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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
December-2018 Volume 18 Issue 6

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
December-2018 Volume 18 Issue 6

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

Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer

  • Authors:
    • Yoshiaki Sato
    • Hironori Yoshino
    • Yuka Kazama
    • Ikuo Kashiwakura
  • View Affiliations / Copyright

    Affiliations: Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036‑8564, Japan, Department of Radiological Technology, Hirosaki University School of Health Sciences, Hirosaki, Aomori 036‑8564, Japan
  • Pages: 5286-5294
    |
    Published online on: October 8, 2018
       https://doi.org/10.3892/mmr.2018.9536
  • 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

Retinoic acid‑inducible gene‑I‑like receptors (RLRs) serve an important role in antiviral immune responses. Recent studies demonstrated that RLR activation exerts antitumor activity by inducing an anticancer immune response and apoptosis in various cancer cells. The authors' recent study demonstrated that the cytotoxic effects of the RLR agonist Poly(I:C)‑HMW/LyoVec™ [Poly(I:C)‑HMW] in human non‑small cell lung cancer (NSCLC) were enhanced by cotreatment with ionizing radiation (IR). Furthermore, cotreatment with Poly(I:C)‑HMW and IR effectively induced cell death, including apoptosis, in a caspase‑dependent manner. However, the mechanisms by which cotreatment with Poly(I:C)‑HMW and IR effectively induce apoptosis remains unclear. Therefore, the pathways involved in the increase in apoptosis elicited by cotreatment with Poly(I:C)‑HMW and IR in the A549 human NSCLC cell line were investigated. Poly(I:C)‑HMW induced the expression of active caspase‑8 and ‑9, and the Poly(I:C)‑HMW‑induced increase in the cell cycle sub‑G1 population, which is one of the hallmarks of apoptosis, was decreased by treatment with a caspase‑8 inhibitor and caspase‑9 inhibitor. When cells were treated with Poly(I:C)‑HMW and IR, the sub‑G1 population, and the active caspase‑8 and caspase‑9 expression were all increased compared with cells treated with Poly(I:C)‑HMW or IR alone. Furthermore, expression of X‑linked inhibitor of apoptosis protein, which negatively regulates caspase activation, was decreased in cells cotreated with Poly(I:C)‑HMW and IR. Notably, treatment with an inhibitor for caspase‑8, not caspase‑9, partially reversed the net increase in the sub‑G1 population induced by cotreatment with Poly(I:C)‑HMW and IR. Collectively, these results suggested that Poly(I:C)‑HMW induces apoptosis through caspase‑8 and caspase‑9 activation; however, the apoptotic pathway mediated by casapse‑8, and not casapse‑9, is involved in the enhancement of apoptosis caused by cotreatment with Poly(I:C)‑HMW and IR.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Yoneyama M and Fujita T: Structural mechanism of RNA recognition by the RIG-I-like receptors. Immunity. 29:178–181. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O and Akira S: IPS-1, an adaptor triggering RIG-I- and MDA5-mediated type I interferon induction. Nat Immunol. 6:981–988. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Johnson CL and Gale M Jr: CARD games between virus and host get a new player. Trends Immunol. 27:1–4. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Wu Y, Wu X, Wu L, Wang X and Liu Z: The anticancer functions of RIG-I-like receptors, RIG-I and MDA5, and their applications in cancer therapy. Transl Res. 190:51–60. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Besch R, Poeck H, Hohenauer T, Senft D, Häcker G, Berking C, Hornung V, Endres S, Ruzicka T, Rothenfusser S and Hartmann G: Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells. J Clin Invest. 119:2399–2411. 2009.PubMed/NCBI

6 

Yuan D, Xia M, Meng G, Xu C, Song Y and Wei J: Anti-angiogenic efficacy of 5′-triphosphate siRNA combining VEGF silencing and RIG-I activation in NSCLCs. Oncotarget. 6:29664–29674. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Poeck H, Besch R, Maihoefer C, Renn M, Tormo D, Morskaya SS, Kirschnek S, Gaffal E, Landsberg J, Hellmuth J, et al: 5′-Triphosphate-siRNA: Turning gene silencing and Rig-I activation against melanoma. Nat Med. 14:1256–1263. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Li D, Gale RP, Liu Y, Lei B, Wang Y, Diao D and Zhang M: 5′-Triphosphate siRNA targeting MDR1 reverses multi-drug resistance and activates RIG-I-induced immune-stimulatory and apoptotic effects against human myeloid leukaemia cells. Leuk Res. 58:23–30. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Yoshino H, Iwabuchi M, Kazama Y, Furukawa M and Kashiwakura I: Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer in vitro. Oncol Lett. 15:4697–4705. 2018.PubMed/NCBI

