Viewing Study NCT00172861



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Last Modification Date: 2024-10-26 @ 9:16 AM
Study NCT ID: NCT00172861
Status: UNKNOWN
Last Update Posted: 2005-09-15
First Post: 2005-09-12

Brief Title: Cyclooxygenase-2-Associated Factors and Gastric Carcinogenesis Mechanisms-Clinical Association and Genomic Investigation
Sponsor: National Taiwan University Hospital
Organization: National Taiwan University Hospital

Study Overview

Official Title: None
Status: UNKNOWN
Status Verified Date: 2005-03
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: Background

Gastric carcinoma GC remains among the most frequent malignancies in Taiwan as well as in the world and also one of leading causes of cancer-related death Accumulating evidence shows that chronic inflammation leads to the occurrence of cancers including GC via multiple mechanisms

Cyclooxygenase-2 COX-2 is a crucial enzyme in inflammatory process and is shown to be up-regulated in a variety of cancers Therefore COX-2 may play an important role in carcinogenesis The hallmarks of cancer include continuing proliferation evading apoptosis prohibiting immunity promoting angiogenesis enhancing invasion and metastasis We hypothesize that COX-2 induces carcinogenesis through multiple mechanistic strategies and interactions of multiple genes simultaneously

Laser capture microdissection LCM for obtaining pure cancer cells and microarray technology and analysis are now generally accepted as powerful tools in genomic research providing reliable microdissection of cancer cells and simultaneous analysis of whole genome

Aim

Use microarray technology to investigate patterns of genomic change related to differential COX-2 expression and their clinicopathological association in GC

Materials

GC cell lines are transfected with COX-2-expressing vector to establish cell lines with differential levels of COX-2 expression Clinical specimens are obtained from surgical resection of GC proved by pathology at the Surgical Department of National Taiwan University Hospital which COX-2 expression is evaluated by Western blotting and immunohistochemical staining

Methods

The present project will use microarray for analysis of genome clustering patterns of surgical tissue GC cells procured by LCM and GC cell lines based on differential COX-2 expression levels to discover significantly positively or negatively associated gene clusterings which contain candidate genes for studies of carcinogenesis mechanisms and establishment of animal experiment models in another component project

Execution

In the first year of this 3-year project we will establish GC cell lines expressing differential COX-2 levels by transfection of COX-2-expressing vector and focus on analyzing their genomes by microarray We also start to collect surgical specimens of GC record clinicopathological characteristics procure cells by LCM and assess RNA quality perform microarray experiments In the second year we will continue LCM RNA extraction and microarray experiments In the third year microarray experiment of a total of 60 pairs including 30 high-COX-2 cases and 30 low-COX-2 cases of tumor and non-tumoral tissues are completed Final analysis is carried out to identify clustering to select candidate genes and investigate their relationship to clinicopathological characteristics according to COX-2 expression These genes are to be subjected to mechanism and animal studies We expect a better understanding of patterns of gene clustering in differential COX-2 gene expression
Detailed Description: Background

Gastric carcinoma GC remains among the most frequent malignancies in Taiwan as well as in the world and also one of leading causes of cancer-related death Accumulating evidence shows that chronic inflammation leads to the occurrence of cancers including GC via multiple mechanisms

Cyclooxygenase-2 COX-2 is a crucial enzyme in inflammatory process and is shown to be up-regulated in a variety of cancers Therefore COX-2 may play an important role in carcinogenesis The hallmarks of cancer include continuing proliferation evading apoptosis prohibiting immunity promoting angiogenesis enhancing invasion and metastasis We hypothesize that COX-2 induces carcinogenesis through multiple mechanistic strategies and interactions of multiple genes simultaneously

Laser capture microdissection LCM for obtaining pure cancer cells and microarray technology and analysis are now generally accepted as powerful tools in genomic research providing reliable microdissection of cancer cells and simultaneous analysis of whole genome

Aim

Use microarray technology to investigate patterns of genomic change related to differential COX-2 expression and their clinicopathological association in GC

Materials

GC cell lines are transfected with COX-2-expressing vector to establish cell lines with differential levels of COX-2 expression Clinical specimens are obtained from surgical resection of GC proved by pathology at the Surgical Department of National Taiwan University Hospital which COX-2 expression is evaluated by Western blotting and immunohistochemical staining

Methods

The present project will use microarray for analysis of genome clustering patterns of surgical tissue GC cells procured by LCM and GC cell lines based on differential COX-2 expression levels to discover significantly positively or negatively associated gene clusterings which contain candidate genes for studies of carcinogenesis mechanisms and establishment of animal experiment models in another component project

Execution

In the first year of this 3-year project we will establish GC cell lines expressing differential COX-2 levels by transfection of COX-2-expressing vector and focus on analyzing their genomes by microarray We also start to collect surgical specimens of GC record clinicopathological characteristics procure cells by LCM and assess RNA quality perform microarray experiments In the second year we will continue LCM RNA extraction and microarray experiments In the third year microarray experiment of a total of 60 pairs including 30 high-COX-2 cases and 30 low-COX-2 cases of tumor and non-tumoral tissues are completed Final analysis is carried out to identify clustering to select candidate genes and investigate their relationship to clinicopathological characteristics according to COX-2 expression These genes are to be subjected to mechanism and animal studies We expect a better understanding of patterns of gene clustering in differential COX-2 gene expression

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