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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
November-2021 Volume 22 Issue 5

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
November-2021 Volume 22 Issue 5

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

Gigantol inhibits cell proliferation and induces apoptosis by regulating DEK in non‑small cell lung cancer

  • Authors:
    • Yuxing Cai
    • Yi Hao
    • Hui Xu
    • Kai Chen
    • Baozhong Ren
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, Baoji Center Hospital, Baoji, Shaanxi 721008, P.R. China, Department of Pediatric Surgery, Baoji Maternal and Child Health Care Hospital, Baoji, Shaanxi 721000, P.R. China, Department of Respiratory Medicine, Baoji Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721001, P.R. China
    Copyright: © Cai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 1317
    |
    Published online on: September 17, 2021
       https://doi.org/10.3892/etm.2021.10752
  • 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

Non‑small cell lung cancer (NSCLC) is a common type of cancer, with a mortality of >80% worldwide. Gigantol is a bibenzyl compound that displays anticancer activity. The aim of the present study was to determine the biological activity of gigantol in NSCLC and to elucidate the underlying molecular mechanism of its action. The expression of DEK proto‑oncogene (DEK) was measured in NSCLC tissues and cell lines by reverse transcription‑quantitative PCR (RT‑qPCR). The results suggested that DEK levels were significantly increased in NSCLC tissues and cell lines compared with adjacent non‑tumor tissues and BEAS‑2B normal bronchial epithelial cells, respectively. A549 cells were exposed to a series of gigantol concentrations (0, 25, 50 and 100 µM) and transfected with DEK small interfering RNA. The results of cell viability measured by MTT assay indicated that gigantol significantly decreased cell viability. Additionally, cell proliferation was assessed by CCK‑8 and apoptosis was measured by flow cytometry. In comparison with the control group, gigantol treatment inhibited cell proliferation and promoted apoptosis, whereas DEK knockdown increased gigantol‑induced suppression of proliferation and acceleration of apoptosis. Additionally, DEK overexpression reversed gigantol‑induced effects on proliferation and apoptosis. Moreover, compared with the control group, gigantol treatment decreased Ki‑67 and Bcl‑2 expression levels, increased Bax expression levels and inactivated the Wnt/β‑catenin signaling pathway, as assessed by RT‑qPCR and/or western blot. DEK knockdown further increased gigantol‑induced effects, but DEK overexpression reversed gigantol‑induced effects. To conclude, the results of the present study suggested that gigantol inhibited cell proliferation and induced apoptosis by decreasing Ki‑67 and Bcl‑2 expression, increasing Bax expression and activating the Wnt/β‑catenin signaling pathway by regulating DEK. The present study indicated the therapeutic potential of gigantol in patients with NSCLC. In addition, DEK may serve as a novel therapeutic target to enhance the effects of gigantol treatment.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Carbone DP, Gandara DR, Antonia SJ, Zielinski C and Paz-Ares L: Non-small-cell lung cancer: Role of the immune system and potential for immunotherapy. J Thorac Oncol. 10:974–984. 2015.PubMed/NCBI View Article : Google Scholar

2 

Gu H, Chen J, Song Y and Shao H: Gastric adenocarcinoma predictive long intergenic non-coding RNA promotes tumor occurrence and progression in non-small cell lung cancer via regulation of the miR-661/eEF2K signaling pathway. Cell Physiol Biochem. 51:2136–2147. 2018.PubMed/NCBI View Article : Google Scholar

3 

Gridelli C, Rossi A, Carbone DP, Guarize J, Karachaliou N, Mok T, Petrella F, Spaggiari L and Rosell R: Non-small-cell lung cancer. Nat Rev Dis Primers. 1(15009)2015.PubMed/NCBI View Article : Google Scholar

4 

Kumarakulasinghe NB, van Zanwijk N and Soo RA: Molecular targeted therapy in the treatment of advanced stage non-small cell lung cancer (NSCLC). Respirology. 20:370–378. 2015.PubMed/NCBI View Article : Google Scholar

