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Trial Title:
Cyclooxygenase-2-Associated Factors and Gastric Carcinogenesis Mechanisms-Clinical Association and Genomic Investigation
NCT ID:
NCT00172861
Condition:
Gastric Cancer
Conditions: Official terms:
Stomach Neoplasms
Conditions: Keywords:
gastric cancer, cyclooxygenase-2, microarray
Study type:
Observational
Overall status:
Unknown status
Study design:
Time perspective:
Prospective
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- surgical resected gastric cancer proved by pathology
Exclusion Criteria:
- Nil
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Jaw-Town Lin
Address:
City:
Taipei
Country:
Taiwan
Status:
Recruiting
Contact:
Last name:
Jaw-Town Lin, MD, PhD
Phone:
886-2-23123456
Phone ext:
5695
Email:
jawtown@ha.mc.ntu.edu.tw
Start date:
January 2005
Lead sponsor:
Agency:
National Taiwan University Hospital
Agency class:
Other
Source:
National Taiwan University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT00172861