Transforming growth factor-beta 3 mediated modulation of cell cycling and attenuation of 5-fluorouracil induced oral mucositis.
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.
Sonis
S T
ST
Department of Oral Medicine, Brigham and Women's Hospital, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.
Van Vugt
A G
AG
Brien
J P
JP
Muska
A D
AD
Bruskin
A M
AM
Rose
A
A
Haley
J D
JD
D000287:Administration, Topical; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D015415:Biomarkers; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D005472:Fluorouracil / Q000009:adverse effects*; D007279:Injections, Subcutaneous; D009061:Mouth Mucosa / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012720:Severity of Illness Index; D013280:Stomatitis / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000627:therapeutic use*; D015431:Weight Loss / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D018809:Proliferating Cell Nuclear Antigen; D016212:Transforming Growth Factor beta; D005472:Fluorouracil