epidermal-growth-factor and Atrophy

BACKGROUND: Atrophic scarring in skin of color is a common, permanent, and distressing result of uncontrolled acne vulgaris. Ablative lasers and chemical peels are frequently used to improve the appearance of atrophic scars, primarily through the stimulation of collagen and elastin; however, these treatment modalities are associated with risks, such as dyspigmentation and hypertrophic scarring, especially in patients with darker skin.

OBJECTIVE: We evaluated the efficacy of topically applied synthetic epidermal growth factor (EGF) serum in reducing the appearance of atrophic acne scars in skin of color.

METHODS: A single-center clinical trial was performed on twelve healthy men and women (average age 32.5) with Fitzpatrick Type IV-V skin and evidence of facial grade II-IV atrophic acne scars. Subjects applied topical EGF serum to the full-face twice daily for 12 weeks. Scar improvement was investigated at each visit using an Investigator Global Assessment (IGA), a Goodman grade, clinical photography, and patient self-assessment.

RESULTS: Eleven subjects completed the trial. Compared to baseline, there was an improvement in mean IGA score from 3.36 (SEM = 0.15) to 2.18 (SEM = 0.33). Mean Goodman grade was reduced from 2.73 (SEM = 0.19) to 2.55 (SEM = 0.21). Of the eleven pairs of before and after photographs, nine were correctly chosen as the post-treatment image by a blind investigator. On self-assessment, 81% reported a "good" to "excellent" improvement in their scars compared to baseline (P = 0.004).

CONCLUSION: Topical EGF may improve the appearance of atrophic acne scars in skin of color. Additional, larger studies should be conducted to better characterize improvement.

J Drugs Dermatol. 2017;16(4):322-326.

Topics: Acne Vulgaris; Administration, Cutaneous; Adolescent; Adult; Atrophy; Cicatrix; Epidermal Growth Factor; Face; Female; Humans; Male; Middle Aged; Pilot Projects; Quality of Life; Self-Assessment; Skin; Skin Pigmentation; Treatment Outcome; Young Adult

Atrophic acne scars are a common and psychologically devastating sequela of acne vulgaris that are refractory to the vast majority of topical treatments.. We evaluated the efficacy of a topically applied synthetic epidermal growth factor (EGF) serum in reducing the appearance of atrophic acne scars.. A single-center clinical trial was performed on nine self-selected male and female patients with Goodman & Baron grade II-IV atrophic acne scars. Subjects followed a standardized treatment regimen, including twice-daily application of EGF serum to scarred areas over 12 weeks. Subject progress was evaluated at baseline and 4-week intervals by clinical photography, Investigator Global Assessment (IGA), Goodman grade and patient self-assessment. Final patient perceptions were shared by written self-assessment at the end of the study. Before and after photographs were also evaluated by a blind investigator.. Eight subjects completed the trial. Compared to baseline, there was an improvement in mean IGA score from 2.875 (SEM= .327) to 2.38 (SEM = .375). Mean Goodman grade was reduced from 3.00 (SEM = .309) to 2.75 (SEM = .25). Of the eight pairs of before and after photographs given to a blind investigator, five were correctly chosen as the post-treatment image. Two were assessed as "excellent" (76-100%) improvement and three were assessed as "good" (50-75%) improvement. A one-tailed paired student t-test (α = .05) using blind investigator ratings of scar severity for each before and after photograph yielded a P-value of .0019, confirming the difference as statistically significant. On final self-assessment, all but one patient reported "good" to "excellent" improvement in their scars compared to baseline. 75% of patients who received alternative treatments in prior years reported EGF serum to be more efficacious.. These results suggest that topical EGF may improve the appearance of atrophic acne scars, though further study and more objective evaluation measures are required for definitive conclusions to be drawn.

