epidermal-growth-factor and Stomatitis

To investigate whether serum amylase can predict the recovery of salivary volume and determine the correlation of the level of cytokines, including epidermal growth factor, hepatocyte growth factor and keratinocyte growth factor, with oral mucositis during chemoradiotherapy for oral cancer.. This study included 84 patients treated with preoperative chemoradiotherapy followed by curative surgery, following a phase II study protocol. We measured and analysed the correlation of the stimulated saliva volume, serum amylase and cytokines in resting saliva at baseline and 1 month after chemoradiotherapy with oral mucositis levels.. We observed a negative correlation between the serum amylase level at the beginning of chemoradiotherapy and the stimulated saliva volume at 1 month after chemoradiotherapy (p = .03). Epidermal growth factor in resting saliva was significantly reduced after chemoradiotherapy (p < .01). The incidence of severe oral mucositis during chemoradiotherapy was significantly higher and negatively associated with the epidermal growth factor and keratinocyte growth factor levels (p = .04, p = .05).. The serum amylase level at the beginning of chemoradiotherapy may be a predictor of the recovery of the saliva volume. Furthermore, cytokines such as epidermal growth factor and keratinocyte growth factor in resting saliva affect the development of oral mucositis during chemoradiotherapy.

Topics: Amylases; Chemoradiotherapy; Cytokines; Epidermal Growth Factor; Humans; Saliva; Stomatitis

To estimate the efficacy of traditional Chinese medicine (Chining decoction, CHIN) for radiation-induced oral mucositis in patients with head and neck cancer.. From May 2014 to December 2015, 70 consecutive patients were randomly assigned to receive CHIN (treatment group) or recombinant human epidermal growth factor (rhEGF) spray (control group) at a 1:1 ratio. CHIN was administered to treatment group from the first day of radiotherapy until the completion of radiotherapy. Simultaneously, the rhEGF spray was administered to control group on the oral mucosa of irradiated area. The clinical benefit was determined by gradation of mucositis (Common Terminology Criteria for Adverse Events v4.0), oral pain, and xerostomia (visual analysis scale) for each week during radiotherapy. Body mass index was evaluated before and after radiotherapy.. Patients in the treatment group had prominent remission of oral pain and grade of mucositis on each observing point compared with those in control group ( P < .01). Xerostomia was decreased notably in treatment group compared with control group ( P < .01). Body mass index in the treatment group exhibited advantage over control group after radiotherapy, but there was no statistical significance (19.8 ± 3.26 vs 18.8 ± 2.5 kg/m. CHIN presented an obvious advantage in preventing radiation-induced oral mucositis compared with rhEGF spray.

Topics: Adolescent; Adult; Aged; Body Mass Index; Epidermal Growth Factor; Female; Head and Neck Neoplasms; Humans; Male; Medicine, Chinese Traditional; Middle Aged; Mouth Mucosa; Prospective Studies; Radiation Injuries; Radiotherapy; Stomatitis; Young Adult

The aim of this study was to evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) oral spray for oral mucositis (OM) induced by intensive chemotherapy with hematopoietic stem cell transplantation. In this phase 2 study, patients were randomized to either rhEGF (50 microg/mL) or placebo in a 1:1 ratio. The primary endpoint was incidence of National Cancer Institute (NCI) grade ≥2 OM. A total of 138 patients were enrolled in this study. In the intention-to-treat analysis, rhEGF did not reduce the incidence of NCI grade ≥2 OM (p = 0.717) nor reduce its duration (p = 0.725). Secondary endpoints including the day of onset and duration of NCI grade ≥2 OM, the incidence of NCI grade ≥3 OM and its duration, and patient-reported quality of life were also similar between the two groups. In the per-protocol analysis, however, the duration of opioid analgesic use was shorter in the rhEGF group (p = 0.036), and recipients in the rhEGF group required a lower cumulative dose of opioid analgesics than those in the placebo group (p = 0.046), among patients with NCI grade ≥2 OM. Adverse events were mild and transient. This study found no evidence to suggest that rhEGF oral spray reduces the incidence of OM. However, further studies are needed to investigate the effect of rhEGF on OM-induced pain reduction after intensive chemotherapy.

