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 Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
February-2016 Volume 11 Issue 2

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
February-2016 Volume 11 Issue 2

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

Expression and clinical significance of Sirt1 in colorectal cancer

  • Authors:
    • Deng‑Feng Yu
    • Su‑Juan Jiang
    • Zhi‑Peng Pan
    • Wei‑Dong Cheng
    • Wen‑Jun Zhang
    • Xiao‑Kun Yao
    • Yu‑Cheng Li
    • Yong‑Zhi Lun
  • View Affiliations / Copyright

    Affiliations: Liaoning Provincial University Key Laboratory of Biophysics, College of Medicine, Dalian University, Dalian, Liaoning 116622, P.R. China, Department of Anorectal Surgery, Affiliated Xinhua Hospital of Dalian University, Dalian, Liaoning 116021, P.R. China, Department of Dermatology, Yuzhou People's Hospital, Xuchang, Henan 461670, P.R. China
  • Pages: 1167-1172
    |
    Published online on: December 1, 2015
       https://doi.org/10.3892/ol.2015.3982
  • 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 objective of the present study was to examine the expression of Silent information regulator 1 (Sirt1) in colorectal cancer and peritumoral normal mucosa tissue, and therefore analyze the role and molecular mechanism of Sirt1 in the pathogenesis of colorectal cancer. Colorectal cancer tissue specimens were employed as the experimental group, and adjacent normal mucosa tissues >5 cm from tumor lesions were used as the control group. The expression of Sirt1 was detected by the immunohistochemical streptavidin peroxidase detection method in paraffin‑embedded sections, whilst Sirt1 protein expression was examined by western blot analysis in the fresh tissues. Sirt1 protein was primarily expressed in the nuclei of the tumor cells, and positive staining was brownish‑yellow in color. The relative expression quantities of Sirt1 in the peritumoral normal rectal mucosa and rectal carcinoma were 1.15 and 2.62, and the differences between the two groups were statistically significant (P<0.05). The expression level of Sirt1 in colorectal carcinoma was significantly associated with the depth of tumor invasion, differentiation and tumor size (P<0.05). Sirt1 expression was also found to be associated with tumor tissue type, lymph node metastasis, Duke's stage and patient age. These characteristics combined may therefore be used as markers for the early diagnosis of colorectal cancer pathogenesis.
View Figures

Figure 1

Figure 2

View References

1 

Azer SA: Overview of molecular pathways in inflammatory bowel disease associated with colorectal cancer development. Eur J Gastroenterol Hepatol. 25:271–281. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Raskov H, Pommergaard HC, Burcharth J and Rosenberg J: Colorectal carcinogenesis - update and perspectives. World J Gastroenterol. 20:18151–18164. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Newman NA, Votanopoulos KL, Stewart JH, Shen P and Levine EA: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer. Minerva Chir. 67:309–318. 2012.PubMed/NCBI

6 

Hompes D, D'Hoore A, Van Cutsem E, Fieuws S, Ceelen W, Peeters M, Van der Speeten K, Bertrand C, Legendre H and Kerger J: The treatment of peritoneal carcinomatosis of colorectal cancer with complete cytoreductive surgery and hyperthermic intraperitoneal peroperative chemotherapy (HIPEC) with oxaliplatin: A Belgian multicentre prospective phase II clinical study. Ann Surg Oncol. 19:2186–2194. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Fu Z, Shrubsole MJ, Smalley WE, Wu H, Chen Z, Shyr Y, Ness RM and Zheng W: Association of meat intake and meat-derived mutagen exposure with the risk of colorectal polyps by histologic type. Cancer Prev Res (Phila). 4:1686–1697. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Piepoli A, Tavano F, Copetti M, Mazza T, Palumbo O, Panza A, di Mola FF, Pazienza V, Mazzoccoli G, Biscaglia G, et al: MiRNA expression profiles identify drivers in colorectal and pancreatic cancers. PLoS One. 7:e336632012. View Article : Google Scholar : PubMed/NCBI

