epidermal-growth-factor and Ulcer

The information in this paper is presented to summarise various investigations in recent years to develop epidermal growth factor (EGF) delivery systems. EGF is a promising and well-characterised polypeptide that can be used in the treatment of various types of wounds and ulcers. Many approaches have been employed to deliver EGF as a stimulant for cellular activities involved in the processes of wound healing and tissue repair. Recently, emphasis is placed on the development of sustained or controlled delivery technology to optimise EGF delivery.

Topics: Animals; Drug Delivery Systems; Epidermal Growth Factor; Humans; Ulcer; Wounds and Injuries

Polypeptide growth factors regulate cellular processes involved in wound healing. Application of exogenous growth factors can modify the healing process and, with recombinant DNA technology, growth factors can now be made in sufficient quantity to be used therapeutically. Several growth factors are showing promising results in clinical trials, especially in cases of impaired healing, such as chronic ulcers. Preclinical studies indicate that further growth factors may have therapeutic potential in a wide range of wound-healing applications. The use of specifically designed and modified growth factors, growth-factor inhibitors, and sequential and combinatorial dosing regimes offer further possibilities for enhancing wound healing.

Topics: Animals; Chronic Disease; Epidermal Growth Factor; Fibroblast Growth Factors; Growth Substances; Humans; Peptides; Platelet-Derived Growth Factor; Recombinant Proteins; Transforming Growth Factor alpha; Transforming Growth Factor beta; Ulcer; Wound Healing; Wounds and Injuries

This study was conducted to evaluate the efficacy and safety of a novel spray-applied growth factor therapy containing recombinant human epidermal growth factor (rhEGF) for the treatment of chronic diabetic foot ulcers (DFU).. This study was a phase III double-blind, randomized, placebo-controlled trial. 167 adult patients at six medical centers were randomized to receive routine wound care plus either topical spray treatment with 0.005% rhEGF (n = 82) or an equivalent volume of saline spray (n = 85) twice a day until ulcer healing or for up to 12 weeks.. Demographics, medical status, and wound characteristics were comparable between rhEGF and placebo groups. More patients in the rhEGF group significantly had complete wound healing compared to placebo (73.2% versus 50.6%, respectively; P = .001). Wound healing velocity was faster in the rhEGF group (P = .029) regardless of HbA1c levels. The rhEGF group had a shorter median time to 50% ulcer size reduction (21 versus 35 days; hazard ratio = 3.13, P < .001) and shorter time to complete ulcer healing (56 versus 84 days; hazard ratio = 2.13, P < .001).. This study confirms that application of spray-applied rhEGF in DFU patients results in faster healing velocity and higher complete healing rate regardless of HbA1c levels.

Topics: Administration, Topical; Adult; Aged; Diabetic Foot; Double-Blind Method; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Prospective Studies; Treatment Outcome; Ulcer; Wound Healing

A double-blind clinical trial was performed to study the effect of epidermal growth factor (EGF) mouthwash on the healing and recurrence of oral ulceration in 12 patients undergoing cancer chemotherapy. The oral distribution or cytotoxic-induced ulcers corresponded to the salivary gutters. There was no difference in the rate of healing of established ulcers between the experimental and placebo groups. However, there was a small delay in the onset and severity of recurrent ulceration. It was concluded that EGF mouthwash does not accelerate ulcer healing, but it may have the potential to protect the oral epithelium from cytotoxic damage.

Topics: Antineoplastic Agents; Double-Blind Method; Epidermal Growth Factor; Humans; Mouth Diseases; Mouth Mucosa; Mouthwashes; Recombinant Proteins; Ulcer; Wound Healing

To investigate the role of epidermal growth factor (EGF), a small (relative molecular mass 6000) polypeptide with mitogenic properties in the protection of gastrointestinal mucosal integrity.. A prospective, randomized and blinded study.. Twenty-four minipigs with surgically induced portal hypertension underwent four consecutive weekly sessions of oesophageal sclerotherapy with 5 ml 1% polidocanol and were concomitantly treated with either a placebo or human recombinant EGF administered subcutaneously. Mucosal damage was evaluated on a weekly basis by endoscopic estimation of the size of the ulcerated area and by post-mortem morphometry. The EGF-induced morphological changes in the oesophageal epithelium were also evaluated histologically.. In sclerosed and non-sclerosed parts of the oesophagus EGF significantly increased the thickness of the oesophageal epithelium (P < 0.03), but failed to reduce significantly the degree of oesophageal damage associated with sclerotherapy (P = 0.11).. Systemic EGF treatment induces proliferation of the oesophageal mucosa, and EGF may therefore have the potential to reduce sclerotherapy-induced oesophageal damage.

