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 Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
October-2020 Volume 44 Issue 4

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
October-2020 Volume 44 Issue 4

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

Non‑invasive monitoring of paclitaxel and lenvatinib efficacy against anaplastic thyroid cancer in orthotopic SCID mouse models using small‑animal FDG‑PET/CT

  • Authors:
    • Mariko Aoyama
    • Hiromitsu Takizawa
    • Tamaki Otani
    • Seiya Inoue
    • Naoya Kawakita
    • Mitsuhiro Tsuboi
    • Yoshimi Bando
    • Hisanori Uehara
    • Kazuya Kondo
    • Akira Tangoku
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, The University of Tokushima, Tokushima 770‑8503, Japan, Radioisotope Research Center, Tokushima University Graduate School, Tokushima 770‑8503, Japan, Department of Pathology, Tokushima University Hospital, Tokushima 770‑8503, Japan, Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770‑8503, Japan
  • Pages: 1709-1716
    |
    Published online on: August 7, 2020
       https://doi.org/10.3892/or.2020.7720
  • 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

Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid carcinoma with a poor prognosis. Thus, suitable preclinical tumor models are required for the development of new ATC therapies. In the present study, orthotopic tumor xenograft models were established using ATC cell lines and SCID mice, and tumor invasion and the effects of anticancer drugs were evaluated using positron emission tomography/computed tomography (PET/CT) to repeatedly and non‑invasively monitor these models. Three ATC cell lines (8305c, 8505c, and ACT‑1) were used. Their sensitivities to two anticancer drugs (paclitaxel and lenvatinib) were investigated. The 8505c cell line was orthotopically implanted into SCID mice, which were then divided into three groups: No chemotherapy, paclitaxel (5 mg/kg, administered intraperitoneally, every week), and lenvatinib (5 mg/kg, oral route, every day) groups. PET/CT was performed and tumor growth and the effects of anticancer drugs based on tumor volume and fludeoxyglucose (FDG) uptake were evaluated. 8505c cells exhibited the highest sensitivity to the anticancer drugs. In mice implanted with 8505c cells, continuous increases in FDG uptake associated with tumor growth were detected on PET/CT in the group that received no chemotherapy. The tumor volume and FDG uptake increased by 91.5‑ and 2.4‑fold, respectively, within 2 weeks. The increase observed in tumor volume was 26.9‑ and 12.2‑fold in the paclitaxel and lenvatinib groups, respectively, within 2 weeks. Furthermore, the increase in FDG uptake was 1.8 and 1.6‑fold in the paclitaxel and lenvatinib groups, respectively, within 2 weeks. In our orthotopic SCID mouse model, tumor growth and the effects of anticancer drugs were repeatedly and non‑invasively monitored using PET/CT. The present method is useful for the development of new ATC treatments.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Kebebew E, Dreenspan FS, Clark OH, Woeber KA and McMillan A: Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer. 103:1330–1335. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Tennvall J, Lundell G, Wahlberg P, Bergenfelz A, Grimelius L, Akerman M, Hjelm Skog AL and Wallin G: Anaplastic thyroid carcinoma: Three protocols combining doxorubicin, hyperfractionated radiotherapy and surgery. Br J Cancer. 12:1848–1853. 2002. View Article : Google Scholar

3 

Sugitani I, Onoda N, Ito K and Sugitabi S: Management of anaplastic thyroid carcinoma: Fruits from ATC Research Consortium of Japan. J Nippon Med Sch. 85:18–27. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Shimaoka K, Schoenfeld DA, DeWys WD, Creech RH and DeConti R: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advancer thyroid carcinoma. Cancer. 56:2155–2160. 1985. View Article : Google Scholar : PubMed/NCBI

5 

Ahuja S and Emst H: Chemotherapy of thyroid carcinoma. J Endocrinol Invest. 3:303–310. 1987. View Article : Google Scholar

6 

Ain KB, Egorin MJ and DeSimone PA: Treatment of anaplastic thyroid carcinoma with paclitaxel: Phase 2 trial using ninety-six-hour infusion. Collaborative Thyroid Cancer Health Intervention Trials (CATCHIT) Group. Thyroid. 10:587–594. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Onoda N, Sugino K, Higashiyama T, Kammor i, Toda K, Ito K, Yoshida A, Suganuma N, Nakashima N, Suzuki S, et al: The safety and efficacy of weekly paclitaxel administration for anaplastic thyroid cancer patients: A nationwide prospective study. Thyroid. 26:1293–1299. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Tahara M, Kiyota N, Yamazaki T, Chayara N, Nakano K, Inagaki L, Toda K, Enokida T, Minami H, Imamura Y, et al: Lenvatinib for anaplastic thyroid cancer. Front Oncol. 7:252017. View Article : Google Scholar : PubMed/NCBI