9 

Linnekamp JF, Wang X, Medema JP and Vermeulen L: Colorectal cancer heterogeneity and targeted therapy, A case for molecular disease subtypes. Cancer Res. 75:245–249. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Blander G and Guarente L: The Sir2 family of protein deacetylases. Annu Rev Biochem. 73:417–435. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Casatta N, Porro A, Orlandi I, Brambilla L and Vai M: Lack of Sir2 increases acetate consumption and decreases extracellular pro-aging factors. Biochim Biophys Acta. 1833:593–601. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Huffman DM, Grizzle WE, Bamman MM, Kim JS, Eltoum IA, Elgavish A and Nagy TR: SIRT1 is significantly elevated in mouse and human prostate cancer. Cancer Res. 67:6612–6618. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Bradbury CA, Khanim FL, Hayden R, Bunce CM, White DA, Drayson MT, Craddock C and Turner BM: Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors. Leukemia. 19:1751–1759. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Hida Y, Kubo Y, Murao K and Arase S: Strong expression of a longevity-related protein, SIRT1, in Bowen's disease. Arch Dermatol Res. 299:103–106. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Stünkel W, Peh BK, Tan YC, Nayagam VM, Wang X, Salto-Tellez M, Ni B, Entzeroth M and Wood J: Function of the SIRT1 protein deacetylase in cancer. Biotechnol J. 2:1360–1368. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Bass P, Carr N and Du Boulay C: Pathology: A Core Text of Basic Pathological Processes with Self-Assessment (2nd). Edinburgh: Churchill Livingstone. 2004.

17 

Yang J, Guo R, Kang A, Chen X, Su B, Huang X, Jin Y and Li Z: A novel histological typing and grading-scale system of colorectal cancer. Nan Fang Yi Ke Da Xue Xue Bao. 34:169–173. 2014.(In Chinese). PubMed/NCBI

18 

Dukes CE: The classification of cancer of the rectum. J Pathol. 35:323–332. 1932. View Article : Google Scholar

19 

Chueca E, Lanas A and Piazuelo E: Role of gastrin-peptides in Barrett's and colorectal carcinogenesis. World J Gastroenterol. 18:6560–6570. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Fadri-Moskwik M, Weiderhold KN, Deeraksa A, Chuang C, Pan J, Lin SH and Yu-Lee LY: Aurora B is regulated by acetylation/deacetylation during mitosis in prostate cancer cells. FASEB J. 26:4057–4067. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Kim SJ, Ao Z, Warnock G and McIntosh CH: Incretin-stimulated interaction between β-cell Kv1.5 and Kvβ2 channel proteins involves acetylation/deacetylation by CBP/SirT1. Biochem J. 451:227–234. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Hishida T, Nozaki Y, Nakachi Y, Mizuno Y, Iseki H, Katano M, Kamon M, Hirasaki M, Nishimoto M, Okazaki Y and Okuda A: Sirt1, p53, and p38(MAPK) are crucial regulators of detrimental phenotypes of embryonic stem cells with Max expression ablation. Stem Cells. 30:1634–1644. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Muller PA and Vousden KH: p53 mutations in cancer. Nat Cell Biol. 15:2–8. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Castro RE, Ferreira DM, Afonso MB, Borralho PM, Machado MV, Cortez-Pinto H and Rodrigues CM: miR-34a/SIRT1/p53 is suppressed by ursodeoxycholic acid in the rat liver and activated by disease severity in human non-alcoholic fatty liver disease. J Hepatol. 58:119–25. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Zannini L, Buscemi G, Kim JE, Fontanella E and Delia D: DBC1 phosphorylation by ATM/ATR inhibits SIRT1 deacetylase in response to DNA damage. J Mol Cell Biol. 4:294–303. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Liu L, Wang P, Liu X, He D, Liang C and Yu Y: Exogenous NAD(+) supplementation protects H9c2 cardiac myoblasts against hypoxia/reoxygenation injury via Sirt1-p53 pathway. Fundam Clin Pharmacol. 28:180–189. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Marfe G, De Martino L, Tafani M, Irno-Consalvo M, Pasolini MP, Navas L, Papparella S, Gambacurta A and Paciello O: A multicancer-like syndrome in a dog characterized by p53 and cell cycle-checkpoint kinase 2 (CHK2) mutations and sirtuin gene (SIRT1) down-regulation. Res Vet Sci. 93:240–245. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Lee CW, Wong LL, Tse EY, Liu HF, Leong VY, Lee JM, Hardie DG, Ng IO and Ching YP: AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells. Cancer Res. 72:4394–4404. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Kriegl L, Vieth M, Kirchner T and Menssen A: Up-regulation of c-MYC and SIRT1 expression correlates with malignant transformation in the serrated route to colorectal cancer. Oncotarget. 3:1182–1193. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Schweiger MR, Hussong M, Röhr C and Lehrach H: Genomics and epigenomics of colorectal cancer. Wiley Interdiscip Rev Syst Biol Med. 5:205–219. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Chong ZZ, Shang YC, Wang S and Maiese K: SIRT1: New avenues of discovery for disorders of oxidative stress. Expert Opin Ther Targets. 16:167–178. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Hubbard BP, Gomes AP, Dai H, Li J, Case AW, Considine T, Riera TV, Lee JE, E SY, Lamming DW, et al: Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science. 339:1216–1219. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Yao X, Zhao G, Yang H, Hong X, Bie L and Liu G: Overexpression of high-mobility group box 1 correlates with tumor progression and poor prognosis in human colorectal carcinoma. J Cancer Res Clin Oncol. 136:677–684. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Firestein R, Blander G, Michan S, Oberdoerffer P, Ogino S, Campbell J, Bhimavarapu A, Luikenhuis S, de Cabo R, Fuchs C, et al: The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS One. 3:e20202008. View Article : Google Scholar : PubMed/NCBI