Topics: Animals; Epidermal Growth Factor; Esophageal and Gastric Varices; Esophageal Diseases; Esophagoscopy; Female; Humans; Injections, Subcutaneous; Male; Mucous Membrane; Prospective Studies; Recombinant Proteins; Sclerotherapy; Swine; Swine, Miniature; Ulcer

Among several methods used to prevent endoscopic submucosal dissection (ESD) bleeding, the recently developed hemostatic powder (HP) has few technical limitations and is relatively easy-to-use. This study aimed to analyze the hemostatic effects and mechanisms of two HPs using a porcine upper gastrointestinal hemorrhage model.. We evaluated HPs (Endospray and epidermal growth factor [EGF]-endospray) for adhesion, waterproofing ability, permeability, and absorption. The water absorption of HPs was over 20 times the initial value within 30 minutes. The gelated HPs completely blocked water penetration into the applied site within 5 minutes and strongly adhered to the Petri-dish surface for up to 6 hours. The initial hemostasis rates within 5 minutes were 33.3%, 100.0%, and 66.7%, and the rebleeding rates at 6 to 72 hours after HP application were 33.3%, 16.7%, and 33.3% (control, Endospray, and EGF-endospray groups, respectively). Histological analysis revealed the thickness of the regenerated mucosa (522.1, 514.5, and 680.3 μm) and the submucosal layer (1,510.3, 2,848.2, and 3,062.3 μm) and the number of newly formed blood vessels (15.3, 17.9, and 20.5) in the control, Endospray, and EGF-endospray groups, respectively.. The endoscopic HPs demonstrated the ability to elicit effective initial hemostasis and the histological ulcer-healing effect of EGF in an animal model of hemorrhagic gastric ulcers.

Topics: Animals; Endoscopic Mucosal Resection; Epidermal Growth Factor; Gastric Mucosa; Hemostasis; Hemostatics; Powders; Swine; Ulcer

The aim of our study was to investigate the healing effect of propionyl-L-carnitine (PLC) on chronic gastric ulcers and its underlying mechanisms. This study included rats with gastric ulcers induced by applying serosal glacial acetic acid. These rats were then given either saline (vehicle) or PLC at doses of 60 and 120 mg/kg, administered orally 3 days after ulcer induction for 14 consecutive days. Our study found that treatment with PLC resulted in a reduction of the gastric ulcer area, a faster rate of ulcer healing, and stimulated mucosal restoration. Additionally, the treatment with PLC reduced the number of Iba-1+ M1 macrophages while increasing the number of galectin-3+ M2 macrophages, as well as desmin+ microvessels, and α-SMA+ myofibroblasts in the gastric ulcer bed. The mRNA expression of COX-2, eNOS, TGF-β1, VEGFA, and EGF in the ulcerated gastric mucosa was greater in the PLC-treated groups compared with the vehicle-treated rats. In conclusion, these findings suggest that PLC treatment may accelerate gastric ulcer healing by stimulating mucosal reconstruction, macrophage polarization, angiogenesis, and fibroblast proliferation, as well as fibroblast-myofibroblast transition. This process is associated with the upregulation of TGF-β1, VEGFA, and EGF, as well as modulation of the cyclooxygenase/nitric oxide synthase systems.

Topics: Acetic Acid; Animals; Cyclooxygenase 2; Epidermal Growth Factor; Rats; Rats, Wistar; Stomach Ulcer; Transforming Growth Factor beta1; Ulcer

To assess the efficacy of Erzhu Yiren Decoction in treating gastric ulcer of spleen deficiency and dampness-heat and its effect on serum NO, EGF, and PGE2 levels.. A retrospective study was conducted among 64 patients with gastric ulcers of spleen deficiency and dampness heat admitted to our hospital from September 2019 to May 2020, and they were divided at a ratio of 1 : 1 into an observation group (rabeprazole sodium enteric-coated capsules plus Erzhu Yiren Decoction) and a control group (rabeprazole sodium enteric-coated capsules) based on different treatment methods. The clinical symptom scores, the effective rate of ulcer healing under gastroscopy, the quality of ulcer healing (QOUH), serum nitric oxide (NO), endothelial growth factor (EGF), and prostaglandin E2 (PGE2) levels were compared between the two groups.. The clinical symptom scores of the observation group after treatment were significantly lower than those of the control group (. Erzhu Yiren Decoction can relieve the clinical symptoms of patients with gastric ulcers of spleen deficiency and dampness heat; improve the serum NO, EGF, and PGE2 levels; optimize the mucosal maturity; and enhance the overall efficacy, which merits clinical promotion.