Topics: Acne Vulgaris; Administration, Topical; Adult; Atrophy; Cicatrix; Epidermal Growth Factor; Facial Dermatoses; Female; Humans; Male; Middle Aged; Photography; Pilot Projects; Severity of Illness Index; Single-Blind Method; Treatment Outcome; Young Adult

Biomarkers of tubular function such as epidermal growth factor (EGF) may improve prognostication of participants at highest risk for chronic kidney disease (CKD) after hospitalization. To examine this, we measured urinary EGF (uEGF) from samples collected in the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study, a multi-center, prospective, observational cohort of hospitalized participants with and without AKI. Cox proportional hazards regression was used to investigate the association of uEGF/Cr at hospitalization, three months post-discharge, and the change between these time points with major adverse kidney events (MAKE): CKD incidence, progression, or development of kidney failure. Clinical findings were paired with mechanistic studies comparing relative Egf expression in mouse models of kidney atrophy or repair after ischemia-reperfusion injury. MAKE was observed in 20% of 1,509 participants over 4.3 years of follow-up. Each 2-fold higher level of uEGF/Cr at three months was associated with decreased risk of MAKE (adjusted hazards ratio 0.46, 95% confidence interval: 0.39-0.55). Participants with the highest increase in uEGF/Cr from hospitalization to three-month follow-up had a lower risk of MAKE (adjusted hazards ratio 0.52; 95% confidence interval: 0.36-0.74) compared to those with the least change in uEGF/Cr. A model using uEGF/Cr at three months combined with clinical variables yielded moderate discrimination for MAKE (area under the curve 0.73; 95% confidence interval: 0.69-0.77) and strong discrimination for kidney failure at four years (area under the curve 0.96; 95% confidence interval: 0.92-1.00). Accelerated restoration of Egf expression in mice was seen in the model of adaptive repair after injury, compared to a model of progressive atrophy. Thus, urinary EGF/Cr may be a biomarker of distal tubular health, with higher concentrations and increased uEGF/Cr post-discharge independently associated with reduced risk of MAKE in hospitalized patients.

Topics: Acute Kidney Injury; Aftercare; Animals; Atrophy; Biomarkers; Epidermal Growth Factor; Glomerular Filtration Rate; Humans; Kidney; Mice; Patient Discharge; Prospective Studies; Renal Insufficiency, Chronic

Investigating the therapeutic effect of genistein (Gen) on postmenopausal senile vaginitis (SV) and its mechanism of action. Adult SPF female Wistar rats were selected to establish a bilateral ovariectomized animal model (OVX), which simulated senile vaginitis dominated by estrogen deficiency in ovarian dysfunction. After 14 days of continuous treatment, the morphology of vaginal epithelial tissue was observed and various types of epithelial cells were counted, and the body mass and uterine and vaginal index of rats were measured. the levels of vaginal tissue secretion, microorganism, hormone and glycogen in each group were measured and the reproductive health was evaluated clinically. The protein expression and mRNA expression of epidermal growth factor (EGF) and E-cadherin (E-cadherin) in vaginal tissues were detected by immunohistochemistry and RT-PCR, respectively. Result showed that Genistein lowered vaginal pH, increased vaginal index and vaginal health score, thickened epithelial layers and improved vaginal tissue atrophy after administration. Genistein also increased the contents of glycogen and Lactobacillus in vagina, and promoted the expression of EGF, E-cadherin protein and mRNA. To sum up, there is no significant change in serum E2 and FSH levels, indicating that genistein has no effect on hormone levels in rats. genistein promoted the proliferation of vaginal epithelial cells, thickened epithelial layers and the vaginal wall, which improved the resistance of vaginal epithelium, the recovery of self-cleaning ability and healed the vaginal wound and erosive surface to improve atrophy.

Topics: Animals; Atrophy; Cadherins; Epidermal Growth Factor; Female; Genistein; Glycogen; Humans; Ovariectomy; Postmenopause; Rats; Rats, Wistar; RNA, Messenger; Vaginitis

The degree of tubular atrophy and interstitial fibrosis (IFTA) is an important prognostic factor in glomerulonephritis. Imbalance between pro-inflammatory cytokines such as monocyte chemoattractant protein- 1 (MCP-1) and protective cytokines such as epidermal growth factor (EGF) likely determine IFTA severity. In separate studies, elevated MCP-1 and decreased EGF have been shown to be associated with IFTA severity. In this study, we aim to evaluate the predictive value of urinary EGF/MCP-1 ratio compared to each biomarker individually for moderate to severe IFTA in primary glomerulonephritis (GN).. Urine samples were collected at biopsy from primary GN (IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy). MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assay.. EGF, MCP-1 and EGF/MCP-1 ratio from primary GN, all correlated with IFTA (n=58). By univariate analysis, glomerular filtration rate, EGF, and EGF/MCP-1 ratio were associated with IFTA. By multivariate analysis, only EGF/MCP-1 ratio was independently associated with IFTA. EGF/MCP-1 ratio had a sensitivity of 88% and specificity of 74 % for IFTA. EGF/MCP-1 had good discrimination for IFTA (AUC=0.85), but the improvement over EGF alone was not significant.. EGF/MCP-1 ratio is independently associated IFTA severity in primary glomerulonephritis, but the ability of EGF/MCP-1 ratio to discriminate moderate to severe IFTA may not be much better than EGF alone.

