Shi H, Yuan Z, Zhong G, Ren J, et al: Enhanced antitumor effect of cisplatin in human NSCLC cells by tumor suppressor LKB1. Cancer Gene Ther. 19:489–498. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Nemunaitis J, Swisher SG, Timmons T, Connors D, Mack M, Doerksen L, Weill D, Wait J, Lawrence DD, Kemp BL, et al: Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer. J Clin Oncol. 18:609–622. 2000.PubMed/NCBI

19 

Ueda K, Kawashima H, Ohtani S, Deng WG, Ravoori M, Bankson J, Gao B, Girard L, Minna JD, Roth JA, et al: The 3p21.3 tumor suppressor NPRL2 plays an important role in cisplatin-induced resistance in human non-small-cell lung cancer cells. Cancer Res. 66:9682–9690. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Deng WG, Wu G, Ueda K, Xu K, Roth JA and Ji L: Enhancement of antitumor activity of cisplatin in human lung cancer cells by tumor suppressor FUS1. Cancer Gene Ther. 15:29–39. 2008. View Article : Google Scholar

21 

Chen X, Wang X, Wang Y, Yang L, Hu J, Xiao W, Fu A, Cai L, Li X, Ye X, et al: Improved tumor-targeting drug delivery and therapeutic efficacy by cationic liposome modified with truncated bFGF peptide. J Control Release. 145:17–25. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Zhang H, Li Z and Wang K: Combining sorafenib with celecoxib synergistically inhibits tumor growth of non-small cell lung cancer cells in vitro and in vivo. Oncol Rep. 31:1954–1960. 2014.PubMed/NCBI

23 

Lowe SW, Ruley HE, Jacks T and Housman DE: p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell. 74:957–967. 1993. View Article : Google Scholar : PubMed/NCBI

24 

Liu JR, Opipari AW, Tan L, Jiang Y, Zhang Y, Tang H and Nuñez G: Dysfunctional apoptosome activation in ovarian cancer: Implications for chemoresistance. Cancer Res. 62:924–931. 2002.PubMed/NCBI

25 

Wurstle ML, Zink E, Prehn JH and Rehm M: From computational modelling of the intrinsic apoptosis pathway to a systems-based analysis of chemotherapy resistance: Achievements, perspectives and challenges in systems medicine. Cell Death Dis. 5:e12582014. View Article : Google Scholar : PubMed/NCBI

26 

Niedner H, Christen R, Lin X, Kondo A and Howell SB: Identification of genes that mediate sensitivity to cisplatin. Mol Pharmacol. 60:1153–1160. 2001.PubMed/NCBI

27 

Park SA, Park HJ, Lee BI, Ahn YH, Kim SU and Choi KS: Bcl-2 blocks cisplatin-induced apoptosis by suppression of ERK-mediated p53 accumulation in B104 cells. Brain Res Mol Brain Res. 93:18–26. 2001. View Article : Google Scholar : PubMed/NCBI

28 

Zhang L, Gao L, Li Y, Lin G, Shao Y, Ji K, Yu H, Hu J, Kalvakolanu DV, Kopecko DJ, et al: Effects of plasmid-based Stat3-specific short hairpin RNA and GRIM-19 on PC-3 M tumor cell growth. Clin Cancer Res. 14:559–568. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Turkson J: STAT proteins as novel targets for cancer drug discovery. Expert Opin Ther Targets. 8:409–422. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Niu G, Wright KL, Huang M, Song L, Haura E, Turkson J, Zhang S, Wang T, Sinibaldi D, Coppola D, et al: Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene. 21:2000–2008. 2002. View Article : Google Scholar : PubMed/NCBI

31 

Xie TX, Wei D, Liu M, Gao AC, Ali-Osman F, Sawaya R and Huang S: Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis. Oncogene. 23:3550–3560. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Kumar B, Yadav A, Hideg K, Kuppusamy P, Teknos TN and Kumar P: A novel curcumin analog (H-4073) enhances the therapeutic efficacy of cisplatin treatment in head and neck cancer. PloS One. 9:e932082014. View Article : Google Scholar : PubMed/NCBI

33 

Han Z, Feng J, Hong Z, Chen L, Li W, Liao S, Wang X, Ji T, Wang S, Ma D, et al: Silencing of the STAT3 signaling pathway reverses the inherent and induced chemoresistance of human ovarian cancer cells. Biochem Biophys Res Commun. 435:188–194. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Zhou Y, Li M, Wei Y, Feng D, Peng C, Weng H, Ma Y, Bao L, Nallar S, Kalakonda S, et al: Downregulation of GRIM-19 expression is associated with hyperactivation of STAT3-induced gene expression and tumor growth in human cervical cancers. J Interferon Cytokine Res. 29:695–703. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Hao H, Liu J, Liu G, Guan D, Yang Y, Zhang X, Cao X and Liu Q: Depletion of GRIM-19 accelerates hepatocellular carcinoma invasion via inducing EMT and loss of contact inhibition. J Cell Physiol. 227:1212–1219. 2012. View Article : Google Scholar

36 

Okamoto T, Inozume T, Mitsui H, Kanzaki M, Harada K, Shibagaki N and Shimada S: Upregulation of GRIM-19 in cancer cells suppresses STAT3-mediated signal transduction and cancer growth. Mol Cancer Ther. 9:2333–2343. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li M, Li Z, Li J, Jin L, Jin C, Han C, Ji X and Sun F: Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19. Mol Med Rep 12: 8185-8192, 2015.
APA
Li, M., Li, Z., Li, J., Jin, L., Jin, C., Han, C. ... Sun, F. (2015). Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19. Molecular Medicine Reports, 12, 8185-8192. https://doi.org/10.3892/mmr.2015.4423
MLA
Li, M., Li, Z., Li, J., Jin, L., Jin, C., Han, C., Ji, X., Sun, F."Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19". Molecular Medicine Reports 12.6 (2015): 8185-8192.
Chicago
Li, M., Li, Z., Li, J., Jin, L., Jin, C., Han, C., Ji, X., Sun, F."Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19". Molecular Medicine Reports 12, no. 6 (2015): 8185-8192. https://doi.org/10.3892/mmr.2015.4423
Copy and paste a formatted citation
x
Spandidos Publications style
Li M, Li Z, Li J, Jin L, Jin C, Han C, Ji X and Sun F: Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19. Mol Med Rep 12: 8185-8192, 2015.
APA
Li, M., Li, Z., Li, J., Jin, L., Jin, C., Han, C. ... Sun, F. (2015). Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19. Molecular Medicine Reports, 12, 8185-8192. https://doi.org/10.3892/mmr.2015.4423
MLA
Li, M., Li, Z., Li, J., Jin, L., Jin, C., Han, C., Ji, X., Sun, F."Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19". Molecular Medicine Reports 12.6 (2015): 8185-8192.
Chicago
Li, M., Li, Z., Li, J., Jin, L., Jin, C., Han, C., Ji, X., Sun, F."Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19". Molecular Medicine Reports 12, no. 6 (2015): 8185-8192. https://doi.org/10.3892/mmr.2015.4423
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