Serum Epidermal Growth Factor Levels Research Articles

Pathway Targeted Immunotherapy: Rationale and Evidence of Durable Clinical Responses with a Novel, EGF-directed Agent for Advanced NSCLC

Abnormalities in the epidermal growth factor (EGF) and EGFR pathway promote progression of NSCLC. Immunization with EGF vaccine induces specific, neutralizing anti-EGF antibodies that prevent binding of the ligand to its receptor. This concept of pathway targeted immunotherapy (PTI) was validated in vitro by dose-related suppression of EGFR, Akt, and Erk1/2 phosphorylation in cell lines with different mutations. A randomized phase II trial showed improved overall survival (OS) in subgroups with advanced NSCLC showing a clear immunologic response. By per-protocol analysis of the ensuing phase IIb trial, patients receiving EGF PTI survived 3 months longer than controls (12.43 versus 9.43 months; hazard ratio = 0.77 [95% confidence interval, 0.61–0.98]). These data were confirmed in a larger trial showing an OS benefit over control of >3 months. The variable most strongly correlated with efficacy was circulating EGF at enrolment. Patients with serum EGF levels >250 pg/mL benefited most from treatment with EGF PTI. Of 188 patients tested, 94 were above this biomarker threshold. The OS benefit from active versus control treatment was 6.7 months. More than 15% of patients had responses for >5 years. Long-term survivors are seen in all EGF PTI trials. Treatment is well-tolerated, induces high anti-EGF antibody titers, reduces levels of circulating serum EGF, achieves durable responses, and significantly prolongs OS. A threshold of 250 pg/mL has been set to enrich the study population in the ongoing pivotal trial. This biomarker-guided study in an enriched population of patients with both squamous and nonsquamous stage IV NSCLC aims to replicate the favorable efficacy/tolerability balance of earlier studies.

Epidermal growth factor and prostaglandin E2 levels in Helicobacter pylori-positive gastric intraepithelial neoplasia

ObjectiveTo investigate levels of epidermal growth factor (EGF) and prostaglandin E2 (PGE2) in Han Chinese patients with Helicobacter pylori-positive gastric low-grade intraepithelial neoplasia (LGIN).MethodsIn this prospective, observational study, gastric specimens from patients with LGIN were collected by gastroscopy with consecutive biopsy. EGF and PGE2 concentrations in serum and gastric juice from patients with LGIN were measured by enzyme-linked immunosorbent assay. Presence of H. pylori infection was assessed in patients with LGIN and healthy controls.ResultsOut of 5 638 patients and 548 controls, H. pylori infection in patients with chronic gastritis was associated with disease type (endoscopic classification) and disease severity. Patients with H. pylori-positive LGIN had significantly higher concentrations of serum EGF and lower concentrations of serum PGE2 versus patients with H. pylori-negative LGIN. Serum EGF and PGE2 levels in patients with LGIN were not significantly associated with disease type, but were significantly associated with disease severity.ConclusionsH. pylori infection was associated with chronic gastritis type (endoscopic classification) and disease severity. Abnormal EGF and PGE2 levels may be associated with H. pylori-positive LGIN in Han Chinese patients in central China.

Relationship of Epidermal Growth Factor to Cyclosporine-Assocated Magnesium Wasting and Clinical Outcomes Post-Allogeneic Hematopoietic Cell Transplantation

