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
November-2016 Volume 49 Issue 5

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
November-2016 Volume 49 Issue 5

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
Article

Determination of the optimal time for tamoxifen treatment in combination with radiotherapy

  • Authors:
    • Hyunsoo Jang
    • Junyoung Baek
    • Kyung-Soo Nam
    • Soyoung Kim
  • View Affiliations / Copyright

    Affiliations: Department of Radiation Oncology, School of Medicine, Dongguk University, Gyeongju, Gyeongsangbuk-do 780-350, Republic of Korea, Department of Pharmacology, School of Medicine, Dongguk University, Gyeongju, Gyeongsangbuk-do 780-350, Republic of Korea
  • Pages: 2147-2154
    |
    Published online on: September 9, 2016
       https://doi.org/10.3892/ijo.2016.3687
  • 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

Although radiotherapy and tamoxifen have been extensively used to treat estrogen receptor α (ERα)-positive breast cancers, it is still questionable when tamoxifen should be started to maximize clinical benefits in combination with radiotherapy. Generally, clinician's opinion and experience are major determinants in scheduling concurrent or sequential tamoxifen and radiotherapy. Thus, we attempted to determine an optimal time to start tamoxifen treatment by analyzing tamoxifen responses at different times after irradiating MCF-7 cells to cumulative doses of 10 or 20-30 Gy. MCF-7 cells were irradiated with 5 Gy a week, twice (a cumulative dose of 10 Gy) followed by a period of recovery. MTT viability assay for tamoxifen was done with MCF-7 cells harvested immediately after each 5 Gy (MCF-7-5 Gy) or 10 Gy (MCF-7-10 Gy) irradiation or after subsequent culture of surviving MCF-7-10 Gy cells for 40 days (MCF-7-R1). To establish the radioresistant cells, the above cycles of irradiation were repeated for a cumulative dose of 20 Gy (MCF-7-R2) or 30 Gy (MCF-7-R3). In addition, cytotoxic effects of tamoxifen were also measured. Attenuated tamoxifen response was observed in MCF-7-5 Gy and 10 Gy cells, whereas the efficacy of tamoxifen was restored in MCF-7-R1 cells. Furthermore, these responses to tamoxifen correlated with ERα expression. However, the radioresistant MCF-7 cells (MCF-7-R2/R3) exhibited resistance to tamoxifen without change in ER expression, but the phosphorylation of AKT was increased. Taken together, our data suggest that sequential tamoxifen treatment following radiotherapy is more effective than concurrent treatment. Furthermore, the reduced efficacy of tamoxifen on radioresistant cells indicates that an additional targeted therapy, such as AKT inhibitor treatment, is required to improve tamoxifen response in radioresistant breast cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. 2014, http://www.nccn.org.

2 

Komoike Y, Akiyama F, Iino Y, Ikeda T, Akashi-Tanaka S, Ohsumi S, Kusama M, Sano M, Shin E, Suemasu K, et al: Ipsilateral breast tumor recurrence (IBTR) after breast-conserving treatment for early breast cancer: Risk factors and impact on distant metastases. Cancer. 106:35–41. 2006. View Article : Google Scholar

3 

Arriagada R, Lê MG, Contesso G, Guinebretière JM, Rochard F and Spielmann M: Predictive factors for local recurrence in 2006 patients with surgically resected small breast cancer. Ann Oncol. 13:1404–1413. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Ha B, Suh HS, Lee J, Lee KJ, Lee R and Moon BI: Long-term results of forward intensity-modulated radiation therapy for patients with early-stage breast cancer. Radiat Oncol J. 31:191–198. 2013. View Article : Google Scholar

5 

Masood S: Estrogen and progesterone receptors in cytology: A comprehensive review. Diagn Cytopathol. 8:475–491. 1992. View Article : Google Scholar : PubMed/NCBI

6 

Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet. 365:1687–1717. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Fisher B, Dignam J, Bryant J and Wolmark N: Five versus more than five years of tamoxifen for lymph node-negative breast cancer: Updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J Natl Cancer Inst. 93:684–690. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Azria D, Pelegrin A, Dubois JB, Mirimanoff RO and Ozsahin M: Radiation therapy and tamoxifen: concurrent or sequential? It's no longer the question! J Clin Oncol. 23:4239–4241; author reply 4241–4232. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Harris EE, Christensen VJ, Hwang WT, Fox K and Solin LJ: Impact of concurrent versus sequential tamoxifen with radiation therapy in early-stage breast cancer patients undergoing breast conservation treatment. J Clin Oncol. 23:11–16. 2005. View Article : Google Scholar

10 

Whelan T and Levine M: Radiation therapy and tamoxifen: Concurrent or sequential? That is the question. J Clin Oncol. 23:1–4. 2005. View Article : Google Scholar

