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
January-2015 Volume 9 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
January-2015 Volume 9 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

Effect of epigallocatechin-3-gallate on proliferation and phenotype maintenance in rabbit articular chondrocytes in vitro

  • Authors:
    • Haojia Huang
    • Qin Liu
    • Lei Liu
    • Huayu Wu
    • Li Zheng
  • View Affiliations / Copyright

    Affiliations: Graduate School, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Research Center for Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Cell Biology and Genetics, School of Premedical Sciences, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
  • Pages: 213-218
    |
    Published online on: November 10, 2014
       https://doi.org/10.3892/etm.2014.2057
  • 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

In autologous chondrocyte implantation (ACI) to restore defective cartilage, limited cell numbers and dedifferentiation of chondrocytes are the major difficulties. An alternative is the use of growth factors, but their high cost and potential for tumorigenesis are major obstacles. To ensure successful ACI therapy, it is important to find an effective substitute pro‑chondrogenic agent. Epigallocatechin‑3‑gallate (EGCG), one of the green tea catechins, has been widely investigated in studies of interleukin‑1β‑induced chondrocytes. In the present study, the effects of EGCG on rabbit articular chondrocytes were investigated through the examination of cell proliferation, morphology, glycosaminoglycan synthesis and cartilage-specific gene expression. The results showed that EGCG could effectively promote chondrocyte growth and enhance the secretion and synthesis of the cartilage extracellular matrix by upregulating expression levels of aggrecan, collagen II and Sox9 genes. Expression of the collagen I gene was downregulated, which showed that EGCG effectively inhibited the dedifferentiation of chondrocytes. Hypertrophy, which may lead to chondrocyte ossification, was also undetectable in the EGCG groups. In conclusion, the recommended dose of EGCG was found to be in the range of 5 to 20 µM, with the most marked response observed with 10 µM. The present study may provide a basis for the development of a novel agent as a substitute for growth factors in the treatment of articular cartilage defects.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Carranza-Bencano A, García-Paino L, Armas Padrón JR and Cayuela Dominguez A: Neochondrogenesis in repair of full-thickness articular cartilage defects using free autogenous periosteal grafts in the rabbit. A follow-up in six months. Osteoarthritis Cartilage. 8:351–358. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Sánchez M, Anitua E, Azofra J, Andía I, Padilla S and Mujika I: Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin matrices. Am J Sports Med. 35:245–251. 2007. View Article : Google Scholar

3 

Chung C and Burdick JA: Engineering cartilage tissue. Adv Drug Deliv Rev. 60:243–262. 2008. View Article : Google Scholar

4 

Hsieh PC, Thanapipatsiri S, Anderson PC, Wang GJ and Balian G: Repair of full-thickness cartilage defects in rabbit knees with free periosteal graft preincubated with transforming growth factor. Orthopedics. 26:393–402. 2003.PubMed/NCBI

5 

Waterfield MD, Scrace GT, Whittle N, et al: Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature. 304:35–39. 1983. View Article : Google Scholar : PubMed/NCBI

6 

Josephs SF, Guo C, Ratner L and Wong-Staal F: Human-proto-oncogene nucleotide sequences corresponding to the transforming region of simian sarcoma virus. Science. 223:487–491. 1984. View Article : Google Scholar : PubMed/NCBI

7 

Downward J, Yarden Y, Mayes E, et al: Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 307:521–527. 1984. View Article : Google Scholar : PubMed/NCBI

8 

del Peso L, González-García M, Page C, Herrera R and Nuñez G: Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science. 278:687–689. 1997. View Article : Google Scholar : PubMed/NCBI

9 

Rice-Evans CA, Miller NJ and Paganga G: Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med. 20:933–956. 1996. View Article : Google Scholar : PubMed/NCBI

10 

Salah N, Miller NJ, Paganga G, Tijburg L, Bolwell GP and Rice-Evans C: Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain-breaking antioxidants. Arch Biochem Biophys. 322:339–346. 1995. View Article : Google Scholar : PubMed/NCBI

11 

Yang CS and Landau JM: Effects of tea consumption on nutrition and health. J Nutr. 130:2409–2412. 2000.PubMed/NCBI

12 

Blot WJ, McLaughlin JK and Chow WH: Cancer rates among drinkers of black tea. Crit Rev Food Sci Nutr. 37:739–760. 1997. View Article : Google Scholar

13 

Buschman JL: Green tea and cancer in humans: a review of the literature. Nutr Cancer. 31:151–159. 1998. View Article : Google Scholar

14 

Kohlmeier L, Weterings KG, Steck S and Kok FJ: Tea and cancer prevention: an evaluation of the epidemiologic literature. Nutr Cancer. 27:1–13. 1997. View Article : Google Scholar : PubMed/NCBI

