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
December 2013 Volume 30 Issue 6

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
December 2013 Volume 30 Issue 6

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

Effects of rosiglitazone on the growth and lymphangiogenesis of human gastric cancer transplanted in nude mice

  • Authors:
    • Fang-Zhi Chen
    • Xi-Ming Mo
    • Qing-Ping Wang
    • Jun Li
    • Li Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China, Department of Clinical Laboratory, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China, Department of Clinical Laboratory, The Shaoxing Hospital of China Medical University, Shaoxing, Zhejiang 312030, P.R. China
  • Pages: 2705-2712
    |
    Published online on: August 28, 2013
       https://doi.org/10.3892/or.2013.2704
  • 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

Gastric cancer mainly metastasizes via lymphatic vessels. Thus, it is critical to identify efficacious chemopreventive agents for lymphangiogenesis. The present study was undertaken to explore the effects of rosiglitazone (ROSI) on the growth and lymphangiogenesis of human gastric cancer. We established a model of gastric cancer by subcutaneously inoculating the human gastric cancer cell line SGC-7901 into nude mice. Mice were randomly divided into 4 groups and each group received a different agent by oral gavage. The control group received normal saline and treatment groups received different doses of ROSI once every 2 days. The growth of the tumor in vivo was assessed by measuring tumor volume. After 42 days, the mice were sacrificed and the tumors were removed. H&E staining was used to observe the histomorphological features; immunohistochemistry staining for lymphatic vessel density (LVD) was used to evaluate tumor lymphangiogenesis, RT-PCR was performed to determine the mRNA expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor-3 (VEGFR-3), and western blotting was used to detect the protein expression of VEGF-C and VEGFR-3. Compared with the control group, all treatment groups had smaller tumor volume and higher tumor growth inhibitory rate every day. The number of typical tumor cells in the control group was higher compared to that in the treatment groups, and the highest level of LVD was found in the control group. Furthermore, both the expression of VEGF-C and VEGFR-3 mRNA and proteins in the control group were significantly higher compared to those in the treatment groups. Markedly, these changes were correlated in a dose-dependent manner with ROSI. These results demonstrated that, through simultaneously blocking the expression of VEGF-C and VEGFR-3, ROSI suppresses lymphangiogenesis. This may represent a powerful therapeutic approach for controlling gastric cancer cell growth and metastasis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Brenner H, Rothenbacher D and Arndt V: Epidemiology of stomach cancer. Methods Mol Biol. 472:467–477. 2009. View Article : Google Scholar

2 

Jemal A, Center MM, DeSantis C and Ward EM: Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 19:1893–1907. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Macdonald JS, Smalley SR, Benedetti J, et al: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 345:725–730. 2001. View Article : Google Scholar

4 

Achen MG and Stacker SA: Molecular control of lymphatic metastasis. Ann NY Acad Sci. 1131:225–234. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Alitalo K, Tammela T and Petrova TV: Lymphangiogenesis in development and human disease. Nature. 438:946–953. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Mumprecht V and Detmar M: Lymphangiogenesis and cancer metastasis. J Cell Mol Med. 13:1405–1416. 2009. View Article : Google Scholar : PubMed/NCBI

7 

McCarter MD, Clarke JH and Harken AH: Lymphangiogenesis is pivotal to the trials of a successful cancer metastasis. Surgery. 135:121–124. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Matsumoto M, Roufail S, Inder R, et al: Signaling for lymphangiogenesis via VEGFR-3 is required for the early events of metastasis. Clin Exp Metastasis. Apr 17–2013.(Epub ahead of print).

9 

Saltiel AR and Olefsky JM: Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes. 45:1661–1669. 1996. View Article : Google Scholar : PubMed/NCBI

10 

He Q, Pang R, Song X, et al: Rosiglitazone suppresses the growth and invasiveness of SGC-7901 gastric cancer cells and angiogenesis in vitro via PPARγ dependent and independent mechanisms. PPAR Res. 2008:6498082008.PubMed/NCBI

11 

Zhang L, Hu JF, Li GQ, Xiao X and Su Q: Rosiglitazone reverses mitomycin C resistance in human gastric cancer cells. Am J Med Sci. 343:382–387. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Talbert DR, Allred CD, Zaytseva YY and Kilgore MW: Transactivation of ERα by Rosiglitazone induces proliferation in breast cancer cells. Breast Cancer Res Treat. 108:23–33. 2008.