Topics: Administration, Topical; Adolescent; Adult; Aged; Analgesics, Opioid; Antineoplastic Agents; Double-Blind Method; Epidermal Growth Factor; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Male; Middle Aged; Quality of Life; Recombinant Proteins; Stomatitis; Young Adult

Oral mucositis (OM) is considered a painful and debilitating side effect in patients receiving head and neck cancer treatment. Low-level laser therapy (LLLT) proved to be effective to prevent and treat chemoradiotherapy-induced OM. The aim of this study was to evaluate the effect of LLLT in the severity of OM in patients with head and neck cancer and on the release of salivary inflammatory mediators. Clinical (score of OM severity) and biochemical parameters (concentration of inflammatory mediators, growth factors, and enzymes in saliva) were used.. Thirty patients were randomized into two groups: control and laser. LLLT was performed three times a week in the laser group, while control group received sham irradiation. OM severity was assessed according to the World Health Organization (WHO) and National Cancer Institute (NCI) scales. Pro-inflammatory and anti-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-10, TGF-β), growth factors (EGF, FGF, VEGF), and metalloproteinases (MMP2/TIMP2, MMP9/TIMP2) concentrations were assessed using ELISA test. Saliva samples were collected on admission, and at the 7th, 21st, and 35th sessions of radiotherapy.. The laser group showed a reduction in the severity of OM, which coursed with significantly diminished salivary concentration of EGF and VEGF in the 7th radiotherapy session and of IL-6 and FGF in the 35th. There was a trend for reduced levels of IL-1β, TNF-α, IL-10, TGF-β, MMP2/TIMP2, MMP9/TIMP2 in the laser group compared to the control, however, no statistically significant differences were found.. These findings demonstrated that LLLT was effective in reducing the severity of chemoradiotherapy-induced OM and was associated with the reduction of inflammation and repair.

Topics: Carcinoma, Squamous Cell; Chemoradiotherapy; Cytokines; Double-Blind Method; Epidermal Growth Factor; Female; Head and Neck Neoplasms; Humans; Low-Level Light Therapy; Male; Metalloproteases; Middle Aged; Saliva; Severity of Illness Index; Stomatitis; Vascular Endothelial Growth Factor A

Oral mucositis (OM) is one of the most common and debilitating complications in patients undergoing intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) oral spray for OM induced by intensive chemotherapy followed by HSCT. Patients were randomly assigned to either the rhEGF group or placebo group. The severity of OM and self-reported quality of life (QOL) were assessed daily. A total of 58 patients were analyzed. Baseline characteristics were similar between the two groups. The incidence of NCI grade ≥ 2 OM was higher in the rhEGF group (78.6% vs. 50%, P = 0.0496). However, the duration of OM in patients with NCI grade ≥ 2 tended to be shorter in the rhEGF group (8.5 days vs. 14.5 days, P = 0.262). The QOL analysis in patients with World Health Organization (WHO) grade ≥ 3 OM showed that rhEGF significantly reduced limitations in swallowing (P = 0.039) and drinking (P = 0.042). The duration of hospitalization (P = 0.047), administration of total parenteral nutrition (P = 0.012), and the usage of opioid analgesics (P = 0.018) were significantly shorter in the rhEGF group with WHO grade ≥ 3 OM. Adverse events were mild and similar between the two groups. In conclusion, this analysis showed that rhEGF did not reduce the incidence of NCI grade ≥ 2 OM. However, the patients with WHO grade ≥ 3 OM in the rhEGF group showed better results compared to the placebo group for several secondary endpoints.

Topics: Adolescent; Adult; Analgesics, Opioid; Deglutition Disorders; Double-Blind Method; Epidermal Growth Factor; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Length of Stay; Male; Middle Aged; Oral Sprays; Parenteral Nutrition; Quality of Life; Recombinant Proteins; Severity of Illness Index; Stomatitis; Transplantation Conditioning; Young Adult

