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-2016 Volume 12 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-2016 Volume 12 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
Article Open Access

Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy

  • Authors:
    • Deborah Rotoli
    • Manuel Morales
    • María del Carmen Maeso
    • María del Pino García
    • Araceli Morales
    • Julio Ávila
    • Pablo Martín‑Vasallo
  • View Affiliations / Copyright

    Affiliations: Developmental Biology Laboratory, UD- Biochemistry and Molecular Biology and Centre for Biomedical Research of the Canary Islands, La Laguna University, La Laguna, 38206 Tenerife, Spain, Service of Medical Oncology, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain, Service of Pathology, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain, Laboratory of Biopathology, Hospiten® Hospitals, 38010 Tenerife, Spain, Department of Physiology, Institute of Biomedical Technologies, School of Medicine and Centre for Biomedical Research of The Canary Islands, University of La Laguna, La Laguna, 38071 Santa Cruz de Tenerife, Spain
    Copyright: © Rotoli et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1315-1322
    |
    Published online on: June 23, 2016
       https://doi.org/10.3892/ol.2016.4772
  • 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

The immunophilin FK506-binding protein 5 (FKBP51) is a scaffold protein that serves a pivotal role in the regulation of multiple signaling pathways, integrating external and internal stimuli into distinct signal outputs. In a previous study, we identified several genes that are significantly up‑ or downregulated in the peripheral white cells (PWCs) of colorectal adenocarcinoma (CRC) patients undergoing oxaliplatin-based chemotherapy. In our screening, FKBP51 gene expression was downregulated following chemotherapy. In order to determine whether this alteration in gene expression observed in PWCs may be detected at the protein level in tumors and metastases following the administration of adjuvant chemotherapy, an immunohistochemical analysis of FKBP51 in CRC and primary metastasis tissues was performed. The present study confirmed the downregulation of FKBP51 gene expression elicited by chemotherapy with folinic acid (leucovorin), fluorouracil and oxaliplatin in metastasized liver tissue that had been resected after the oxaliplatin-based chemotherapy, compared with tissue section samples of CRC from patients (prior to antineoplastic treatment). Furthermore, the results indicated that, in CRC tissue sections, the expression of FKBP51 protein is associated with an immature phenotype of stromal fibroblasts and with the epithelial-to-mesenchymal transition (EMT) phenotype, suggesting a role for this protein in the EMT process in CRC. Finally, the observation that only certain cells of the stroma express FKBP51 protein suggests a potential role for this immunophilin as a stroma cell subtype marker.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Xu R, Zhou B, Fung PC and Li X: Recent advances in the treatment of colon cancer. Histol Histopathol. 21:867–872. 2006.PubMed/NCBI

3 

André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, et al: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 350:2343–2351. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Raymond E, Chaney SG, Taamma A and Cvitkovic E: Oxaliplatin: A review of preclinical and clinical studies. Ann Oncol. 9:1053–1071. 1998. View Article : Google Scholar : PubMed/NCBI

5 

Morales M, Ávila J, González-Fernández R, Boronat L, Soriano ML and Martín-Vasallo P: Differential transcriptome profile of peripheral white cells to identify biomarkers involved in oxaliplatin induced neuropathy. J Pers Med. 4:282–296. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Erlejman AG, De Leo SA, Mazaira GI, Molinari AM, Camisay MF, Fontana V, Cox MB, Piwien-Pilipuk G and Galigniana MD: NF-kB transcriptional activity is modulated by FK506-binding proteins FKBP51 and FKBP52: A role for peptidyl-prolyl isomerase activity. J Biol Chem. 289:26263–26276. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Gallo LI, Lagadari M, Piwien-Pilipuk G and Galigniana MD: The 90-kDa heat-shock protein (Hsp90)-binding immunophilin FKBP51 is a mitochondrial protein that translocates to the nucleus to protect cells against oxidative stress. J Biol Chem. 286:30152–30160. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Li L, Lou Z and Wang L: The role of FKBP5 in cancer aetiology and chemoresistance. Br J Cancer. 104:19–23. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Pei H, Li L, Fridley BL, Jenkins GD, Kalari KR, Lingle W, Petersen G, Lou Z and Wang L: FKBP51 affects cancer cell response to chemotherapy by negatively regulating Akt. Cancer Cell. 16:259–266. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Romano S, D'Angelillo A, Pacelli R, Staibano S, De Luna E, Bisogni R, Eskelinen EL, Mascolo M, Cali G, Arra C and Romano MF: Role of FK506-binding protein 51 in the control of apoptosis of irradiated melanoma cells. Cell Death Differ. 17:145–157. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Romano S, Staibano S, Greco A, Brunetti A, Nappo G, Ilardi G, Martinelli R, Sorrentino A, Di Pace A, Mascolo M, et al: FK506 binding protein 51 positively regulates melanoma stemness and metastatic potential. Cell Death Dis. 4:e5782013. View Article : Google Scholar : PubMed/NCBI

