Basic fibroblast growth factor and epidermal growth factor reverse impaired ulcer healing of the rabbit oral mucosa

Fujisawa, Kenji; Miyamoto, Youji; Nagayama, Masaru

doi:10.1034/j.1600-0714.2003.t01-1-00111.x

Cited by 92 publications

(86 citation statements)

References 26 publications

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“…Fujisawa et al 111) reported that healing of acetic acid ulcers induced in rabbit oral mucosa was delayed after removal of submandibular glands or subcutaneous injection of cisplatin and peplomycin sulfate. Such delayed healing by gland removal or drug administration was reversed with either systemic treatment with bFGF and EGF or topical application of bFGF.…”

Section: Growth Factors Epidermal Growth Factor (Egf)mentioning

confidence: 99%

An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—

Okabe

Amagase

2005

Biological & Pharmaceutical Bulletin

207

166

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Four types of experimental chronic ulcer models, named acetic acid ulcer models, have been developed to examine the healing process of peptic ulcers, screen anti-ulcer drugs, and better evaluate the adverse effects of various anti-inflammatory drugs on the gastrointestinal mucosa. The model easily and reliably produces round, deep ulcers in the stomach and duodenum, allowing acetic acid ulcer production in mice, rats, Mongolian gerbils, guinea pigs, cats, dogs, miniature pigs, and monkeys. These ulcer models highly resemble human ulcers in terms of both pathological features and healing process. The models have been established over the past 35 years and are now used throughout the world by basic and clinical scientists. One of the characteristic features of acetic acid ulcers in rats is the spontaneous relapse of healed ulcers Ͼ100 d after ulceration, an endoscopically confirmed phenomenon. Indomethacin significantly delays the healing of acetic acid ulcers, probably by reducing endogenous prostaglandins and inhibiting angiogenesis in ulcerated tissue. Helicobacter pylori significantly delays healing of acetic acid ulcers and causes relapse of healed ulcers at a high incidence in Mongolian gerbils. Anti-secretory drugs (e.g. omeprazole), prostaglandin analogs, mucosal defense agents (e.g. sucralfate), and various growth factors all significantly enhance healing of acetic acid ulcers. Gene therapy with epidermal growth factor and vascular endothelial growth factor applied to the base of acetic acid ulcers in rats is effective in enhancing ulcer healing. Since an inhibitor of nitric oxide syntase prevents ulcer healing, nitric oxide might be involved in the mechanism underlying ulcer healing. We conclude that acetic acid ulcer models are quite useful for various studies related to peptic ulcers.

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Section: Growth Factors Epidermal Growth Factor (Egf)mentioning

confidence: 99%

An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—

Okabe

Amagase

2005

Biological & Pharmaceutical Bulletin

207

166

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“…Until now, epidermal growth factor (EGF) studies have been performed only for oral keratinocytes, but not for oropharyngeal keratinocytes. For example, it was found that EGF promotes the proliferation of keratinocytes isolated from gingival tissue of the rabbit in vitro [Fujisawa et al, 2003]. Furthermore, it was discovered that when the oral mucosa is injured, a physiological concentration of EGF in saliva stimulates the proliferation and migration of oral epithelial cells for wound healing [Ohshima et al, 2002].…”

Section: Introductionmentioning

confidence: 99%

Effects of Epidermal Growth Factor and Keratinocyte Growth Factor on the Growth of Oropharyngeal Keratinocytes in Coculture with Autologous Fibroblasts in a Three-Dimensional Matrix