10 

Green DR and Llambi F: Cell death signaling. Cold Spring Harb Perspect Biol. 7:pii: a006080. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Rongvaux A: Innate immunity and tolerance toward mitochondria. Mitochondrion. 41:14–20. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Mohamed MS, Bishr MK, Almutairi FM and Ali AG: Inhibitors of apoptosis: Clinical implications in cancer. Apoptosis. 22:1487–1509. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Takahashi K, Inanami O, Hayashi M and Kuwabara M: Protein synthesis-dependent apoptotic signalling pathway in X-irradiated MOLT-4 human leukaemia cell line. Int J Radiat Biol. 78:115–124. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Kim MJ, Lee KH and Lee SJ: Ionizing radiation utilizes c-Jun N-terminal kinase for amplification of mitochondrial apoptotic cell death in human cervical cancer cells. FEBS J. 275:2096–2108. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Yoshino H, Kumai Y and Kashiwakura I: Effects of endoplasmic reticulum stress on apoptosis induction in radioresistant macrophages. Mol Med Rep. 15:2867–2872. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Wakasaya T, Yoshino H, Fukushi Y, Yoshizawa A and Kashiwakura I: A liquid crystal-related compound induces cell cycle arrest at the G2/M phase and apoptosis in the A549 human non-small cell lung cancer cell line. Int J Oncol. 42:1205–1211. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Fukushi S, Yoshino H, Yoshizawa A and Kashiwakura I: p53-independent structure-activity relationships of 3-ring mesogenic compounds' activity as cytotoxic effects against human non-small cell lung cancer lines. BMC Cancer. 16:5212016. View Article : Google Scholar : PubMed/NCBI

18 

Yoshino H, Chiba K, Saitoh T and Kashiwakura I: Ionizing radiation affects the expression of Toll-like receptors 2 and 4 in human monocytic cells through c-Jun N-terminal kinase activation. J Radiat Res. 55:876–884. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Larionov A, Krause A and Miller W: A standard curve based method for relative real time PCR data processing. BMC Bioinformatics. 6:622005. View Article : Google Scholar : PubMed/NCBI

20 

Yoshino H and Kashiwakura I: Involvement of reactive oxygen species in ionizing radiation-induced upregulation of cell surface toll-like receptor 2 and 4 expression in human monocytic cells. J Radiat Res. 58:626–635. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Darzynkiewicz Z, Buruno S, Del Bino G, Gorczyca W, Hotz MA, Lassota P and Traganos F: Features of apoptotic cells measured by flow cytometry. Cytometry. 13:795–808. 1992. View Article : Google Scholar : PubMed/NCBI

22 

Yoshino H, Saitoh T, Kozakai M and Kashiwakura I: Effects of ionizing radiation on retinoic acid-inducible gene-I-like receptors. Biomed Rep. 3:59–62. 2015. View Article : Google Scholar : PubMed/NCBI

23 

El Maadidi S, Faletti L, Berg B, Wenzl C, Wieland K, Chen ZJ, Maurer U and Borner C: A novel mitochondrial MAVS/Caspase-8 platform links RNA virus-induced innate antiviral signaling to Bax/Bak-independent apoptosis. J Immunol. 192:1171–1183. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Kalkavan H and Green DR: MOMP, cell suicide as a BCL-2 family business. Cell Death Differ. 25:46–55. 2018. View Article : Google Scholar : PubMed/NCBI

25 

Liu C, Sarkaria JN, Petell CA, Paraskevakou G, Zollman PJ, Schroeder M, Carlson B, Decker PA, Wu W, James CD, et al: Combination of measles virus virotherapy and radiation therapy has synergistic activity in the treatment of glioblastoma multiforme. Clin Cancer Res. 13:7155–7165. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Porter AG and Jänicke RU: Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 6:99–104. 1999. View Article : Google Scholar : PubMed/NCBI

