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
September-2018 Volume 40 Issue 3

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
September-2018 Volume 40 Issue 3

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

Aryl hydrocarbon receptor, a tumor grade‑associated marker of oral cancer, is directly downregulated by polydatin: A pilot study

  • Authors:
    • Manuela Martano
    • Paola Stiuso
    • Angelo Facchiano
    • Salvatore De Maria
    • Daniela Vanacore
    • Brunella Restucci
    • Corrado Rubini
    • Michele Caraglia
    • Giampietro Ravagnan
    • Lorenzo Lo Muzio
  • View Affiliations / Copyright

    Affiliations: Department of Veterinary Medicine and Animal Production, University Federico II of Naples, I-80137 Naples, Italy, Department of Biochemical, Biophysical and General Pathology, Università della Campania ‘Luigi Vanvitelli’, I-80138 Naples, Italy, CNR‑ISA National Research Council, Institute of Food Science, I-83100 Avellino, Italy, Ministry of Education, University and Research (MIUR); CPIA Naples City 1, Pasquale Scura’ Polo Tecnico Fermi Gadda, I‑80141 Naples, Italy, Department of Veterinary Medicine and Animal Production, University Federico II of Naples, I-80137 Naples, Italy, Department of Clinical Sciences, Polytechnic University of Marche, I-60121 Ancona, Italy, Glures spin‑off CNR‑IFT National Research Council, Translational Institute of Pharmacology, I‑00133 Rome, Italy, Department of Clinical and Experimental Medicine, University of Foggia, I-71122 Foggia, Italy
  • Pages: 1435-1442
    |
    Published online on: July 10, 2018
       https://doi.org/10.3892/or.2018.6555
  • 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

Oral squamous cell carcinoma (OSCC) is one of the most aggressive and deadliest tumors worldwide. The aryl hydrocarbon receptor (AHR) is a nuclear transcription factor known as a dioxin receptor and mediates the toxic effects of industrial contaminants. In addition, AHR has been implicated in multiple cellular processes and its expression has been shown to play a critical role in tumorigenesis, including human oral cancer cell lines. In the present study, we evaluated the expression of AHR/HSP-90 in 25 formalin‑fixed, paraffin-embedded human oral cancer specimens by IHC analysis. CYP1A1 expression was regarded as an AHR reporter gene. The data indicated a complete correlation between AHR expression and cancer grade enabling us to propose AHR as a prognostic marker of oral cancer. Moreover, in OSCC cell line CAL27, we observed the modulatory effect of polydatin, a widespread natural substance and direct precursor of resveratrol, on AHR expression. A computational approach was performed to predict the site of interaction of polydatin on the AHR surface. Our studies confirm the involvement of AHR signaling in the clinicopathological specimens of oral cancer and suggest the use of polydatin for oral cancer prevention.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Poland A, Palen D and Glover E: Tumour promotion by TCDD in skin of HRS/J hairless mice. Nature. 300:271–273. 1982. View Article : Google Scholar : PubMed/NCBI

2 

Murray IA, Patterson AD and Perdew GH: Aryl hydrocarbon receptor ligands in cancer: Friend and foe. Nat Rev Cancer. 14:801–814. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Meyer BK, Pray-Grant MG, Vanden Heuvel JP and Perdew GH: Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity. Mol Cell Biol. 18:978–88. 1998. View Article : Google Scholar : PubMed/NCBI

4 

Zhou S, Liu J and Chowbay B: Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev. 41:89–295. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Stanford EA, Ramirez-Cardenas A, Wang Z, Novikov O, Alamoud K, Koutrakis P, Mizgerd JP, Genco CA, Kukuruzinska M, Monti S, et al: Role for the Aryl hydrocarbon receptor and diverse ligands in oral squamous cell carcinoma migration and tumorigenesis. Mol Cancer Res. 14:696–706. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Quattrochi LC and Tukey RH: Nuclear uptake of the Ah (dioxin) receptor in response to omeprazole: Transcriptional activation of the human CYP1A1 gene. Mol Pharmacol. 43:504–508. 1993.PubMed/NCBI

7 

Singh SU, Casper RF, Fritz PC, Sukhu B, Ganss B, Girard B Jr, Savouret JF and Tenenbaum HC: Inhibition of dioxin effects on bone formation in vitro by a newly described aryl hydrocarbon receptor antagonist, resveratrol. J Endocrinol. 167:183–195. 2000. View Article : Google Scholar : PubMed/NCBI

8 

Lee JE and Safe S: Involvement of a post-transcriptional mechanism in the inhibition of CYP1A1 expression by resveratrol in breast cancer cells. Biochem Pharmacol. 62:1113–1124. 2001. View Article : Google Scholar : PubMed/NCBI