12 

Romano S, D'Angelillo A, D'Arrigo P, Staibano S, Greco A, Brunetti A, Scalvenzi M, Bisogni R, Scala I and Romano MF: FKBP51 increases the tumour-promoter potential of TGF-beta. Clin Transl Med. 3:12014. View Article : Google Scholar : PubMed/NCBI

13 

Storer CL, Dickey CA, Galigniana MD, Rein T and Cox MB: FKBP51 and FKBP52 in signaling and disease. Trends Endocrinol Metab. 22:481–490. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Hubler TR, Denny WB, Valentine DL, Cheung-Flynn J, Smith DF and Scammell JG: The FK506-binding immunophilin FKBP51 is transcriptionally regulated by progestin and attenuates progestin responsiveness. Endocrinology. 144:2380–2387. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Jinwal UK, Koren J III, Borysov SI, Schmid AB, Abisambra JF, Blair LJ, Johnson AG, Jones JR, Shults CL, O'Leary JC III, et al: The Hsp90 cochaperone, FKBP51, increases Tau stability and polymerizes microtubules. J Neurosci. 30:591–599. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Chambraud B, Sardin E, Giustiniani J, Dounane O, Schumacher M, Goedert M and Baulieu EE: A role for FKBP52 in Tau protein function. Proc Natl Acad Sci USA. 107:2658–2663. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Li L, Fridley B, Kalari K, Jenkins G, Batzler A, Safgren S, Hildebrandt M, Ames M, Schaid D and Wang L: Gemcitabine and cytosine arabinoside cytotoxicity: Association with lymphoblastoid cell expression. Cancer Res. 68:7050–7058. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Varghese F, Bukhari AB, Malhotra R and De A: IHC Profiler: An open source plugin for the quantitative evaluation and automated scoring of immunohistochemistry images of human tissue samples. PLoS One. 9:e968012014. View Article : Google Scholar : PubMed/NCBI

19 

Bleau AM, Agliano A, Larzabal L, de Aberasturi AL and Calvo A: Metastatic dormancy: A complex network between cancer stem cells and their microenvironment. Histol Histopathol. 29:1499–1510. 2014.PubMed/NCBI

20 

Ha SY, Yeo SY, Xuan Y and Kim SH: The prognostic significance of cancer-associated fibroblasts in esophageal squamous cell carcinoma. PLoS One. 9:e999552014. View Article : Google Scholar : PubMed/NCBI

21 

Nalbantoglu IL, Tan BR Jr, Linehan DC, Gao F and Brunt EM: Histological features and severity of oxaliplatin-induced liver injury and clinical associations. J Dig Dis. 15:553–560. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Davies TH, Ning YM and Sánchez ER: A new first step in activation of steroid receptors: Hormone-induced switching of FKBP51 and FKBP52 immunophilins. J Biol Chem. 277:4597–4600. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Galigniana MD, Radanyi C, Renoir JM, Housley PR and Pratt WB: Evidence that the peptidylprolyl isomerase domain of the hsp90-binding immunophilin FKBP52 is involved in both dynein interaction and glucocorticoid receptor movement to the nucleus. J Biol Chem. 276:14884–14889. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Wochnik GM, Rüegg J, Abel GA, Schmidt U, Holsboer F and Rein T: FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells. J Biol Chem. 280:4609–4616. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Sidler D, Renzulli P, Schnoz C, Berger B, Schneider-Jakob S, Flück C, Inderbitzin D, Corazza N, Candinas D and Brunner T: Colon cancer cells produce immunoregulatory glucocorticoids. Oncogene. 30:2411–2419. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Baughman G, Wiederrecht GJ, Chang F, Martin MM and Bourgeois S: Tissue distribution and abundance of human FKBP51, and FK506-binding protein that can mediate calcineurin inhibition. Biochem Biophys Res Commun. 232:437–443. 1997. View Article : Google Scholar : PubMed/NCBI