11 

Osborne CK, Boldt DH, Clark GM and Trent JM: Effects of tamoxifen on human breast cancer cell cycle kinetics: Accumulation of cells in early G1 phase. Cancer Res. 43:3583–3585. 1983.PubMed/NCBI

12 

Paulsen GH, Strickert T, Marthinsen AB and Lundgren S: Changes in radiation sensitivity and steroid receptor content induced by hormonal agents and ionizing radiation in breast cancer cells in vitro. Acta Oncol. 35:1011–1019. 1996. View Article : Google Scholar : PubMed/NCBI

13 

Wazer DE, Tercilla OF, Lin PS and Schmidt-Ullrich R: Modulation in the radiosensitivity of MCF-7 human breast carcinoma cells by 17B-estradiol and tamoxifen. Br J Radiol. 62:1079–1083. 1989. View Article : Google Scholar : PubMed/NCBI

14 

Bentzen SM, Skoczylas JZ, Overgaard M and Overgaard J: Radiotherapy-related lung fibrosis enhanced by tamoxifen. J Natl Cancer Inst. 88:918–922. 1996. View Article : Google Scholar : PubMed/NCBI

15 

Koc M, Polat P and Suma S: Effects of tamoxifen on pulmonary fibrosis after cobalt-60 radiotherapy in breast cancer patients. Radiother Oncol. 64:171–175. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Ellis PA, Saccani-Jotti G, Clarke R, Johnston SR, Anderson E, Howell A, A'Hern R, Salter J, Detre S, Nicholson R, et al: Induction of apoptosis by tamoxifen and ICI 182780 in primary breast cancer. Int J Cancer. 72:608–613. 1997. View Article : Google Scholar : PubMed/NCBI

17 

Ahn PH, Vu HT, Lannin D, Obedian E, DiGiovanna MP, Burtness B and Haffty BG: Sequence of radiotherapy with tamoxifen in conservatively managed breast cancer does not affect local relapse rates. J Clin Oncol. 23:17–23. 2005. View Article : Google Scholar

18 

Pierce LJ, Hutchins LF, Green SR, Lew DL, Gralow JR, Livingston RB, Osborne CK and Albain KS: Sequencing of tamoxifen and radiotherapy after breast-conserving surgery in early-stage breast cancer. J Clin Oncol. 23:24–29. 2005. View Article : Google Scholar

19 

Chun SY, Kwon YS, Nam KS and Kim S: Lapatinib enhances the cytotoxic effects of doxorubicin in MCF-7 tumorspheres by inhibiting the drug efflux function of ABC transporters. Biomed Pharmacother. 72:37–43. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Shou J, Massarweh S, Osborne CK, Wakeling AE, Ali S, Weiss H and Schiff R: Mechanisms of tamoxifen resistance: Increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J Natl Cancer Inst. 96:926–935. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Haynes MP, Sinha D, Russell KS, Collinge M, Fulton D, Morales-Ruiz M, Sessa WC and Bender JR: Membrane estrogen receptor engagement activates endothelial nitric oxide synthase via the PI3-kinase-Akt pathway in human endothelial cells. Circ Res. 87:677–682. 2000. View Article : Google Scholar : PubMed/NCBI

22 

Santen RJ, Song RX, McPherson R, Kumar R, Adam L, Jeng MH and Yue W: The role of mitogen-activated protein (MAP) kinase in breast cancer. J Steroid Biochem Mol Biol. 80:239–256. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, et al: Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science. 270:1491–1494. 1995. View Article : Google Scholar : PubMed/NCBI

24 

Rupnow BA and Knox SJ: The role of radiation-induced apoptosis as a determinant of tumor responses to radiation therapy. Apoptosis. 4:115–143. 1999. View Article : Google Scholar

25 

Verheij M: Clinical biomarkers and imaging for radiotherapy-induced cell death. Cancer Metastasis Rev. 27:471–480. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Galluzzi L, Maiuri MC, Vitale I, Zischka H, Castedo M, Zitvogel L and Kroemer G: Cell death modalities: Classification and pathophysiological implications. Cell Death Differ. 14:1237–1243. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Eriksson D, Löfroth PO, Johansson L, Riklund KA and Stigbrand T: Cell cycle disturbances and mitotic catastrophes in HeLa Hep2 cells following 2.5 to 10 Gy of ionizing radiation. Clin Cancer Res. 13:S5501–S5508. 2007. View Article : Google Scholar

28 

Kristiansen G, Winzer KJ, Mayordomo E, Bellach J, Schlüns K, Denkert C, Dahl E, Pilarsky C, Altevogt P, Guski H, et al: CD24 expression is a new prognostic marker in breast cancer. Clin Cancer Res. 9:4906–4913. 2003.PubMed/NCBI