Blaimauer

Watzinger²,

Erovic³

et al. 2006

Cells Tissues Organs

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Tissue engineering of oropharyngeal mucosa is rendered complex by the fact that oropharyngeal keratinocytes are difficult to culture in the long term and do not grow well after several subcultivations. Three populations of oropharyngeal keratinocytes were isolated by a method based on different levels of β₁-integrin expression. In particular, keratinocytes were isolated between cell fractions that adhere rapidly on collagen-IV-coated culture dishes (RAC-IV) and populations that are less adherent (RAC-IV-D). The total fraction of both subpopulations served as a control (RAC-IV-T). The epidermal growth factor (EGF) and the keratinocyte growth factor (KGF) were examined with regard to their effects on the growth of the three populations. Growth curves of all three cell fractions grown with or without EGF were generated, and different concentrations of EGF and KGF were tested. EGF did not change any growth characteristics of the cells, with the exception of the speed of growth. Best growth was achieved with a physiologic EGF concentration of 0.15–1.5 ng/ml and a KGF concentration of 15 ng/ml. Finally, we cocultured oropharyngeal keratinocytes and their autologous fibroblasts in a three-dimensional matrix using Matrigel™. Oropharyngeal keratinocytes grown in coculture formed larger colonies than keratinocytes grown without fibroblasts. In conclusion, we were able to optimize the supplement of EGF and KGF in standard medium for the long-term culture of primary oropharyngeal keratinocytes. The use of Matrigel as a scaffold for three-dimensional cocultures of oropharyngeal keratinocytes and fibroblasts might signify a step forward in the development of a transplantable mucosa construct.

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“…Acetic acid is applied after either a sialoadenectomy or intravenous treatment with cisplatin and peplomycin sulfate. Both procedures create a state of impaired healing from the acetic acid injury and, ultimately, ulceration at the injury site (Fujisawa et al, 2003). Most preclinical studies focus on oral mucositis; however, a few do measure intestinal mucositis and loss of structural integrity of intestinal crypts.…”

Section: Preclinical Studies On Treatment Of Mucositis and Associatedmentioning

confidence: 99%

“…They showed that systemic EGF accelerated mucosal healing. However, topical EGF application did not significantly accelerate wound healing (Fujisawa et al, 2003). A clinical trial evaluated a recombinant human EGF oral spray in 58 patients with oral mucositis induced by intensive chemotherapy followed by stem cell transplant.…”

Section: Epidermal Growth Factormentioning

confidence: 99%

Review of Preclinical Studies on Treatment of Mucositis and Associated Pain

et al. 2014

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Oral mucositis is a significant problem in cancer patients treated with radiation or chemotherapy, often hindering definitive cancer treatment. For patients with oral mucositis, pain is the most distressing symptom, leading to loss of orofacial function and poor quality of life. While oral mucositis has been well-described, its pathophysiology is poorly understood. Oral health professionals treating patients with mucositis have almost no effective therapies to treat or prevent oral mucositis. The purpose of this review is to (1) describe the current preclinical models of oral mucositis and their contribution to the understanding of mucositis pathophysiology, (2) explore preclinical studies on therapies targeting mucositis and discuss the clinical trials that have resulted from these preclinical studies, and (3) describe the proposed pathophysiology of oral mucositis pain and preclinical modeling of oral mucositis pain.

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Basic fibroblast growth factor and epidermal growth factor reverse impaired ulcer healing of the rabbit oral mucosa

Abstract: Basic FGF may be effective for refractory oral mucosal lesions.

Cited by 92 publications

References 26 publications

An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—

An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—

Effects of Epidermal Growth Factor and Keratinocyte Growth Factor on the Growth of Oropharyngeal Keratinocytes in Coculture with Autologous Fibroblasts in a Three-Dimensional Matrix

Review of Preclinical Studies on Treatment of Mucositis and Associated Pain

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Basic fibroblast growth factor and epidermal growth factor reverse impaired ulcer healing of the rabbit oral mucosa

Abstract: Basic FGF may be effective for refractory oral mucosal lesions.

Cited by 92 publications

References 26 publications

An Overview of Acetic Acid Ulcer Models<br>&mdash;The History and State of the Art of Peptic Ulcer Research&mdash;

An Overview of Acetic Acid Ulcer Models<br>&mdash;The History and State of the Art of Peptic Ulcer Research&mdash;

Effects of Epidermal Growth Factor and Keratinocyte Growth Factor on the Growth of Oropharyngeal Keratinocytes in Coculture with Autologous Fibroblasts in a Three-Dimensional Matrix

Review of Preclinical Studies on Treatment of Mucositis and Associated Pain

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An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—

An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—