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
June-2020 Volume 19 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
June-2020 Volume 19 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 Open Access

Icaritin enhances the efficacy of cetuximab against triple‑negative breast cancer cells

  • Authors:
    • Li Yin
    • Xiao‑Wei Qi
    • Xun‑Zhou Liu
    • Ze‑Yu Yang
    • Rui‑Li Cai
    • Hong‑Juan Cui
    • Li Chen
    • Shi‑Cang Yu
  • View Affiliations / Copyright

    Affiliations: Department of Stem Cell and Regenerative Medicine, Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China, Breast Disease Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China, State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, P.R. China
    Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3950-3958
    |
    Published online on: March 31, 2020
       https://doi.org/10.3892/ol.2020.11496
  • 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

Triple‑negative breast cancer (TNBC) has a greater risk of recurrence and metastasis along with a worse prognosis compared with other subtypes of breast cancer. Studies have revealed that mitogenic estrogen signaling is involved in the malignant proliferation of TNBC cells through a novel variant of the estrogen receptor, estrogen receptor α‑36 (ER‑α36). The results of the present study demonstrated that knockdown of ER‑α36 expression in TNBC cells using short hairpin RNA inhibited rapid estrogen signaling bypass activation of the PI3K/AKT signaling pathway. Moreover, the ER‑α36 modulator icaritin inhibited the proliferation of TNBC cells both in vitro and in vivo. Here, it was revealed that the combination of icaritin and cetuximab, a therapeutic epidermal growth factor receptor (EGFR) neutralizing antibody, induced apoptosis and inhibited cell proliferation synergistically in TNBC cells. The results of the present study improved the understanding of the underlying mechanisms of TNBC progression and supported the therapeutic potential of combined treatment targeting the ER‑α36 and EGFR.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

DeSantis CE, Ma J, Goding Sauer A, Newman LA and Jemal A: Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 67:439–448. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y and Pietenpol JA: Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 121:2750–2767. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Foulkes WD, Smith IE and Reis-Filho JS: Triple-negative breast cancer. N Engl J Med. 363:1938–1948. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas J, Harris L, Hait W and Toppmeyer D: Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol. 24:5652–5657. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P and Narod SA: Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin Cancer Res. 13:4429–4434. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML and Perou CM: The triple negative paradox: Primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 13:2329–2334. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Hudis CA and Gianni L: Triple-negative breast cancer: An unmet medical need. Oncologist. 16 (Suppl 1):S1–S11. 2011. View Article : Google Scholar

8 

Chang-Qing Y, Jie L, Shi-Qi Z, Kun Z, Zi-Qian G, Ran X, Hui-Meng L, Ren-Bin Z, Gang Z, Da-Chuan Y and Chen-Yan Z: Recent treatment progress of triple negative breast cancer. Prog Biophys Mol Biol. Nov 21–2019.(Epub ahead of print). PubMed/NCBI

9 

Troyer KL and Lee DC: Regulation of mouse mammary gland development and tumorigenesis by the ERBB signaling network. J Mammary Gland Biol Neoplasia. 6:7–21. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Kumar R and Wang RA: Protein kinases in mammary gland development and cancer. Microsc Res Tech. 59:49–57. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, et al: Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 10:5367–5374. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Corkery B, Crown J, Clynes M and O'Donovan N: Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer. Ann Oncol. 20:862–867. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Park HS, Jang MH, Kim EJ, Kim HJ, Lee HJ, Kim YJ, Kim JH, Kang E, Kim SW, Kim IA and Park SY: High EGFR gene copy number predicts poor outcome in triple-negative breast cancer. Mod Pathol. 27:1212–1222. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Masuda H, Zhang D, Bartholomeusz C, Doihara H, Hortobagyi GN and Ueno NT: Role of epidermal growth factor receptor in breast cancer. Breast Cancer Res Treat. 136:331–345. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Gelmon K, Dent R, Mackey JR, Laing K, McLeod D and Verma S: Targeting triple-negative breast cancer: Optimising therapeutic outcomes. Ann Oncol. 23:2223–2234. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Nakai K, Hung MC and Yamaguchi H: A perspective on anti-EGFR therapies targeting triple-negative breast cancer. Am J Cancer Res. 6:1609–1623. 2016.PubMed/NCBI

