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
May-2016 Volume 13 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
May-2016 Volume 13 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

Expression of MIF and c-erbB-2 in endometrial cancer

  • Authors:
    • Wei Xiao
    • Xiujuan Dong
    • Honghui Zhao
    • Shiyu Han
    • Ruixue Nie
    • Xiahua Zhang
    • Ruifang An
  • View Affiliations / Copyright

    Affiliations: Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi 710061, P.R. China, Department of Gynaecology and Obstetrics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China
    Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3828-3834
    |
    Published online on: March 16, 2016
       https://doi.org/10.3892/mmr.2016.4992
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The aim of the present study was to investigate the expression of c-erbB-2 and macrophage migration inhibitory factor (MIF) in endometrial cancer and to elucidate the significance of the early diagnosis and prognosis of endometrial cancer. The gene copy number of c‑erbB‑2 and MIF was characterized by reverse transcription quantitative polymerase chain reaction and the reactivity was assessed by immunohistochemistry in 70 patients using a polyclonal antibody, and evaluated semiquantitatively according to the percentage of cells demonstrating membranous or diffuse cytoplasmic staining. A correlation between age, tumor stage, grade, myometrial invasion and lymph node metastasis was observed. The mRNA expression of c‑erbB‑2 and MIF was high in endometrial carcinoma. The positive expression rate of MIF protein in normal endometrium, atypical hyperplasia and endometrial carcinoma significantly increased along with the degree of aggravation of the disease by 20 (3/15), 45 (9/20) and 70% (35/50), respectively. The positive expression of MIF and c‑erbB‑2 was highest in endometrial cancer and a significantly higher level of protein was observed in tumors at stage I, stage G1, with a depth of myometrial invasion <0.4 cm and no lymph node metastasis. The protein expression of c‑erbB‑2 in endometrial cancer was higher in tumors at the G2‑3 phase, clinical stage III‑IV, lymph node metastasis, and had no association with the depth of myometrial invasion and age. MIF and c‑erbB‑2 were correlated with the occurrence and the development of endometrial cancer, and thus can be used for the early diagnosis and prognosis of endometrial cancer. The present study laid the foundation for identifying new treatments for endometrial cancer.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Mhawech-Fauceglia P, Wang D, Samrao D, Godoy H, Pejovic T, Liu S and Lele S: Pair-Box (PAX8) protein positive expression is associated with poor disease outcome in women with endometrial cancer. Br J Cancer. 107:370–374. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Verit FF and Yucel O: Endometriosis, leiomyoma and adenomyosis: The risk of gynecologic malignancy. Asian Pac J Cancer Prev. 14:5589–5597. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Xu Z and Ford BD: Uperegulation of erbB recepters in rat brain after middle cerebrial arterial occlusion. Neurosci Lett. 375:181–186. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Araújo A, Ribeiro R, Azevedo I, Coelho A, Soares M, Sousa B, Pinto D, Lopes C, Medeiros R and Scagliotti GV: Genetic polymorphisms of the epidermal growth factor and related receptor in non-small cell lung cancer-a review of the literature. Oncologist. 12:201–210. 2007. View Article : Google Scholar

6 

Oshima CT, Lanzoni VP, Iriya K and Forones NM: C-erbB-2 oncoprotein expression in gastric carcinoma: Correlation with clinical stage and prognosis. Int J Biol Markers. 16:250–254. 2001.

7 

Potti A, Forseen SE, Koka VK, Pervez H, Koch M, Fraiman G, Mehdi SA and Levitt R: Determination of HER-2/neu overexpression and clinical predictors of survival in a cohort of 347 patients with primary malignant brain tumors. Cancer Invest. 22:537–544. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Rotter M, Block T, Busch R, Thanner S and Höfer H: Expression of Her-2/neu in renal-cell carcinoma. Correlation with histologic subtypes and differentiation. Int J Cancer. 52:213–217. 1992. View Article : Google Scholar : PubMed/NCBI

9 

Manavi M, Bauer M, Baghestanian M, Berger A, Kucera E, Pischinger K, Battistutti W and Czerwenka K: Oncogenic potential of c-erbB-2 and its association with c-K-ras in premalignant and malignant lesions of the human uterine endometrium. Tumour Biol. 22:299–309. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Xi L, Satpathy M, Zhao Q, Qian W, Yang L and Jiang H: HER-2/neu targeted delivery of a nanoprobe enables dual photoacoustic and fluorescence tomography of ovarian cancer. Nanomedicine. 10:669–677. 2014.

