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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
April-2016 Volume 13 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
April-2016 Volume 13 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

Connexin32‑mediated antitumor effects of suicide gene therapy against hepatocellular carcinoma: In vitro and in vivo anticancer activity

  • Authors:
    • Lun Wu
    • Wen‑Bo Zhou
    • Feng Shen
    • Wei Liu
    • Hong‑Wei Wu
    • Shi‑Ji Zhou
    • Sheng‑Wei Li
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary Surgery, Experiment Center of Medicine, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442001, P.R. China, Department of Obstetrics, Haikou Hospital of Maternal and Child Health, Haikou, Hainan 570100, P.R. China, Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China, Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China
  • Pages: 3213-3219
    |
    Published online on: February 16, 2016
       https://doi.org/10.3892/mmr.2016.4895
  • 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

Normal hepatocytes express connexin32 (Cx32), which forms gap junctions at cell‑cell contact areas. The aim of the present study was to investigate whether Cx32 mediates the cell death‑inducing effects of ultrasound microbubbles carrying the herpes simplex virus thymidine kinase (HSV‑TK) suicide gene against hepatocellular carcinoma cells in vitro and in vivo. HepG2 cells were exposed to different concentrations of trans‑retinoic acid (ATRA) in culture, to evaluate the intrinsic antitumor effect of ATRA. Detailed in‑vitro and in‑vivo investigations on the antitumor effects of ATRA via Cx32 mediation were performed, and the possible underlying mechanisms of action of the compound were then examined. The gene expression of HSV‑TK transfected by ultrasound wave irradiation in the HepG2 cells was quantified using reverse transcription‑quantitative polymerase chain reaction analysis. The effects on cell death were assessed using an MTT assay. The protein expression levels of Cx32 in ATRA‑untreated or ATRA‑treated tissues were quantified by immunohistochemical analysis and Western blot assays. The HSV‑TK gene was successfully transfected into the HepG2 cell using ultrasound wave irradiation, and was stably expressed. Compared with the other groups, the HSV‑TK gene group treated with ATRA exhibited an increased number of apoptotic cells (P<0.05) and improved tumor suppression (P<0.05). ATRA significantly increased the expression of Cx32 in the hepatoma tissues (P<0.01). The present study demonstrated that ATRA elevated the protein expression of Cx32 and enhanced the bystander effect of the HSV‑TK/GCV suicide gene therapy system, which may provide a potential strategy for hepatocellular carcinoma treatment.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Liao YJ, Fang CC, Yen CH, Hsu SM, Wang CK, Huang SF, Liang YC, Lin YY, Chu YT and Arthur Chen YM: Niemann-Pick type C2 protein regulates liver cancer progression via modulating ERK1/2 pathway: Clinicopathological correlations and therapeutical implications. Int J Cancer. 137:1341–1351. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Qu L, Wang Y, Gong L, Zhu J, Gong R and Si J: Suicide gene therapy for hepatocellular carcinoma cells by survivin promoter-driven expression of the herpes simplex virus thymidine kinase gene. Oncol Rep. 29:1435–1440. 2013.PubMed/NCBI

3 

Yu BF, Wu J, Zhang Y, Sung HW, Xie J and Li RK: Ultrasound targeted HSVTK and Timp3 gene delivery for synergistically enhanced antitumor effects in hepatoma. Cancer Gene Ther. 20:290–297. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Xiao J, Zhang G, Qiu P, Liu X, Wu Y, Du B, Li J, Zhou J, Li J and Tan Y: Tanshinone IIA increases the bystander effect of herpes simplex virus thymidine kinase/ganciclovir gene therapy via enhanced gap junctional intercellular communication. PLoS One. 8:e676622013. View Article : Google Scholar : PubMed/NCBI

5 

Wygoda MR, Wilson MR, Davis MA, Trosko JE, Rehemtulla A and Lawrence TS: Protection of herpes simplex virus thymidine kinase-transduced cells from ganciclovir-ediated cytotoxicity by bystander cells: The Good Samaritan effect. Cancer Res. 57:1699–1703. 1997.PubMed/NCBI

6 

Lawrence TS, Rehemtulla A, Ng EY, Wilson M, Trosko JE and Stetson PL: Preferential cytotoxicity of cells transduced with cytosine deaminase compared to bystander cells after treatment with 5-flucytosine. Cancer Res. 58:2588–2593. 1998.PubMed/NCBI

7 

McLachlan E, Shao Q, Wang HL, Langlois S and Laird DW: Connexins act as tumor suppressors in three-dimensional mammary cell organoids by regulating differentiation and angiogenesis. Cancer Res. 66:9886–9894. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Maes M, Crespo Yanguas S, Willebrords J and Vinken M: Models and methods for in vitro testing of hepatic gap junctional communication. Toxicol In Vitro. 30:569–577. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Garcia-Rodríguez L, Pérez-Torras S, Carrió M, Cascante A, García-Ribas I, Mazo A and Fillat C: Connexin-26 is a key factor mediating gemcitabine bystander effect. Mol Cancer Ther. 10:505–517. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Banoub RW, Fernstrom M, Malkinson AM and Ruch RJ: Enhancement of gap junctional intercellular communication by dibutyryl cyclic AMP in lung epithelial cells. Anticancer Res. 16:3715–3719. 1996.PubMed/NCBI