27 

Nakhaei P, Sun Q, Solis M, Mesplede T, Bonneil E, Paz S, Lin R and Hiscott J: IκB kinase ε-dependent phosphorylation and degradation of X-linked inhibitor of apoptosis sensitizes cells to virus-induced apoptosis. J Virol. 86:726–737. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Cao C, Mu Y, Hallahan DE and Lu B: XIAP and survivin as therapeutic targets for radiation sensitization in preclinical models of lung cancer. Oncogene. 23:7047–7052. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Eckelman BP, Salvesen GS and Scott FL: Human inhibitor of apoptosis proteins: Why XIAP is the black sheep of the family. EMBO Rep. 7:988–994. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Hiramatsu N, Messah C, Han J, LaVail MM, Kaufman RJ and Lin JH: Translational and posttranslational regulation of XIAP by eIF2α and ATF4 promotes ER stress-induced cell death during the unfolded protein response. Mol Biol Cell. 25:1411–1420. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Galbán S and Duckett CS: XIAP as a ubiquitin ligase in cellular signaling. Cell Death Differ. 7:54–60. 2010. View Article : Google Scholar

32 

Yang Y, Fang S, Jensen JP, Weissman AM and Ashwell JD: Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science. 288:874–877. 2000. View Article : Google Scholar : PubMed/NCBI

33 

Afshar G, Jelluma N, Yang X, Basila D, Arvold ND, Karlsson A, Yount GL, Dansen TB, Koller E and Haas-Kogan DA: Radiation-induced caspase-8 mediates p53-independent apoptosis in glioma cells. Cancer Res. 66:4223–4232. 2006. View Article : Google Scholar : PubMed/NCBI

34 

Hamasu T, Inanami O, Asanuma T and Kuwabara M: Enhanced induction of apoptosis by combined treatment of human carcinoma cells with X rays and death receptor agonists. J Radiat Res. 46:103–110. 2005. View Article : Google Scholar : PubMed/NCBI

35 

Duewell P, Steger A, Lohr H, Bourhis H, Hoelz H, Kirchleitner SV, Stieg MR, Grassmann S, Kobold S, Siveke JT, et al: RIG-I-like helicases induce immunogenic cell death of pancreatic cancer cells and sensitize tumors toward killing by CD8(+) T cells. Cell Death Differ. 21:1825–1837. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Sato Y, Yoshino H, Kazama Y and Kashiwakura I: Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer. Mol Med Rep 18: 5286-5294, 2018.
APA
Sato, Y., Yoshino, H., Kazama, Y., & Kashiwakura, I. (2018). Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer. Molecular Medicine Reports, 18, 5286-5294. https://doi.org/10.3892/mmr.2018.9536
MLA
Sato, Y., Yoshino, H., Kazama, Y., Kashiwakura, I."Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer". Molecular Medicine Reports 18.6 (2018): 5286-5294.
Chicago
Sato, Y., Yoshino, H., Kazama, Y., Kashiwakura, I."Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer". Molecular Medicine Reports 18, no. 6 (2018): 5286-5294. https://doi.org/10.3892/mmr.2018.9536
Copy and paste a formatted citation
x
Spandidos Publications style
Sato Y, Yoshino H, Kazama Y and Kashiwakura I: Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer. Mol Med Rep 18: 5286-5294, 2018.
APA
Sato, Y., Yoshino, H., Kazama, Y., & Kashiwakura, I. (2018). Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer. Molecular Medicine Reports, 18, 5286-5294. https://doi.org/10.3892/mmr.2018.9536
MLA
Sato, Y., Yoshino, H., Kazama, Y., Kashiwakura, I."Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer". Molecular Medicine Reports 18.6 (2018): 5286-5294.
Chicago
Sato, Y., Yoshino, H., Kazama, Y., Kashiwakura, I."Involvement of caspase‑8 in apoptosis enhancement by cotreatment with retinoic acid‑inducible gene‑I‑like receptor agonist and ionizing radiation in human non‑small cell lung cancer". Molecular Medicine Reports 18, no. 6 (2018): 5286-5294. https://doi.org/10.3892/mmr.2018.9536
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