Trial Information

the Garduate Institute of Microbiology in National Taiwan University

Nasopharyngeal carcinoma (NPC), a human malignancy derived from the nasopharyngeal
epithelial cells, is occurring highly frequently in Taiwan. Of note, the average ages of NPC
individuals are usually ten years younger than those of patients with other head and neck
cancers. Clinically, this early onset and high incidence of metastasis in NPC may contribute
to its poor prognosis. Fortunately, NPC is usually radio-and chemo-therapy sensitive during
the early stage. So, the more we understand NPC pathogenesis, the more efficient detection
methods would be developed for NPC early diagnosis and prognosis.

Four unique characteristics have been reported for NPC: geographic preference, heavy
infiltration of lymphocytes, high incidence of metastasis and association with Epstein-Barr
virus (EBV). According to our hypothesis that both cellular changes and viral factors are
crucial for NPC development, four major long-term study goals have been carried out in our
lab: (1) identification and characterization of the cellular and viral factors that are
involved in NPC formation, (2) elucidation of potencies of these molecules as clinical
diagnosis and prognosis markers of NPC, (3) investigation of the molecular and biological
linkage between EBV infection and NPC development and (4) establishment of a drug-screening
system for NPC chemotherapy.

Based on our assumption that both cellular genes and viral factors are involved in NPC
carcinogenesis, the following genes are chosen as the major study targets in this five-year
grant. Firstly, to asses the alteration of cellular gene expression, we choose three
cytokine genes 【interleukin (IL)-1, IL-7 and IL-13】, three inhibitors of apoptosis proteins
(IAP) genes (survivin, HIAP-1, and HIAP-2), two specific cellular genes (osteoblast-specific
factor-2 and polymeric immunoglobulin receptor) and one tumor suppressor gene (tumor
susceptibility gene TSG101) in our proposal. All these genes exhibit special expression
profiles in NPC biopsies in our preliminary study. So, the regulation and effect of these
genes in epithelial cells would be the study focus. Secondly, two EBV viral genes, Zta and
LMP2A, the former encoded immediately early lytic product and the later encoded latent
membrane protein, are selected for this study. In our previous grant, we found that Zta can
up-regulate TKT (trk-related tyrosine kinase) and matrix metalloproteinases (MMP)-1 which is
a down-stream effector of TKT. Therefore we will extend the study on how Zta and LMP2A
regulate and influence anti-apoptotic network and metastasis progression. Based on our
preliminary data, this proposal is highly approachable and the results may provide valuable
information for NPC diagnosis, prognosis and treatment.