Topics: Capsules; Dinoprostone; Epidermal Growth Factor; Hot Temperature; Humans; Rabeprazole; Retrospective Studies; Spleen; Stomach Ulcer; Ulcer

This study's objective is to analyze the effect of epidermal growth factor (EGF) nanoparticles on the healing of diabetic skin wounds and also, simultaneously, to investigate the mechanism of EGF nanoparticles to promote healing. In this manuscript, EGF nanoparticles were prepared, and also the drug loading rate of EGF nanoparticles was measured. In the meantime, a diabetic skin wound model was prepared with the use of rats. Then, the rats were split into four groups: EGF nanogroup, EGF group, empty particle group, and control group. Additionally, the results indicate that this study was successful in preparing EGF nanoparticles with a stable performance, and the drug was released for 24 hours. The wound healing in the EGF nanoparticle group was quicker than that in the EGF group. Furthermore, the area of EGF receptor-positive cells in the wound surface of the EGF nanogroup was higher than that of the EGF group, with the results demonstrating that EGF nanoparticles upregulated the expression of EGF receptors in wound surface cells, promoted wound surface healing, and had better efficacy than EGF.

Topics: Animals; Diabetes Mellitus; Epidermal Growth Factor; Nanoparticles; Rats; Regeneration; Skin; Ulcer; Wound Healing

Although mucoactive proteins, such as epidermal growth factor (EGF), could improve clinical outcomes of intestinal ulcerative diseases, their gastrointestinal application is limited because of their proteolytic digestion or concerns about tumor promotion. In the present study, ATP-binding cassette (ABC) transporter-linked secretion of human EGF from probiotic Escherichia coli (EGF-EcN) was created to promote beneficial actions of the EGF receptor, which is notably attenuated in patients with intestinal ulcerative injuries. Preventive and postinjury treatment with EGF-EcN alleviated intestinal ulcers and other readouts of disease severity in murine intestinal ulcer models. EGF-EcN administration promoted the restitutive recovery of damaged epithelial layers, particularly via upward expansion of highly proliferating progenitor cells from the lower crypts. Along with the epithelial barrier benefit, EGF-EcN improved goblet cell-associated mucosal integrity, which controls the access of luminal microbiota to the underlying host tissues. Despite concern about the oncogenic action of EGF, EGF-EcN did not aggravate colitis-associated colon cancer; instead, it alleviated protumorigenic activities and improved barrier integrity in the lesions. All findings indicate that probiotic bacteria-based precision delivery of human EGF is a promising mucosal intervention against gastrointestinal ulcers and malignant distress through crypt-derived barrier restoration.

Topics: Animals; ATP-Binding Cassette Transporters; Cell Line; Cells, Cultured; Disease Models, Animal; Drug Delivery Systems; Epidermal Growth Factor; Escherichia coli; Female; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestinal Neoplasms; Mice; Mice, Inbred C57BL; Probiotics; Ulcer

This case report describes the first successful use of recombinant human epidermal growth factor (rh-EGF) in radiation-induced chronic wound of bone and skin which remains to be difficult to treat. Such wound on the chest of a 59-year-old female patient is presented lasting 3 years despite flap surgery and conventional treatment. The treatment with rh-EGF achieved healing within 16 weeks but further study to evaluate its potential for radiation-induced chronic wounds is warranted.

Topics: Breast Neoplasms; Chronic Disease; Epidermal Growth Factor; Female; Humans; Middle Aged; Radiation Injuries; Recombinant Proteins; Ulcer; Wound Healing

