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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
April-2022 Volume 60 Issue 4

Full Size Image

Cover Legend PDF

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-2022 Volume 60 Issue 4

Full Size Image

Cover Legend PDF

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

Discovery of a potent cytotoxic agent that promotes G2/M phase cell cycle arrest and apoptosis in a malignant human pharyngeal squamous carcinoma cell line

  • Authors:
    • Manunya Nuth
    • Manjunatha R. Benakanakere
    • Robert P. Ricciardi
  • View Affiliations / Copyright

    Affiliations: Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • Article Number: 41
    |
    Published online on: February 24, 2022
       https://doi.org/10.3892/ijo.2022.5331
  • 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

Squamous cell carcinoma is the major form of malignancy that arises in head and neck cancer. The modest improvement in the 5‑year survival rate underpins its complex etiology and provides the impetus for the discovery of new therapeutics. The present study describes the discovery of an indole‑based small molecule (24a) that was a potent cytotoxic agent with antiproliferative and pro‑apoptotic properties against a pharyngeal carcinoma cell line, Detroit 562, effectively killing the cells at a half‑maximal inhibitory concentration of 0.03 µM, as demonstrated using cell proliferation studies. The antiproliferative property of 24a was demonstrated by its ability to promote G2/M blockade, as assessed by cell cycle analysis using flow cytometry and the monitoring of real‑time cell cycle progression by the fluorescence ubiquitination‑based cell cycle indicator. This pro‑apoptotic property is supported by the promotion of TUNEL‑staining and increase in the activities of caspases‑3/7 and ‑6, in addition to the expression of death receptors and the cleavage of poly (ADP‑ribose) polymerase 1 protein as demonstrated by western blotting. Given that Detroit 562 lacks functional p53, it is suggested that 24a acts independently of the tumor suppressor.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Vigneswaran N and Williams MD: Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral Maxillofac Surg Clin North Am. 26:123–141. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Brennan JA, Boyle JO, Koch WM, Goodman SN, Hruban RH, Eby YJ, Couch MJ, Forastiere AA and Sidransky D: Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck. N Engl J Med. 332:712–717. 1995. View Article : Google Scholar : PubMed/NCBI

3 

D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH and Gillison ML: Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 356:1944–1956. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

5 

Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Haddad RI and Shin DM: Recent advances in head and neck cancer. N Engl J Med. 359:1143–1154. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Poeta ML, Manola J, Goldwasser MA, Forastiere A, Benoit N, Califano JA, Ridge JA, Goodwin J, Kenady D, Saunders J, et al: TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med. 357:2552–2561. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Martin D, Abba MC, Molinolo AA, Vitale-Cross L, Wang Z, Zaida M, Delic NC, Samuels Y, Lyons JG and Gutkind JS: The head and neck cancer cell oncogenome: A platform for the development of precision molecular therapies. Oncotarget. 5:8906–8923. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Algazi AP and Grandis JR: Head and neck cancer in 2016: A watershed year for improvements in treatment? Nat Rev Clin Oncol. 14:76–78. 2017. View Article : Google Scholar

10 

Siegel RL, Miller KD, Fuchs HE and Jemal A: Cancer statistics, 2021. CA Cancer J Clin. 71:7–33. 2021. View Article : Google Scholar : PubMed/NCBI

11 

Bar-Ad V, Palmer J, Yang H, Cognetti D, Curry J, Luginbuhl A, Tuluc M, Campling B and Axelrod R: Current management of locally advanced head and neck cancer: The combination of chemotherapy with locoregional treatments. Semin Oncol. 41:798–806. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Dasari S and Tchounwou PB: Cisplatin in cancer therapy: Molecular mechanisms of action. Eur J Pharmacol. 740:364–378. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Hartner L: Chemotherapy for oral cancer. Dent Clin North Am. 62:87–97. 2018. View Article : Google Scholar

14 

Sano D, Xie TX, Ow TJ, Zhao M, Pickering CR, Zhou G, Sandulache VC, Wheeler DA, Gibbs RA, Caulin C and Myers JN: Disruptive TP53 mutation is associated with aggressive disease characteristics in an orthotopic murine model of oral tongue cancer. Clin Cancer Res. 17:6658–6670. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Nuth M, Guan H, Zhukovskaya N, Saw YL and Ricciardi RP: Design of potent poxvirus inhibitors of the heterodimeric processivity factor required for viral replication. J Med Chem. 56:3235–3246. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Nuth M, Guan H, Xiao Y, Kulp JL III, Parker MH, Strobel ED, Isaacs SN, Scott RW, Reitz AB and Ricciardi RP: Mutation and structure guided discovery of an antiviral small molecule that mimics an essential C-Terminal tripeptide of the vaccinia D4 processivity factor. Antiviral Res. 162:178–185. 2019. View Article : Google Scholar

17 

Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol. 35:495–516. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Koh SB, Mascalchi P, Rodriguez E, Lin Y, Jodrell DI, Richards FM and Lyons SK: A quantitative FastFUCCI assay defines cell cycle dynamics at a single-cell level. J Cell Sci. 130:512–520. 2017.