11 

Carson WE, Parihar R, Lindemann MJ, Personeni N, Dierksheide J, Meropol NJ, Baselga J and Caligiuri MA: Interleukin-2 enhances the natural killer cell response to Herceptin-coated Her2/neupositive breast cancer cells. Eur J Immunol. 31:3016–3025. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, et al: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 344:783–792. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Apte RS, Sinha D, Mayhew E, Wistow GJ and Niederkorn JY: Cutting edge: Role of macrophage migration inhibitory factor in inhibiting NK cell activity and preserving immune privilege. J Immunol. 160:5693–5696. 1998.PubMed/NCBI

14 

Rendon BE, Roger T, Teneng I, Zhao M, Al-Abed Y, Calandra T and Mitchell RA: Regulation of human lung adenocarcinoma cell migration and invasion by macrophage migration inhibitory factor. J Biol Chem. 282:29910–29918. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Liao H, Bucala R and Mitchell RA: Adhesion-dependent signaling by macrophage migration inhibitory factor (MIF). J Biol Chem. 278:76–81. 2003. View Article : Google Scholar

16 

Amin MA, Volpert OV, Woods JM, Kumar P, Harlow LA and Koch AE: Migration inhibitory factor mediates angiogenesis via mitogen-activated protein kinase and phosphatidylinositol kinase. Circ Res. 93:321–329. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Baumann R, Casaulta C, Simon D, Conus S, Yousefi S and Simon HU: Macrophage migration inhibitory factor delays apoptosis in neutrophils by inhibiting the mitochondria-dependent death pathway. FASEB J. 17:2221–2230. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Bacher M, Schrader J, Thompson N, Kuschela K, Gemsa D, Waeber G and Schlegel J: Up-regulation of macrophage migration inhibitory factor gene and protein expression in glial tumour cells during hypoxic and hypoglycemic stress indicates a critical role for angiogenesis in glioblastoma multiforme. Am J Pathol. 162:11–17. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Repp AC, Mayhew ES, Apte S and Niederkorn JY: Human uveal melanoma cells produce macrophage migration-inhibitory factor to prevent lysis by NK cells. J Immunol. 165:710–715. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Krockenberger M, Dombrowski Y, Weidler C, Ossadnik M, Hönig A, Häusler S, Voigt H, Becker JC, Leng L, Steinle A, et al: Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D. J Immunol. 180:7338–7348. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Xia HH, Yang Y, Chu KM, Gu Q, Zhang YY, He H, Wong WM, Leung SY, Yuen ST, Yuen MF, et al: Serum macrophage migration-inhibitory factor as a diagnostic and prognostic biomarker for gastric cancer. Cancer. 115:5441–5449. 2009. View Article : Google Scholar : PubMed/NCBI

22 

White ES, Flaherty KR, Carskadon S, Brant A, Iannettoni MD, Yee J, Orringer MB and Arenberg DA: Macrophage migration inhibitory factor and CXC chemokine expression in non-small cell lung cancer: Role in angiogenesis and prognosis. Clin Cancer Res. 9:853–860. 2003.PubMed/NCBI

23 

Zheng J and Zhu YM: Expression of c-erbB-2 proto-oncogene in extrahepatic cholangiocarcinoma and its clinical significance. Hepatobiliary Pancreat Dis Int. 6:412–415. 2007.PubMed/NCBI

24 

Wu S, Lian J, Tao H, Shang H and Zhang L: Correlation of macrophage migration inhibitory factor gene polymorphism with the risk of early-stage cervical cancer and lymphatic metastasis. Oncol Lett. 2:1261–1267. 2011.

25 

Lambropoulou M, Stefanou D, Alexiadis G, Tamiolakis D, Tripsianis G, Chatzaki E, Vandoros GP, Kiziridou A, Papadopoulou E and Papadopoulos N: Cytoplasmic expression of c-erbB-2 in endometrial carcinomas. Onkologie. 30:495–500. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Bhatavdekar JM, Patel DD, Shah NG, Vora HH, Suthar TP, Chikhlikar PR, Ghosh N and Trivedi TI: Prognostic significance of immunohistochemically localized biomarkers in stage II and stage III breast cancer. A multivariate analysis. Ann Surg Oncol. 7:305–311. 2000. View Article : Google Scholar : PubMed/NCBI

27 

Kim R, Arihiro K, Emi M, Tanabe K and Osaki A: Potential role of HER-2; in primary breast tumor with bone metastasis. Oncol Rep. 15:1477–1484. 2006.PubMed/NCBI

28 

Pérez-Regadera J, Sánchez-Muñoz A, De-la-Cruz J, Ballestín C, Lora D, García-Martín R, Mendiola C, Alonso L, Alba E and Lanzós E: Negative prognostic impact of the coexpression of epidermal growth factor receptor and c-erbB-2 in locally advanced cervical cancer. Oncology. 76:133–141. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Toi M, Kashitani T and Tominaga T: Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma. Int J Cancer. 55:371–374. 1993. View Article : Google Scholar : PubMed/NCBI