Several GI peptides linked to intestinal barrier function could be involved in the modification of intestinal permeability and the onset of diarrhea during adjuvant chemotherapy. The aim of the study was to evaluate the circulating levels of zonulin, glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF) and ghrelin and their relationship with intestinal permeability and chemotherapy induced diarrhea (CTD).. Sixty breast cancer patients undergoing an FEC60 regimen were enrolled, 37 patients completed the study. CTD(+) patients were discriminated by appropriate questionnaire and criteria. During chemotherapy, intestinal permeability was assessed by lactulose/mannitol urinary test on day 0 and day 14. Zonulin, GLP-2, EGF and ghrelin circulating levels were evaluated by ELISA tests at five time-points (days 0, 3, 10, 14, and 21).. During FEC60 administration, the lactulose/mannitol ratio was significantly higher on day 14 than at baseline. Zonulin levels were not affected by chemotherapy, whereas GLP-2 and EGF levels decreased significantly. GLP-2 levels on day 14 were significantly lower than those on day 0 and day 3, while EGF values were significantly lower on day 10 than at the baseline. In contrast, the total concentrations of ghrelin increased significantly at day 3 compared to days 0 and 21, respectively. Ten patients (27%) suffered from diarrhea. On day 14 of chemotherapy, a significant increase of the La/Ma ratio occurred in CTD(+) patients compared to CTD(-) patients. With regards to circulating gut peptides, the AUCg of GLP-2 and ghrelin were significantly lower and higher in CTD(+) patients than CTD(-) ones, respectively. Finally in CTD(+) patients a significant and inverse correlation between GLP-2 and La/Ma ratio was found on day 14.. Breast cancer patients undergoing FEC60 showed alterations in the intestinal permeability, which was associated with modifications in the levels of GLP-2, ghrelin and EGF. In CTD(+) patients, a different GI peptide profile and increased intestinal permeability was found in comparison to CTD(-) patients. This evidence deserves further studies for investigating the potentially different intestinal luminal and microbiota conditions.. Clinical trial NCT01382667.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Cholera Toxin; Cyclophosphamide; Diarrhea; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Epirubicin; Female; Fluorouracil; Ghrelin; Glucagon-Like Peptide 2; Haptoglobins; Humans; Intestinal Absorption; Intestinal Mucosa; Italy; Lactulose; Mannitol; Middle Aged; Peptides; Permeability; Prospective Studies; Protein Precursors; Stomatitis; Time Factors; Treatment Outcome

The objective of this study was to evaluate the effect of salivary stimulation therapies on the salivary flow, oral mucositis, and salivary cytokine levels in patients receiving allogeneic hematopoietic stem cell transplantation.. Thirty-five eligible patients were randomized into 4 groups: control, mechanical sialogogue, transcutaneous electrical nerve stimulation (TENS) sialogogue, and combined mechanical/electrical sialogogue. Saliva was collected from patients before transplantation and at days 3, 7, and 14 after transplantation. The volume was measured and salivary cytokines were assessed using enzyme-linked immunosorbent assay.. By day 14, resting and stimulated salivary flow levels were diminished. Resting salivary flow rates decreased the most in the control and mechanical groups. In contrast, TENS alone or in combination with mechanical stimulatory therapy benefited the patients. TENS-treated patients showed increase in resting salivary flow. Also, the groups treated with TENS had fewer patients affected by grades 3 and 4 mucositis, and less mucositis was associated with better patient survival (P = .027).. TENS-associated salivary stimulation therapies minimized the reduction of salivary flow and prevented severe chemotherapy-induced oral mucositis.

Topics: Adult; Analysis of Variance; Epidermal Growth Factor; Female; Hematopoietic Stem Cell Transplantation; Humans; Interleukin-10; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Mucositis; Physical Stimulation; Prospective Studies; Saliva; Salivation; Statistics, Nonparametric; Stomatitis; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Transcutaneous Electric Nerve Stimulation; Transplantation Conditioning; Tumor Necrosis Factor-alpha; Young Adult

We evaluated the efficacy of topically applied human recombinant epidermal growth factor (rhEGF) for the treatment of oral mucositis induced by radiotherapy (RT), with or without chemotherapy, in patients with head and neck cancer.. Patients receiving definitive chemoradiotherapy, definitive RT, or postoperative RT to the oral cavity or oropharynx were recruited from 6 institutions and enrolled in a randomized, double-blind, placebo-controlled phase 2 trial. Patients were assigned to a placebo group or to 1 of 3 EGF-treatment groups (10, 50, or 100 microg/mL doses, delivered in a spray, twice daily). The grade of mucositis was evaluated using the Radiation Therapy Oncology Group (RTOG) scoring criteria. Responders to EGF were defined as having an RTOG grade of 2 or lower at the fourth- or fifth-week examinations during RT, but an enduring RTOG grade 2 for 2 weeks was an exception.. Of the 113 patients included in the study, 28 received placebo and 29 received EGF at 10 microg/mL, 29 at 50 microg/mL, and 27 at 100 microg/mL. EGF significantly reduced the incidence of severe oral mucositis at the primary endpoint (a 64% response was observed with 50 microg/mL EGF vs a 37% response in the control group; P = .0246).. The EGF oral spray may have potential benefit for oral mucositis in patients undergoing RT for head and neck cancer. Phase 3 studies are ongoing to confirm these results.