19 

Sakaue-Sawano A, Kurokawa H, Morimura T, Hanyu A, Hama H, Osawa H, Kashiwagi S, Fukami K, Miyata T, Miyoshi H, et al: Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell. 132:487–498. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Kaufmann SH, Desnoyers S, Ottaviano Y, Davidson NE and Poirier GG: Specific proteolytic cleavage of poly(ADP-ribose) polymerase: An early marker of chemotherapy-induced apoptosis. Cancer Res. 53:3976–3985. 1993.PubMed/NCBI

21 

Chaitanya GV, Alexander JS and Babu PP: PARP-1 cleavage fragments: Signatures of cell-death proteases in neurodegeneration. Cell Commun Signal. 8:312010. View Article : Google Scholar : PubMed/NCBI

22 

Vogelstein B, Lane D and Levine AJ: Surfing the p53 network. Nature. 408:307–310. 2000. View Article : Google Scholar : PubMed/NCBI

23 

Somers KD, Merrick MA, Lopez ME, Incognito LS, Schechter GL and Casey G: Frequent p53 mutations in head and neck cancer. Cancer Res. 52:5997–6000. 1992.PubMed/NCBI

24 

Giaccia AJ and Kastan MB: The complexity of p53 modulation: Emerging patterns from divergent signals. Genes Dev. 12:2973–2983. 1998. View Article : Google Scholar : PubMed/NCBI

25 

Bode AM and Dong Z: Post-translational modification of p53 in tumorigenesis. Nat Rev Cancer. 4:793–805. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Deyoung MP and Ellisen LW: p63 and p73 in human cancer: Defining the network. Oncogene. 26:5169–5183. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Sniezek JC, Matheny KE, Westfall MD and Pietenpol JA: Dominant negative p63 isoform expression in head and neck squamous cell carcinoma. Laryngoscope. 114:2063–2072. 2004. View Article : Google Scholar : PubMed/NCBI

28 

Nylander K, Coates PJ and Hall PA: Characterization of the expression pattern of p63α and δnp63α in benign and malignant oral epithelial lesions. Int J Cancer. 87:368–372. 2000. View Article : Google Scholar : PubMed/NCBI

29 

Bisso A, Collavin L and Del Sal G: p73 as a pharmaceutical target for cancer therapy. Curr Pharm Des. 17:578–590. 2011. View Article : Google Scholar : PubMed/NCBI

30 

el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW and Vogelstein B: WAF1, a potential mediator of p53 tumor suppression. Cell. 75:817–825. 1993. View Article : Google Scholar : PubMed/NCBI

31 

Georgakilas AG, Martin OA and Bonner WM: p21: A two-faced genome guardian. Trends Mol Med. 23:310–319. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Leemans CR, Braakhuis BJM and Brakenhoff RH: The molecular biology of head and neck cancer. Nat Rev Cancer. 11:9–22. 2011. View Article : Google Scholar

33 

Bailly C, Thuru X and Quesnel B: Combined cytotoxic chemotherapy and immunotherapy of cancer: Modern times. NAR Cancer. 2:zcaa0022020. View Article : Google Scholar : PubMed/NCBI

34 

Knox RJ, Friedlos F, Lydall DA and Roberts JJ: Mechanism of cytotoxicity of anticancer platinum drugs: Evidence that cis-di amminedichloroplatinum(II) and cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(ii) differ only in the kinetics of their interaction with dna. Cancer Res. 46:1972–1979. 1986.PubMed/NCBI

35 

Boeckman HJ, Trego KS and Turchi JJ: Cisplatin sensitizes cancer cells to ionizing radiation via inhibition of nonhomologous end joining. Mol Cancer Res. 3:277–285. 2005. View Article : Google Scholar : PubMed/NCBI

36 

Grem JL: 5-Fluorouracil: Forty-plus and still ticking. A review of its preclinical and clinical development. Invest New Drugs. 18:299–313. 2000. View Article : Google Scholar : PubMed/NCBI

