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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
April-2017 Volume 13 Issue 4

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
April-2017 Volume 13 Issue 4

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

Calcitonin gene-related peptide protects type II alveolar epithelial cells from hyperoxia-induced DNA damage and cell death

  • Authors:
    • Hongmin Fu
    • Tiesong Zhang
    • Rongwei Huang
    • Zhen Yang
    • Chunming Liu
    • Ming Li
    • Fang Fang
    • Feng Xu
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Internal Medicine, Children's Hospital, Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Pediatric Intensive Care Unit, Children's Hospital, Chongqing Medical University, Chongqing 400014, P.R. China
    Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1279-1284
    |
    Published online on: February 16, 2017
       https://doi.org/10.3892/etm.2017.4132
  • 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

Hyperoxia therapy for acute lung injury (ALI) may unexpectedly lead to reactive oxygen species (ROS) production and cause additional ALI. Calcitonin gene‑related peptide (CGRP) is a 37 amino acid neuropeptide that regulates inflammasome activation. However, the role of CGRP in DNA damage during hyperoxia is unclear. Therefore, the aim of the present study was to investigate the effects of CGRP on DNA damage and the cell death of alveolar epithelial type II cells (AEC II) exposed to 60% oxygen. AEC II were isolated from 19‑20 gestational day fetal rat lungs and were exposed to air or to 60% oxygen during treatment with CGRP or the specific CGRP receptor antagonist CGRP8‑37. The cells were evaluated using immunofluorescence to examine surfactant protein‑C and ROS levels were measured by probing with 2',7'-dichlorofluorescin diacetate. The apoptosis rate and cell cycle of AEC II were analyzed by flow cytometry, and apoptosis was determined by western blotting analysis of activated caspase 3. The DNA damage was confirmed with immunofluorescence of H2AX via high‑content analysis. The ROS levels, apoptotic cell number and the expression of γH2AX were markedly increased in the hyperoxia group compared with those in the air group. Concordantly, ROS levels, apoptotic cell number and the expression of γH2AX were significantly lower with a significant arrest of S and G2/M phases in the CGRP/O2 group than in the hyperoxia or CGRP8‑37/O2 groups. CGRP was concluded to protect lung epithelium cells against hyperoxic insult, and upregulation of CGRP may be a possible novel therapeutic target to treat hyperoxic lung injury.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Kallet RH and Matthay MA: Hyperoxic acute lung injury. Respir Care. 58:123–141. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, et al: Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 Countries. JAMA. 315:788–800. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Singh G, Gladdy G, Chandy TT and Sen N: Incidence and outcome of acute lung injury and acute respiratory distress syndrome in the surgical intensive care unit. Indian J Crit Care Med. 18:659–665. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Ward NS, Waxman AB, Homer RJ, Mantell LL, Einarsson O, Du Y and Elias JA: Interleukin-6-induced protection in hyperoxic acute lung injury. Am J Respir Cell Mol Biol. 22:535–542. 2000. View Article : Google Scholar : PubMed/NCBI

5 

Fukumoto J, Fukumoto I, Parthasarathy PT, Cox R, Huynh B, Ramanathan GK, Venugopal RB, Allen-Gipson DS, Lockey RF and Kolliputi N: NLRP3 deletion protects from hyperoxia-induced acute lung injury. Am J Physiol Cell Physio. 305:C182–C189. 2013. View Article : Google Scholar

6 

Crapo JD: Morphologic changes in pulmonary oxygen toxicity. Annu Rev Physiol. 48:721–731. 1986. View Article : Google Scholar : PubMed/NCBI

7 

Durr RA, Dubaybo BA and Thet LA: Repair of chronic hyperoxic lung injury: Changes in lung ultrastructure and matrix. Exp Mol Pathol. 47:219–240. 1987. View Article : Google Scholar : PubMed/NCBI

8 

Wang Y, Feinstein SI, Manevich Y, Ho YS and Fisher AB: Lung injury and mortality with hyperoxia are increased in peroxiredoxin 6 gene-targeted mice. Free Radic Biol Med. 37:1736–1743. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Warner BB, Stuart LA, Papes RA and Wispe JR: Functional and pathological effects of prolonged hyperoxia in neonatal mice. Am J Physiol. 275:L110–L117. 1998.PubMed/NCBI

10 

Russo AF: Calcitonin gene-related peptide (CGRP): A new target for migraine. Annu Rev Pharmacol Toxicol. 55:533–552. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Li WJ and Wang TK: Calcitonin gene-related peptide inhibits interleukin-1beta-induced interleukin-8 secretion in human type II alveolar epithelial cells. Acta Pharmacol Sin. 27:1340–1345. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Filomeni G, De Zio D and Cecconi F: Oxidative stress and autophagy: The clash between damage and metabolic needs. Cell Death Differ. 22:377–388. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Bennett MR: Reactive oxygen species and death: Oxidative DNA damage in atherosclerosis. Cir Res. 88:648–650. 2001. View Article : Google Scholar

