Ignite Creation Date:
2024-05-05 @ 11:51 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00155181
Status:
UNKNOWN
Last Update Posted:
2005-09-12
First Post:
2005-09-09
Brief Title:
Molecular Mechanism of Nasopharyngeal Carcinoma
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
the Garduate Institute of Microbiology in National Taiwan University
Status:
UNKNOWN
Status Verified Date:
2005-01
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
EBV infection process immortalization B lymphocytes Epithelial cells co-culture Epstein-Barr virus EBV belongs to human γ-herpes viruses Unlike other human herpes viruses EBV can only predominately infect two types of human cells lymphoid cells and epithelial cells and its infection is associated with several human malignancies of these two cell types The lymphoid cancers associated with EBV infection include Burkitts lymphoma Hodgkins disease B lymphoma in immunodeficient patients and TNK cell lymphoma The carcinomas associated with EBV are nasopharyngeal carcinoma and gastric carcinoma One unique biological feature of EBV is that it can infect and immortalize primary B lymphocytes in vitro into lymphoblastoid cell lines LCL So far limited information is known about the whole EBV infection process and its regulation mechanism for immortalization In this project three EBV infection models are setting up to reveal the cellular events and signal transduction pathway possibly involved in EBV infection process and immortalization course of action
Detailed Description:
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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NHRI-EX94-9419BI | None | None | None |