15 

Na HK and Surh YJ: Intracellular signaling network as a prime chemopreventive target of (−)-epigallocatechin gallate. Mol Nutr Food Res. 50:152–159. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Bar-Sela G, Epelbaum R and Schaffer M: Curcumin as an anti-cancer agent: review of the gap between basic and clinical applications. Curr Med Chem. 17:190–197. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Li Y, Kong D, Wang Z and Sarkar FH: Regulation of microRNAs by natural agents: An emerging field in chemoprevention and chemotherapy research. Pharm Res. 27:1027–1041. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Mak JC: Potential role of green tea catechins in various disease therapies: progress and promise. Clin Exp Pharmacol Physiol. 39:265–273. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Ahmed S: Green tea polyphenol epigallocatechin 3-gallate in arthritis: progress and promise. Arthritis Res Ther. 12:2082010. View Article : Google Scholar : PubMed/NCBI

20 

Pandey KB and Rizvi SI: Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2:270–278. 2009. View Article : Google Scholar

21 

Mandel SA, Amit T, Weinreb O and Youdim MB: Understanding the broad-spectrum neuroprotective action profile of green tea polyphenols in aging and neurodegenerative diseases. J Alzheimers Dis. 25:187–208. 2011.PubMed/NCBI

22 

Stangl V, Lorenz M and Stangl K: The role of tea and tea flavonoids in cardiovascular health. Mol Nutr Food Res. 50:218–228. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Shanmugam MK, Kannaiyan R and Sethi G: Targeting cell signaling and apoptotic pathways by dietary agents: role in the prevention and treatment of cancer. Nutr Cancer. 63:161–173. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Pan MH, Lai CS, Dushenkov S and Ho CT: Modulation of inflammatory genes by natural dietary bioactive compounds. J Agric Food Chem. 57:4467–4477. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Bae JY, Kanamune J, Han DW, Matsumura K and Hyon SH: Reversible regulation of cell cycle-related genes by epigallocatechin gallate for hibernation of neonatal human tarsal fibroblasts. Cell Transplant. 18:459–469. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Akhtar N and Haqqi TM: Epigallocatechin-3-gallate suppresses the global interleukin-1beta-induced inflammatory response in human chondrocytes. Arthritis Res Ther. 13:R932011. View Article : Google Scholar : PubMed/NCBI

27 

Rasheed Z, Anbazhagan AN, Akhtar N, Ramamurthy S, Voss FR and Haqqi TM: Green tea polyphenol epigallocatechin-3-gallate inhibits advanced glycation end product-induced expression of tumor necrosis factor-alpha and matrix metalloproteinase-13 in human chondrocytes. Arthritis Res Ther. 11:R712009. View Article : Google Scholar : PubMed/NCBI

28 

Ahmed S, Wang N, Lalonde M, Goldberg VM and Haqqi TM: Green tea polyphenol epigallocatechin-3-gallate (EGCG) differentially inhibits interleukin-1 beta-induced expression of matrix metalloproteinase-1 and -13 in human chondrocytes. J Pharmacol Exp Ther. 308:767–773. 2004. View Article : Google Scholar

29 

Buschmann MD and Grodzinsky AJ: A molecular model of proteoglycan-associated electrostatic forces in cartilage mechanics. J Biomech Eng. 117:179–192. 1995. View Article : Google Scholar : PubMed/NCBI

30 

Robinson D, Ash H, Yayon A, Nevo Z and Aviezer D: Characteristics of cartilage biopsies used for autologous chondrocytes transplantation. Cell Transplant. 10:203–208. 2001.PubMed/NCBI

31 

Akiyama H: Transcriptional regulation in chondrogenesis by Sox9. Clin Calcium. 21:845–851. 2011.(In Japanese). PubMed/NCBI

32 

Tew SR and Clegg PD: Analysis of post transcriptional regulation of SOX9 mRNA during in vitro chondrogenesis. Tissue Eng Part A. 17:1801–1807. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Ng LJ, Wheatley S, Muscat GE, et al: SOX9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse. Dev Biol. 183:108–121. 1997. View Article : Google Scholar : PubMed/NCBI

34 

Marshall OJ and Harley VR: Molecular mechanisms of SOX9 action. Mol Genet Metab. 71:455–462. 2000. View Article : Google Scholar : PubMed/NCBI

35 

Davies SR, Chang LW, Patra D, et al: Computational identification and functional validation of regulatory motifs in cartilage-expressed genes. Genome Res. 17:1438–1447. 2007. View Article : Google Scholar : PubMed/NCBI

36 

Tew SR, Li Y, Pothacharoen P, Tweats LM, Hawkins RE and Hardingham TE: Retroviral transduction with SOX9 enhances re-expression of the chondrocyte phenotype in passaged osteoarthritic human articular chondrocytes. Osteoarthritis Cartilage. 13:80–89. 2005. View Article : Google Scholar : PubMed/NCBI

