In the present study, we investigate the expression profile of the epidermal growth factor receptor family, which comprises EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia (LP). The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus (OLP) and normal oral mucosa (NOM) from 14 healthy donors by real-time polymerase chain reaction (PCR) and immunohistochemistry. Synchronous mRNA coexpression of ErbB1, ErbB2, ErbB3 and ErbB4 was detected in LP lesions. Out of the receptors, only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues. These were strongly expressed by epithelial keratinocytes in LP lesions, as shown by immunohistochemistry. Regarding the ligands, the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues. Therefore, enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.
Adult ; Aged ; Amphiregulin ; Betacellulin ; EGF Family of Proteins ; Epidermal Growth Factor ; metabolism ; Epiregulin ; Female ; Gene Expression Profiling ; Glycoproteins ; metabolism ; Heparin ; metabolism ; Heparin-binding EGF-like Growth Factor ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Keratinocytes ; metabolism ; Leukoplakia, Oral ; metabolism ; Lichen Planus, Oral ; metabolism ; Ligands ; Male ; Middle Aged ; Mouth Mucosa ; metabolism ; Nerve Growth Factors ; Neuregulins ; metabolism ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptor, ErbB-3 ; metabolism ; Receptor, ErbB-4 ; Receptors, Cell Surface ; metabolism ; Transforming Growth Factor alpha ; metabolism ; Up-Regulation ; physiology

OBJECTIVETo detect the expression and distribution of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) in periodontal tissues, and analyze the role of EGF in orthodontic tooth movement.

METHODSAccording to Kings methods, 40 g mesial force was applied to pull the left maxillary first molar in the rat. Using immunohistochemical method (HI-SABC method) to localize and examine the expression of EGF and EGFR in decalcified alveodental connective tissues at 24 hours and 168 hours of tooth movement.

RESULTSEGF and EGFR were stained at some of periodontal ligament of furcation and radical regions in control group. These expressions of EGF and EGFR increased in periodontal tissues (P < 0.01), with the expressions at 168 hours higher than those at 24 hours (P < 0.01). And levels of EGF and EGFR at tension side were higher than those at pressure side at the same time (P < 0.01).

CONCLUSIONSEpidermal growth factor participated in the tissues remodeling during orthodontic tooth movement and especially played a more important role in orthodontic bone formation.

Animals ; EGF Family of Proteins ; Molar ; Periodontal Ligament ; metabolism ; Periodontium ; metabolism ; Rats ; Receptor, Epidermal Growth Factor ; Tooth Movement Techniques

OBJECTIVETo examine the change of epidermal growth factor (EGF) concentration in saliva of recurrent aphthous ulcer (RAU) patients during the ulcerous and interval period and epidermal growth factor receptor (EGFR) in ulcer biopsy samples.

METHODSECF data of the samples, which were 27 saliva samples from RAU gained not only in the ulcerous period but also in interval period and 33 ones from normal persons, were acquired through enzyme linked immunosorhent assay (ELISA) and EGF standard curve. ECFR-RNA date of RAU biopsies, which were 31 biopsy samples from RAU got during the ulcerous period and 35 ones from normal persons, were surveyed by QF-RT-PCR. All RAU samples were obtained under the same level, which were the whole patients were minor aphthous ulcers and their ulcers occurred not over the first four days. All patients and normal persons were selected seriously under the rule of physical situations without any other diseases and histories of using medicines.

RESULTSThe EGF concentration of saliva in RAU group at ulcer occurrence was higher than that in the interval period and the normal control with a significant test (F = 3.24, P < 0.05). The EGF concentration of saliva in RAU group during the interval period was lower than that in the control, which was significant on statistics (t = 2.73, P < 0.05). The EGFR-RNA in RAU group at ulcer occurrence was higher than the normal control with a significant test (t = 3.15, P < 0.05).

CONCLUSIONIt was suggested that the ulcer occasion of RAU patients could be related with the decreasing of EGF in saliva during interval period, and that the ulcer sell-cure of RAU patients would be contributed to

Adult ; Biopsy ; EGF Family of Proteins ; Female ; Humans ; Male ; Middle Aged ; Receptor, Epidermal Growth Factor ; Saliva ; Stomatitis, Aphthous