Topics: Adult; Atrophy; Biomarkers; Chemokine CCL2; Epidermal Growth Factor; Female; Fibrosis; Glomerulonephritis; Humans; Kidney Tubules; Male; Middle Aged; Sensitivity and Specificity; Severity of Illness Index

Recent studies suggest a close interaction between epidermal growth factor (EGF) and TLR signaling in the modulation of intestinal epithelial cell (IEC) proliferation; however, how these signaling pathways adjust IEC proliferation is poorly understood. We utilized a model of total parenteral nutrition (TPN), or enteral nutrient deprivation, to study this interaction as TPN results in mucosal atrophy due to decreased IEC proliferation and increased apoptosis. We identified the novel finding of decreased mucosal atrophy in TLR4 knockout (TLR4KO) mice receiving TPN. We hypothesized that EGF signaling is preserved in TLR4KO-TPN mice and prevents mucosal atrophy. C57Bl/6 and strain-matched TLR4KO mice were provided either enteral feeding or TPN. IEC proliferation and apoptosis were measured. Cytokine and growth factor abundances were detected in both groups. To examine interdependence of these pathways, ErbB1 pharmacologic blockade was used. The marked decline in IEC proliferation with TPN was nearly prevented in TLR4KO mice, and intestinal length was partially preserved. EGF was significantly increased, and TNF-α decreased in TLR4KO-TPN versus wild-type (WT)-TPN mice. Apoptotic positive crypt cells were 15-fold higher in WT-TPN versus TLR4KO-TPN mice. Bcl-2 was significantly increased in TLR4KO-TPN mice, while Bax decreased 10-fold. ErbB1 blockade prevented this otherwise protective effect in TLR4KO-sTPN mice. TLR4 blockade significantly prevented TPN-associated atrophy by preserving proliferation and preventing apoptosis. This is driven by a reduction in TNF-α abundance and increased EGF. Potential manipulation of this regulatory pathway may have significant clinical potential to prevent TPN-associated atrophy.

Topics: Animals; Apoptosis; Atrophy; Cell Proliferation; Epidermal Growth Factor; ErbB Receptors; Gefitinib; Interferon-gamma; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Parenteral Nutrition, Total; Quinazolines; RNA, Messenger; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Acinar cell regeneration from tubular structures has been reported to occur in duct-deligated salivary glands. However, the detailed process of acinar cell regeneration has not been clarified. We have developed a mouse duct ligation model to clarify the mechanisms underlying acinar cell regeneration, and we analyzed the epidermal growth factor receptor (EGFR) and epidermal growth factor (EGF) ligands using the model. We studied these ligands expressions in the course of acinar cell regeneration using immunohistochemistry and RT-PCR methods. In the duct-ligated portion of the submandibular gland (SMG) that underwent atrophy, newly formed acinar cells were observed arising from the tubular structures after the release of the duct obstruction. The constitutive expression of EGFR was observed by immunohistochemistry in both the duct-ligated and duct-deligated animals as well as in normal controls. The EGFR phosphorylation detected on the tubular structures after duct ligation paralleled the acinar cell regeneration. RT-PCR showed an increase in the epiregulin and heparin-binding EGF levels from day 0 to day 3 after the release of the duct obstruction. The EGF level was increased only after day 7. In vitro, cultured cells isolated from ligated SMGs proliferated and produced EGF ligands following the addition of epiregulin to the culture medium. These findings suggest that the tubular structures localized in an atrophic gland are the source of acinar cell regeneration of the salivary gland. The induction of EGF ligands, in particular epiregulin, may play an important role in acinar cell regeneration in this model.

