Duodenal ulcer. Discovery of a new mechanism and development of angiogenic therapy that accelerates healing.
The complete purification of the first angiogenic molecule, basic fibroblast growth factor (bFGF), was carried out in the authors' laboratory in 1983. Application of this peptide to chronic wounds enhances angiogenesis and accelerates wound healing. The authors showed that an acid-stable form of bFGF (i.e., bFGF-CS23) could be administered orally to rats with duodenal ulcers. The peptide promoted a ninefold increase of angiogenesis in the ulcer bed and accelerated ulcer healing more potently than cimetidine. Basic fibroblast growth factor did not reduce gastric acid. The authors now show that bFGF exists as a naturally occurring peptide in rat and human gastric and duodenal mucosa. This endogenous bFGF is present also in the bed of chronic ulcers in rats. Sucralfate binds bFGF and protects it from acid degradation. The sucralfate is angiogenic, based on its affinity for bFGF. When sucralfate is administered orally to rats, it significantly elevates the level of bFGF in the ulcer bed. Cimetidine, by its capacity to reduce gastric acid, also elevates bFGF in the ulcer bed. A hypothetical model is proposed in which prevention of ulcer formation or accelerated healing of ulcers by conventional therapies may be FGF dependent. Acid-stable bFGF-CS23 may be considered as a form of replacement therapy in the treatment of duodenal ulcers.
Folkman
J
J
Department of Surgery, Children's Hospital, Boston, MA 02115.
Szabo
S
S
Stovroff
M
M
McNeil
P
P
Li
W
W
Shing
Y
Y
D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D000863:Antacids / Q000494:pharmacology; D004338:Drug Combinations; D004381:Duodenal Ulcer / Q000188:drug therapy* / Q000503:physiopathology; D004386:Duodenum / Q000098:blood supply* / Q000737:chemistry; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D005753:Gastric Mucosa / Q000737:chemistry; D006801:Humans; D008276:Magnesium Hydroxide / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D051381:Rats; D013392:Sucralfate / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
D000863:Antacids; D004338:Drug Combinations; D016222:Fibroblast Growth Factor 2; C013591:aluminum hydroxide, magnesium hydroxide, drug combination; D013392:Sucralfate; D000536:Aluminum Hydroxide; D008276:Magnesium Hydroxide