17 

Wang Z, Zhang X, Shen P, Loggie BW, Chang Y and Deuel TF: Identification, cloning, and expression of human estrogen receptor-alpha36, a novel variant of human estrogen receptor-alpha66. Biochem Biophys Res Commun. 336:1023–1027. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Lee LM, Cao J, Deng H, Chen P, Gatalica Z and Wang ZY: ER-alpha36, a novel variant of ER-alpha, is expressed in ER-positive and -negative human breast carcinomas. Anticancer Res. 28:479–483. 2008.PubMed/NCBI

19 

Shi L, Dong B, Li Z, Lu Y, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B, et al: Expression of ER-{alpha}36, a novel variant of estrogen receptor {alpha}, and resistance to tamoxifen treatment in breast cancer. J Clin Oncol. 27:3423–3429. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Wang ZY and Yin L: Estrogen receptor alpha-36 (ER-α36): A new player in human breast cancer. Mol Cell Endocrinol. 418:193–206. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Wang Z, Zhang X, Shen P, Loggie BW, Chang Y and Deuel TF: A variant of estrogen receptor-{alpha}, hER-{alpha}36: Transduction of estrogen- and antiestrogen-dependent membrane-initiated mitogenic signaling. Proc Natl Acad Sci USA. 103:9063–9068. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Yang XJ, Xi YM and Li ZJ: Icaritin: A novel natural candidate for hematological malignancies therapy. Biomed Res Int. 2019:48602682019.PubMed/NCBI

23 

Hong J, Zhang Z, Lv W, Zhang M, Chen C, Yang S, Li S, Zhang L, Han D and Zhang W: Icaritin synergistically enhances the radiosensitivity of 4T1 breast cancer cells. PLoS One. 8:e713472013. View Article : Google Scholar : PubMed/NCBI

24 

Li S, Priceman SJ, Xin H, Zhang W, Deng J, Liu Y, Huang J, Zhu W, Chen M, Hu W, et al: Icaritin inhibits JAK/STAT3 signaling and growth of renal cell carcinoma. PLoS One. 8:e816572013. View Article : Google Scholar : PubMed/NCBI

25 

Zhu JF, Li ZJ, Zhang GS, Meng K, Kuang WY, Li J, Zhou XF, Li RJ, Peng HL, Dai CW, et al: Icaritin shows potent anti-leukemia activity on chronic myeloid leukemia in vitro and in vivo by regulating MAPK/ERK/JNK and JAK2/STAT3/AKT signalings. PLoS One. 6:e237202011. View Article : Google Scholar : PubMed/NCBI

26 

Wang X, Zheng N, Dong J, Liu L and Huang J: Estrogen receptor-α36 is involved in icaritin induced growth inhibition of triple-negative breast cancer cells. J Steroid Biochem Mol Biol. 171:318–327. 2017. View Article : Google Scholar : PubMed/NCBI

27 

Brinkley BR, Beall PT, Wible LJ, Mace ML, Turner DS and Cailleau RM: Variations in cell form and cytoskeleton in human breast carcinoma cells in vitro. Cancer Res. 40:3118–3129. 1980.PubMed/NCBI

28 

Cailleau R, Young R, Olive M and Reeves WJ Jr: Breast tumor cell lines from pleural effusions. J Natl Cancer Inst. 53:661–674. 1974. View Article : Google Scholar : PubMed/NCBI

29 

Chavez KJ, Garimella SV and Lipkowitz S: Triple negative breast cancer cell lines: One tool in the search for better treatment of triple negative breast cancer. Breast Dis. 32:35–48. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Kang L and Wang ZY: Breast cancer cell growth inhibition by phenethyl isothiocyanate is associated with down-regulation of oestrogen receptor-alpha36. J Cell Mol Med. 14:1485–1493. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F and Salomon DS: Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 366:2–16. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Sigismund S, Avanzato D and Lanzetti L: Emerging functions of the EGFR in cancer. Mol Oncol. 12:3–20. 2018. View Article : Google Scholar : PubMed/NCBI