13 

Miao R, Xu T, Liu L, et al: Rosiglitazone and retinoic acid inhibit proliferation and induce apoptosis in the HCT-15 human colorectal cancer cell line. Exp Ther Med. 2:413–417. 2011.PubMed/NCBI

14 

Cerquetti L, Sampaoli C, Amendola D, et al: Rosiglitazone induces autophagy in H295R and cell cycle deregulation in SW13 adrenocortical cancer cells. Exp Cell Res. 317:1397–1410. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Chiu SJ, Hsaio CH, Tseng HH, et al: Rosiglitazone enhances the radiosensitivity of p53-mutant HT-29 human colorectal cancer cells. Biochem Biophys Res Commun. 394:774–779. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Lyon CM, Klinge DM, Do KC, et al: Rosiglitazone prevents the progression of preinvasive lung cancer in a murine model. Carcinogenesis. 30:2095–2099. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Yee LD, Williams N, Wen P, et al: Pilot study of rosiglitazone therapy in women with breast cancer: effects of short-term therapy on tumor tissue and serum markers. Clin Cancer Res. 13:246–252. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Esteva FJ, Moulder SL, Gonzalez-Angulo AM, et al: Phase I trial of exemestane in combination with metformin and rosiglitazone in nondiabetic obese postmenopausal women with hormone receptor-positive metastatic breast cancer. Cancer Chemother Pharmacol. 71:63–72. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Luconi M, Mangoni M, Gelmini S, et al: Rosiglitazone impairs proliferation of human adrenocortical cancer: preclinical study in a xenograft mouse model. Endocr Relat Cancer. 17:169–177. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA and Hamilton SM: Gastric adenocarcinoma: review and considerations for future directions. Ann Surg. 241:27–39. 2005.PubMed/NCBI

21 

Ohno M, Nakamura T, Kunimoto Y, Nishimura K, Chung-Kang C and Kuroda Y: Lymphagenesis correlates with expression of vascular endothelial growth factor-C in colorectal cancer. Oncol Rep. 10:939–943. 2003.PubMed/NCBI

22 

Mangelsdorf DJ, Thummel C, Beato M, et al: The nuclear receptor superfamily: the second decade. Cell. 83:835–839. 1995. View Article : Google Scholar : PubMed/NCBI

23 

Siersbaek R, Nielsen R and Mandrup S: PPARγ in adipocyte differentiation and metabolism - novel insights from genome-wide studies. FEBS Lett. 584:3242–3249. 2010.

24 

Nedergaard J, Petrovic N, Lindgren EM, Jacobsson A and Cannon B: PPARγ in the control of brown adipocyte differentiation. Biochim Biophys Acta. 1740:293–304. 2005.

25 

Fernyhough ME, Okine E, Hausman G, Vierck JL and Dodson MV: PPARγ and GLUT-4 expression as developmental regulators/markers for preadipocyte differentiation into an adipocyte. Domest Anim Endocrinol. 33:367–378. 2007.

26 

Elrod HA and Sun SY: PPARγ and apoptosis in cancer. PPAR Res. 2008:7041652008.

27 

Kim S, Lee JJ and Heo DS: PPARγ ligands induce growth inhibition and apoptosis through p63 and p73 in human ovarian cancer cells. Biochem Biophys Res Commun. 406:389–395. 2011.

28 

Zhou J, Zhang W, Liang B, et al: PPARγ activation induces autophagy in breast cancer cells. Int J Biochem Cell Biol. 41:2334–2342. 2009.

29 

Zaytseva YY, Wallis NK, Southard RC and Kilgore MW: The PPARγ antagonist T0070907 suppresses breast cancer cell proliferation and motility via both PPARγ-dependent and -independent mechanisms. Anticancer Res. 31:813–823. 2011.

30 

Kitamura S, Miyazaki Y, Hiraoka S, et al: PPARγ inhibits the expression of c-MET in human gastric cancer cells through the suppression of Ets. Biochem Biophys Res Commun. 265:453–456. 1999.

31 

Takahashi H, Hosono K, Uchiyama T, et al: PPARγ ligand as a promising candidate for colorectal cancer chemoprevention: a pilot study. PPAR Res. 2010:2578352010. View Article : Google Scholar

32 

Wood WM, Sharma V, Bauerle KT, et al: PPARγ promotes growth and invasion of thyroid cancer cells. PPAR Res. 2011:1717652011. View Article : Google Scholar

33 

Sato H, Ishihara S, Kawashima K, et al: Expression of peroxisome proliferator-activated receptor (PPAR)γ in gastric cancer and inhibitory effects of PPARγ agonists. Br J Cancer. 83:1394–1400. 2000.

34 

Lu J, Imamura K, Nomura S, et al: Chemopreventive effect of peroxisome proliferator-activated receptor γ on gastric carcinogenesis in mice. Cancer Res. 65:4769–4774. 2005.

35 

Chen J, Zhi Y, Chang X, Zhang S and Dai D: Expression of ADAMTS1 and its correlation with angiogenesis in primary gastric cancer and lymph node metastasis. Dig Dis Sci. 58:405–413. 2013. View Article : Google Scholar : PubMed/NCBI

36 

Wu H, Xin Y, Xu C and Xiao Y: Capecitabine combined with (−)-epigallocatechin-3-gallate inhibits angiogenesis and tumor growth in nude mice with gastric cancer xenografts. Exp Ther Med. 3:650–654. 2012.

