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
October-2020 Volume 44 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
October-2020 Volume 44 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

  • Supplementary Files
    • Supplementary_Data.pdf
Article

Sensitivity of human papillomavirus‑positive and ‑negative oropharyngeal cancer cell lines to ionizing irradiation

  • Authors:
    • Stefan Holzhauser
    • Evelyne Pirotte
    • Joanne Jones
    • David Owens
    • Ali Al‑Hussaini
    • Peter Giles
    • Mererid Evans
    • Stephen Man
    • Ned Powell
  • View Affiliations / Copyright

    Affiliations: HPV Research Group, Cardiff University, School of Medicine, Cardiff CF14 4XN, UK, Ear Nose/Throat/Head and Neck Surgery Department, University Hospital of Wales, Cardiff and Vale University Health Board, Cardiff CF14 4XW, UK, Wales Gene Park, Cardiff University, Cardiff CF14 4XN, UK, Velindre Cancer Centre, Cardiff CF14 2TL, UK, Division of Cancer and Genetics, Cardiff University, School of Medicine, Cardiff CF14 4XN, UK
  • Pages: 1717-1726
    |
    Published online on: July 31, 2020
       https://doi.org/10.3892/or.2020.7709
  • 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

Human papillomavirus‑positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) has increased in incidence and has a much better prognosis than HPV‑negative (HPV‑) OPSCC with radiotherapy alone, but exactly why is unknown. The present study therefore aimed to further examine the sensitivity and possible changes in gene expression of several HPV+ and HPV‑ OPSCC, including various novel cell lines, upon ionizing irradiation (IR). Previously established HPV+ UM‑SCC‑47, UPCI‑SCC‑90, CU‑OP‑2, CU‑OP‑3 and HPV‑ UM‑SCC‑4, UM‑SCC‑6, UM‑SCC‑74a, UM‑SCC‑19 and newly established CU‑OP‑17 and CU‑OP‑20, characterised here, were subjected to 0‑6 Gy. Surviving fractions of each cell line were tested by clonogenic assays, and irregularities in cell cycle responses were examined by flow cytometry, while changes in gene expression were followed by mRNA sequencing. HPV+ OPSCC cell lines showed greater variation in sensitivity to ionizing irradiation (IR) and tended to be more sensitive than HPV‑ OPSCC cell lines. However, their IR sensitivity was not correlated to the proportion of cells in G2 arrest, and HPV‑ cell lines generally showed lower increases in G2 after IR. Upon IR with 2 Gy, mRNA sequencing revealed an increase in minor HPV integration sites in HPV+ cell lines, and some changes in gene expression in OPSCC cell lines, but not primarily those associated with DNA repair. To conclude, HPV+ OPSCC cell lines showed greater variation in their sensitivity to IR, with some that were radioresistant, but overall the HPV+ OPSCC group still tended to be more sensitive to IR than the HPV‑ OPSCC group. In addition, HPV+ OPSCC lines were more frequently in G2 as compared to HPV‑ cell lines, but the increase in G2 arrest upon IR in HPV+ OPSCC was not correlated to sensitivity to IR. Increases in minor HPV integration sites and changes in gene expression were also demonstrated after irradiation with 2 Gy.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Evans M, Newcombe R, Fiander A, Powell J, Rolles M, Thavaraj S, Robinson M and Powell N: Human papillomavirus-associated oropharyngeal cancer: An observational study of diagnosis, prevalence and prognosis in a UK population. BMC Cancer. 13:2202013. View Article : Google Scholar : PubMed/NCBI

2 

Haeggblom L, Attoff T, Yu J, Holzhauser S, Vlastos A, Mirzae L, Ährlund-Richter A, Munck-Wikland E, Marklund L, Hammarstedt-Nordenvall L, et al: Changes in incidence and prevalence of human papillomavirus in tonsillar and base of tongue cancer during 2000–2016 in the Stockholm region and Sweden. Head Neck. 41:1583–1590. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Näsman A, Nordfors C, Holzhauser S, Vlastos A, Tertipis N, Hammar U, Hammarstedt-Nordenvall L, Marklund L, Munck-Wikland E, Ramqvist T, et al: Incidence of human papillomavirus positive tonsillar and base of tongue carcinoma: A stabilisation of an epidemic of viral induced carcinoma? Eur J Cancer. 51:55–61. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, et al: Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 29:4294–4301. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Näsman A, Du J and Dalianis T: A global epidemic increase of an HPV-induced tonsil and tongue base cancer-potential benefit from a pan-gender use of HPV vaccine. J Intern Med. 287:134–152. 2020. View Article : Google Scholar : PubMed/NCBI