Topics: Acinar Cells; Amphiregulin; Animals; Atrophy; Betacellulin; Cell Culture Techniques; Cell Proliferation; Cells, Cultured; Disease Models, Animal; EGF Family of Proteins; Epidermal Growth Factor; Epigen; Epiregulin; ErbB Receptors; Female; Heparin-binding EGF-like Growth Factor; Kallikreins; Ligation; Mice; Mice, Inbred C57BL; Peptidylprolyl Isomerase; Proliferating Cell Nuclear Antigen; Regeneration; Salivary Ducts; Submandibular Gland; Submandibular Gland Diseases; Transforming Growth Factor alpha

Early weaning induces villous atrophy in the small intestine of piglets. We evaluated an influence of early weaning at 16 days old in mice for the use of villous atrophy model observed in early-weaned piglets. Five pregnant BALB/c mice were obtained and half of pups were weaned at 16 days old (early-weaned), while the others were allowed to suckle. Their small intestine was collected at 17, 18 and 19 days old in each group. Villous was shorting at 17 and 18 days old, but obscured at 19 days old. The gene expressions of epidermal and platelet-derived growth factor were associated with the villous height. Early weaning induced villous atrophy in the mouse small intestine as well as the piglets.

Topics: Animals; Animals, Newborn; Atrophy; Disease Models, Animal; DNA; Epidermal Growth Factor; Female; Histocytochemistry; Intestinal Diseases; Intestinal Mucosa; Mice; Mice, Inbred BALB C; Platelet-Derived Growth Factor; Polymerase Chain Reaction; Swine; Swine Diseases

Skin atrophy is a common manifestation of aging and is frequently accompanied by ulceration and delayed wound healing. With an increasingly aging patient population, management of skin atrophy is becoming a major challenge in the clinic, particularly in light of the fact that there are no effective therapeutic options at present.. Atrophic skin displays a decreased hyaluronate (HA) content and expression of the major cell-surface hyaluronate receptor, CD44. In an effort to develop a therapeutic strategy for skin atrophy, we addressed the effect of topical administration of defined-size HA fragments (HAF) on skin trophicity. Treatment of primary keratinocyte cultures with intermediate-size HAF (HAFi; 50,000-400,000 Da) but not with small-size HAF (HAFs; <50,000 Da) or large-size HAF (HAFl; >400,000 Da) induced wild-type (wt) but not CD44-deficient (CD44-/-) keratinocyte proliferation. Topical application of HAFi caused marked epidermal hyperplasia in wt but not in CD44-/- mice, and significant skin thickening in patients with age- or corticosteroid-related skin atrophy. The effect of HAFi on keratinocyte proliferation was abrogated by antibodies against heparin-binding epidermal growth factor (HB-EGF) and its receptor, erbB1, which form a complex with a particular isoform of CD44 (CD44v3), and by tissue inhibitor of metalloproteinase-3 (TIMP-3).. Our observations provide a novel CD44-dependent mechanism for HA oligosaccharide-induced keratinocyte proliferation and suggest that topical HAFi application may provide an attractive therapeutic option in human skin atrophy.

Topics: Adult; Animals; Atrophy; Blotting, Western; Cell Proliferation; Cells, Cultured; Epidermal Growth Factor; ErbB Receptors; Female; Filaggrin Proteins; Humans; Hyaluronan Receptors; Hyaluronic Acid; Immunoprecipitation; Intermediate Filament Proteins; Keratinocytes; Male; Membrane Proteins; Mice; Mice, Knockout; Oligosaccharides; Platelet Endothelial Cell Adhesion Molecule-1; Skin; Skin Diseases; Vimentin

Elemental diets are associated with intestinal atrophy and reduced intestinal integrity. Growth factors such as keratinocyte growth factor (KGF) and epidermal growth factor (EGF) have considerable potential for the therapeutic reversal of such atrophy and may have greater actions if given in combination. We examined the effects of recombinant human KGF (rHuKGF), EGF and their combination on tissue mass, cell proliferation and crypt fission throughout the intestine of mice fed elemental diets. rHuKGF significantly increased the relative wet weight of the intestine, with EGF having a lesser effect. Cell proliferation of the stomach, small intestine and colon were significantly increased by rHuKGF, but EGF only increased proliferation in the small intestine. Crypt fission in the small intestine and colon was significantly decreased by rHuKGF. An interactive effect of rHuKGF and EGF on the weight of stomach and the proliferation of the fundus and antrum was observed. Moreover, an interactive effect of the agents was also seen on crypt fission in the colon. We concluded that (1) rHuKGF and EGF have significant trophic effects on the stomach, small intestine and colon, (2) these actions vary between different sites in the gastrointestinal tract, and (3) interactive effects occur.