37 

Paul R, Haydon RC, Cheng H, et al: Potential use of Sox9 gene therapy for intervertebral degenerative disc disease. Spine (Phila Pa 1976). 28:755–763. 2003. View Article : Google Scholar

38 

Tsuchiya H, Kitoh H, Sugiura F and Ishiguro N: Chondrogenesis enhanced by overexpression of sox9 gene in mouse bone marrow-derived mesenchymal stem cells. Biochem Biophys Res Commun. 301:338–343. 2003. View Article : Google Scholar : PubMed/NCBI

39 

Benya PD and Shaffer JD: Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell. 30:215–224. 1982. View Article : Google Scholar : PubMed/NCBI

40 

Schnabel M, Marlovits S, Eckhoff G, Fichtel I, Gotzen L, Vécsei V and Schlegel J: Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture. Osteoarthritis Cartilage. 10:62–70. 2002. View Article : Google Scholar : PubMed/NCBI

41 

Karlsen TA, Shahdadfar A and Brinchmann JE: Human primary articular chondrocytes, chondroblasts-like cells, and dedifferentiated chondrocytes: differences in gene, microRNA, and protein expression and phenotype. Tissue Eng Part C Methods. 17:219–227. 2010. View Article : Google Scholar : PubMed/NCBI

42 

Kwan KM, Pang MK, Zhou S, et al: Abnormal compartmentalization of cartilage matrix components in mice lacking collagen X: implications for function. J Cell Biol. 136:459–471. 1997. View Article : Google Scholar : PubMed/NCBI

43 

Adcocks C, Collin P and Buttle DJ: Catechins from green tea (Camellia sinensis) inhibit bovine and human cartilage proteoglycan and type II collagen degradation in vitro. J Nutr. 132:341–346. 2002.PubMed/NCBI

44 

Vankemmelbeke MN, Jones GC, Fowles C, et al: Selective inhibition of ADAMTS-1, -4 and -5 by catechin gallate esters. Eur J Biochem. 270:2394–2403. 2003. View Article : Google Scholar : PubMed/NCBI

45 

Andriamanalijaona R, Kypriotou M, Baugé C, et al: Comparative effects of 2 antioxidants, selenomethionine and epigallocatechin-gallate, on catabolic and anabolic gene expression of articular chondrocytes. J Rheumatol. 32:1958–1967. 2005.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Huang H, Liu Q, Liu L, Wu H and Zheng L: Effect of epigallocatechin-3-gallate on proliferation and phenotype maintenance in rabbit articular chondrocytes in vitro. Exp Ther Med 9: 213-218, 2015.
APA
Huang, H., Liu, Q., Liu, L., Wu, H., & Zheng, L. (2015). Effect of epigallocatechin-3-gallate on proliferation and phenotype maintenance in rabbit articular chondrocytes in vitro. Experimental and Therapeutic Medicine, 9, 213-218. https://doi.org/10.3892/etm.2014.2057
MLA
Huang, H., Liu, Q., Liu, L., Wu, H., Zheng, L."Effect of epigallocatechin-3-gallate on proliferation and phenotype maintenance in rabbit articular chondrocytes in vitro". Experimental and Therapeutic Medicine 9.1 (2015): 213-218.
Chicago
Huang, H., Liu, Q., Liu, L., Wu, H., Zheng, L."Effect of epigallocatechin-3-gallate on proliferation and phenotype maintenance in rabbit articular chondrocytes in vitro". Experimental and Therapeutic Medicine 9, no. 1 (2015): 213-218. https://doi.org/10.3892/etm.2014.2057
Copy and paste a formatted citation
x
Spandidos Publications style
Huang H, Liu Q, Liu L, Wu H and Zheng L: Effect of epigallocatechin-3-gallate on proliferation and phenotype maintenance in rabbit articular chondrocytes in vitro. Exp Ther Med 9: 213-218, 2015.
APA
Huang, H., Liu, Q., Liu, L., Wu, H., & Zheng, L. (2015). Effect of epigallocatechin-3-gallate on proliferation and phenotype maintenance in rabbit articular chondrocytes in vitro. Experimental and Therapeutic Medicine, 9, 213-218. https://doi.org/10.3892/etm.2014.2057
MLA
Huang, H., Liu, Q., Liu, L., Wu, H., Zheng, L."Effect of epigallocatechin-3-gallate on proliferation and phenotype maintenance in rabbit articular chondrocytes in vitro". Experimental and Therapeutic Medicine 9.1 (2015): 213-218.
Chicago
Huang, H., Liu, Q., Liu, L., Wu, H., Zheng, L."Effect of epigallocatechin-3-gallate on proliferation and phenotype maintenance in rabbit articular chondrocytes in vitro". Experimental and Therapeutic Medicine 9, no. 1 (2015): 213-218. https://doi.org/10.3892/etm.2014.2057
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