Topics: Administration, Inhalation; Adult; Aged; Combined Modality Therapy; Double-Blind Method; Epidermal Growth Factor; Female; Head and Neck Neoplasms; Humans; Middle Aged; Placebos; Radiation Injuries; Recombinant Proteins; Stomatitis

To explore the effect of quadruple fluid aerosol inhalation on oral mucositis induced by radiotherapy in nasopharyngeal carcinoma (NPC) and its mechanism.. One hundred and twenty NPC patients were divided into a treatment group (n=60) and a control group (n=60). Radiation therapy was administered conventionally over 7 weeks with 2.0 Gy daily fractions for 5 days each week at the 70 Gy. Patients in the control group accepted oral care conventionally, and patients in the treatment group used quadruple fluids aerosol inhalation before the radiotherapy. The saliva volume was measured by a nurse twice a week and the concentration of epidemal growth factor (EGF) was examined by ELISA.. The number of patients with mucositis in the treatment group was significantly fewer than that in the control group when the total doses were up to 30 Gy and 60 Gy (P<0.05). The concentration of EGF in the control group significantly decreased when total doses were up to 30 Gy and 60 Gy (P<0.01). The concentration of EGF in the treatment group was not significantly different compared with pre-radiotherapy when the total doses were up to 30 Gy, but when total doses were up to 60 Gy, the concentration of EGF in the treatment group obviously decreased compared with that of pre-radiotherapy.. The quadruple fluid aerosol inhalation is effective to reduce oral mucositis resulted from radiotherapy in NPC patients, which is related to the delay of the EGF decrease in the saliva.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Drug Combinations; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Gentamicins; Humans; Male; Menthol; Middle Aged; Nasopharyngeal Neoplasms; Procaine; Radiotherapy; Saliva; Stomatitis; Treatment Outcome; Vitamin B 12; Vitamins

To study the effect of Qingre Liyan Decoction (QRLYD) in the prevention and treatment of acute radiative oral mucositis (AROM), and to explore the mechanism of QRLYD by detecting epidermal growth factor (EGF) and T lymphocytes (CD3, CD4, and CD8).. Sixty patients conforming with the standard were randomly assigned to two groups, 30 patients in each group. Patients in the trial group were treated with QRLYD, and those in the control group were treated with Dobell's solution, both groups receiving conventional radiation treatment. The treatment course for both groups was 6 weeks on average. Blood routine test, CD3, CD4, and CD8 in the peripheral blood and EGF in the saliva were detected one day before and on the 14th and 28th day of radio-therapy.. Patients in the trial group were in good condition with normal spirits and intake of food and drinks. The incidence of AROM is lower and the effect in preventing AROM is higher in the trial group than those in the control group (P<0.05). The EGF in saliva, and CD4 and CD8 in the blood of patients in the trial group were higher than those in the control group (P<0.05).. QRLYD can cure and prevent AROM. The mechanism may be related with its effects in enhancing body immunity and promoting salivary EGF.

Topics: Acute Disease; Adult; Carcinoma; Drugs, Chinese Herbal; Epidermal Growth Factor; Female; Head and Neck Neoplasms; Humans; Incidence; Leukocyte Count; Male; Middle Aged; Phytotherapy; Platelet Count; Radiation Injuries; Stomatitis; T-Lymphocyte Subsets; Treatment Outcome

This study aimed to investigate correlations of the severity of radiation-induced oral mucositis (RIOM) with epidermal growth factor (EGF) and inflammatory cytokines in patients with head and neck cancer (HNC).. Levels of inflammatory cytokines and EGF in saliva of HNC patients were measured. Correlations of inflammatory cytokines and EGF levels with RIOM severity and pain degree, and their diagnostic values on RIOM severity were determined.. Elevated IFN-γ, TNF-α, IL-2, and IL-6 levels, and reduced IL-4, IL-10, and EGF levels were found in patients with severe RIOM. IFN-γ, TNF-α, IL-2, and IL-6 were positively correlated with RIOM severity, while IL-10, IL-4, and EGF were negatively correlated with it. All factors were effective in predicting the severity of RIOM.. IFN-γ, TNF-α, IL-2, and IL-6 in saliva of patients with HNC are positively correlated with the severity of RIOM, and IL-4, IL-10, and EGF were negatively correlated with it.