37 

Fidler IJ: The biology of cancer metastasis. Semin Cancer Biol. 21:712011. View Article : Google Scholar

38 

Al-Rawi MA and Jiang WG: Lymphangiogenesis and cancer metastasis. Front Biosci. 16:723–739. 2011. View Article : Google Scholar

39 

Raica M, Cimpean AM and Ribatti D: The role of podoplanin in tumor progression and metastasis. Anticancer Res. 28:2997–3006. 2008.PubMed/NCBI

40 

Yu JW, Wu JG, Tajima Y, et al: Study on lymph node metastasis correlated to lymphangiogenesis, lymphatic vessel invasion, and lymph node micrometastasis in gastric cancer. J Surg Res. 168:188–196. 2011. View Article : Google Scholar : PubMed/NCBI

41 

Makinen T, Veikkola T, Mustjoki S, et al: Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3. EMBO J. 20:4762–4773. 2001. View Article : Google Scholar : PubMed/NCBI

42 

Van Trappen PO, Steele D, Lowe DG, et al: Expression of vascular endothelial growth factor (VEGF)-C and VEGF-D, and their receptor VEGFR-3, during different stages of cervical carcinogenesis. J Pathol. 201:544–554. 2003.PubMed/NCBI

43 

Su JL, Chen PS, Chien MH, et al: Further evidence for expression and function of the VEGF-C/VEGFR-3 axis in cancer cells. Cancer Cell. 13:557–560. 2008. View Article : Google Scholar : PubMed/NCBI

44 

Takizawa H, Kondo K, Fujino H, et al: The balance of VEGF-C and VEGFR-3 mRNA is a predictor of lymph node metastasis in non-small cell lung cancer. Br J Cancer. 95:75–79. 2006. View Article : Google Scholar : PubMed/NCBI

45 

Arigami T, Natsugoe S, Uenosono Y, et al: Vascular endothelial growth factor-C and -D expression correlates with lymph node micrometastasis in pN0 early gastric cancer. J Surg Oncol. 99:148–153. 2009. View Article : Google Scholar : PubMed/NCBI

46 

Liu ZY, Qiu HO, Yuan XJ, et al: Suppression of lymphangiogenesis in human lymphatic endothelial cells by simultaneously blocking VEGF-C and VEGF-D/VEGFR-3 with norcantharidin. Int J Oncol. 41:1762–1772. 2012.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen F, Mo X, Wang Q, Li J and Zhang L: Effects of rosiglitazone on the growth and lymphangiogenesis of human gastric cancer transplanted in nude mice. Oncol Rep 30: 2705-2712, 2013.
APA
Chen, F., Mo, X., Wang, Q., Li, J., & Zhang, L. (2013). Effects of rosiglitazone on the growth and lymphangiogenesis of human gastric cancer transplanted in nude mice. Oncology Reports, 30, 2705-2712. https://doi.org/10.3892/or.2013.2704
MLA
Chen, F., Mo, X., Wang, Q., Li, J., Zhang, L."Effects of rosiglitazone on the growth and lymphangiogenesis of human gastric cancer transplanted in nude mice". Oncology Reports 30.6 (2013): 2705-2712.
Chicago
Chen, F., Mo, X., Wang, Q., Li, J., Zhang, L."Effects of rosiglitazone on the growth and lymphangiogenesis of human gastric cancer transplanted in nude mice". Oncology Reports 30, no. 6 (2013): 2705-2712. https://doi.org/10.3892/or.2013.2704
Copy and paste a formatted citation
x
Spandidos Publications style
Chen F, Mo X, Wang Q, Li J and Zhang L: Effects of rosiglitazone on the growth and lymphangiogenesis of human gastric cancer transplanted in nude mice. Oncol Rep 30: 2705-2712, 2013.
APA
Chen, F., Mo, X., Wang, Q., Li, J., & Zhang, L. (2013). Effects of rosiglitazone on the growth and lymphangiogenesis of human gastric cancer transplanted in nude mice. Oncology Reports, 30, 2705-2712. https://doi.org/10.3892/or.2013.2704
MLA
Chen, F., Mo, X., Wang, Q., Li, J., Zhang, L."Effects of rosiglitazone on the growth and lymphangiogenesis of human gastric cancer transplanted in nude mice". Oncology Reports 30.6 (2013): 2705-2712.
Chicago
Chen, F., Mo, X., Wang, Q., Li, J., Zhang, L."Effects of rosiglitazone on the growth and lymphangiogenesis of human gastric cancer transplanted in nude mice". Oncology Reports 30, no. 6 (2013): 2705-2712. https://doi.org/10.3892/or.2013.2704
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