Topics: Animals; Atrophy; Cell Division; Colon; Drug Synergism; Epidermal Growth Factor; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Food, Formulated; Intestine, Small; Male; Mice; Organ Size; Recombinant Proteins

Tubular atrophy is a major feature of most renal diseases and is closely associated with loss of renal function. The present study sought to investigate tubular epithelial cell apoptosis in experimental diabetic nephropathy and to explore the role of pro-apoptotic [transforming growth factor-beta (TGF-beta) and anti-apoptotic growth factors [epidermal growth factor (EGF)]. The effects of renoprotective therapy with blockade of the renin-angiotensin system (RAS) also were examined.. Six-week-old female Ren-2 rats were injected with streptozotocin (STZ) and maintained diabetic for 12 weeks. Further groups of diabetic rats were treated with the angiotensin-converting enzyme (ACE) inhibitor, perindopril, or the angiotensin II type 1 (AT1) receptor antagonist, valsartan, for 12 weeks.. Widespread apoptosis, identified immunohistochemically by single stranded DNA and TUNEL, was noted in the tubules of diabetic Ren-2 rats. These changes were associated with a 50% decrease in EGF expression and a twofold increase in TGF-beta1 mRNA. Treatment of diabetic Ren-2 rats with either valsartan (20 mg/kg/day) or perindopril (6 mg/kg/day) reduced apoptosis to control levels in association with supranormal levels of EGF mRNA (P < 0.01) and a reduction in TGF-beta1 gene expression (P < 0.05) to that of control rats.. Tubular apoptosis is a prominent feature of diabetic Ren-2 rats that is attenuated by blockade of the RAS in association with modulation of pro- and anti-apoptotic growth factor expression.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Animals, Genetically Modified; Antihypertensive Agents; Apoptosis; Atrophy; Autoradiography; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Epidermal Growth Factor; Female; Fibrosis; Gene Expression; In Situ Hybridization; In Situ Nick-End Labeling; Kidney Tubules; Nephritis, Interstitial; Perindopril; Rats; Renin-Angiotensin System; RNA, Messenger; Tetrazoles; Transforming Growth Factor beta; Valine; Valsartan

Epidermal growth factor is a low molecular weight polypeptide with 53 amino acids and is known to stimulate cell proliferation and differentiation in a wide range of tissues. The submandibulary gland in the mouse is a rich source of epidermal growth factor and decreased plasma epidermal growth factor levels have been observed after sialoadenectomy (removal of the submandibular glands). Furthermore. there is evidence that epidermal growth factor stimulates spermatogenesis and reverses antiandrogen induced cryptorchidism.. In the present study, the teratogenic effects of sialoadenectomy and antiandrogen (flutamide) administration on rat skin were investigated histologically.. Thirty Spraque-Dawley female rats were separated into three groups (n = 10), a control (sham-operated) and two experimental groups. The first experimental group of rats were subjected to sialoadenectomy in order to create maternal EGF deficiency one month before copulation. The second experimental group of rats were given flutamide (10 mg/100 g) for ten days during pregnancy. Three months after birth, a penile skin biopsy was taken from respective offspring in all groups.. A statistically significant reduced body weight and length were noted in the first group of litters (maternal EGF deficient) and in the flutamide administered group when compared to the control group. Atrophic epidermis and dermal adnexa were observed histologically as the teratogenic effects of sialoadenectomy and flutamide administration on rat skin development.. Epidermal growth factor is a key hormone for skin development and antiandrogen administration may insult this process by interfering with epidermal growth factor metabolism.