Interstitial cystitis (IC) is a chronic bladder disorder, with symptoms including pelvic and or perineal pain, urinary frequency, and urgency. The etiology of IC is unknown, but sensitive and specific biomarkers have been described, including antiproliferative factor (APF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), and epidermal growth factor (EGF). However, the relative sensitivity of these biomarkers in ulcerative vs. nonulcerative IC is unknown, and these markers have yet to be validated in another laboratory. We therefore measured these markers in urine from patients with or without Hunner's ulcer, as well as normal controls, patients with bladder cancer, and patients with bacterial cystitis, at the First Hospital of China Medical University.. Urine specimens were collected from two groups of Chinese IC patients (38 IC patients with Hunner's ulcers, 26 IC patients without Hunner's ulcers), 30 normal controls, 10 bacterial cystitis patients and 10 bladder cancer patients. APF activity was determined by measuring 3H-thymidine incorporation in vitro, and HB-EGF and EGF levels were determined by ELISA.. APF activity (inhibition of thymidine incorporation) was significantly greater in all IC patient urine specimens than in normal control specimens or in specimens from patients with bacterial cystitis or bladder cancer (p < 0.0001 for each comparison). Urine HB-EGF levels were also significantly lower and EGF levels significantly higher in both groups of IC patients than in the three control groups (p < 0.0001 for each comparison). Although APF and HB-EGF levels were similar in ulcerative and nonulcerative IC patients, EGF levels were significantly higher in IC patients with vs. without ulcers (p < 0.004).. These findings indicate that APF, HB-EGF and EGF are good biomarkers for both ulcerative and nonulcerative IC and validate their measurement as biomarkers for IC in Chinese patients.

Topics: Adult; Biomarkers; China; Cystitis, Interstitial; Epidermal Growth Factor; Female; Glycoproteins; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Ulcer; Urinary Bladder Diseases

Ulceration is a common feature of inflammatory bowel diseases, where subepithelial cell growth is frequently necessary for resolution. In order to further understand the role of colonic fibroblasts in this process, we have used an in vitro model of wound repair to study the response of human colonic fibroblasts to several growth factors expressed in colonic tissues.. Proliferation was determined by [(3)H]thymidine incorporation into DNA in subconfluent fibroblast cultures. In vitro wound repair was determined in confluent fibroblast monolayers after mechanical denudation. The presence of growth factors secreted by fibroblasts was studied in conditioned medium by heparin affinity chromatography and immunodetection with specific antibodies.. Serum and platelet-derived growth factor (PDGF-BB) induced a dramatic increase in both colonic fibroblast proliferation and closure of wounded cell monolayers. Epidermal growth factor (EGF) stimulated both fibroblast activities, but the effect was less potent. However, colonic fibroblasts did not respond to transforming growth factor-beta(1). Conditioned medium stimulated fibroblast proliferation and wound repair activity, which was reverted by the addition of suramin. Furthermore, a PDGF-like factor was isolated from colonic fibroblast-conditioned medium.. EGF and PDGF-BB promote human colonic fibroblast-dependent wound repair activities. Human colonic fibroblasts may exert an autocrine regulation via the production of growth factors.

Topics: Cell Division; Cells, Cultured; Colon; Colonic Diseases; Culture Media, Conditioned; Epidermal Growth Factor; Fibroblasts; Humans; Platelet-Derived Growth Factor; Transforming Growth Factor beta; Ulcer; Wound Healing

The effect of subcutaneous and luminal epidermal growth factor (EGF) administration on acetic acid-induced colonic ulceration was determined in adult rats. Application of acetic acid to the distal colonic lumen caused epithelial denudation, mucosal ulceration and inflammation in the exposed segment. Re-epithelialization was detectable 5 to 7 days later, with near-complete resolution of the lesion by 14 days post-injury. Luminal EGF (1.6 mg/kg bw/day) or subcutaneous EGF (200 micromilligrams/kg bw/day), administered for 4 or 6 days from the time of ulceration failed to enhance re-epithelialization of the acid-exposed segment. However, mucosal and submucosal thickening was attenuated 20-40% by subcutaneous EGF, reflecting a reduction in edema. Luminal EGF had a similar but less substantial effect in the submucosa, but was more effective at attenuating muscularis thickening adjacent to the lesion. In conclusion, administration of exogenous EGF for up to 6 days failed to enhance re-epithelialization of acetic acid-induced colonic ulcerations but did attenuate the associated edematous response.