Topics: Cytokines; Epidermal Growth Factor; Head and Neck Neoplasms; Humans; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-6; Radiation Injuries; Stomatitis; Tumor Necrosis Factor-alpha

Oral mucositis is frequently a toxic effect of chemotherapeutic and/or radiotherapeutic treatment, resulting from complex multifaceted biological events involving DNA damage. The clinical manifestations have a negative impact on the life quality of cancer patients. Preventive measures and curative treatment of mucositis are still not well established. The glycine has anti-inflammatory, immunomodulatory, and cytoprotective actions, being a potential therapeutic in mucositis. The objective was to evaluate the effects of glycine on the expression of collagen and growth factors, platelet and epidermal in a hamster model oral mucositis. The mucositis was induced by the protocol of Sonis. There were 40 hamsters used, divided into two groups: Group I-control; Group II-supplemented with 5% intraperitoneal glycine, 2.0 mg/g diluted in hepes. Histopathological sections were used to perform the immune-histochemical method, the evaluation of collagen expression, and the growth factors: Epidermal growth factor (EGF) and platelet (PDGF). It was observed that the group supplemented with glycine experienced higher amounts of collagen expression and predominance type of collagen I. The glycine group presented lower immunoexpression of the growth factors, EGF and PDGF. The group supplemented with glycine showed a marked healing process of the oral mucosite, demonstrated by the predominance of collagen type I and reduction of growth factors, EGF and PDGF.

Topics: Animals; Anti-Inflammatory Agents; Collagen Type I; Cricetinae; Dietary Supplements; Epidermal Growth Factor; Female; Glycine; Mouth Mucosa; Platelet-Derived Growth Factor; Stomatitis; Wound Healing

A newly acquired rhesus macaque was suffering from rapid destruction of the left cheek caused by necrotizing stomatitis.. To restore reconstructive surgery and intensive care with antibiotics, wound protection, wound healing agents, and debridement were applied.. Staphylococcus aureus and Enterococcus faecalis were isolated from the culture of the lesion, and the antibiotic susceptibility test revealed methicillin-resistant Staphylococcus aureus infection. Vancomycin and ampicillin-sulbactam effectively treated the bacterial infections, and reconstructive surgery was performed once the infection was cleared. Topical application of recombinant human epidermal growth factor (rhEGF) was useful to treat exposed wound of the noma lesion.. Simian noma associated with methicillin-resistant Staphylococcus aureus (MRSA) had not previously been reported in non-human primates. Although noma associated with MRSA is hard to cure because of its rapid and destructive progress, the aggressive therapy used in this study led to the successful resolution of an acute necrotic stomatitis lesion in a rhesus macaque.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Enterococcus faecalis; Epidermal Growth Factor; Gram-Positive Bacterial Infections; Humans; Macaca mulatta; Male; Methicillin-Resistant Staphylococcus aureus; Monkey Diseases; Mouth; Necrosis; Noma; Oral Surgical Procedures; Plastic Surgery Procedures; Staphylococcal Infections; Stomatitis; Sulbactam; Vancomycin; Wound Healing

Concurrent chemotherapy with radiotherapy (CCRT) has been applied for the treatment of advanced stage of head and neck cancer patients. However CCRT is associated with several complications including mucositis, dermatitis, stomatitis, etc. This study was conducted to evaluate the therapeutic effect of systemically administrated recombinant human epidermal growth factor (rhEGF) in CCRT-induced oral mucositis in a mouse model. Oral mucositis was induced in male BALB/c mice through combination treatment with cisplatin (11 mg/kg, i.p.) and irradiation (17 Gy) of the head and neck area. rhEGF (1.0 mg/kg/day for consecutive 3 days) was administered systemically, and the therapeutic effect was determined by histological evaluation of the oral mucosa. To elucidate optimal dose of rhEGF on CCRT-induced mucositis, various concentrations (0.04-3 mg/kg) of rhEGF were injected for 3 days. Systemic rhEGF administration accelerated the recovery of body weight. Histologically, rhEGF-treated mice showed significantly increased epithelial cell layer thickness, basal cell number, and expression of Ki-67 compared to control mice. Most effective dose was 1 mg/kg among other doses tested. Systemic administration of 1 mg/kg of rhEGF reduces the severity of oral mucositis induced by CCRT in a mouse model, suggesting that rhEGF can be used for treating CCRT-induced mucositis during the cancer treatment.