6 

Mellin H, Friesland S, Lewensohn R, Dalianis T and Munck-Wikland E: Human papillomavirus (HPV) DNA in tonsillar cancer: Clinical correlates, risk of relapse, and survival. Int J Cancer. 89:300–304. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Schache AG, Powell NG, Cuschieri KS, Robinson M, Leary S, Mehanna H, Rapozo D, Long A, Cubie H, Junor E, et al: HPV-related oropharynx cancer in the United Kingdom: An evolution in the understanding of disease etiology. Cancer Res. 76:6598–6606. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Schache AG, Simcock R, Gilbert DC and Shaw RJ: Changing face of HPV related cancer in the UK. BMJ. 343:d66752011. View Article : Google Scholar : PubMed/NCBI

9 

Bersani C, Mints M, Tertipis N, Haeggblom L, Sivars L, Ährlund-Richter A, Vlastos A, Smedberg C, Grün N, Munck-Wikland E, et al: A model using concomitant markers for predicting outcome in human papillomavirus positive oropharyngeal cancer. Oral Oncol. 68:53–59. 2017. View Article : Google Scholar : PubMed/NCBI

10 

Owadally W, Hurt C, Timmins H, Parsons E, Townsend S, Patterson J, Hutcheson K, Powell N, Beasley M, Palaniappan N, et al: PATHOS: A phase II/III trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for human papillomavirus (HPV) positive oropharyngeal cancer. BMC Cancer. 15:6022015. View Article : Google Scholar : PubMed/NCBI

11 

Arenz A, Ziemann F, Mayer C, Wittig A, Dreffke K, Preising S, Wagner S, Klussmann JP, Engenhart-Cabillic R and Wittekindt C: Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis. Strahlenther Onkol. 190:839–846. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Kimple RJ, Smith MA, Blitzer GC, Torres AD, Martin JA, Yang RZ, Peet CR, Lorenz LD, Nickel KP, Klingelhutz AJ, et al: Enhanced radiation sensitivity in HPV-positive head and neck cancer. Cancer Res. 73:4791–4800. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Rieckmann T, Tribius S, Grob TJ, Meyer F, Busch CJ, Petersen C, Dikomey E and Kriegs M: HNSCC cell lines positive for HPV and p16 possess higher cellular radiosensitivity due to an impaired DSB repair capacity. Radiother Oncol. 107:242–246. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Vlashi E, Chen AM, Boyrie S, Yu G, Nguyen A, Brower PA, Hess CB and Pajonk F: Radiation-induced dedifferentiation of head and neck cancer cells into cancer stem cells depends on human papillomavirus status. Int J Radiat Oncol Biol Phys. 94:1198–1206. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Wang L, Wang X, Li Y, Han S, Zhu J, Wang X, Molkentine DP, Blanchard P, Yang Y, Zhang R, et al: Human papillomavirus status and the relative biological effectiveness of proton radiotherapy in head and neck cancer cells. Head Neck. 39:708–715. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Reid P, Wilson P, Li Y, Marcu LG, Staudacher AH, Brown MP and Bezak E: Experimental investigation of radiobiology in head and neck cancer cell lines as a function of HPV status, by MTT assay. Sci Rep. 8:77442018. View Article : Google Scholar : PubMed/NCBI

17 

Reid P, Wilson P, Li Y, Marcu LG, Staudacher AH, Brown MP and Bezak E: In vitro investigation of head and neck cancer stem cell proportions and their changes following X-ray irradiation as a function of HPV status. PLoS One. 12:e01861862017. View Article : Google Scholar : PubMed/NCBI

18 

Pirotte EF, Holzhauser S, Owens D, Quine S, Al-Hussaini A, Christian AD, Giles PJ, Man ST, Evans M and Powell NG: Sensitivity to inhibition of DNA repair by olaparib in novel oropharyngeal cancer cell lines infected with human papillomavirus. PLoS One. 13:e02079342018. View Article : Google Scholar : PubMed/NCBI

19 

Nordfors C, Vlastos A, Du J, Ahrlund-Richter A, Tertipis N, Grün N, Romanitan M, Haeggblom L, Roosaar A, Dahllöf G, et al: Human papillomavirus prevalence is high in oral samples of patients with tonsillar and base of tongue cancer. Oral Oncol. 50:491–497. 2014. View Article : Google Scholar : PubMed/NCBI

20 

West CM, Davidson SE, Roberts SA and Hunter RD: Intrinsic radiosensitivity and prediction of patient response to radiotherapy for carcinoma of the cervix. Br J Cancer. 68:819–823. 1993. View Article : Google Scholar : PubMed/NCBI

21 

Watson JV, Chambers SH and Smith PJ: A pragmatic approach to the analysis of DNA histograms with a definable G1 peak. Cytometry. 8:1–8. 1987. View Article : Google Scholar : PubMed/NCBI

22 

Liao Y, Smyth GK and Shi W: FeatureCounts: An efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 30:923–930. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Robinson JT, Thorvaldsdottir H, Winckler W, Guttman M, Lander ES, Getz G and Mesirov JP: Integrative genomics viewer. Nat Biotechnol. 29:24–26. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Love MI, Huber W and Anders S: Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15:5502014. View Article : Google Scholar : PubMed/NCBI

25 

Benjamini Y and Hochberg Y: Controlling the false fiscovery rate: A practical and powerful approach to multiple testing. J R Stat Soc B. 57:289–300. 1995.