5 

Lam Y, Ng TB, Yao RM, Shi J, Xu K, Sze SC and Zhang KY: Evaluation of chemical constituents and important mechanism of pharmacological biology in Dendrobium plants. Evid Based Compement Alternat Med. 2015(841752)2015.PubMed/NCBI View Article : Google Scholar

6 

Chen X, Wang F, Wang Y, Li X, Wang A, Wang C and Guo S: Discrimination of the rare medicinal plant Dendrobium officinale based on naringenin, bibenzyl, and polysaccharides. Sci China Life Sci. 55:1092–1099. 2012.PubMed/NCBI View Article : Google Scholar

7 

Zheng S, Zhu Y, Jiao C, Shi M, Wei L, Zhou Y, Jin Q and Cai Y: Extraction and analysis of gigantol from Dendrobium officinale with response surface methodology. Molecules. 23(818)2018.PubMed/NCBI View Article : Google Scholar

8 

Ng TB, Liu J, Wong JH, Ye X, Wing Sze SC, Tong Y and Zhang KY: Review of research on Dendrobium, a prized folk medicine. Appl Microbiol Biotechnol. 93:1795–1803. 2012.PubMed/NCBI View Article : Google Scholar

9 

Won JH, Kim JY, Yun KJ, Lee JH, Back NI, Chung HG, Chung SA, Jeong TS, Choi MS and Lee KT: Gigantol isolated from the whole plants of Cymbidium goeringii inhibits the LPS-induced iNOS and COX-2 expression via NF-kappaB inactivation in RAW 264.7 macrophages cells. Planta Med. 72:1181–1187. 2006.PubMed/NCBI View Article : Google Scholar

10 

Simmler C, Antheaume C and Lobstein A: Antioxidant biomarkers from Vanda coerulea stems reduce irradiated HaCaT PGE-2 production as a result of COX-2 inhibition. PLoS One. 5(e13713)2010.PubMed/NCBI View Article : Google Scholar

11 

Fan C, Wang W, Wang Y, Qin G and Zhao W: Chemical constituents from Dendrobium densiflorum. Phytochemistry. 57:1255–1258. 2001.PubMed/NCBI View Article : Google Scholar

12 

Wu J, Li X, Wan W, Yang Q, Ma W, Chen D, Hu J, Chen CO and Wei X: Gigantol from Dendrobium chrysotoxum Lindl. binds and inhibits aldose reductase gene to exert its anti-cataract activity: An in vitro mechanistic study. J Ethnopharmacol. 198:255–261. 2017.PubMed/NCBI View Article : Google Scholar

13 

Wu J, Li X, Fang H, Yi Y, Chen D, Long Y, Gao X, Wei X and Chen CY: Investigation of synergistic mechanism and identification of interaction site of aldose reductase with the combination of gigantol and syringic acid for prevention of diabetic cataract. BMC Complement Altern Med. 16(286)2016.PubMed/NCBI View Article : Google Scholar

14 

Yu S, Wang Z, Su Z, Song J, Zhou L, Sun Q, Liu S, Li S, Li Y, Wang M, et al: Gigantol inhibits Wnt/β-catenin signaling and exhibits anticancer activity in breast cancer cells. BMC Complement Altern Med. 18(59)2018.PubMed/NCBI View Article : Google Scholar

15 

Chen H, Huang Y, Huang J, Lin L and Wei G: Gigantol attenuates the proliferation of human liver cancer HepG2 cells through the PI3K/Akt/NF-κB signaling pathway. Oncol Rep. 37:865–870. 2017.PubMed/NCBI View Article : Google Scholar

16 

Unahabhokha T, Chanvorachote P and Pongrakhananon V: The attenuation of epithelial to mesenchymal transition and induction of anoikis by gigantol in human lung cancer H460 cells. Tumour Biol. 37:8633–8641. 2016.PubMed/NCBI View Article : Google Scholar