35 

Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA and Mayo MW: Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 23:2369–2380. 2004. View Article : Google Scholar : PubMed/NCBI

36 

Leko V, Park GJ, Lao U, Simon JA and Bedalov A: Enterocyte-specific inactivation of SIRT1 reduces tumor load in the APC(+/min) mouse model. PLoS One. 8:e662832013. View Article : Google Scholar : PubMed/NCBI

37 

Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, et al: Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 425:191–196. 2003. View Article : Google Scholar : PubMed/NCBI

38 

Simic P, Zainabadi K, Bell E, Sykes DB, Saez B, Lotinun S, Baron R, Scadden D, Schipani E and Guarente L: SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating β-catenin. EMBO Mol Med. 5:430–440. 2013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yu DF, Jiang SJ, Pan ZP, Cheng WD, Zhang WJ, Yao XK, Li YC and Lun YZ: Expression and clinical significance of Sirt1 in colorectal cancer. Oncol Lett 11: 1167-1172, 2016.
APA
Yu, D., Jiang, S., Pan, Z., Cheng, W., Zhang, W., Yao, X. ... Lun, Y. (2016). Expression and clinical significance of Sirt1 in colorectal cancer. Oncology Letters, 11, 1167-1172. https://doi.org/10.3892/ol.2015.3982
MLA
Yu, D., Jiang, S., Pan, Z., Cheng, W., Zhang, W., Yao, X., Li, Y., Lun, Y."Expression and clinical significance of Sirt1 in colorectal cancer". Oncology Letters 11.2 (2016): 1167-1172.
Chicago
Yu, D., Jiang, S., Pan, Z., Cheng, W., Zhang, W., Yao, X., Li, Y., Lun, Y."Expression and clinical significance of Sirt1 in colorectal cancer". Oncology Letters 11, no. 2 (2016): 1167-1172. https://doi.org/10.3892/ol.2015.3982
Copy and paste a formatted citation
x
Spandidos Publications style
Yu DF, Jiang SJ, Pan ZP, Cheng WD, Zhang WJ, Yao XK, Li YC and Lun YZ: Expression and clinical significance of Sirt1 in colorectal cancer. Oncol Lett 11: 1167-1172, 2016.
APA
Yu, D., Jiang, S., Pan, Z., Cheng, W., Zhang, W., Yao, X. ... Lun, Y. (2016). Expression and clinical significance of Sirt1 in colorectal cancer. Oncology Letters, 11, 1167-1172. https://doi.org/10.3892/ol.2015.3982
MLA
Yu, D., Jiang, S., Pan, Z., Cheng, W., Zhang, W., Yao, X., Li, Y., Lun, Y."Expression and clinical significance of Sirt1 in colorectal cancer". Oncology Letters 11.2 (2016): 1167-1172.
Chicago
Yu, D., Jiang, S., Pan, Z., Cheng, W., Zhang, W., Yao, X., Li, Y., Lun, Y."Expression and clinical significance of Sirt1 in colorectal cancer". Oncology Letters 11, no. 2 (2016): 1167-1172. https://doi.org/10.3892/ol.2015.3982
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