11 

Trottier C, Colombo M, Mann KK, Miller WH Jr and Ward BJ: Retinoids inhibit measles virus through a type I IFN-dependent bystander effect. FASEB J. 23:3203–3212. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Wolf G: Tissue-specific increases in endogenous all-trans retinoic acid: Possible contributing factor in ethanol toxicity. Nutr Rev. 68:689–692. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Zhou S, Li S, Liu Z, Tang Y, Wang Z, Gong J and Liu C: Ultrasound-targeted microbubble destruction mediated herpes simplex virus-thymidine kinase gene treats hepatoma in mice. JExp Clin Cancer Res. 29:1702010. View Article : Google Scholar

14 

Wu L, Fu Z, Zhou S, Gong J, Liu CA, Qiao Z and Li S: HIF-1α and HIF-2α: Siblings in promoting angiogenesis of residual hepatocellular carcinoma after high-intensity focused ultrasound ablation. PLoS One. 9:e889132014. View Article : Google Scholar

15 

Wang ZX, Wang ZG, Ran HT, Ren JL, Zhang Y, Li Q, Zhu YF and Ao M: The treatment of liver fibrosis induced by hepatocyte growth factor-directed, ultrasound-targeted microbubble destruction in rats. Clin Imaging. 33:454–461. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Aoi A, Watanabe Y, Mori S, Takahashi M, Vassaux G and Kodama T: Herpes simplex virus thymidine kinase-mediated suicide gene therapy using nano/microbubbles and ultrasound. Ultrasound Med Biol. 34:425–434. 2008. View Article : Google Scholar

17 

Wang P, Sheng L, Wang G, Wang H, Huang X, Yan X, Yang X and Pei R: Association of transarterial chemoembolization with survival in patients with unresectable hepatocellular carcinoma. Mol Clin Oncol. 2:203–206. 2014.PubMed/NCBI

18 

Vachani A, Moon E, Wakeam E and Albelda SM: Gene therapy for mesothelioma and lung cancer. Am J Respir Cell Mol Biol. 42:385–393. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Määttä AM, Samaranayake H, Pikkarainen J, Wirth T and Ylä-Herttuala S: Adenovirus mediated herpes simplex virus-thymidine kinase/ganciclovir gene therapy for resectable malignant glioma. Curr Gene Ther. 9:356–367. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Kakinoki K, Nakamoto Y, Kagaya T, Tsuchiyama T, Sakai Y, Nakahama T, Mukaida N and Kaneko S: Prevention of intra-hepatic metastasis of liver cancer by suicide gene therapy and chemokine ligand 2/monocyte chemoattractant protein-1 delivery in mice. J Gene Med. 12:1002–1013. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Yu DS, Zhao W, Huang HZ, Hu XW, Liu XQ and Tang HK: Synthetic radiation-inducible promoters mediated HSV-TK/GCV gene therapy in the treatment of oral squamous cell carcinoma. Oral Dis. 16:445–452. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Li Z, Tan Q, Ding Z and Liu D: Mechanism of DADS in the bystander effect of HSV-TK/GCV suicide gene therapy system in lens epithelial cells. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 36:329–334. 2011.In Chinese. PubMed/NCBI

23 

Yang J, Liu TJ, Jiang YX and Lu Y: ATRA enhances the bystander effect of suicide gene therapy driven by the specific promoter LEP 503 in human lens epithelial cells. Mol Vis. 18:2053–2066. 2012.PubMed/NCBI

24 

Yang L, Chiang Y, Lenz HJ, Danenberg KD, Spears CP, Gordon EM, Anderson WF and Parekh D: Intercellular communication mediates the bystander effect during herpes simplex thymidine kinase/ganciclovir-based gene therapy of human gastrointestinal tumor cells. Hum Gene Ther. 9:719–728. 1998. View Article : Google Scholar : PubMed/NCBI

25 

Sato T, Neschadim A, Lavie A, Yanagisawa T and Medin JA: The engineered thymidylate kinase (TMPK)/AZT enzymeprodrug axis offers efficient bystander cell killing for suicide gene therapy of cancer. PLoS One. 8:e787112013. View Article : Google Scholar

26 

Tang N, Wang Q, Wu D, Zhang S, Zhang Y and Tao L: Differential effects of paclitaxel and docetaxel on gap junctions affects their cytotoxicities in transfected HeLa cells. Mol Med Rep. 8:638–644. 2013.PubMed/NCBI

27 

Cronier L, Crespin S, Strale PO, Defamie N and Mesnil M: Gap junctions and cancer: New function for an old story. Antioxid Redox Signal. 11:323–338. 2009. View Article : Google Scholar