37 

Bossi P, Resteghini C, Paielli N, Licitra L, Pilotti S and Perrone F: Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma. Oncotarget. 7:74362–74379. 2016. View Article : Google Scholar : PubMed/NCBI

38 

Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, et al: Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 359:1116–1127. 2008. View Article : Google Scholar : PubMed/NCBI

39 

Pendleton KP and Grandis JR: Cisplatin-based chemotherapy options for recurrent and/or metastatic squamous cell cancer of the head and neck. Clin Med Insights Ther. 2013:10.4137/CMT.S10409. 2013.PubMed/NCBI

40 

Johnstone RW, Frew AJ and Smyth MJ: The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer. 8:782–798. 2008. View Article : Google Scholar : PubMed/NCBI

41 

Wu GS, Burns TF, McDonald ER III, Jiang W, Meng R, Krantz ID, Kao G, Gan DD, Zhou JY, Muschel R, et al: KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene. Nat Genet. 17:141–143. 1997. View Article : Google Scholar : PubMed/NCBI

42 

Sheikh MS and Fornace AJ Jr: Death and decoy receptors and p53-mediated apoptosis. Leukemia. 14:1509–1513. 2000. View Article : Google Scholar : PubMed/NCBI

43 

Hainaut P and Hollstein M: p53 and human cancer: The first ten thousand mutations. Adv Cancer Res. 77:81–137. 2000. View Article : Google Scholar

44 

Liu DP, Song H and Xu Y: A common gain of function of p53 cancer mutants in inducing genetic instability. Oncogene. 29:949–956. 2010. View Article : Google Scholar :

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Nuth M, Benakanakere MR and Ricciardi RP: Discovery of a potent cytotoxic agent that promotes G<sub>2</sub>/M phase cell cycle arrest and apoptosis in a malignant human pharyngeal squamous carcinoma cell line. Int J Oncol 60: 41, 2022.
APA
Nuth, M., Benakanakere, M.R., & Ricciardi, R.P. (2022). Discovery of a potent cytotoxic agent that promotes G<sub>2</sub>/M phase cell cycle arrest and apoptosis in a malignant human pharyngeal squamous carcinoma cell line. International Journal of Oncology, 60, 41. https://doi.org/10.3892/ijo.2022.5331
MLA
Nuth, M., Benakanakere, M. R., Ricciardi, R. P."Discovery of a potent cytotoxic agent that promotes G<sub>2</sub>/M phase cell cycle arrest and apoptosis in a malignant human pharyngeal squamous carcinoma cell line". International Journal of Oncology 60.4 (2022): 41.
Chicago
Nuth, M., Benakanakere, M. R., Ricciardi, R. P."Discovery of a potent cytotoxic agent that promotes G<sub>2</sub>/M phase cell cycle arrest and apoptosis in a malignant human pharyngeal squamous carcinoma cell line". International Journal of Oncology 60, no. 4 (2022): 41. https://doi.org/10.3892/ijo.2022.5331
Copy and paste a formatted citation
x
Spandidos Publications style
Nuth M, Benakanakere MR and Ricciardi RP: Discovery of a potent cytotoxic agent that promotes G<sub>2</sub>/M phase cell cycle arrest and apoptosis in a malignant human pharyngeal squamous carcinoma cell line. Int J Oncol 60: 41, 2022.
APA
Nuth, M., Benakanakere, M.R., & Ricciardi, R.P. (2022). Discovery of a potent cytotoxic agent that promotes G<sub>2</sub>/M phase cell cycle arrest and apoptosis in a malignant human pharyngeal squamous carcinoma cell line. International Journal of Oncology, 60, 41. https://doi.org/10.3892/ijo.2022.5331
MLA
Nuth, M., Benakanakere, M. R., Ricciardi, R. P."Discovery of a potent cytotoxic agent that promotes G<sub>2</sub>/M phase cell cycle arrest and apoptosis in a malignant human pharyngeal squamous carcinoma cell line". International Journal of Oncology 60.4 (2022): 41.
Chicago
Nuth, M., Benakanakere, M. R., Ricciardi, R. P."Discovery of a potent cytotoxic agent that promotes G<sub>2</sub>/M phase cell cycle arrest and apoptosis in a malignant human pharyngeal squamous carcinoma cell line". International Journal of Oncology 60, no. 4 (2022): 41. https://doi.org/10.3892/ijo.2022.5331
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