30 

Morrison C, Zanagnolo V, Ramirez N, Cohn DE, Kelbick N, Copeland L, Maxwell GL and Fowler JM: HER-2 is an independent prognostic factor in endometrial cancer: Association with outcome in a large cohort of surgically staged patients. J Clin Oncol. 24:2376–2385. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Bondza PK, Metz CN and Akoum A: Macrophage migration inhibitory factor upregulates alpha(v)beta (3) integrin and vascular endothelial growth factor expression in endometrial adenocarcinoma cell line Ishikawa. J Reprod Immunol. 77:142–151. 2008. View Article : Google Scholar

32 

Hagemann T, Robinson SC, Thompson RG, Charles K, Kulbe H and Balkwill FR: Ovarian cancer cell-derived migration inhibitory factor enhances tumor growth, progression and angiogenesis. Mol Cancer Ther. 6:1993–2002. 2007. View Article : Google Scholar : PubMed/NCBI

33 

Nishihira J, Ishibashi T, Fukushima T, Sun B, Sato Y and Todo S: Macrophage migration inhibitory factor (MIF): Its potential role in tumor growth and tumor-associated angiogenesis. Ann NY Acad Sci. 995:171–182. 2003. View Article : Google Scholar : PubMed/NCBI

34 

Denz A, Pilarsky C, Muth D, Rückert F, Saeger HD and Grützmann R: Inhibition of MIF leads to cell cycle arrest and apoptosis in pancreatic cancer cells. J Surg Res. 160:29–34. 2010. View Article : Google Scholar

35 

Verjans E, Noetzel E, Bektas N, Schütz AK, Lue H, Lennartz B, Hartmann A, Dahl E and Bernhagen J: Dual role of macrophage migration inhibitory factor (MIF) in human breast cancer. BMC Cancer. 9(230)2009. View Article : Google Scholar : PubMed/NCBI

36 

Schulz R, Streller F, Scheel AH, Rüschoff J, Reinert MC, Dobbelstein M, Marchenko ND and Moll UM: HER2/ErbB2 activates HSF1 and thereby controls HSP90 clients including MIF in HER2-overexpressing breast cancer. Cell Death Dis. 5:e9802014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xiao W, Dong X, Zhao H, Han S, Nie R, Zhang X and An R: Expression of MIF and c-erbB-2 in endometrial cancer. Mol Med Rep 13: 3828-3834, 2016.
APA
Xiao, W., Dong, X., Zhao, H., Han, S., Nie, R., Zhang, X., & An, R. (2016). Expression of MIF and c-erbB-2 in endometrial cancer. Molecular Medicine Reports, 13, 3828-3834. https://doi.org/10.3892/mmr.2016.4992
MLA
Xiao, W., Dong, X., Zhao, H., Han, S., Nie, R., Zhang, X., An, R."Expression of MIF and c-erbB-2 in endometrial cancer". Molecular Medicine Reports 13.5 (2016): 3828-3834.
Chicago
Xiao, W., Dong, X., Zhao, H., Han, S., Nie, R., Zhang, X., An, R."Expression of MIF and c-erbB-2 in endometrial cancer". Molecular Medicine Reports 13, no. 5 (2016): 3828-3834. https://doi.org/10.3892/mmr.2016.4992
Copy and paste a formatted citation
x
Spandidos Publications style
Xiao W, Dong X, Zhao H, Han S, Nie R, Zhang X and An R: Expression of MIF and c-erbB-2 in endometrial cancer. Mol Med Rep 13: 3828-3834, 2016.
APA
Xiao, W., Dong, X., Zhao, H., Han, S., Nie, R., Zhang, X., & An, R. (2016). Expression of MIF and c-erbB-2 in endometrial cancer. Molecular Medicine Reports, 13, 3828-3834. https://doi.org/10.3892/mmr.2016.4992
MLA
Xiao, W., Dong, X., Zhao, H., Han, S., Nie, R., Zhang, X., An, R."Expression of MIF and c-erbB-2 in endometrial cancer". Molecular Medicine Reports 13.5 (2016): 3828-3834.
Chicago
Xiao, W., Dong, X., Zhao, H., Han, S., Nie, R., Zhang, X., An, R."Expression of MIF and c-erbB-2 in endometrial cancer". Molecular Medicine Reports 13, no. 5 (2016): 3828-3834. https://doi.org/10.3892/mmr.2016.4992
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