Medicine research news Return to previous page
Article Released Thu-27th-November-2014 07:31 GMT
Contact: University of Malaya Institution: University of Malaya
 Another Set of "Twin" Publications in The Journal of Pathology From University of Malaya

High Impact Research (HIR) is pleased to announce “twin” publications in the Journal of Pathology (Impact factor 7.33; Ranked 3/76 in Pathology and 15/203 in Oncology) by Dr. Yap Lee Fah and her research team from the Faculty of Dentistry, University of Malaya.

Picture 1
Dr. Yap Lee Fah
HIR is pleased to announce “twin” publications in the Journal of Pathology (Impact factor 7.33; Ranked 3/76 in Pathology and 15/203 in Oncology) by Dr. Yap Lee Fah and her research team from the Faculty of Dentistry, together with her collaborators from UK, in particular with Prof. Paul Murray (UM Academic Icon) from the University of Birmingham.

About the Twins

Although almost 90% of the world’s population are infected with Epstein-Barr virus (EBV), a human herpesvirus, most people do not develop cancer. However, EBV infection has been strongly linked to the development of a number of cancers, including nasopharyngeal carcinoma (NPC) and lymphoma, indicating additional factors other than the virus alone are required in driving carcinogenesis. NPC is a major health problem in Malaysia, being the fourth most common cancer overall. The first of the twin publications addresses for the first time, the aberrant activation of an oncogenic pathway, lysophosphatidic acid (LPA) signalling, in NPC. Dr. Yap and her team demonstrated that LPA enhances the migration of NPC cells but inhibits the activation of EBV-specific T cells. These results suggest therapeutic targeting of LPA signalling in NPC patients might not only inhibit tumour metastasis but could also enhance the effectiveness of adoptive EBV-specific CTL or vaccine-based therapies. The group also discovered that the aberrant LPA signalling in NPC is mediated through EBV-induced down-regulation of LPA receptor 5 (LPAR5), a novel tumour suppressor gene in NPC. Their data point to a central role for EBV in mediating the oncogenic effects of LPA in NPC and identify LPA signalling as a potential therapeutic target in this disease.

The second publication touches on the contribution of EBV to the cancer development in lymphoid tissues. It discusses our current understanding of the role of EBV in the pathogenesis of various types of lymphoma, including Burkitt’s lymphoma, Hodgkin’s lymphoma, and NK/T-cell lymphoma. This paper explains the different aetiological roles of EBV in each tumour and discusses the co-factors (such as HIV, tumour microenvironment) involved in the pathogenesis of EBV-associated lymphomagenesis.

These twin publications result directly from invaluable and long-standing collaboration with various local and international institutes. The financial support from HIR MoHE has been instrumental in driving forward this collaborative effort and has provided invaluable support to the postgraduate students.

1) L.F. Yap*, S. Velapasamy, H.M. Lee, S. Thavaraj, R. Pathmanathan, W. Wei, K. Vrzalikova, M.H. Ibrahim, A. Khoo, S.W. Tsao, I.C. Paterson, G.S. Taylor, C.W. Dawson and P.G. Murray*. Down-regulation of LPA receptor 5 to aberrant LPA signalling in EBV-associated nasopharyngeal carcinoma. Journal of Pathology. 2014 Oct 8. doi: 10.1002/path.4460. PMID: 25294670 (*Corresponding author)

Abstract
Undifferentiated nasopharyngeal carcinoma (NPC) is a highly metastatic disease that is consistently associated with the Epstein-Barr virus (EBV) infection. In this study, we have investigated the contribution of lysophosphatidic acid (LPA) signalling to the pathogenesis of NPC. Here we demonstrate two distinct functional roles for LPA in NPC. First, we show that LPA enhances the migration of NPC cells, and second that it can inhibit the activity of EBV-specific cytotoxic T cells. Focussing in more detail on the first of these phenotypes, we show that one of the LPA receptors, LPA receptor 5 (LPAR5), is down-regulated in primary NPC tissues, and that in cell lines, this down-regulation promotes the LPA-induced migration of NPC cell lines. Furthermore, we found that EBV infection or ectopic expression of the EBV-encoded LMP2A gene was sufficient to down-regulate LPAR5 in NPC cell lines. Our data point to a central role for EBV in mediating the oncogenic effects of LPA in NPC and identify LPA signalling as a potential therapeutic target in this disease.

2) M. Vockerodt, L.F. Yap, C. Shannon-Lowe, H. Curley, W. Wei, K. Vrzalikova, P.G. Murray. The Epstein-Barr virus and the pathogenesis of lymphoma. Journal of Pathology. 2014 Oct 8. doi: 10.1002/path.4459. PMID: 25294567

Abstract
Since the discovery in 1964 of the Epstein-Barr virus (EBV) in African Burkitt lymphoma, this virus has been associated with a remarkably diverse range of cancer types. Because EBV persists in the B cells of the asymptomatic host, it can easily be envisaged how it contributes to the development of B cell lymphomas. However, EBV is also found in other cancers, including T cell/natural killer cell lymphomas and several epithelial malignancies. Explaining the aetiological role of EBV is challenging, partly because the virus probably contributes differently to each tumour and partly because the available disease models cannot adequately recapitulate the subtle variations in the virus-host balance that exist between the different EBV-associated cancers. A further challenge is to identify the co-factors involved; because most persistently infected individuals will never develop an EBV-associated cancer, the virus cannot be working alone. This article will review what is known about the contribution of EBV to lymphoma development.

Keywords associated to this article:
Create Account...