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 Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
August-2021 Volume 22 Issue 2

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
August-2021 Volume 22 Issue 2

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 Open Access

Exosome‑derived microRNA‑433 inhibits tumorigenesis through incremental infiltration of CD4 and CD8 cells in non‑small cell lung cancer

  • Authors:
    • Boyang Liu
    • Ruiping Zhang
    • Yungang Zhu
    • Ruisheng Hao
  • View Affiliations / Copyright

    Affiliations: Department of Radiation, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China, Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China, Department of Radiation Oncology, Tianjin Teda Hospital, Tianjin 300457, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 607
    |
    Published online on: June 15, 2021
       https://doi.org/10.3892/ol.2021.12868
  • 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

Tumor‑derived exosomal microRNAs (miRNAs/miRs) serve a vital biological role in tumorigenesis and development, but the effects and underlying mechanisms remain unclear. To explore the impact of exosomal miR‑433 in non‑small cell lung cancer (NSCLC) and understand its mechanism of action in NSCLC progression, the present study isolated the exosomes from the plasma of patients with NSCLC after chemotherapy and found that miR‑433 expression was lower in plasma of patients with resistant NSCLC compared with in plasma of patients with sensitive NSCLC and in normal serum. Additionally, miR‑433 expression was markedly negatively associated with a large tumor size, distant metastasis, advanced TNM stage and a poor prognosis in patients with NSCLC. miR‑433 inhibited tumor growth by blocking the cell cycle in vitro and in vivo, as well as by promoting apoptosis and T‑cell infiltration in the tumor microenvironment. Additionally, miR‑433 inhibited chemoresistance to cisplatin by regulating DNA damage. Moreover, miR‑433 inactivated the WNT/β‑catenin signaling pathway by targeting transmembrane p24 trafficking protein 5 in NSCLC. Overall, the current findings may provide a potential prognostic biomarker and therapeutic target for patients with NSCLC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Nasim F, Sabath BF and Eapen GA: Lung cancer. Med Clin North Am. 103:463–473. 2019. View Article : Google Scholar : PubMed/NCBI

2 

Duma N, Santana-Davila R and Molina JR: Non-small cell lung cancer: Epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc. 94:1623–1640. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Hoy H, Lynch T and Beck M: Surgical treatment of lung cancer. Crit Care Nurs Clin North Am. 31:303–313. 2019. View Article : Google Scholar : PubMed/NCBI

4 

Skoulidis F and Heymach JV: Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy. Nat Rev Cancer. 19:495–509. 2019. View Article : Google Scholar : PubMed/NCBI

5 

Yoneda K, Imanishi N, Ichiki Y and Tanaka F: Immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). J UOEH. 40:173–189. 2018. View Article : Google Scholar : PubMed/NCBI

6 

Xie Y, Dang W, Zhang S, Yue W, Yang L, Zhai X, Yan Q and Lu J: The role of exosomal noncoding RNAs in cancer. Mol Cancer. 18:372019. View Article : Google Scholar : PubMed/NCBI

7 

Hu C, Meiners S, Lukas C, Stathopoulos GT and Chen J: Role of exosomal microRNAs in lung cancer biology and clinical applications. Cell Prolif. 53:e128282020. View Article : Google Scholar : PubMed/NCBI

8 

Williams M, Cheng YY, Blenkiron C and Reid G: Exploring mechanisms of microRNA downregulation in cancer. Microrna. 6:2–16. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Deng S, Calin GA, Croce CM, Coukos G and Zhang L: Mechanisms of microRNA deregulation in human cancer. Cell Cycle. 7:2643–2646. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Rupaimoole R, Calin GA, Lopez-Berestein G and Sood AK: miRNA deregulation in cancer cells and the tumor microenvironment. Cancer Discov. 6:235–246. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Svoronos AA, Engelman DM and Slack FJ: OncomiR or tumor suppressor? The duplicity of microRNAs in cancer. Cancer Res. 76:3666–3670. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Han F, Huang D, Huang X, Wang W, Yang S and Chen S: Exosomal microRNA-26b-5p down-regulates ATF2 to enhance radiosensitivity of lung adenocarcinoma cells. J Cell Mol Med. 24:7730–7742. 2020. View Article : Google Scholar : PubMed/NCBI

14 

Wang HX, Wang XY, Fei JW, Li FH, Han J and Qin X: MicroRNA-23B inhibits non-small cell lung cancer proliferation, invasion and migration via downregulation of RUNX2 and inhibition of Wnt/Β-catenin signaling pathway. J Biol Regul Homeost Agents. 34:825–835. 2020.PubMed/NCBI

