Publication Name	World Journal of Gastroenterology
Manuscript ID	39989
Country	Thailand

Category	Gastroenterology & Hepatology
Manuscript Type	Basic Study
Article Title	Delta-like ligand 4 in hepatocellular carcinoma intrinsically promotes tumour growth and suppresses hepatitis B virus replication
Manuscript Source	Unsolicited Manuscript
All Author List	Areerat Kunanopparat, Jiraphorn Issara-Amphorn, Asada Leelahavanichkul, Anapat Sanpavat, Suthiluk Patumraj, Pisit Tangkijvanich, Tanapat Palaga and Nattiya Hirankarn
Funding Agency and Grant Number	Funding Agency Grant Number National Research Council of Thailand 2013 the Ratchadaphiseksomphot Matching Fund from the Faculty of Medicine, Chulalongkorn University the International Research Integration, Chula Research Scholar, Ratchadaphisek somphot Endowment Fund, Center of Excellence in Immunology and Immune-mediated Diseases the Rachadapisaek Sompote Post-Doctoral Fund, Chulalongkorn University
Corresponding Author	Nattiya Hirankarn, MD, PhD, Lecturer, Professor, Center of Excellence in Immunology and Immune Mediated Diseases, Chulalongkorn University, 1873 Rama 4 Road, Khwaeng Pathum Wan, Khet Pathum Wan, Bangkok 10330, Thailand. nattiya.h@chula.ac.th
Key Words	hepatocellular carcinoma; Notch signalling; Delta-like ligand 4; HepG2.2.15
Core Tip	We demonstrated that Delta-like ligand 4 (DLL4) is important for tumour growth of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) in a xenograft model. We found that the level of angiogenesis regulators, VEGF-A and VEGF-R2 were significantly decreased in HCC xenograft tumours with suppressed DLL4 compared with the control group. Consistent with these findings, the suppression of DLL4 expression in the tumour cells reduced cell proliferation and the formation of new blood vessels in the tumour. Furthermore, this is the first report that DLL4 in an HBV expressing HCC cell line plays a key role in regulating tumour growth, angiogenesis, and viral replication in a mouse model of xenograft transplantation.
Citation	Kunanopparat A, Issara-Amphorn J, Leelahavanichkul A, Sanpavat A, Patumraj S, Tangkijvanich P, Palaga T, Hirankarn N. Delta-like ligand 4 in hepatocellular carcinoma intrinsically promotes tumour growth and suppresses hepatitis B virus replication. World J Gastroenterol 2018; 24(34): 3861-3870

Received	2018-05-25 08:00
Peer-Review Started	2018-05-25 22:48
To Make the First Decision	2018-06-21 01:34
Return for Revision	2018-06-29 12:34
Revised	2018-07-05 15:18
Second Decision	2018-07-13 09:33
Accepted by Journal Editor-in-Chief
Accepted by Company Editor-in-Chief	2018-07-16 01:41
Articles in Press	2018-07-16 01:41
Publication Fee Transferred
Edit the Manuscript by Language Editor	2018-07-21 23:06
Typeset the Manuscript	2018-09-03 08:09

ISSN	1007-9327 (print) and 2219-2840 (online)
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