Topics: Androgen Antagonists; Animals; Atrophy; Epidermal Growth Factor; Epidermis; Female; Flutamide; Hair Follicle; Male; Maternal-Fetal Exchange; Nerve Growth Factor; Pregnancy; Rats; Rats, Sprague-Dawley; Sebaceous Glands; Skin; Submandibular Gland

1. Fasting causes atrophy of small bowel mucosa which rapidly resolves with luminal feeding. This effect of enteral nutrient may be mediated by stimulation of growth factor secretion. We therefore evaluated whether luminal administration of epidermal growth factor, a peptide hormone found in gastro-intestinal contents and trophic for small bowel mucosa, would prevent the mucosal atrophy associated with starvation. 2. Adult rats were: (i) fasted for 3 days, (ii) fasted and then refed for 1 day or (iii) fasted and then refed for 2 days. During the 2 days before study, animals in each group received infusions of epidermal growth factor (2.5 micrograms/day) or diluent alone into distal jejunum. 3. Epidermal growth factor treatment of fasted animals resulted in a tripling of mucosal ornithine decarboxylase activity (P < 0.001) and a doubling of mucosal DNA content (P < 0.001) in the jejunum, values similar to those of refed animals. Epidermal growth factor infusion in refed rats resulted in a further doubling of mucosal ornithine decarboxylase activity (P < 0.001), but no additional increase in DNA content. Effects of epidermal growth factor infusion were generally greater in jejunum than ileum. 4. In conclusion, luminal exposure to epidermal growth factor prevents starvation-induced mucosal atrophy in the small bowel, but does not enhance the mucosal growth associated with refeeding. Effects are greatest at the site of administration. Luminal epidermal growth factor is a potential mediator of the indirect effects of nutrient on mucosal growth in the small bowel. Enteral administration of epidermal growth factor holds promise for preventing atrophy and maintaining mucosal integrity in starved and post-operative patients.

Topics: Administration, Topical; Animals; Atrophy; Epidermal Growth Factor; Fasting; Ileum; Intestinal Mucosa; Intestine, Small; Jejunum; Male; Ornithine Decarboxylase; Rats; Rats, Sprague-Dawley

1. Intestinal atrophy contributes to the clinical difficulties of patients on parenteral nutrition. Systemic administration of epidermal growth factor reverses this effect, but there is concern over the clinical safety of intravenous administration of growth factors. We therefore investigated whether administration of luminal epidermal growth factor could reverse the atrophy induced in a rat model of parenteral nutrition when epidermal growth factor was given alone or in combination with soya bean trypsin inhibitor to reduce proteolytic digestion of the epidermal growth factor. 2. Infusion of soya bean trypsin inhibitor alone decreased intraluminal tryptic activity by about 90% but did not result in increased proliferation. Intragastric infusion of epidermal growth factor (72 micrograms/day per rat) caused a 26% increase in proliferation (determined by 2-h metaphase arrest) in the duodenum (P < 0.01) when compared with animals receiving 'control' intragastric infusion. However, intragastric epidermal growth factor had no effect on more distal regions of the bowel, probably reflecting rapid proteolysis of the epidermal growth factor by luminal proteases. In contrast, a trophic effect of luminal epidermal growth factor was seen in the duodenum (28% increase, P < 0.01) and jejunum (24% increase, P < 0.05) of animals which had received epidermal growth factor with soya bean trypsin inhibitor. This was probably due to the soya bean trypsin inhibitor decreasing the rate of degradation of epidermal growth factor by intestinal proteases, allowing biologically active epidermal growth factor to reach more distal portions of the bowel.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrophy; Cell Division; Digestion; Epidermal Growth Factor; Intestine, Small; Male; Parenteral Nutrition, Total; Rats; Rats, Wistar; Trypsin Inhibitors

In order to more clearly define the status of epidermal growth factor receptor (EGFR) in prostate cancer, expression of EGFR transcript and protein was analyzed in paired samples of benign and malignant tissues from 30 radical prostatectomy specimens. Prostate tumors and high grade prostatic intraepithelial neoplasias (PINs) expressed significantly less EGFR protein than benign tissues or low grade PINs (P < 0.001). Expression of EGFR mRNA was analyzed in a subset of the same samples, and was higher in more prostate tumors than benign specimens (P < 0.05). However, differences in mean mRNA expression between malignant and benign tissues were not significant. EGFR mRNA was expressed at moderate or low levels in equivalent numbers of PIN lesions. These results suggest that, although EGFR mRNA expression is somewhat elevated in prostate tumors, EGFR protein expression may be down-regulated in the same malignant tissues. Furthermore, our data demonstrate phenotypic similarity between prostate tumors and high grade PIN at the level of EGFR protein expression.