17 

Charoenrungruang S, Chanvorachote P, Sritularak B and Pongrakhananon V: Gigantol, a bibenzyl from Dendrobium draconis, inhibits the migratory behavior of non-small cell lung cancer cells. J Nat Prod. 77:1359–1366. 2014.PubMed/NCBI View Article : Google Scholar

18 

von Lindern M, Breems D, van Baal S, Adriaansen H and Grosveld G: Characterization of the translocation breakpoint sequences of two DEK-CAN fusion genes present in t(6;9) acute myeloid leukemia and a SET-CAN fusion gene found in a case of acute undifferentiated leukemia. Genes Chromosomes Cancer. 5:227–234. 1992.PubMed/NCBI View Article : Google Scholar

19 

Waldmann T, Scholten I, Kappes F, Hu HG and Knippers R: The DEK protein-an abundant and ubiquitous constituent of mammalian chromatin. Gene. 343:1–9. 2004.PubMed/NCBI View Article : Google Scholar

20 

Hu HG, Scholten I, Gruss C and Knippers R: The distribution of the DEK protein in mammalian chromatin. Biochem Biophys Res Commun. 358:1008–1014. 2007.PubMed/NCBI View Article : Google Scholar

21 

Riveiro-Falkenbach E and Soengas MS: Control of tumorigenesis and chemoresistance by the DEK oncogene. Clin Cancer Res. 16:2932–2938. 2010.PubMed/NCBI View Article : Google Scholar

22 

Liu X, Qi D, Qi J, Mao Z, Li X, Zhang J, Li J and Gao W: Significance of DEK overexpression for the prognostic evaluation of non-small cell lung carcinoma. Oncol Rep. 35:155–162. 2016.PubMed/NCBI View Article : Google Scholar

23 

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

24 

Feng T, Liu Y, Li C, Li Z and Cai H: DEK proto-oncogene is highly expressed in astrocytic tumors and regulates glioblastoma cell proliferation and apoptosis. Tumour Biol. 39(1010428317716248)2017.PubMed/NCBI View Article : Google Scholar

25 

Wise-Draper TM, Mintz-Cole RA, Morris TA, Simpson DS, Wikenheiser-Brokamp KA, Currier MA, Cripe TP, Grosveld GC and Wells SI: Overexpression of the cellular DEK protein promotes epithelial transformation in vitro and in vivo. Cancer Res. 69:1792–1799. 2009.PubMed/NCBI View Article : Google Scholar

26 

Hui W, Ma X, Zan Y, Song L, Zhang S and Dong L: MicroRNA-1292-5p inhibits cell growth, migration and invasion of gastric carcinoma by targeting DEK. Am J Cancer Res. 8:1228–1238. 2018.PubMed/NCBI

27 

Piao J, Shang Y, Liu S, Piao Y, Cui X, Li Y and Lin Z: High expression of DEK predicts poor prognosis of gastric adenocarcinoma. Diagn Pathol. 9(67)2014.PubMed/NCBI View Article : Google Scholar

28 

Lin L, Piao J, Gao W, Piao Y, Jin G, Ma Y, Li J and Lin Z: DEK over expression as an independent biomarker for poor prognosis in colorectal cancer. BMC Cancer. 13(366)2013.PubMed/NCBI View Article : Google Scholar

29 

Zhou QC, Deng XF, Yang J, Jiang H, Qiao MX, Liu HH, Qian Z, Hou LL and Hu HG: Oncogene DEK is highly expressed in lung cancerous tissues and positively regulates cell proliferation as well as invasion. Oncol Lett. 15:8573–8581. 2018.PubMed/NCBI View Article : Google Scholar

30 

Bhummaphan N and Chanvorachote P: Gigantol suppresses cancer stem cell-like phenotypes in lung cancer cells. Evid Based Complement Alternat Med. 2015(836564)2015.PubMed/NCBI View Article : Google Scholar