33 

Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al: Molecular portraits of human breast tumours. Nature. 406:747–752. 2000. View Article : Google Scholar : PubMed/NCBI

34 

Liu D, He J, Yuan Z, Wang S, Peng R, Shi Y, Teng X and Qin T: EGFR expression correlates with decreased disease-free survival in triple-negative breast cancer: A retrospective analysis based on a tissue microarray. Med Oncol. 29:401–405. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Carey LA, Rugo HS, Marcom PK, Mayer EL, Esteva FJ, Ma CX, Liu MC, Storniolo AM, Rimawi MF, Forero-Torres A, et al: TBCRC 001: Randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol. 30:2615–2623. 2012. View Article : Google Scholar : PubMed/NCBI

36 

Zhang X, Ding L, Kang L and Wang ZY: Estrogen receptor-alpha 36 mediates mitogenic antiestrogen signaling in ER-negative breast cancer cells. PLoS One. 7:e301742012. View Article : Google Scholar : PubMed/NCBI

37 

Zhang XT, Ding L, Kang LG and Wang ZY: Involvement of ER-α36, Src, EGFR and STAT5 in the biphasic estrogen signaling of ER-negative breast cancer cells. Oncol Rep. 27:2057–2065. 2012.PubMed/NCBI

38 

Tsai EM, Wang SC, Lee JN and Hung MC: Akt activation by estrogen in estrogen receptor-negative breast cancer cells. Cancer Res. 61:8390–8392. 2001.PubMed/NCBI

39 

Friedl A and Jordan VC: Oestradiol stimulates growth of oestrogen receptor-negative MDA-MB-231 breast cancer cells in immunodeficient mice by reducing cell loss. Eur J Cancer. 30A:1559–1564. 1994. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yin L, Qi XW, Liu XZ, Yang ZY, Cai RL, Cui HJ, Chen L and Yu SC: Icaritin enhances the efficacy of cetuximab against triple‑negative breast cancer cells. Oncol Lett 19: 3950-3958, 2020.
APA
Yin, L., Qi, X., Liu, X., Yang, Z., Cai, R., Cui, H. ... Yu, S. (2020). Icaritin enhances the efficacy of cetuximab against triple‑negative breast cancer cells. Oncology Letters, 19, 3950-3958. https://doi.org/10.3892/ol.2020.11496
MLA
Yin, L., Qi, X., Liu, X., Yang, Z., Cai, R., Cui, H., Chen, L., Yu, S."Icaritin enhances the efficacy of cetuximab against triple‑negative breast cancer cells". Oncology Letters 19.6 (2020): 3950-3958.
Chicago
Yin, L., Qi, X., Liu, X., Yang, Z., Cai, R., Cui, H., Chen, L., Yu, S."Icaritin enhances the efficacy of cetuximab against triple‑negative breast cancer cells". Oncology Letters 19, no. 6 (2020): 3950-3958. https://doi.org/10.3892/ol.2020.11496
Copy and paste a formatted citation
x
Spandidos Publications style
Yin L, Qi XW, Liu XZ, Yang ZY, Cai RL, Cui HJ, Chen L and Yu SC: Icaritin enhances the efficacy of cetuximab against triple‑negative breast cancer cells. Oncol Lett 19: 3950-3958, 2020.
APA
Yin, L., Qi, X., Liu, X., Yang, Z., Cai, R., Cui, H. ... Yu, S. (2020). Icaritin enhances the efficacy of cetuximab against triple‑negative breast cancer cells. Oncology Letters, 19, 3950-3958. https://doi.org/10.3892/ol.2020.11496
MLA
Yin, L., Qi, X., Liu, X., Yang, Z., Cai, R., Cui, H., Chen, L., Yu, S."Icaritin enhances the efficacy of cetuximab against triple‑negative breast cancer cells". Oncology Letters 19.6 (2020): 3950-3958.
Chicago
Yin, L., Qi, X., Liu, X., Yang, Z., Cai, R., Cui, H., Chen, L., Yu, S."Icaritin enhances the efficacy of cetuximab against triple‑negative breast cancer cells". Oncology Letters 19, no. 6 (2020): 3950-3958. https://doi.org/10.3892/ol.2020.11496
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