9 

Hundahl SA, Fleming ID, Fremgen AM and Menck HR: A national cancer data base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995. Cancer. 83:2638–2648. 1998. View Article : Google Scholar : PubMed/NCBI

10 

Kitamura Y, Shimizu K, Hagahama M, Sugino K, Osaki O, Mimura T, Ito K, Ito K and Tanaka S: Immediate causes of death in thyroid carcinoma: Clinicopathological analysis of 161 fetal cases. J Clin Endocrinol Metab. 84:4034–4039. 1999. View Article : Google Scholar

11 

Kim S, Park YW, Schiff BA, Doan DD, Yazici Y, Jasser SA, Younes M, Mandal M, Bekele BN and Myers JN: An orthotopic model of anaplastic thyroid carcinoma in athymic nude mice. Clin Cancer Res. 11:1713–1721. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Nucera C, Nehs MA, Mekel M, Zhang X, Hodin R, Lawler J, Nose V and Parangi S: A novel orthotopic mouse model of human anaplastic thyroid carcinoma. Thyroid. 19:1077–1084. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Sewell W, Reeb A and Lin RY: An orthotopic mouse model of anaplastic thyroid carcinoma. J Vis Exp. 74:500972013.

14 

Paget S: The distribution of secondary growths in cancer of the breast. Lancet. 133:571–573. 1889. View Article : Google Scholar

15 

Bibby MC: Orthotopic models of cancer for preclinical drug evaluation: Advantages and disadvantages. Eur J Cancer. 40:852–857. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Nehas MA, Nucera C, Nagarkatti SS, Sado w, Morales-Garcia D, Hodin RA and Parangi S: Late intervention with anti-BRAFV600E therapy induces tumor regression in an orthotopic mouse model of anaplastic thyroid cancer. Endocrinology. 153:985–994. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Cha W, Kim DW, Kim SD, Jeon EH, Jeong WJ and Ahn SH: Effect of perioperative treatment with a hypoxia-inducible factor-1-alpha inhibitor in an orthotopic surgical mouse models of thyroid cancer. Anticancer Res. 35:2049–2054. 2015.PubMed/NCBI

18 

Nehs MA, Nagarkatti S, Nucera C, Hodin RA and Parangi S: Thyroidectomy with neoadjuvant PLX4720 extends survival and decreases tumor burden in an orthotopic mouse models of anaplastic thyroid cancer. Surgery. 148:1154–1162. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Mokhtar M, Kondo K, Takizawa H, Ohtani T, Otsuka H, Kubo H, Kajiura K, Nakagawa Y, Kawanaka Y, Yoshida M, et al: Non-invasive monitoring of anticancer effects of cisplatin on lung cancer in an orthotopic SICD mouse model using [18F] FDG PET-CT. Oncol Rep. 31:2007–2014. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Otani T, Kondo K, Takizawa H, Kajiura K, Fujino H, Otsuka H and Miyoshi H: Non-invasive monitoring of cisplatin and erlotinib efficacy against lung cancer in orthotopic SCID mouse models by small animal FDG-PET/CT and CT. Oncol Rep. 41:447–454. 2019.PubMed/NCBI

21 

Marcus C, Whitworth PW, Surasi DS, Pai SI and Subramaniam RM: PET/CT in the Management of thyroid cancers. AJR Am J Roentgenol. 202:1316–1329. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Poisson T, Deandreis D, Leboulleux S, Bidault F, Bonniaud G, Baillot S, Auperin A, AI Ghuzlan A, Travagli JP and Lumbroso J: 18F-fluorodeoxyglucose positron emission tomography and computed tomography in anaplastic thyroid cancer. Eur J Nucl Med Mol Imaging. 37:2277–2285. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Killkenny C, Browne WJ, Cuthill IC, Emerson M and Altman DG: Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. Osteoarthritis Cartilage. 20:256–260. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Jing C, Gao Z, Wang R, Yang Z, Shi B and Hou P: Lenvatinib enhances the antitumor effects of paclitaxel in anaplastic thyroid cancer. Am J Cancer Res. 4:903–912. 2017.

