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

NCT ID: NCT01627119

Last Updated: 2012-06-25

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 120 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2012-06-30

Brief Summary

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.

Conditions

Gastric Cancer

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: RETROSPECTIVE

Study Groups

Gastric cancer patients

Gastric cancer patients who receive curative surgery at National Taiwan University Hospital

No interventions assigned to this group

Eligibility 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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

National Taiwan University Hospital

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Chiung-Nien Chen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

NTUH

Locations

National Taiwan University Hospital

Taipei, Taipei, Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Chiung-Nien Chen, MD, PhD

Role: CONTACT

cnchen@ntu.edu.tw

+886 972651435

Facility Contacts

Chiung-Nien Chen, MD, PhD

Role: primary

cnchen@ntu.edu.tw

+886 972651435

Chia-I Chen, MS

Role: backup

chrisnile@gmail.com

+886 932235914

Other Identifiers

200906054R

Identifier Type: -

Identifier Source: org_study_id