9 

He H, Zhao Y, Chen X, Zheng Y, Wu X, Wang R, Li T, Yu Q, Jing J, Ma L, et al: Quantitative determination of trans-polydatin, a natural strong anti-oxidative compound, in rat plasma and cellular environment of a human colon adenocarcinoma cell line for pharmacokinetic studies. J Chromatogr B Analyt Technol Biomed Life Sci. 855:145–151. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Henry-Vitrac C, Desmoulière A, Girard D, Mérillon JM and Krisa S: Transport, deglycosylation, and metabolism of trans-piceid by small intestinal epithelial cells. Eur J Nutr. 45:376–382. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Rotches-Ribalta M, Andres-Lacueva C, Estruch R, Escribano E and Urpi-Sarda M: Pharmacokinetics of resveratrol metabolic profile in healthy humans after moderate consumption of red wine and grape extract tablets. Pharmacol Res. 66:375–382. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Ravagnan GP: Extracts from spermatophyte plants with antitumor activity Euoropean Patent EP1292319B1. Filed May 29, 2001; issued Aug 15. 2002

13 

Wang C, Luo Y, Lu J, Wang Y and Sheng G: Polydatin induces apoptosis and inhibits growth of acute monocytic leukemia cells. J Biochem Mol Toxicol. 30:200–205. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Cao WJ, Wu K, Wang C and Wan DM: Polydatin-induced cell apoptosis and cell cycle arrest are potentiated by Janus kinase 2 inhibition in leukemia cells. Mol Med Rep. 13:3297–3302. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Zhang Y, Zhuang Z, Meng Q, Jiao Y, Xu J and Fan S: Polydatin inhibits growth of lung cancer cells by inducing apoptosis and causing cell cycle arrest. Oncol Lett. 7:295–301. 2014. View Article : Google Scholar : PubMed/NCBI

16 

De Maria S, Scognamiglio I, Lombardi A, Amodio N, Caraglia M, Cartenì M, Ravagnan G and Stiuso P: Polydatin, a natural precursor of resveratrol, induces cell cycle arrest and differentiation of human colorectal Caco-2 cell. J Transl Med. 11:2642013. View Article : Google Scholar : PubMed/NCBI

17 

Hogg SJ, Chitcholtan K, Hassan W, Sykes PH and Garrill A: Resveratrol, acetyl-resveratrol, and polydatin exhibit antigrowth activity against 3D cell aggregates of the SKOV-3 and OVCAR-8 ovarian cancer cell lines. Obstet Gynecol Int. 2015:2795912015. View Article : Google Scholar : PubMed/NCBI

18 

Hughes D, Guttenplan JB, Marcus CB, Subbaramaiah K and Dannenberg AJ: Heat shock protein 90 inhibitors suppress aryl hydrocarbon receptor-mediated activation of CYP1A1 and CYP1B1 transcription and DNA adduct formation. Cancer Prev Res. 1:485–493. 2008. View Article : Google Scholar

19 

Tsuji N, Fukuda N, Nagata Y, Okada H, Haga A, Hatakeyama S, Yoshida S, Okamoto T, Hosaka M, Sekine K, et al: The activation mechanism of the aryl hydrocarbon receptor (AhR) by molecular chaperone HSP-90. FEBS Open Bio. 4:796–803. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Salzano M, Marabotti A, Milanesi L and Facchiano A: Human aryl-hydrocarbon receptor and its interaction with dioxin and physiological ligands investigated by molecular modelling and docking simulations. Biochem Biophys Res Commun. 413:176–181. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Bryne M, Koppang HS, Lilleng R, Stene T, Bang G and Dabelsteen E: New malignancy grading is a better prognostic indicator than Broder's grading in oral squamous cell carcinomas. J Oral Pathol Med. 18:432–437. 1989. View Article : Google Scholar : PubMed/NCBI

22 

Martano M, Carella F, Squillacioti C, Restucci B, Mazzotta M, Lo Muzio L and Maiolino P: Metallothionein expression in canine cutaneous apocrine gland tumors. Anticancer Res. 32:747–752. 2012.PubMed/NCBI

23 

John K, Lahoti TS, Wagner K, Hughes JM and Perdew GH: The Ah receptor regulates growth factor expression in head and neck squamous cell carcinoma cell lines. Mol Carcinog. 53:765–76. 2014. View Article : Google Scholar : PubMed/NCBI

24 

DiNatale BC, Smith K, John K, Krishnegowda G, Amin SG and Perdew GH: Ah receptor antagonism represses head and neck tumor cell aggressive phenotype. Mol Cancer Res. 10:1369–1379. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Yin XF, Chen J, Mao W, Wang YH and Chen MH: Downregulation of aryl hydrocarbon receptor expression decreases gastric cancer cell growth and invasion. Oncol Rep. 30:364–370. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Tsai CH, Li CH, Cheng YW, Lee CC, Liao PL, Lin CH, Huang SH and Kang JJ: The inhibition of lung cancer cell migration by AhR-regulated autophagy. Sci Rep. 7:419272017. View Article : Google Scholar : PubMed/NCBI

