Association and Mechanism Between Cyclooxygenase-2 and Interleukin-6 in Gastric Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2004 by National Taiwan University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00172627
First received: September 12, 2005
Last updated: NA
Last verified: December 2004
History: No changes posted
  Purpose

Evidence is rapidly accumulating that chronic inflammation may contribute to carcinogenesis through multiple mechanisms in a number of malignancies, including gastric carcinoma (GC). Cyclooxygenase-2 (COX-2), an inducible enzyme pivotal in the inflammatory response, converts arachidonic acid to the prostaglandins (PGs) required in initiating and maintaining reactions during the inflammatory process. Over-expression of COX-2 has been reported in a wide variety of cancers and is therefore implicated to play an important role in carcinogenesis. COX-2 can be blocked by non-steroidal anti-inflammatory drugs (NSIADs) and is currently the most studied therapeutic target of NSAIDs. Clinically, NSAIDs have long been used to treat various inflammatory or rheumatologic disorders.

Earlier clinical studies have confirmed an association between COX-2 over-expression and GC occurrence. The known mechanisms by which COX-2 promotes carcinogenesis include evasion from apoptosis, suppression of immunity, promotion of angiogenesis, and facilitation of invasiveness. However, inflammation-associated factors mediating the effects of COX-2 on carcinogenesis remain largely unknown. Interleukin-6 (IL-6) is a pro-inflammatory cytokine associated with gastritis and GC. Our earlier works has disclosed that IL-6 can promote angiogenic and anti-apoptotic ability of GC. However, the relationship between COX-2 and IL-6 in GC remains unknown.

The present study aims to investigate the clinical association between COX-2 and IL-6 in GC, to use a GC cell model for experimental study on causation and mechanism, and to verify the in vivo effect of COX-2 on IL-6 by an animal model.

We will collect 100 consecutive surgical samples of GC from the pathology archive of National Taiwan University Hospital and use immunohistochemical stain to compare protein expression in GC. The clinical study is to define certain subgroups of GC exhibiting an association between COX-2 and IL-6. In experimental study, we will clarify the causal relationship by the dose- and time-dependent experiments of COX-2 transient transfection in a GC cell line. COX-2 acts mainly via PGs, like PGE2. Therefore, we also stimulate GC cells with exogenous stimulation of PGE2 and EP receptor 1-4 agonists to determine the possible way(s) by which COX-2 induces IL-6 expression. A selective COX-2 inhibitor NS-398 and various inhibitors of PGE2 receptors are used as well to block COX-2 for determining the signaling pathway of COX-2 on IL-6. Finally, we will establish a stable COX-2 over-expressing transfectant of GC cells and its control vector transfectant for xenograft implantation study on mice. A COX-2 selective agent, celecoxib, will be administered orally to mice and tumor blocks will be harvested for determination of IL-6 expression.

The present study will provide clearer understanding of the role of COX-2 on the pro-inflammatory cytokine IL-6 in GC in both clinical and basic aspects. It might also stand for a model capable of systemically investigating the role of COX-2 on various cytokines implicated in GC.


Condition
Gastric Cancer

Study Type: Observational
Study Design: Time Perspective: Cross-Sectional
Official Title: Association and Mechanism Between Cyclooxygenase-2 and Interleukin-6 in Gastric Cancer

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Further study details as provided by National Taiwan University Hospital:

Estimated Enrollment: 60
Study Start Date: January 2005
Detailed Description:

Evidence is rapidly accumulating that chronic inflammation may contribute to carcinogenesis through multiple mechanisms in a number of malignancies, including gastric carcinoma (GC). Cyclooxygenase-2 (COX-2), an inducible enzyme pivotal in the inflammatory response, converts arachidonic acid to the prostaglandins (PGs) required in initiating and maintaining reactions during the inflammatory process. Over-expression of COX-2 has been reported in a wide variety of cancers and is therefore implicated to play an important role in carcinogenesis. COX-2 can be blocked by non-steroidal anti-inflammatory drugs (NSIADs) and is currently the most studied therapeutic target of NSAIDs. Clinically, NSAIDs have long been used to treat various inflammatory or rheumatologic disorders.

Earlier clinical studies have confirmed an association between COX-2 over-expression and GC occurrence. The known mechanisms by which COX-2 promotes carcinogenesis include evasion from apoptosis, suppression of immunity, promotion of angiogenesis, and facilitation of invasiveness. However, inflammation-associated factors mediating the effects of COX-2 on carcinogenesis remain largely unknown. Interleukin-6 (IL-6) is a pro-inflammatory cytokine associated with gastritis and GC. Our earlier works has disclosed that IL-6 can promote angiogenic and anti-apoptotic ability of GC. However, the relationship between COX-2 and IL-6 in GC remains unknown.

The present study aims to investigate the clinical association between COX-2 and IL-6 in GC, to use a GC cell model for experimental study on causation and mechanism, and to verify the in vivo effect of COX-2 on IL-6 by an animal model.

We will collect 100 consecutive surgical samples of GC from the pathology archive of National Taiwan University Hospital and use immunohistochemical stain to compare protein expression in GC. The clinical study is to define certain subgroups of GC exhibiting an association between COX-2 and IL-6. In experimental study, we will clarify the causal relationship by the dose- and time-dependent experiments of COX-2 transient transfection in a GC cell line. COX-2 acts mainly via PGs, like PGE2. Therefore, we also stimulate GC cells with exogenous stimulation of PGE2 and EP receptor 1-4 agonists to determine the possible way(s) by which COX-2 induces IL-6 expression. A selective COX-2 inhibitor NS-398 and various inhibitors of PGE2 receptors are used as well to block COX-2 for determining the signaling pathway of COX-2 on IL-6. Finally, we will establish a stable COX-2 over-expressing transfectant of GC cells and its control vector transfectant for xenograft implantation study on mice. A COX-2 selective agent, celecoxib, will be administered orally to mice and tumor blocks will be harvested for determination of IL-6 expression.

The present study will provide clearer understanding of the role of COX-2 on the pro-inflammatory cytokine IL-6 in GC in both clinical and basic aspects. It might also stand for a model capable of systemically investigating the role of COX-2 on various cytokines implicated in GC.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • surgical samples of GC from the pathology archive of National Taiwan University Hospital

Exclusion Criteria:

  • nil
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00172627

Locations
Taiwan
Shih-Pei Huang Recruiting
Taipei, Taiwan
Contact: Shih-Pei Huang, MD    886-2-23123456 ext 3353    dtmeda5@ha.mc.ntu.edu.tw   
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Shih-Pei Huang, MD Department of Internal Medicine, National Taiwan University Hospital
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00172627     History of Changes
Other Study ID Numbers: 9361701204
Study First Received: September 12, 2005
Last Updated: September 12, 2005
Health Authority: Taiwan: Department of Health

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases

ClinicalTrials.gov processed this record on August 20, 2014