Transforming growth factor-beta 3 mediated modulation of cell cycling and attenuation of 5-fluorouracil induced oral mucositis.

Abstract

Mucositis is a common, dose-limiting complication in patients receiving cancer chemotherapy, which derives from damage to the epithelial cell layer. We have shown that transforming growth factor-beta 3 (TGF-beta 3) negatively regulates epithelial cell proliferation and reduces the incidence of oral mucositis. Here, we report the findings of a large study examining the effects of TGF-beta 3 administration in a hamster model on oral epithelial cell cycling in vivo, on oral mucositis, on weight retention and on survival. Topical application of TGF-beta 3 to the buccal mucosa significantly reduced basal cell proliferation, as measured by proliferating cell nuclear antigen (PCNA) immunohistochemistry and DNA ploidy. Administration of topical TGF-beta 3 prior to chemotherapy with 5-fluorouracil (5-FU) significantly reduced the severity of mucositis with respect to time, reduced chemotherapy-associated weight loss and increased survival.

• Authors: S T Sonis, A G Van Vugt, J P Brien, A D Muska, A M Bruskin, A Rose, J D Haley
• Journal: Oral oncology (Oral Oncol) Vol. 33 Issue 1 Pg. 47-54 (Jan 1997) ISSN: 1368-8375 [Print] England
• PMID: 9192553 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Biomarkers
• Proliferating Cell Nuclear Antigen
• Transforming Growth Factor beta
• Fluorouracil

Topics

• Administration, Topical
• Animals
• Antimetabolites, Antineoplastic (adverse effects)
• Biomarkers
• Cell Division (drug effects)
• Cricetinae
• Fluorouracil (adverse effects)
• Injections, Subcutaneous
• Mouth Mucosa (pathology)
• Proliferating Cell Nuclear Antigen (metabolism)
• Severity of Illness Index
• Stomatitis (blood, chemically induced, pathology, prevention & control)
• Survival Rate
• Transforming Growth Factor beta (pharmacology, therapeutic use)
• Weight Loss (drug effects)