27 

Brooks J and Eltom SE: Malignant transformation of mammary epithelial cells by ectopic overexpression of the aryl hydrocarbon receptor. Curr Cancer Drug Targets. 11:654–669. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Al-Dhfyan A, Alhoshani A and Korashy HM: Aryl hydrocarbon receptor/Cytochrome P450 1A1 pathway mediates breast cancer stem cells expansion through PTEN inhibition and β-Catenin and Akt activation. Mol Cancer. 16:692017. View Article : Google Scholar : PubMed/NCBI

29 

Androutsopoulos VP, Tsatsakis AM and Spandidos DA: Cytochrome P450 CYP1A1: Wider roles Androutsopoulos in cancer progression and prevention. BMC Cancer. 9:1872009. View Article : Google Scholar : PubMed/NCBI

30 

Moyer BJ, Rojas IY, Murray IA, Lee S, Hazlett HF, Perdew GH and Tomlinson CR: Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors activate the aryl hydrocarbon receptor. Toxicol Appl Pharmacol. 323:74–80. 2017. View Article : Google Scholar : PubMed/NCBI

31 

Hamidullah, Kumar R, Saini KS, Kumar A, Kumar S, Ramakrishna E, Maurya R, Konwar R and Chattopadhyay N: Quercetin-6-C-β-D-glucopyranoside, natural analog of quercetin exhibits anti-prostate cancer activity by inhibiting Akt-mTOR pathway via aryl hydrocarbon receptor. Biochimie. 119:68–79. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Chang CH, Lee CY, Lu CC, Tsai FJ, Hsu YM, Tsao JW, Juan YN, Chiu HY, Yang JS and Wang CC: Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral cancer CAR cells: A key role of AMPK and Akt/mTOR signaling. Int J Oncol. 50:873–882. 2017. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Martano M, Stiuso P, Facchiano A, De Maria S, Vanacore D, Restucci B, Rubini C, Caraglia M, Ravagnan G, Lo Muzio L, Lo Muzio L, et al: Aryl hydrocarbon receptor, a tumor grade‑associated marker of oral cancer, is directly downregulated by polydatin: A pilot study. Oncol Rep 40: 1435-1442, 2018.
APA
Martano, M., Stiuso, P., Facchiano, A., De Maria, S., Vanacore, D., Restucci, B. ... Lo Muzio, L. (2018). Aryl hydrocarbon receptor, a tumor grade‑associated marker of oral cancer, is directly downregulated by polydatin: A pilot study. Oncology Reports, 40, 1435-1442. https://doi.org/10.3892/or.2018.6555
MLA
Martano, M., Stiuso, P., Facchiano, A., De Maria, S., Vanacore, D., Restucci, B., Rubini, C., Caraglia, M., Ravagnan, G., Lo Muzio, L."Aryl hydrocarbon receptor, a tumor grade‑associated marker of oral cancer, is directly downregulated by polydatin: A pilot study". Oncology Reports 40.3 (2018): 1435-1442.
Chicago
Martano, M., Stiuso, P., Facchiano, A., De Maria, S., Vanacore, D., Restucci, B., Rubini, C., Caraglia, M., Ravagnan, G., Lo Muzio, L."Aryl hydrocarbon receptor, a tumor grade‑associated marker of oral cancer, is directly downregulated by polydatin: A pilot study". Oncology Reports 40, no. 3 (2018): 1435-1442. https://doi.org/10.3892/or.2018.6555
Copy and paste a formatted citation
x
Spandidos Publications style
Martano M, Stiuso P, Facchiano A, De Maria S, Vanacore D, Restucci B, Rubini C, Caraglia M, Ravagnan G, Lo Muzio L, Lo Muzio L, et al: Aryl hydrocarbon receptor, a tumor grade‑associated marker of oral cancer, is directly downregulated by polydatin: A pilot study. Oncol Rep 40: 1435-1442, 2018.
APA
Martano, M., Stiuso, P., Facchiano, A., De Maria, S., Vanacore, D., Restucci, B. ... Lo Muzio, L. (2018). Aryl hydrocarbon receptor, a tumor grade‑associated marker of oral cancer, is directly downregulated by polydatin: A pilot study. Oncology Reports, 40, 1435-1442. https://doi.org/10.3892/or.2018.6555
MLA
Martano, M., Stiuso, P., Facchiano, A., De Maria, S., Vanacore, D., Restucci, B., Rubini, C., Caraglia, M., Ravagnan, G., Lo Muzio, L."Aryl hydrocarbon receptor, a tumor grade‑associated marker of oral cancer, is directly downregulated by polydatin: A pilot study". Oncology Reports 40.3 (2018): 1435-1442.
Chicago
Martano, M., Stiuso, P., Facchiano, A., De Maria, S., Vanacore, D., Restucci, B., Rubini, C., Caraglia, M., Ravagnan, G., Lo Muzio, L."Aryl hydrocarbon receptor, a tumor grade‑associated marker of oral cancer, is directly downregulated by polydatin: A pilot study". Oncology Reports 40, no. 3 (2018): 1435-1442. https://doi.org/10.3892/or.2018.6555
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