31 

Unahabhokha T, Chanvorachote P, Sritularak B, Kitsongsermthon J and Pongrakhananon V: Gigantol inhibits epithelial to mesenchymal process in human lung cancer cells. Evid Based Complement Alternat Med. 2016(4561674)2016.PubMed/NCBI View Article : Google Scholar

32 

Gerdes J, Schwab U, Lemke H and Stein H: Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 31:13–20. 1983.PubMed/NCBI View Article : Google Scholar

33 

Harris MH and Thompson CB: The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death Differ. 7:1182–1191. 2000.PubMed/NCBI View Article : Google Scholar

34 

Lin L, Piao J, Ma Y, Jin T, Quan C, Kong J, Li Y and Lin Z: Mechanisms underlying cancer growth and apoptosis by DEK overexpression in colorectal cancer. PLoS One. 9(e111260)2014.PubMed/NCBI View Article : Google Scholar

35 

Stewart DJ: Wnt signaling pathway in non-small cell lung cancer. J Natl Cancer Inst. 106(djt356)2014.PubMed/NCBI View Article : Google Scholar

36 

Privette Vinnedge LM, Benight NM, Wagh PK, Pease NA, Nashu MA, Serrano-Lopez J, Adams AK, Cancelas JA, Waltz SE and Wells SI: The DEK oncogene promotes cellular proliferation through paracrine Wnt signaling in Ron receptor-positive breast cancers. Oncogene. 34:2325–2336. 2015.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Cai Y, Hao Y, Xu H, Chen K and Ren B: Gigantol inhibits cell proliferation and induces apoptosis by regulating DEK in non‑small cell lung cancer. Exp Ther Med 22: 1317, 2021.
APA
Cai, Y., Hao, Y., Xu, H., Chen, K., & Ren, B. (2021). Gigantol inhibits cell proliferation and induces apoptosis by regulating DEK in non‑small cell lung cancer. Experimental and Therapeutic Medicine, 22, 1317. https://doi.org/10.3892/etm.2021.10752
MLA
Cai, Y., Hao, Y., Xu, H., Chen, K., Ren, B."Gigantol inhibits cell proliferation and induces apoptosis by regulating DEK in non‑small cell lung cancer". Experimental and Therapeutic Medicine 22.5 (2021): 1317.
Chicago
Cai, Y., Hao, Y., Xu, H., Chen, K., Ren, B."Gigantol inhibits cell proliferation and induces apoptosis by regulating DEK in non‑small cell lung cancer". Experimental and Therapeutic Medicine 22, no. 5 (2021): 1317. https://doi.org/10.3892/etm.2021.10752
Copy and paste a formatted citation
x
Spandidos Publications style
Cai Y, Hao Y, Xu H, Chen K and Ren B: Gigantol inhibits cell proliferation and induces apoptosis by regulating DEK in non‑small cell lung cancer. Exp Ther Med 22: 1317, 2021.
APA
Cai, Y., Hao, Y., Xu, H., Chen, K., & Ren, B. (2021). Gigantol inhibits cell proliferation and induces apoptosis by regulating DEK in non‑small cell lung cancer. Experimental and Therapeutic Medicine, 22, 1317. https://doi.org/10.3892/etm.2021.10752
MLA
Cai, Y., Hao, Y., Xu, H., Chen, K., Ren, B."Gigantol inhibits cell proliferation and induces apoptosis by regulating DEK in non‑small cell lung cancer". Experimental and Therapeutic Medicine 22.5 (2021): 1317.
Chicago
Cai, Y., Hao, Y., Xu, H., Chen, K., Ren, B."Gigantol inhibits cell proliferation and induces apoptosis by regulating DEK in non‑small cell lung cancer". Experimental and Therapeutic Medicine 22, no. 5 (2021): 1317. https://doi.org/10.3892/etm.2021.10752
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