26 

Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D, Jones SJ and Marra MA: Circos: An information aesthetic for comparative genomics. Genome Res. 19:1639–1645. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Nulton TJ, Kim NK, DiNardo LJ, Morgan IM and Windle B: Patients with integrated HPV16 in head and neck cancer show poor survival. Oral Oncol. 80:52–55. 2018. View Article : Google Scholar : PubMed/NCBI

28 

McBride AA and Warburton A: The role of integration in oncogenic progression of HPV-associated cancers. PLoS Pathog. 13:e10062112017. View Article : Google Scholar : PubMed/NCBI

29 

Haeggblom L, Nordfors C, Tertipis N, Bersani C, Ramqvist T, Näsman A and Dalianis T: Effects of irradiation on human leukocyte antigen class I expression in human papillomavirus positive and negative base of tongue and mobile tongue squamous cell carcinoma cell lines. Int J Oncol. 50:1423–1430. 2017. View Article : Google Scholar

30 

Spanos WC, Nowicki P, Lee DW, Hoover A, Hostager B, Gupta A, Anderson ME and Lee JH: Immune response during therapy with cisplatin or radiation for human papillomavirus-related head and neck cancer. Arch Otolaryngol Head Neck Surg. 135:1137–1146. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Vermeer DW, Spanos WC, Vermeer PD, Bruns AM, Lee KM and Lee JH: Radiation-induced loss of cell surface CD47 enhances immune-mediated clearance of human papillomavirus-positive cancer. Int J Cancer. 133:120–129. 2013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Holzhauser S, Pirotte E, Jones J, Owens D, Al‑Hussaini A, Giles P, Evans M, Man S and Powell N: Sensitivity of human papillomavirus‑positive and ‑negative oropharyngeal cancer cell lines to ionizing irradiation. Oncol Rep 44: 1717-1726, 2020.
APA
Holzhauser, S., Pirotte, E., Jones, J., Owens, D., Al‑Hussaini, A., Giles, P. ... Powell, N. (2020). Sensitivity of human papillomavirus‑positive and ‑negative oropharyngeal cancer cell lines to ionizing irradiation. Oncology Reports, 44, 1717-1726. https://doi.org/10.3892/or.2020.7709
MLA
Holzhauser, S., Pirotte, E., Jones, J., Owens, D., Al‑Hussaini, A., Giles, P., Evans, M., Man, S., Powell, N."Sensitivity of human papillomavirus‑positive and ‑negative oropharyngeal cancer cell lines to ionizing irradiation". Oncology Reports 44.4 (2020): 1717-1726.
Chicago
Holzhauser, S., Pirotte, E., Jones, J., Owens, D., Al‑Hussaini, A., Giles, P., Evans, M., Man, S., Powell, N."Sensitivity of human papillomavirus‑positive and ‑negative oropharyngeal cancer cell lines to ionizing irradiation". Oncology Reports 44, no. 4 (2020): 1717-1726. https://doi.org/10.3892/or.2020.7709
Copy and paste a formatted citation
x
Spandidos Publications style
Holzhauser S, Pirotte E, Jones J, Owens D, Al‑Hussaini A, Giles P, Evans M, Man S and Powell N: Sensitivity of human papillomavirus‑positive and ‑negative oropharyngeal cancer cell lines to ionizing irradiation. Oncol Rep 44: 1717-1726, 2020.
APA
Holzhauser, S., Pirotte, E., Jones, J., Owens, D., Al‑Hussaini, A., Giles, P. ... Powell, N. (2020). Sensitivity of human papillomavirus‑positive and ‑negative oropharyngeal cancer cell lines to ionizing irradiation. Oncology Reports, 44, 1717-1726. https://doi.org/10.3892/or.2020.7709
MLA
Holzhauser, S., Pirotte, E., Jones, J., Owens, D., Al‑Hussaini, A., Giles, P., Evans, M., Man, S., Powell, N."Sensitivity of human papillomavirus‑positive and ‑negative oropharyngeal cancer cell lines to ionizing irradiation". Oncology Reports 44.4 (2020): 1717-1726.
Chicago
Holzhauser, S., Pirotte, E., Jones, J., Owens, D., Al‑Hussaini, A., Giles, P., Evans, M., Man, S., Powell, N."Sensitivity of human papillomavirus‑positive and ‑negative oropharyngeal cancer cell lines to ionizing irradiation". Oncology Reports 44, no. 4 (2020): 1717-1726. https://doi.org/10.3892/or.2020.7709
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