The Functional and Clinicopathological Roles and Therapeutic Implication of Connective Tissue Growth Factor in Peritoneal Metastasis of Gastric Cancer (CTGF)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by National Taiwan University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01627119
First received: June 21, 2012
Last updated: June 22, 2012
Last verified: June 2012
  Purpose

For the past 50 years, gastric cancer has been one of the ten most frequent cancers and the second leading cause of cancer-related death in the world. In Taiwan, it is the fifth most common cause of cancer-related deaths, accounting for 6.3% of all cancer deaths. The poor prognosis of gastric cancer is mostly caused by the extensive metastasis to the lymph nodes, liver, and peritoneal dissemination even if curative resection was performed. The main cause of recurrence after curative or noncurative resection of advanced tumors is peritoneal metastasis because of possible direct spillage and dissemination of tumor cells as a result of surgical manipulation, and it is associated with a poor prognosis. As yet, no effective treatment has been developed for this condition. The development of peritoneal metastasis is a multistep process, beginning with attachment to peritoneal mesothelial cells, retraction of the mesothelial cells and exposure of the basement membrane, attachment to the basement membrane, degradation in the extracellular matrix, proliferation by the cancer cells, and angiogenesis, and it is clear that many types of agents are involved at the various stages of this process. Developing a new therapeutic method for this mode of metastasis is very important for improvement of gastric cancer treatment.

CTGF is a secretory protein belonging to the CCN family (one among the three originally discovered members: cysteine-rich61, CTGF, and nephroblastoma-overexpressed gene). It is a multifunctional growth factor involved in wound healing, inflammation, cell adhesion, chemotaxis, apoptosis, tumor growth, and fibrosis. Recent studies showed that overexpression of CTGF in human oral squamous cell carcinoma reduces cell growth and tumorigenecity. Similar tumor growth inhibitory effects were observed in lung cancer cells in which CTGF overexpression was less angiogenic and metastatic due to blocking of the VEGF A signaling pathway. CTGF was also reported to be a key regulator of colorectal cancer invasion and metastasis, and it appears to be a better prognostic factor. These studies suggest that CTGF may involve the processes of peritoneal metastasis which includes cancer cell adhesion in peritoneum, proliferation and angiogenesis. Peritoneal mesothelium is the first surface encountered by disseminated tumor cells and successful adhesion is, therefore, of paramount importance in metastasis formation. Therefore, we hypothesized that CTGF is a potential molecule target, which may be related to cell adhesion to peritoneum, the first step of peritoneal metastasis, and its exact mechanism may includes proliferation and angiogenesis.

In order to answer these important questions, first, we have performed the preliminary studies to prove CTGF did express in different gastric cancer cell lines including AGS, N87, TSGH, and MKN-45 by using RT-PCR and Western blotting, and gastric cancer tissues by using immunohistochemical method. Second, we demonstrated different levels of CTGF expression in different cell lines pose different adhesion ability in in-vitro adhesion assay. Third, we conducted a transient CTGF-overexpressed MKN45 gastric cancer cell line, and CTGF-overexpressed cell line had lower adhesive ability compared to the control.

Next step in this project, we will be studying the roles of CTGF plays in cellular and molecular biology in vitro and in vivo and clinical significance associated with therapeutic potential of peritoneal metastasis from gastric cancer. We will generate stable clones of MKN45 cells harboring CTGF and its control cell line to elucidate the roles of CTGF in cancer cell adhesion, proliferation and angiogenesis in peritoneum.


Condition
Gastric Cancer

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: The Functional and Clinicopathological Roles and Therapeutic Implication of Connective Tissue Growth Factor in Peritoneal Metastasis of Gastric Cancer

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • To measure the expression level of CTGF in patient blood and tissue [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    To determine the level of CTGF expression in gastric cancer patient specimens collected during surgery.


Secondary Outcome Measures:
  • To determine the survival probability of gastric cancer patients after surgery [ Time Frame: 10 years from date of surgery ] [ Designated as safety issue: No ]
    To determine the survival probability of gastric cancer patients after surgery


Biospecimen Retention:   Samples With DNA

Cancer tissue and adjacent normal tissue Urine Blood serum and blood plasma


Estimated Enrollment: 120
Study Start Date: July 2009
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Gastric cancer patients
Gastric cancer patients who receive curative surgery at National Taiwan University Hospital

  Eligibility

Ages Eligible for Study:   25 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Gastric cancer patients Age 25-90

Criteria

Inclusion Criteria:

  • Gastric cancer patients who are elegible for curative surgery
  • Age 25-90

Exclusion Criteria:

  • Gastric cancer patients who are not elegible for curative surgery
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01627119

Contacts
Contact: Chiung-Nien Chen, MD, PhD +886 972651435 cnchen@ntu.edu.tw

Locations
Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Chiung-Nien Chen, MD, PhD    +886 972651435    cnchen@ntu.edu.tw   
Contact: Chia-I Chen, MS    +886 932235914    chrisnile@gmail.com   
Principal Investigator: Chiung-Nien Chen, MD, PhD         
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Chiung-Nien Chen, MD, PhD NTUH
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital, MD, PhD
ClinicalTrials.gov Identifier: NCT01627119     History of Changes
Other Study ID Numbers: 200906054R
Study First Received: June 21, 2012
Last Updated: June 22, 2012
Health Authority: Taiwan: Institutional Review Board

Keywords provided by National Taiwan University Hospital:
CTGF
Peritoneal metastasis

Additional relevant MeSH terms:
Stomach Neoplasms
Neoplasm Metastasis
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Neoplastic Processes
Pathologic Processes
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014