Topics: Acetic Acid; Animals; Cell Division; Colon; Colonic Diseases; Edema; Epidermal Growth Factor; Epithelium; Histocytochemistry; Intestinal Mucosa; Male; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley; Ulcer

Topics: Chronic Disease; Epidermal Growth Factor; Gastrointestinal Diseases; Humans; Intercellular Signaling Peptides and Proteins; Mucins; Muscle Proteins; Neuropeptides; Parasympatholytics; Peptides; Remission, Spontaneous; Trefoil Factor-2; Trefoil Factor-3; Ulcer

Human epidermal growth factor (EGF), a small polypeptide (6 kDa) with mitogenic properties, has been implicated in the protection of gastrointestinal mucosal integrity. The efficacy of EGF in the prevention and healing of sclerotherapy-induced esophageal lesions was investigated in 24 minipigs with surgically induced portal hypertension. In addition, the effect of EGF on intragastric acidity and pharmacokinetics was investigated as possible means to explain its protective mechanism of action. The animals underwent three weekly sessions of sclerotherapy with polidocanol 2% and were concomitantly and for an additional three weeks treated with either placebo or EGF administered paravenously in the esophagus and/or subcutaneously. The subcutaneous treatment with EGF significantly (P < 0.05) reduced esophageal stricture and scar formations associated with sclerotherapy. Gastric pH values were significantly (P < 0.01) elevated only in animals receiving subcutaneous injections of EGF. Furthermore, the subcutaneous administration of EGF was associated with unexpected prolonged plasma concentration of the peptide. These results suggest a possible clinical value of EGF as an adjunctive treatment with the sclerotherapy.

Topics: Animals; Epidermal Growth Factor; Esophageal Diseases; Esophageal Stenosis; Gastric Juice; Humans; Hydrogen-Ion Concentration; Male; Polidocanol; Polyethylene Glycols; Recombinant Proteins; Sclerosing Solutions; Sclerotherapy; Swine; Swine, Miniature; Ulcer

Human epidermal growth factor (EGF), a naturally occurring protein, has been implicated in the protection of gastrointestinal mucosal integrity. The efficacy of EGF in the prevention of sclerotherapy-induced esophageal lesions was investigated in 18 minipigs with surgically induced portal hypertension. The animals underwent five weekly sessions of sclerotherapy with polidocanol 2% and were concomitantly treated with either placebo or EGF administered either paravenously or subcutaneously. EGF significantly (P < 0.05) reduced esophageal ulcerations, stricture formations, and mucosal histological damage associated with sclerotherapy. The drug was well-tolerated with no overt toxicity. These results suggest a potentially important clinical value of EGF as an adjunctive treatment with the sclerotherapy.

Topics: Animals; Epidermal Growth Factor; Esophageal Diseases; Esophageal Stenosis; Esophagoscopy; Female; Mucous Membrane; Recombinant Proteins; Sclerotherapy; Swine; Swine, Miniature; Ulcer

Topics: Brunner Glands; Epidermal Growth Factor; Gastrointestinal Diseases; Humans; Pyloric Antrum; Ulcer

Ulcerative mucositis is a common, bothersome, and dose-limiting complication of cancer chemotherapy. It has been hypothesized that mucosal susceptibility to the degenerative effects of stomatotoxic drugs is related to the renewal rate of the buccal epithelium. This study was undertaken to evaluate the effect of epidermal growth factor, a molecule known to stimulate epidermal cell division, on the course, frequency, and healing of ulcerative mucositis in an animal model. Golden Syrian hamsters were subjected to a standard mucositis-induction protocol with 5-fluorouracil. Osmotic pumps were implanted into a space between the retractor muscle and the platysma cervicale muscle, and delivered epidermal growth factor or placebo at a constant rate for 7 or 14 days. Epidermal growth factor increased oral mucosal breakdown in the face of antineoplastic therapy. The course and extent of mucositis was influenced by the timing of epidermal growth factor pump placement relative to the initiation of stomatotoxic therapy. These results support the hypothesis that the epithelial basal cell rate is one of the key elements in determining mucosal sensitivity to cancer chemotherapy.

Topics: Animals; Cell Division; Cricetinae; Epidermal Growth Factor; Epithelial Cells; Epithelium; Fluorouracil; Infusion Pumps, Implantable; Male; Mesocricetus; Mouth Mucosa; Stomatitis; Time Factors; Ulcer

Topics: Biological Transport; Body Fluids; EGF Family of Proteins; Epidermal Growth Factor; Female; Gastrointestinal Hormones; Gonadotrophs; Humans; Pharmacology; Pregnancy; Rats; Research; Ulcer

Topics: Alkalies; EGF Family of Proteins; Epidermal Growth Factor; Gastrointestinal Hormones; Nutrition Therapy; Peptic Ulcer; Ulcer; Vitamin U; Vitamins

Topics: EGF Family of Proteins; Epidermal Growth Factor; Humans; Peptic Ulcer; Ulcer

Topics: Animals; EGF Family of Proteins; Epidermal Growth Factor; Humans; Rats; Ulcer