Topics: Animals; Combined Modality Therapy; Disease Models, Animal; Epidermal Growth Factor; Humans; Male; Mice; Mice, Inbred BALB C; Mouth Mucosa; Radiotherapy; Recombinant Proteins; Stomatitis

Mucositis of the oral cavity and pharynx is a major dose-limiting factor in the application of radiotherapy (RT) to patients with head and neck cancer. Therefore, we evaluated the wound healing effect of human recombinant epidermal growth factor (rhEGF) in head and neck cancer and lymphoma patients with irradiation (with or without combined chemotherapy-induced oral mucositis). Patients at Asan Medical Center who had undergone definitive RT of the head and neck region with or without combined chemotherapy and who had developed severe oral mucositis (higher than the Radiation Therapy Oncology Group grade 3) were treated with topical rhEGF twice daily for 7 days. The evaluation of response with regard to oral mucositis was performed 1 week later. Of the 11 treated patients, three had nasopharyngeal carcinoma, three had carcinoma of the oropharynx, two had carcinoma of the oral cavity, one had carcinoma of the hypopharynx and two had lymphoma of the head and neck. Six patients received RT only, and five patients received concurrent chemoradiotherapy. All patients showed improvements in their oral mucositis after topical treatment with rhEGF in that the Radiation Therapy Oncology Group grade was significantly decreased (P = 0.0000). This finding suggests that rhEGF is effective and safe for the treatment of radiation-induced mucositis. Further studies are needed to determine the optimal dosage and fractionation schedule.

Topics: Administration, Topical; Adult; Aged; Epidermal Growth Factor; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Mouth Mucosa; Pilot Projects; Radiation Injuries; Radiation-Protective Agents; Radiotherapy; Recombinant Proteins; Stomatitis; Treatment Outcome; Wound Healing

We tested the efficacy of oral recombinant human epidermal growth factor (rhEGF) against radiation-induced oral mucositis in a rat model.. Each of 35 Sprague-Dawley rats, 7 to 8 weeks of age and weighing 178 +/- 5 grams, was irradiated once in the head region with 25 Gy, using a 4-MV therapeutic linear accelerator at a rate of 2 Gy/min. The irradiated rats were randomly divided into four groups: those receiving no treatment (Group 1), those treated with vehicle only three times per day (Group 2), and those treated with 50 microg/mL (Group 3), or 100 microg/mL (Group 4) rhEGF three times per day.. Rats were monitored for survival rate and daily activity, including hair loss, sensitivity, and anorexia. We found that survival rate and oral intake were significantly increased and histologic changes were significantly decreased in the rhEGF-treated rats. There was no difference, however, between rats treated with 50 microg/mL or 100 microg/mL rhEGF.. These findings suggest that orally administered rhEGF decreased radiation-induced oral mucositis in rats.

Topics: Administration, Oral; Animals; Anti-Ulcer Agents; Drug Evaluation, Preclinical; Epidermal Growth Factor; Mouth Mucosa; Radiation Injuries; Random Allocation; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Stomatitis

The objective of this study was to assess changes in salivary epidermal growth factor (EGF) in patients receiving radiation therapy to the head and neck and to determine whether salivary EGF levels correlate with the severity of radiation-induced oral mucositis.. Thirteen patients and 18 control subjects were enrolled in the study. Saliva was collected before, during (weekly), and after radiation therapy. Salivary total protein (TP) and EGF concentrations were measured and correlated with the severity of oral mucositis. The variability in normalized EGF (ngEGF/mgTP) values and mucositis scores were analyzed with analysis of covariance, and the adjusted correlation coefficient was calculated.. EGF levels decreased (P =.004), whereas TP levels increased over time (P =.039). A strong correlation was seen with decreasing normalized EGF values and more severe mucositis (P =. 0001).. A strong negative correlation between normalized EGF and mucositis severity suggests a possible role for EGF in the progression of radiation-induced mucosal breakdown.