14 

Kim SJ, Cheresh P, Williams D, Cheng Y, Ridge K, Schumacker PT, Weitzman S, Bohr VA and Kamp DW: Mitochondria-targeted Ogg1 and aconitase-2 prevent oxidant-induced mitochondrial DNA damage in alveolar epithelial cells. J Biol Chem. 289:6165–6176. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Shao L, Perez RE, Gerthoffer WT, Truog WE and Xu D: Heat shock protein 27 protects lung epithelial cells from hyperoxia-induced apoptotic cell death. Pediatr Res. 65:328–333. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Li Y, Teruya K, Katakura Y, Kabayama S, Otsubo K, Morisawa S, Ishii Y, Gadek Z and Shirahata S: Effect of Reduced Water on the Apoptotic Cell Death Triggered by Oxidative Stress in Pancreatic β HIT-T15 Cell. In: Animal cell technology meets Genomics. Springer. 2:pp121–124. 2005.

17 

Thome UH, Davis IC, Nguyen SV, Shelton BJ and Matalon S: Modulation of sodium transport in fetal alveolar epithelial cells by oxygen and corticosterone. Am J Physiol Lung Cell Mol Physiol. 284:L376–L385. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Li Z, Fang F and Xu F: Effects of different states of oxidative stress on fetal rat alveolar type II epithelial cells in vitro and ROSinduced changes in Wnt signaling pathway expression. Mol Med Rep. 7:1528–1532. 2013.PubMed/NCBI

19 

Li F, He J, Wei J, Cho WC and Liu X: Diversity of epithelial stem cell types in adult lung. Stem Cells Int. 2015:7283072015. View Article : Google Scholar : PubMed/NCBI

20 

De Paepe ME, Mao Q, Chao Y, Powell JL, Rubin LP and Sharma S: Hyperoxia-induced apoptosis and Fas/FasL expression in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol. 289:L647–L659. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Kidane D, Chae WJ, Czochor J, Eckert KA, Glazer PM, Bothwell AL and Sweasy JB: Interplay between DNA repair and inflammation and the link to cancer. Crit Rev Biochem Mol Biol. 49:116–139. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Branzei D and Foiani M: Regulation of DNA repair throughout the cell cycle. Nat Rev Mol Cell Biol. 9:297–308. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Jankov RP, Luo X, Campbell A, Belcastro R, Cabacungan J, Johnstone L, Frndova H, Lye SJ and Tanswell AK: Fibroblast growth factor receptor-1 and neonatal compensatory lung growth after exposure to 95% oxygen. Am J Respir Crit Care Med. 167:1554–1561. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Rogers LK, Tipple TE, Nelin LD and Welty SE: Differential responses in the lungs of newborn mouse pups exposed to 85% or >95% oxygen. Pediatr Res. 65:33–38. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Lee J, Reddy R, Barsky L, Weinberg K and Driscoll B: Contribution of proliferation and DNA damage repair to alveolar epithelial type 2 cell recovery from hyperoxia. Am J Physiol Lung Cell Mol Physiol. 290:L685–L694. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Pace PW, Yao LJ, Wilson JX, Possmayer F, Veldhuizen RA and Lewis JF: The effects of hyperoxia exposure on lung function and pulmonary surfactant in a rat model of acute lung injury. Exp Lung Res. 35:380–398. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Michaelis KA, Agboke F, Liu T, Han K, Muthu M, Galambos C, Yang G, Dennery PA and Wright CJ: IκBβ-mediated NF-κB activation confers protection against hyperoxic lung injury. Am J Respir Cell Mol Biol. 50:429–438. 2014.PubMed/NCBI

28 

Vadivel A, Alphonse RS, Ionescu L, Machado DS, O'Reilly M, Eaton F, Haromy A, Michelakis ED and Thébaud B: Exogenous hydrogen sulfide (H 2 S) protects alveolar growth in experimental O2-induced neonatal lung injury. PLoS One. 9:e909652014. View Article : Google Scholar : PubMed/NCBI

29 

Springer J, Geppetti P, Fischer A and Groneberg DA: Calcitonin gene-related peptide as inflammatory mediator. Pulm Pharmacol Ther. 16:121–130. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Nong YH, Titus RG, Ribeiro JM and Remold HG: Peptides encoded by the calcitonin gene inhibit macrophage function. J Immunol. 143:45–49. 1989.PubMed/NCBI