Previous studies suggested an association between the EGF +61 A>G polymorphism and susceptibility to gastric cancer, but the results have been inconsistent. To draw a more precise risk estimation of the association, we performed a meta-analysis of published studies. PubMed, EMBASE, Google Scholar and the Chinese Wanfang databases were systematically searched to identify relevant studies. There were 7 studies involving 1992 cases of gastric cancer and 3202 controls in this meta-analysis. Our study showed that, overall, the EGF +61 A>G polymorphism was significantly associated with the increased risk of gastric cancer in allele model (G vs. A: OR=1.18, 95% CI=1.00-1.39), dominant model (GG + GA vs. AA: OR=1.28, 95% CI=1.05-1.55), homozygous model (GG vs. AA: OR=1.31, 95% CI=1.06-1.63) and heterozygous model (GA vs. AA: OR=1.25, 95% CI=1.01-1.53). The stratified analysis by ethnicity revealed a significant association between EGF +61 A>G polymorphism and gastric cancer risks in Asians. This meta-analysis indicates that EGF +61 A>G polymorphism may increase the risk of gastric cancer, especially in Asians. Large-sized, well-designed studies involving different ethnic groups should be conducted to confirm this association.
Asian Continental Ancestry Group ; genetics ; EGF Family of Proteins ; genetics ; Epidermal Growth Factor ; genetics ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Single Nucleotide ; Regression Analysis ; Stomach Neoplasms ; genetics

Menetrier's disease is a rare protein-losing hypertrophic gastropathy. Histologically, it can be mistaken for other disorders showing hypertrophic gastropathy. The pathogenesis of Menetrier's disease is not fully understood; however, it appears that the epidermal growth factor receptor (EGFR) ligand, transforming growth factor alpha, contributes to the pathogenesis of this disorder. In this review, we will discuss disease entities that can mimic Menetrier's disease and the role of EGFR signaling in Menetrier's disease.
Gastritis, Hypertrophic* ; Receptor, Epidermal Growth Factor ; Transforming Growth Factor alpha

OBJECTIVETo investigate the anti-angiogenic effect of amphiregulin (AR) antisense RNA expression in breast cancer.

METHODSHuman AR cDNA antisense plasmid was transfected into NS2T2A1 cells (a human breast cancer cell line). Two selected clones expressed AR antisense RNA (AR AS1 and AR AS3 cell lines) in which AR protein expression was reduced. Control cell line NS2T2A1 V was obtained by empty vector transfection. These cells were injected subcutaneously into nude mice. The effects of conditioned media on proliferation of human microvascular endothelial cells (HMEC) were evaluated and VEGF secreted by the cells was measured by ELISA method. In tumor tissues, VEGF expression levels were measured by quantitative RT-PCR, and CD31-immunostaining was used for intra-tumoral vascular quantification.

RESULTSThe proliferation index of HMEC cells grown in conditioned media with AR AS1 and AR AS3 was significantly reduced in comparison with that of control cells, accompanied by a decreased VEGF secretion. In tumors derived from AR AS1 and AR AS3 cells, intra-tumoral vascularization was reduced to about 50% of that derived from control cell line, accompanied with a decrease of VEGF expression.

CONCLUSIONAmphiregulin antisense RNA expression inhibits efficiently the angiogenesis in breast cancer, suggesting this growth factor could represent a novel therapeutic target in breast cancer.

Adenocarcinoma ; blood supply ; pathology ; Amphiregulin ; Angiogenesis Inhibitors ; biosynthesis ; genetics ; Animals ; Breast Neoplasms ; blood supply ; pathology ; EGF Family of Proteins ; Glycoproteins ; biosynthesis ; genetics ; Humans ; Intercellular Signaling Peptides and Proteins ; biosynthesis ; genetics ; Mice ; Mice, Nude ; Neovascularization, Pathologic ; RNA, Antisense ; biosynthesis ; genetics ; Vascular Endothelial Growth Factors ; antagonists & inhibitors

OBJECTIVE: Cellular, animal, and human epidemiological studies suggested that benzodiazepines increase the risk of cancer and cancer mortality. Obesity is also clearly linked to carcinogenesis. However, no human studies have examined benzodiazepine-associated carcinogenesis as assessed by changes in cancer biomarkers. METHODS: A total of 19 patients were recruited, and received a 6-week treatment of 0.5 mg lorazepam. The measured cancer biomarkers were angiopoietin-2 (ANG-2), soluble CD40 ligand, epidermal growth factor, endoglin, soluble Fas ligand (sFASL), heparin-binding EGF-like growth factor (HB-EGF), insulin-like growth factor binding protein, interleukin (IL)-6, IL-8, IL-18, plasminogen activator inhibitor (PLGF), placental growth factor, transforming growth factor (TGF)-α, tumor necrosis factor (TNF)-α, urokinase-type plasminogen (uPA), vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D. RESULTS: Six cancer biomarkers were significantly increased in all patients as a whole. The subgroup analysis revealed a distinct pattern of change. Overweight patients showed a significant increase in 11 cancer biomarkers, including ANG-2, sFASL, HB-EGF, IL-8, PLGF, TGF-α, TNF-α, uPA, VEGF-A, VEGF-C, and VEGF-D. However, normal-weight patients did not show any changes in cancer biomarkers. CONCLUSION: Adiposity may have primed the carcinogenic potential, leading to lorazepam-associated carcinogenesis in overweight patients. Epidemiological studies addressing this issue should consider the potential modulator contributing to benzodiazepine-associated carcinogenesis.
Adiposity ; Angiopoietin-2 ; Animals ; Benzodiazepines ; Biomarkers, Tumor ; Carcinogenesis* ; Carrier Proteins ; CD40 Ligand ; Epidemiologic Studies ; Epidermal Growth Factor ; Fas Ligand Protein ; Heparin-binding EGF-like Growth Factor ; Humans ; Interleukin-18 ; Interleukin-8 ; Interleukins ; Lorazepam ; Mortality ; Obesity ; Overweight* ; Plasminogen ; Plasminogen Activators ; Transforming Growth Factors ; Tumor Necrosis Factor-alpha ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor C ; Vascular Endothelial Growth Factor D