29 

Lee HJ, Choe G, Jheon S, Sung SW, Lee CT and Chung JH: CD24, a novel cancer biomarker, predicting disease-free survival of non-small cell lung carcinomas: A retrospective study of prognostic factor analysis from the viewpoint of forthcoming (seventh) new TNM classification. J Thorac Oncol. 5:649–657. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 100:3983–3988. 2003. View Article : Google Scholar : PubMed/NCBI

31 

Ahmed KM, Dong S, Fan M and Li JJ: Nuclear factor-kappaB p65 inhibits mitogen-activated protein kinase signaling pathway in radioresistant breast cancer cells. Mol Cancer Res. 4:945–955. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Kunigal S, Lakka SS, Joseph P, Estes N and Rao JS: Matrix metalloproteinase-9 inhibition down-regulates radiation-induced nuclear factor-kappa B activity leading to apoptosis in breast tumors. Clin Cancer Res. 14:3617–3626. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Duru N, Fan M, Candas D, Menaa C, Liu HC, Nantajit D, Wen Y, Xiao K, Eldridge A, Chromy BA, et al: HER2-associated radioresistance of breast cancer stem cells isolated from HER2-negative breast cancer cells. Clin Cancer Res. 18:6634–6647. 2012. View Article : Google Scholar : PubMed/NCBI

34 

No M, Choi EJ and Kim IA: Targeting HER2 signaling pathway for radiosensitization: Alternative strategy for therapeutic resistance. Cancer Biol Ther. 8:2351–2361. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Lin F, Luo J, Gao W, Wu J, Shao Z, Wang Z, Meng J, Ou Z and Yang G: COX-2 promotes breast cancer cell radioresistance via p38/MAPK-mediated cellular anti-apoptosis and invasiveness. Tumour Biol. 34:2817–2826. 2013. View Article : Google Scholar : PubMed/NCBI

36 

Chang L, Graham PH, Hao J, Ni J, Bucci J, Cozzi PJ, Kearsley JH and Li Y: Acquisition of epithelial-mesenchymal transition and cancer stem cell phenotypes is associated with activation of the PI3K/Akt/mTOR pathway in prostate cancer radioresistance. Cell Death Dis. 4:e8752013. View Article : Google Scholar : PubMed/NCBI

37 

Clark AS, West K, Streicher S and Dennis PA: Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol Cancer Ther. 1:707–717. 2002.PubMed/NCBI

38 

Guo RX, Wei LH, Tu Z, Sun PM, Wang JL, Zhao D, Li XP and Tang JM: 17 beta-estradiol activates PI3K/Akt signaling pathway by estrogen receptor (ER)-dependent and ER-independent mechanisms in endometrial cancer cells. J Steroid Biochem Mol Biol. 99:9–18. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Jang H, Baek J, Nam K and Kim S: Determination of the optimal time for tamoxifen treatment in combination with radiotherapy. Int J Oncol 49: 2147-2154, 2016.
APA
Jang, H., Baek, J., Nam, K., & Kim, S. (2016). Determination of the optimal time for tamoxifen treatment in combination with radiotherapy. International Journal of Oncology, 49, 2147-2154. https://doi.org/10.3892/ijo.2016.3687
MLA
Jang, H., Baek, J., Nam, K., Kim, S."Determination of the optimal time for tamoxifen treatment in combination with radiotherapy". International Journal of Oncology 49.5 (2016): 2147-2154.
Chicago
Jang, H., Baek, J., Nam, K., Kim, S."Determination of the optimal time for tamoxifen treatment in combination with radiotherapy". International Journal of Oncology 49, no. 5 (2016): 2147-2154. https://doi.org/10.3892/ijo.2016.3687
Copy and paste a formatted citation
x
Spandidos Publications style
Jang H, Baek J, Nam K and Kim S: Determination of the optimal time for tamoxifen treatment in combination with radiotherapy. Int J Oncol 49: 2147-2154, 2016.
APA
Jang, H., Baek, J., Nam, K., & Kim, S. (2016). Determination of the optimal time for tamoxifen treatment in combination with radiotherapy. International Journal of Oncology, 49, 2147-2154. https://doi.org/10.3892/ijo.2016.3687
MLA
Jang, H., Baek, J., Nam, K., Kim, S."Determination of the optimal time for tamoxifen treatment in combination with radiotherapy". International Journal of Oncology 49.5 (2016): 2147-2154.
Chicago
Jang, H., Baek, J., Nam, K., Kim, S."Determination of the optimal time for tamoxifen treatment in combination with radiotherapy". International Journal of Oncology 49, no. 5 (2016): 2147-2154. https://doi.org/10.3892/ijo.2016.3687
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