Topics: Adult; Aged; Analysis of Variance; Epidermal Growth Factor; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Mucous Membrane; Saliva; Salivary Proteins and Peptides; Severity of Illness Index; Statistics, Nonparametric; Stomatitis; Time Factors

Epidermal growth factor (EGF) is present in biologic fluids, including saliva, and plays a role in maintenance of the epithelial barrier and in healing of damaged mucosa. The purpose of this study was to assess the relation between salivary EGF and the severity of oral mucositis in patients with carcinoma of the head and neck during radiation therapy.. Whole resting saliva (WRS) and whole stimulated saliva (WSS) were collected prior to radiation and each week during radiation treatment for 11 men and 7 women. Oral mucositis was evaluated using the National Cancer Institute (NCI) scale of 0-4 and the Oral Mucositis Assessment Scale (OMAS), which evaluates the extent of erythema (scale of 0-2) and ulcerations (scale of 0-3) in nine oral sites. The overall OMAS score of 0-45 reflected the mucosal condition. EGF was assayed in the saliva specimens.. The total mean radiation dose delivered to the head and neck was 5667 centigrays (cGy) in a mean of 24 fractions. Ulcerative oral mucositis occurred in 94% of patients. The mean OMAS score ranged from 2.83 in the first week of treatment to 14.77 in the fifth week. The mean WRS and WSS volumes decreased significantly from pretreatment to the first week of radiation treatment and then remained stable. A similar pattern was seen for the mean total output of EGF. A significant and negative correlation was found between higher levels of EGF in stimulated saliva and low OMAS score, reflecting less severe erythema and ulceration. A general trend showing that less tissue damage was associated with a higher EGF level in resting saliva also was illustrated. EGF levels were correlated with the OMAS score; however, no correlation was found when assessing the NCI score, which combines tissue damage with function and symptoms in a single score.. Radiation-induced mucositis appeared to be modified by saliva volume, total EGF, and concentration of EGF in the oral environment. Saliva volume and total EGF output decreased significantly in the first weeks of treatment and remained reduced throughout radiation therapy. The findings suggest that higher levels of EGF in saliva, particularly in stimulated saliva, prior to and during radiation treatment may be associated with less severe mucosal damage due to radiation therapy. It is also postulated that human EGF may affect the development and healing of radiation-damaged mucosa.

Topics: Adult; Aged; Epidermal Growth Factor; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Mouth Mucosa; Oropharynx; Radiation Injuries; Saliva; Stomatitis

Biological response modifiers have been studied in animal models of oral mucositis. We assessed the presence of epidermal growth factor (EGF) in patients during radiation therapy for head and neck cancer. The findings of this preliminary study showed that it is possible to measure the presence of EGF in oral secretions during radiation therapy. EGF was shown to decrease during the course of radiation therapy, and a trend was seen with decreasing EGF and increasing oral ulceration (P = 0.10) and increasing total mucositis score (P = 0.09).

Topics: Adult; Aged; Epidermal Growth Factor; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Male; Middle Aged; Mouth Mucosa; Oral Ulcer; Radiation Injuries; Saliva; Stomatitis

Human epidermal growth factor (hEGF) stimulates the growth and differentiation of various tissues. We measured EGF levels in saliva (n = 128), urine (n = 94), and serum (n = 99) with radioimmunoassay in order to study the kinetics of hEGF in saliva of normal subjects and patients with oral disease. Salivary EGF levels showed an apparent diurnal rhythm related to the taking of meals. Urinary and serum EGF levels showed no obvious diurnal rhythm. There was no significant correlation between salivary and urinary EGF levels, nor between salivary and serum EGF levels. Salivary EGF levels were significantly lower in the younger group (0-9 years old, 3.06 +/- 0.32 ng/ml, p < 0.05) than in the elder group (10-79 years old, 4.78 +/- 3.5 ng/ml), but did not correlate with age in the elder group. There was no significant difference between males and females between EGF levels in saliva, urine or serum. The relative proportion of EGF levels in submandibular gland saliva, parotid saliva, and whole saliva was 1:6:4. The positive rate of immunohistochemical EGF showed no significant differences between submandibular gland, parotid gland, sublingual gland or minor salivary gland. Salivary EGF levels were markedly low in patients with oral inflammations (stomatitis aphthosa, or peritonsillar abscess) or head and neck tumors (squamous cell carcinoma of the tongue, oral cavity, hypopharynx or larynx). These findings may be significant pathophysiologically. Low salivary EGF levels may reduce the capacity of oral mucosal defense mechanisms to fight against injury by physiochemical agents.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Circadian Rhythm; Epidermal Growth Factor; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Radioimmunoassay; Reference Values; Saliva; Salivary Gland Neoplasms; Salivary Glands; Sialadenitis; Stomatitis

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