28 

Thévenin AF, Kowal TJ, Fong JT, Kells RM, Fisher CG and Falk MM: Proteins and mechanisms regulating gap-junction assembly, internalization and degradation. Physiology (Bethesda). 28:93–116. 2013. View Article : Google Scholar

29 

Lin SC, Dollé P, Ryckebüsch L, Noseda M, Zaffran S, Schneider MD and Niederreither K: Endogenous retinoic acid regulates cardiac progenitor differentiation. Proc Natl Acad Sci USA. 107:9234–9239. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Yang J, Liu TJ, Jiang YX and Lu Y: ATRA enhances the bystander effect of suicide gene therapy driven by the specific promoter LEP 503 in human lens epithelial cells. Mol Vis. 18:2053–2066. 2012.PubMed/NCBI

31 

Li S, Gao Y, Pu K, Ma L, Song X and Liu Y: All-trans retinoic acid enhances bystander effect of suicide-gene therapy against medulloblastomas. Neurosci Lett. 503:115–119. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Panje CM, Wang DS and Willmann JK: Ultrasound and microbubble-mediated gene delivery in cancer: Progress and perspectives. Invest Radiol. 48:755–769. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Sorace AG, Saini R, Rosenthal E, Warram JM, Zinn KR and Hoyt K: Optical fluorescent imaging to monitor temporal effects of microbubble-mediated ultrasound therapy. IEEE Trans Ultrason Ferroelectr Freq Control. 60:281–289. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Sorace AG, Warram JM, Umphrey H and Hoyt K: Microbubble-mediated ultrasonic techniques for improved chemotherapeutic delivery in cancer. J Drug Target. 20:43–54. 2012. View Article : Google Scholar :

35 

Chen Y, Wang G, Kong D, Zhang Z, Yang K, Liu R, Zhao W and Xu Y: Double-targeted and double-enhanced suicide gene therapy mediated by generation 5 polyamidoamine dendrimers for prostate cancer. Mol Carcinog. 52:237–246. 2013. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wu L, Zhou WB, Shen F, Liu W, Wu HW, Zhou SJ and Li SW: Connexin32‑mediated antitumor effects of suicide gene therapy against hepatocellular carcinoma: In vitro and in vivo anticancer activity. Mol Med Rep 13: 3213-3219, 2016.
APA
Wu, L., Zhou, W., Shen, F., Liu, W., Wu, H., Zhou, S., & Li, S. (2016). Connexin32‑mediated antitumor effects of suicide gene therapy against hepatocellular carcinoma: In vitro and in vivo anticancer activity. Molecular Medicine Reports, 13, 3213-3219. https://doi.org/10.3892/mmr.2016.4895
MLA
Wu, L., Zhou, W., Shen, F., Liu, W., Wu, H., Zhou, S., Li, S."Connexin32‑mediated antitumor effects of suicide gene therapy against hepatocellular carcinoma: In vitro and in vivo anticancer activity". Molecular Medicine Reports 13.4 (2016): 3213-3219.
Chicago
Wu, L., Zhou, W., Shen, F., Liu, W., Wu, H., Zhou, S., Li, S."Connexin32‑mediated antitumor effects of suicide gene therapy against hepatocellular carcinoma: In vitro and in vivo anticancer activity". Molecular Medicine Reports 13, no. 4 (2016): 3213-3219. https://doi.org/10.3892/mmr.2016.4895
Copy and paste a formatted citation
x
Spandidos Publications style
Wu L, Zhou WB, Shen F, Liu W, Wu HW, Zhou SJ and Li SW: Connexin32‑mediated antitumor effects of suicide gene therapy against hepatocellular carcinoma: In vitro and in vivo anticancer activity. Mol Med Rep 13: 3213-3219, 2016.
APA
Wu, L., Zhou, W., Shen, F., Liu, W., Wu, H., Zhou, S., & Li, S. (2016). Connexin32‑mediated antitumor effects of suicide gene therapy against hepatocellular carcinoma: In vitro and in vivo anticancer activity. Molecular Medicine Reports, 13, 3213-3219. https://doi.org/10.3892/mmr.2016.4895
MLA
Wu, L., Zhou, W., Shen, F., Liu, W., Wu, H., Zhou, S., Li, S."Connexin32‑mediated antitumor effects of suicide gene therapy against hepatocellular carcinoma: In vitro and in vivo anticancer activity". Molecular Medicine Reports 13.4 (2016): 3213-3219.
Chicago
Wu, L., Zhou, W., Shen, F., Liu, W., Wu, H., Zhou, S., Li, S."Connexin32‑mediated antitumor effects of suicide gene therapy against hepatocellular carcinoma: In vitro and in vivo anticancer activity". Molecular Medicine Reports 13, no. 4 (2016): 3213-3219. https://doi.org/10.3892/mmr.2016.4895
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