31 

Li W, Wang T, Ma C, Xiong T, Zhu Y and Wang X: Calcitonin gene-related peptide inhibits interleukin-1beta-induced endogenous monocyte chemoattractant protein-1 secretion in type II alveolar epithelial cells. Am J Physiol Cell Physiol. 291:C456–C465. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Yee M, Vitiello PF, Roper JM, Staversky RJ, Wright TW, McGrath-Morrow SA, Maniscalco WM, Finkelstein JN and O'Reilly MA: Type II epithelial cells are critical target for hyperoxia-mediated impairment of postnatal lung development. Am J Physiol Lung Cell Mol Physiol. 291:L1101–L1111. 2006. View Article : Google Scholar : PubMed/NCBI

33 

O'Reilly MA: DNA damage and cell cycle checkpoints in hyperoxic lung injury: Braking to facilitate repair. Am J Physiol Lung Cell Mol Physiol. 281:L291–L305. 2001.PubMed/NCBI

34 

Drissi H, Lasmoles F, Le Mellay V, Marie PJ and Lieberherr M: Activation of phospholipase C-beta1 via Galphaq/11 during calcium mobilization by calcitonin gene-related peptide. J Biol Chem. 273:20168–20174. 1998. View Article : Google Scholar : PubMed/NCBI

35 

Brigelius-Flohé R, Banning A, Kny M and Böl GF: Redox events in interleukin-1 signaling. Arch Biochem Biophys. 423:66–73. 2004. View Article : Google Scholar : PubMed/NCBI

36 

Fu HM, Li L, Wang YJ, Tang CH, Mi HY, Xu F and Kuang FW: The proliferation-promoting effects of calcitonin gene-related peptide on type II alveolar epithelial cell exposed to hyperoxia mediated by protein kinase C alpha pathway. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 22:263–266. 2010.(In Chinese). PubMed/NCBI

37 

Piette J, Piret B, Bonizzi G, Schoonbroodt S, Merville MP, Legrand-Poels S and Bours V: Multiple redox regulation in NF-kappaB transcription factor activation. Biol Chem. 378:1237–1245. 1997.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Fu H, Zhang T, Huang R, Yang Z, Liu C, Li M, Fang F and Xu F: Calcitonin gene-related peptide protects type II alveolar epithelial cells from hyperoxia-induced DNA damage and cell death. Exp Ther Med 13: 1279-1284, 2017.
APA
Fu, H., Zhang, T., Huang, R., Yang, Z., Liu, C., Li, M. ... Xu, F. (2017). Calcitonin gene-related peptide protects type II alveolar epithelial cells from hyperoxia-induced DNA damage and cell death. Experimental and Therapeutic Medicine, 13, 1279-1284. https://doi.org/10.3892/etm.2017.4132
MLA
Fu, H., Zhang, T., Huang, R., Yang, Z., Liu, C., Li, M., Fang, F., Xu, F."Calcitonin gene-related peptide protects type II alveolar epithelial cells from hyperoxia-induced DNA damage and cell death". Experimental and Therapeutic Medicine 13.4 (2017): 1279-1284.
Chicago
Fu, H., Zhang, T., Huang, R., Yang, Z., Liu, C., Li, M., Fang, F., Xu, F."Calcitonin gene-related peptide protects type II alveolar epithelial cells from hyperoxia-induced DNA damage and cell death". Experimental and Therapeutic Medicine 13, no. 4 (2017): 1279-1284. https://doi.org/10.3892/etm.2017.4132
Copy and paste a formatted citation
x
Spandidos Publications style
Fu H, Zhang T, Huang R, Yang Z, Liu C, Li M, Fang F and Xu F: Calcitonin gene-related peptide protects type II alveolar epithelial cells from hyperoxia-induced DNA damage and cell death. Exp Ther Med 13: 1279-1284, 2017.
APA
Fu, H., Zhang, T., Huang, R., Yang, Z., Liu, C., Li, M. ... Xu, F. (2017). Calcitonin gene-related peptide protects type II alveolar epithelial cells from hyperoxia-induced DNA damage and cell death. Experimental and Therapeutic Medicine, 13, 1279-1284. https://doi.org/10.3892/etm.2017.4132
MLA
Fu, H., Zhang, T., Huang, R., Yang, Z., Liu, C., Li, M., Fang, F., Xu, F."Calcitonin gene-related peptide protects type II alveolar epithelial cells from hyperoxia-induced DNA damage and cell death". Experimental and Therapeutic Medicine 13.4 (2017): 1279-1284.
Chicago
Fu, H., Zhang, T., Huang, R., Yang, Z., Liu, C., Li, M., Fang, F., Xu, F."Calcitonin gene-related peptide protects type II alveolar epithelial cells from hyperoxia-induced DNA damage and cell death". Experimental and Therapeutic Medicine 13, no. 4 (2017): 1279-1284. https://doi.org/10.3892/etm.2017.4132
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