15 

Qu Y, Zhu J, Liu J and Qi L: Circular RNA circ_0079593 indicates a poor prognosis and facilitates cell growth and invasion by sponging miR-182 and miR-433 in glioma. J Cell Biochem. 120:18005–18013. 2019. View Article : Google Scholar : PubMed/NCBI

16 

Ding L and Zhang H: Circ-ATP8A2 promotes cell proliferation and invasion as a ceRNA to target EGFR by sponging miR-433 in cervical cancer. Gene. 705:103–108. 2019. View Article : Google Scholar : PubMed/NCBI

17 

Yan L, You WQ, Sheng NQ, Gong JF, Hu LD, Tan GW, Chen HQ and Wang ZG: A CREB1/miR-433 reciprocal feedback loop modulates proliferation and metastasis in colorectal cancer. Aging (Albany NY). 10:3774–3793. 2018. View Article : Google Scholar : PubMed/NCBI

18 

Zhang T, Jiang K, Zhu X, Zhao G, Wu H, Deng G and Qiu C: miR-433 inhibits breast cancer cell growth via the MAPK signaling pathway by targeting Rap1a. Int J Biol Sci. 14:622–632. 2018. View Article : Google Scholar : PubMed/NCBI

19 

Shi Q, Wang Y, Mu Y, Wang X and Fan Q: miR-433-3p inhibits proliferation and invasion of esophageal squamous cell carcinoma by targeting GRB2. Cell Physiol Biochem. 46:2187–2196. 2018. View Article : Google Scholar : PubMed/NCBI

20 

Wang YJ, Zhang ZF, Fan SH, Zhuang J, Shan Q, Han XR, Wen X, Li MQ, Hu B, Sun CH, et al: MicroRNA-433 inhibits oral squamous cell carcinoma cells by targeting FAK. Oncotarget. 8:100227–100241. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Liu N, Liu Z, Zhang W, Li Y, Cao J, Yang H and Li X: MicroRNA-433 reduces cell proliferation and invasion in non-small cell lung cancer via directly targeting E2F transcription factor 3. Mol Med Rep. 18:1155–1164. 2018.PubMed/NCBI

22 

Li J, Chen M and Yu B: miR-433 suppresses tumor progression via Smad2 in non-small cell lung cancer. Pathol Res Pract. 215:1525912019. View Article : Google Scholar : PubMed/NCBI

23 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Yang Z, Sun Q, Guo J, Wang S, Song G, Liu W, Liu M and Tang H: GRSF1-mediated MIR-G-1 promotes malignant behavior and nuclear autophagy by directly upregulating TMED5 and LMNB1 in cervical cancer cells. Autophagy. 4:668–685. 2019. View Article : Google Scholar : PubMed/NCBI

25 

Vishnoi A and Rani S: miRNA biogenesis and regulation of diseases: An overview. Methods Mol Biol. 1509:1–10. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Sandiford OA, Moore CA, Du J, Boulad M, Gergues M, Eltouky H and Rameshwar P: Human aging and cancer: Role of miRNA in tumor microenvironment. Adv Exp Med Biol. 1056:137–152. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Liu S, Lin Z, Zheng Z, Rao W, Lin Y, Chen H, Xie Q, Chen Y and Hu Z: Serum exsomal miR-766-3p expression is associated with poor prognosis of esophageal squamous cell carcinoma. Cancer Sci. 110:3881–3892. 2020. View Article : Google Scholar : PubMed/NCBI

28 

Lin H, Zhang L, Zhang C and Liu P: Exosomal miR-500a-3p promotes cisplatin resistance and stemness via negatively regulating FBXW7 in gastric cancer. J Cell Mol Med. 24:8930–8941. 2020. View Article : Google Scholar : PubMed/NCBI

29 

Weiner-Gorzel K, Dempsey E, Milewska M, McGoldrick A, Toh V, Walsh A, Lindsay S, Gubbins L, Cannon A, Sharpe D, et al: Overexpression of the microRNA miR-433 promotes resistance to paclitaxel through the induction of cellular senescence in ovarian cancer cells. Cancer Med. 4:745–758. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Weng L, Qiu K, Gao W, Shi C and Shu F: LncRNA PCGEM1 accelerates non-small cell lung cancer progression via sponging miR-433-3p to upregulate WTAP. BMC Pulm Med. 20:2132020. View Article : Google Scholar : PubMed/NCBI

31 

Santos P and Almeida F: Role of exosomal miRNAs and the tumor microenvironment in drug resistance. Cells. 9:14502020. View Article : Google Scholar : PubMed/NCBI

32 

Bland CL, Byrne-Hoffman CN, Fernandez A, Rellick SL, Deng W and Klinke DJ 2nd: Exosomes derived from B16F0 melanoma cells alter the transcriptome of cytotoxic T cells that impacts mitochondrial respiration. FEBS J. 285:1033–1050. 2018. View Article : Google Scholar : PubMed/NCBI