Topics: Aged; Atrophy; Carcinoma in Situ; Epidermal Growth Factor; ErbB Receptors; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization; Male; Middle Aged; Precancerous Conditions; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; RNA, Messenger; Transforming Growth Factor alpha

Duct-ligated submandibular and sublingual glands of rats were evaluated immunohistochemically for changes in keratin (MoAb 1164), actin, S-100 protein and rat-EGF (rEGF). Normal salivary glands were reactive for keratin, S-100 protein and rEGF in the granular convoluted tubule (GCT) and duct cells, and for actin in the myoepithelium. Submandibular glands showed a marked reduction of S-100 protein and rEGF staining following duct ligation, and no increased staining of proliferating epithelial cells of the late stage in duct ligated glands. Sublingual glands revealed no marked changes for actin staining in myoepithelial cells, irrespective of atrophic changes occurring in acinar and duct cells after duct ligation. Immunohistochemical patterns differed for each type of gland; changes associated with the obstructive lesion were more prominent in the submandibular gland.

Topics: Actins; Animals; Atrophy; Cytoplasmic Granules; Epidermal Growth Factor; Epithelium; Keratins; Ligation; Male; Rats; Rats, Wistar; S100 Proteins; Salivary Gland Diseases; Sublingual Gland; Submandibular Gland; Submandibular Gland Diseases; Time Factors

The role of epidermal growth factor in the proliferation of normal and premalignant colonocytes in vivo is not fully understood. In particular, the relative importance of its possible systemic and intraluminal routes of action has not been fully clarified. Rats with surgically defunctioned distal colorectums were used, and mini osmotic pumps were implanted to study the effects of intraluminal and IV administration of epidermal growth factor on colonocyte proliferation. Within 2 weeks of bypass, colonocyte proliferation in defunctioned colorectum has decreased to about one third the rate in normal colorectum or in colorectum proximal to the defunctioning colostomy. Intraluminal epidermal growth factor, infused from the time of operation did not reverse this hypoplasia, whereas IV epidermal growth factor maintained colonocyte proliferation at approximately the normal rate in bypassed colorectum. This model is suitable for testing other putative colonic mitogens for possible intraluminal and systemic effects.

Topics: Animals; Atrophy; Cell Cycle; Cell Division; Colon; Colostomy; Epidermal Growth Factor; Injections; Injections, Intravenous; Male; Rats; Rats, Inbred Strains; Rectum

This study was undertaken to evaluate the effect of epidermal growth factor (EGF) on the morphological changes and polyamine metabolism in the atrophic small intestinal mucosa of rats caused by feeding elemental diet (ED; Elental, Ajinomoto, Tokyo) for several weeks. Four-week-old Wistar male rats were given ad libitum ED (1 kcal/ml) for 4 weeks. The body weight increased to the same extent as the control group fed a pellet diet. However, the small intestine became atrophic: the mucosal wet weight of the jejunum decreased to 70%, while that of the ileum decreased to 60%. EGF (10 micrograms/kg) was subcutaneously injected into these rats every 8 hours. Ornithine decarboxylase (ODC) activities of the jejunal and ileal mucosa rose within 12 hours of the initial EGF administration. Mucosal DNA specific activities tended to increase. Next, EGF (30 micrograms/kg/day) was intraperitoneally administered with a Mini-osmotic pump for one week. The wet weight, protein and DNA contents of the ileal mucosa increased significantly compared with those of the saline administered controls, while the crypt cell production rate (CCPR) also increased. Histologically, increases in both villus height and crypt depth were confirmed. These findings indicate that EGF causes mucosal proliferation through polyamine metabolism even in the atrophic small intestine of mature rats after ED administration for 4 weeks.

Topics: Animals; Atrophy; Cell Division; DNA; Epidermal Growth Factor; Food, Formulated; Intestinal Mucosa; Intestine, Small; Male; Ornithine Decarboxylase; Polyamines; Rats; Rats, Inbred Strains; Time Factors

Topics: Atrophy; Diarrhea; Epidermal Growth Factor; Female; Humans; Infant; Injections, Intravenous; Intestinal Mucosa; Microvilli; Peptide Fragments; Recombinant Proteins; Syndrome

Topics: Adrenal Glands; Adrenalectomy; Androstenedione; Animals; Atrophy; Castration; Cortisone; Epidermal Growth Factor; Fluorescent Antibody Technique; Male; Mice; Mice, Inbred Strains; Submandibular Gland; Testis; Testosterone