25 

Ahmed S, Ghazarian MP, Cabanillas ME, Zafereo ME, Williams MD, Vu T, Schomer DF and Debnam JM: Imaging of anaplastic thyroid carcinoma. AJNR AM J Neuroradiol. 3:547–551. 2018. View Article : Google Scholar

26 

Deeken-Draisey A, Yang GY, Gao J and Alexiev BA: Anaplastic thyroid carcinoma: An epidemiologic, histologic, immunohistochemical, and molecular single-institution study. Hum Pathol. 82:140–148. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Kostakoglu L and Chauvie S: Metabolic tumor volume metrics in lymphoma. Semin Nucl Med. 48:50–66. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Dibble EH, Alvarez AC, Truong MT, Mercier G, Cook EF and Subramaniam RM: 18F-FDG metabolic tumor volume and total glycolytic activity of oral cavity and oropharyngeal squamous cell cancer: Adding value to clinical staging. J Nucl Med. 53:709–715. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Manohar PM, Beesley LJ, Bellile EL, Worden FP and Avram AM: Prognostic value of FDG-PET/CT metabolic parameters in metastatic radioiodine-refractory differentiated thyroid cancer. Clin Nucl Med. 43:641–647. 2018. View Article : Google Scholar : PubMed/NCBI

30 

Tohyama O, Matsui J, Kodama K, Hata-Sugi N, Kimura T, Okamoto K, Minoshima Y, Iwata M and Funahashi Y: Antitumor activity of lenvatinib (e7080): An angiogenesis inhibitor that targets multiple receptor tyrosine kinases in preclinical human thyroid cancer models. J Thyroid Res. 2014:132014. View Article : Google Scholar

31 

Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkiier T, Cella D and Davidson NA: Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 26:2666–2676. 2007. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Aoyama M, Takizawa H, Otani T, Inoue S, Kawakita N, Tsuboi M, Bando Y, Uehara H, Kondo K, Tangoku A, Tangoku A, et al: Non‑invasive monitoring of paclitaxel and lenvatinib efficacy against anaplastic thyroid cancer in orthotopic SCID mouse models using small‑animal FDG‑PET/CT. Oncol Rep 44: 1709-1716, 2020.
APA
Aoyama, M., Takizawa, H., Otani, T., Inoue, S., Kawakita, N., Tsuboi, M. ... Tangoku, A. (2020). Non‑invasive monitoring of paclitaxel and lenvatinib efficacy against anaplastic thyroid cancer in orthotopic SCID mouse models using small‑animal FDG‑PET/CT. Oncology Reports, 44, 1709-1716. https://doi.org/10.3892/or.2020.7720
MLA
Aoyama, M., Takizawa, H., Otani, T., Inoue, S., Kawakita, N., Tsuboi, M., Bando, Y., Uehara, H., Kondo, K., Tangoku, A."Non‑invasive monitoring of paclitaxel and lenvatinib efficacy against anaplastic thyroid cancer in orthotopic SCID mouse models using small‑animal FDG‑PET/CT". Oncology Reports 44.4 (2020): 1709-1716.
Chicago
Aoyama, M., Takizawa, H., Otani, T., Inoue, S., Kawakita, N., Tsuboi, M., Bando, Y., Uehara, H., Kondo, K., Tangoku, A."Non‑invasive monitoring of paclitaxel and lenvatinib efficacy against anaplastic thyroid cancer in orthotopic SCID mouse models using small‑animal FDG‑PET/CT". Oncology Reports 44, no. 4 (2020): 1709-1716. https://doi.org/10.3892/or.2020.7720
Copy and paste a formatted citation
x
Spandidos Publications style
Aoyama M, Takizawa H, Otani T, Inoue S, Kawakita N, Tsuboi M, Bando Y, Uehara H, Kondo K, Tangoku A, Tangoku A, et al: Non‑invasive monitoring of paclitaxel and lenvatinib efficacy against anaplastic thyroid cancer in orthotopic SCID mouse models using small‑animal FDG‑PET/CT. Oncol Rep 44: 1709-1716, 2020.
APA
Aoyama, M., Takizawa, H., Otani, T., Inoue, S., Kawakita, N., Tsuboi, M. ... Tangoku, A. (2020). Non‑invasive monitoring of paclitaxel and lenvatinib efficacy against anaplastic thyroid cancer in orthotopic SCID mouse models using small‑animal FDG‑PET/CT. Oncology Reports, 44, 1709-1716. https://doi.org/10.3892/or.2020.7720
MLA
Aoyama, M., Takizawa, H., Otani, T., Inoue, S., Kawakita, N., Tsuboi, M., Bando, Y., Uehara, H., Kondo, K., Tangoku, A."Non‑invasive monitoring of paclitaxel and lenvatinib efficacy against anaplastic thyroid cancer in orthotopic SCID mouse models using small‑animal FDG‑PET/CT". Oncology Reports 44.4 (2020): 1709-1716.
Chicago
Aoyama, M., Takizawa, H., Otani, T., Inoue, S., Kawakita, N., Tsuboi, M., Bando, Y., Uehara, H., Kondo, K., Tangoku, A."Non‑invasive monitoring of paclitaxel and lenvatinib efficacy against anaplastic thyroid cancer in orthotopic SCID mouse models using small‑animal FDG‑PET/CT". Oncology Reports 44, no. 4 (2020): 1709-1716. https://doi.org/10.3892/or.2020.7720
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