Date of Award
Open Access Thesis
Medical Doctor (MD)
Irvin M Modlin MD
Carcinoid tumors of the small bowel often present with fibrosis in the peritumoral tissues, distant in the heart or lungs, and locally in the peritoneal cavity. The mechanism of the fibroblastic lesions in patients with small bowel carcinoids is unclear and their timely diagnosis impossible. There exists no test to determine the risk of fibrosis, detect its presence, or monitor its progression once discovered. Furthermore, no current therapy protects against such fibrosis. We have proposed that CTGF, a mediator of the profibrotic activities of TGFâ1 (a known regulator of fibrosis)is directly involved in the genesis of ileal carcinoid-related fibrosis. The aim of this study was to assess the potential correlation of serum and tissue CTGF with the diagnosis of carcinoid-related fibrosis. Serum and tissue samples from patients with GI carcinoids, other GI and extra-GI malignancies, and control patients were collected prospectively. A GI carcinoid tissue microarray (TMA) was stained immunohistochemically with anti-CTGF, semiquantitatively measured, and analyzed for correlation with clinical fibrosis. Significantly higher serum CTGF levels were found in patients with ileal carcinoids than in patients with gastric ECL cell carcinoids (the latter of which are not associated with fibrosis) and control patients. Our results demonstrated that CTGF protein is over-expressed in small bowel carcinoid tumors associated with fibrosis and that the secreted protein is stable and detectable in patient serum. The correlation of CTGF with TGFâ1 suggests that CTGF is a co-secreted fibrotic factor. Since the relationship of CTGF to fibrosis is well defined, this cytokine may be involved in the genesis of ileal carcinoid-related fibrosis. The detection of elevated levels may provide a diagnostic opportunity to predict fibrosis and pre-empt its local and systemic complications. Furthermore, CTGF may represent a therapeutic target for management of fibrosis-related complications in patients with carcinoid tumors.
Shapirio, Michael David, "The Role of Connective Tissue Growth Factor (CTGF) in Fibrosis Associated With Intestinal Neuroendocrine Tumors" (2005). Yale Medicine Thesis Digital Library. 479.