27 

Mukaide H, Adachi Y, Taketani S, Iwasaki M, Koike-Kiriyama N, Shigematsu A, Shi M, Yanai S, Yoshioka K, Kamiyama Y and Ikehara S: FKBP51 expressed by both normal epithelial cells and adenocarcinoma of colon suppresses proliferation of colorectal adenocarcinoma. Cancer Invest. 26:385–390. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Jiang W, Cazacu S, Xiang C, Zenklusen JC, Fine HA, Berens M, Armstrong B, Brodie C and Mikkelsen T: FK506 binding protein mediates glioma cell growth and sensitivity to rapamycin treatment by regulating NF-kappaB signaling pathway. Neoplasia. 10:235–243. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Vandamme M, Pauwels W and Bleecker JD: A case of delayed oxaliplatin-induced pseudo-obstruction: An atypical presentation of oxaliplatin neurotoxicity. Acta Clin Belg. 70:207–210. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M, Sevillano M, Palomo-Ponce S, Tauriello DV, Byrom D, et al: Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet. 10:320–329. 2015. View Article : Google Scholar

31 

Kuroda N, Nakayama H, Miyazaki E, Toi M, Hiroi M and Enzan H: The distribution of CD34-positive stromal cells and myofibroblasts in colorectal carcinoid tumors. Histol Histopathol. 20:27–33. 2005.PubMed/NCBI

32 

Sugimoto H, Mundel TM, Kieran MW and Kalluri R: Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol Ther. 5:1640–1646. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Rotoli D, Morales M, Maeso Md, García Md, Morales A, Ávila J and Martín‑Vasallo P: Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy. Oncol Lett 12: 1315-1322, 2016.
APA
Rotoli, D., Morales, M., Maeso, M.d., García, M.d., Morales, A., Ávila, J., & Martín‑Vasallo, P. (2016). Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy. Oncology Letters, 12, 1315-1322. https://doi.org/10.3892/ol.2016.4772
MLA
Rotoli, D., Morales, M., Maeso, M. d., García, M. d., Morales, A., Ávila, J., Martín‑Vasallo, P."Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy". Oncology Letters 12.2 (2016): 1315-1322.
Chicago
Rotoli, D., Morales, M., Maeso, M. d., García, M. d., Morales, A., Ávila, J., Martín‑Vasallo, P."Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy". Oncology Letters 12, no. 2 (2016): 1315-1322. https://doi.org/10.3892/ol.2016.4772
Copy and paste a formatted citation
x
Spandidos Publications style
Rotoli D, Morales M, Maeso Md, García Md, Morales A, Ávila J and Martín‑Vasallo P: Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy. Oncol Lett 12: 1315-1322, 2016.
APA
Rotoli, D., Morales, M., Maeso, M.d., García, M.d., Morales, A., Ávila, J., & Martín‑Vasallo, P. (2016). Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy. Oncology Letters, 12, 1315-1322. https://doi.org/10.3892/ol.2016.4772
MLA
Rotoli, D., Morales, M., Maeso, M. d., García, M. d., Morales, A., Ávila, J., Martín‑Vasallo, P."Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy". Oncology Letters 12.2 (2016): 1315-1322.
Chicago
Rotoli, D., Morales, M., Maeso, M. d., García, M. d., Morales, A., Ávila, J., Martín‑Vasallo, P."Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy". Oncology Letters 12, no. 2 (2016): 1315-1322. https://doi.org/10.3892/ol.2016.4772
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