Psoriasis is a chronic inflammatory disease related to genome-wide and surroundings, it is important to develop a suitable animal model to research psoriasis pathogenesis and evolve pharmacotherapeutics. With the development of transgenetic technology in the past few years, psoriasis virulence gene animal model become a hotspot. Research of animal model of human psoriasis genes is reviewed in the paper.
Aminoquinolines ; toxicity ; Amphiregulin ; Animals ; Disease Models, Animal ; EGF Family of Proteins ; genetics ; metabolism ; Humans ; Keratin-14 ; genetics ; metabolism ; Keratin-5 ; genetics ; metabolism ; Keratinocytes ; metabolism ; Membrane Glycoproteins ; agonists ; Mice, Transgenic ; Psoriasis ; etiology ; genetics ; metabolism ; Receptor, TIE-2 ; genetics ; metabolism ; STAT3 Transcription Factor ; genetics ; metabolism ; Toll-Like Receptor 7 ; agonists ; Transforming Growth Factor beta1 ; genetics ; metabolism

OBJECTIVEThis study aims to investigate the expression levels of serum and urinary vascular endothelial growth factor-A (VEGF-A) and epidermal growth factor-like domain 7 (EGFL7) in proliferating infantile hemangioma patients under propranolol treatment.

METHODSPropranolol (0.5-2 mg x kg(-1)) was orally administered to 30 infants every day for 4-8 months. The Achauer method was used to measure the tumor radius and thus evaluate the clinical curative effects of the treatment. Enzyme-linked immunosorbent assay was used to measure the serum and urinary concentrations of VEGF-A and EGFL7 at 0, 4, and 12 weeks after the treatment.

RESULTSThe treatment response was excellent in 2 patients, good in 11, moderate in 14, and poor in 3. Serum VEGF-A (335.692 pg x mL(-1) ± 136.146 pg x mL(-1)) was high before the treatment and then significantly decreased after 4 weeks (264.853 pg x mL(-1) ± 122.120 pg x mL(-1)) and 12 weeks (211.345 pg x mL(-1) ± 104.035 pg x mL(-1)) of treatment (P < 0.05). Urinary VEGF-A (76.234 pg x mL(-1) ± 24.169 pg x mL(-1)) was high before the treatment and then significantly decreased after four weeks (56.454 pg x mL(-1) ± l6.111 pg x mL(-1)) and twelve weeks (34.728 pg x mL(-1)) ± 12.656 pg x mL(-1)) of treatment (P < 0.05). Serum and urinary EGFL7 also decreased after the treatment, showing a positive relationship with VEGF-A.

CONCLUSIONPropranolol can be safely and effectively used to treat proliferating infantile hemangiomas. This treatment can reduce the peripheral serum and urinary concentrations of VEGF-A and EGFL7 in affected children.

EGF Family of Proteins ; Enzyme-Linked Immunosorbent Assay ; Hemangioma ; Humans ; Infant ; Propranolol ; Vascular Endothelial Growth Factor A

epidermal growth factor(EGF) and transforming growth factor-alpha(TGF-alpha) on the growth of squamous cancer cell lines established from human oral cancer tissue with moderate differentiation were studied in vitro. After culturing in serum-free media for 24 hours, growth factors-EGF only, TGF-alpha only and EGF, TGF-alpha together- were added to the media and numbers of cells were analysed by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide(MTT) assay and compared with the control at 96, 144 hours. Each of EGF and TGF-alpha showed statistically significant stimulatory effects on the growth of cells respectively. Dose-dependent relationship of the stimulatory effects were not clearly demonstrated. The effects of EGF were higher than those of TGF-alpha and combinative administration showed higher effects than those of single uses. In conclusion, EGF may play an important and major role in differentiation and growth of human oral squamous cancer cells. TGF-alpha, produced from cells activated by EGF, also can stimulate the cell growth and could be an alternative ligand for EGF receptor.]]>
Cell Line ; Culture Media, Serum-Free ; Epidermal Growth Factor ; Humans ; Mouth Neoplasms ; Receptor, Epidermal Growth Factor ; Transforming Growth Factor alpha