33 

Ye SB, Li ZL, Luo DH, Huang BJ, Chen YS, Zhang XS, Cui J, Zeng YX and Li J: Tumor-derived exosomes promote tumor progression and T-cell dysfunction through the regulation of enriched exosomal microRNAs in human nasopharyngeal carcinoma. Oncotarget. 5:5439–5452. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Taciak B, Pruszynska I, Kiraga L, Bialasek M and Krol M: Wnt signaling pathway in development and cancer. J Physiol Pharmacol. 69:185–196. 2018.PubMed/NCBI

35 

Kassumeh S, Weber GR, Nobl M, Priglinger SG and Ohlmann A: The neuroprotective role of Wnt signaling in the retina. Neural Regen Res. 16:1524–1528. 2021. View Article : Google Scholar : PubMed/NCBI

36 

Stewart DJ: Wnt signaling pathway in non-small cell lung cancer. J Natl Cancer Inst. 106:djt3562014. View Article : Google Scholar : PubMed/NCBI

37 

Tang J, Gao W, Liu G, Sheng W, Zhou J, Dong Q and Dong M: miR-944 suppresses EGF-induced EMT in colorectal cancer cells by directly targeting GATA6. Onco Targets Ther. 14:2311–2325. 2021. View Article : Google Scholar : PubMed/NCBI

38 

Wu Z, Zhang Y, Yang Z, Zhu Y, Xie Y, Zhou F and Cai L: Elevation of miR-302b prevents multiple myeloma cell growth and bone destruction by blocking DKK1 secretion. Cancer Cell Int. 21:1872021. View Article : Google Scholar : PubMed/NCBI

39 

Xie Y, Xue C, Guo S and Yang L: MicroRNA-520a suppresses pathogenesis and progression of non-small-cell lung cancer through targeting the RRM2/Wnt axis. Anal Cell Pathol (Amst). 2021:96524202021.PubMed/NCBI

40 

Wang H, Yang Q, Li J, Chen W, Jin X and Wang Y: MicroRNA-15a-5p inhibits endometrial carcinoma proliferation, invasion and migration via downregulation of VEGFA and inhibition of the Wnt/β-catenin signaling pathway. Oncol Lett. 21:3102021. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu B, Zhang R, Zhu Y and Hao R: Exosome‑derived microRNA‑433 inhibits tumorigenesis through incremental infiltration of CD4 and CD8 cells in non‑small cell lung cancer. Oncol Lett 22: 607, 2021.
APA
Liu, B., Zhang, R., Zhu, Y., & Hao, R. (2021). Exosome‑derived microRNA‑433 inhibits tumorigenesis through incremental infiltration of CD4 and CD8 cells in non‑small cell lung cancer. Oncology Letters, 22, 607. https://doi.org/10.3892/ol.2021.12868
MLA
Liu, B., Zhang, R., Zhu, Y., Hao, R."Exosome‑derived microRNA‑433 inhibits tumorigenesis through incremental infiltration of CD4 and CD8 cells in non‑small cell lung cancer". Oncology Letters 22.2 (2021): 607.
Chicago
Liu, B., Zhang, R., Zhu, Y., Hao, R."Exosome‑derived microRNA‑433 inhibits tumorigenesis through incremental infiltration of CD4 and CD8 cells in non‑small cell lung cancer". Oncology Letters 22, no. 2 (2021): 607. https://doi.org/10.3892/ol.2021.12868
Copy and paste a formatted citation
x
Spandidos Publications style
Liu B, Zhang R, Zhu Y and Hao R: Exosome‑derived microRNA‑433 inhibits tumorigenesis through incremental infiltration of CD4 and CD8 cells in non‑small cell lung cancer. Oncol Lett 22: 607, 2021.
APA
Liu, B., Zhang, R., Zhu, Y., & Hao, R. (2021). Exosome‑derived microRNA‑433 inhibits tumorigenesis through incremental infiltration of CD4 and CD8 cells in non‑small cell lung cancer. Oncology Letters, 22, 607. https://doi.org/10.3892/ol.2021.12868
MLA
Liu, B., Zhang, R., Zhu, Y., Hao, R."Exosome‑derived microRNA‑433 inhibits tumorigenesis through incremental infiltration of CD4 and CD8 cells in non‑small cell lung cancer". Oncology Letters 22.2 (2021): 607.
Chicago
Liu, B., Zhang, R., Zhu, Y., Hao, R."Exosome‑derived microRNA‑433 inhibits tumorigenesis through incremental infiltration of CD4 and CD8 cells in non‑small cell lung cancer". Oncology Letters 22, no. 2 (2021): 607. https://doi.org/10.3892/ol.2021.12868
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