Background: Hypomagnesemia is a frequent complication of allogeneic hematopoietic cell transplantation (HCT) and is related to cyclosporine-induced renal magnesium (Mg) loss. The importance of epidermal growth factor (EGF) in renal Mg reabsorption was suggested after identification of EGF mutation in isolated autosomal recessive hypomagnesemia (IRH). Mg wasting is also associated with EGFR tyrosine kinase inhibitors used in oncologic treatment. Recently, a link between EGF, Mg, and cyclosporine (CSA) in renal transplant recipients has been proposed through downregulation of EGF leading to inhibition of the Mg channel TRMP6 in the distal convoluted tubule, but similar associations have not been investigated post-allogeneic HCT. We hypothesized that lower serum EGF would be associated with higher CSA levels, acute graft versus host disease (GVHD) status, and more severe Mg wasting after allogeneic HCT. Patients and Methods: 107 adult allogeneic HCT recipients from the University of Minnesota enrolled on an immune monitoring study had EGF levels measured by magnetic bead array at day +100 post-allogeneic HCT. Clinical variables collected for analysis included patient age, sex, underlying diagnosis, donor type, HCT conditioning regimen, maximum acute GVHD overall grade and organ involvement prior to day +100, use of oral and intravenous supplemental Mg including cumulative requirements over 2 weeks, and concurrent immunosuppressive drug therapy including cyclosporine (N=66), tacrolimus (N=13), mycophenolate mofetil (N=5), sirolimus (N=22), and prednisone (N=40). Lab variables analyzed included serum creatinine and estimated glomerular filtration rate (GFR), immune suppressive drug levels, Mg levels, and lymphocyte subsets including absolute counts and percentages of NK cells, B cells, CD4+ T cells, CD8+ T cells, and regulatory T cells. Results: 54 patients had acute GVHD (grade I-II n= 34, grade III-IV n =20) and 53 patients did not have acute GVHD prior to the day +100 serum sample collection. The median serum EGF in this cohort was 101 pg/mL (not detectable in 5 samples). Levels of EGF at day +100 showed no relationship with age, underlying diagnosis, donor type, or conditioning intensity. EGF was significantly lower in patients who had acute GVHD grade III-IV prior to day +100 (Figure 1) and nearly 3-fold lower in those with upper GI GVHD involvement versus no upper GI GVHD involvement (median 43 pg/mL versus 119 pg/ml, p=0.007). Serum EGF negatively correlated with CSA level (Spearman's rho = -0.34, p=0.007), but not with tacrolimus levels, sirolimus levels, prednisone dose, or serum creatinine. Mg requirements, measured as either daily dose or cumulative dose over 2 weeks prior to the EGF sampling, were not associated with serum EGF overall, but those with EGF > 100 pg/mL showed higher magnesium requirements (average daily dose (1060 ± 142 mg/day versus 600 ± 85 mg mg/day, p=0.02) and average cumulative dose over 2 weeks (14.6 ± 2 grams versus 9 ± 1.3 grams, p=0.04) prior to the blood draw. Patients with or without acute GVHD required similar Mg supplementation. EGF levels showed a modest correlation with overall lymphocyte percentage in the peripheral blood (Spearman's rho = 0.24, p=0.01), but not with specific lymphocyte subsets at day +100. Serum EGF levels > 100 pg/mL at day +100 were associated with improved 2-year survival (RR 0.46, 95% CI 0.22–0.94, p=0.03, Figure 2). Conclusions: Patients with prior grade III-IV acute GVHD, and in particular upper GI GVHD, had lower EGF levels at day +100. This may be due in part to decreased EGF production from Brunner's glands in the duodenum versus excess EGF losses. The inverse relationship between CSA and EGF may be direct or may represent patients with more severe acute GVHD being maintained with higher drug levels. Serum EGF was negatively correlated with CSA levels but not Mg requirements or serum creatinine/estimated GFR. While studies in renal transplantation identified a connection between urinary EGF, Mg wasting, and diminished renal function, circulating levels of EGF in allogeneic HCT did not show a similar correlation. Differences in EGF post-allogeneic HCT are predominantly due to grade III-IV GVHD status, although a potential contribution from CSA effect on the kidney cannot be ruled out. The role of circulating EGF in the long-term outcomes of allogeneic HCT should be further studied. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Effect of psoriasis activity on epidermal growth factor (EGF) and the concentration of soluble EGF receptor in serum and plaque scales.

Epidermal growth factor receptors (EGFRs) are overexpressed in psoriatic keratinocytes, and regulate cell growth, proliferation and differentiation through binding to epidermal growth factor (EGF). The role of EGF and EGFRs in the pathogenesis of psoriasis and the contribution of their measurement to psoriasis management are still unknown. To evaluate serum concentrations of EGF, soluble (s)EGFRs and EGF content in psoriatic scales of patients with severe psoriasis, and to analyse their association with the clinical activity of the disease. Serum samples and plaque scales were collected from 51 patients with plaque-type psoriasis. Concentrations of EGF and sEGFR in serum and of EGF in scales were measured using enzyme immunoassay. Data were analysed with respect to baseline Psoriasis Area and Severity Index (PASI). Mean serum EGF concentration in patients was higher than in controls (701±72 vs. 586±63pg/mL), but the difference was not significant. Mean serum concentration of sEGFR was significantly lower than controls (40.8±1.4 vs. 86.4±11.3ng/mL, P<0.001). Serum levels of EGF showed a significant positive correlation and EGFR showed a significant negative correlation with PASI (P<0.05). No correlation was seen between PASI and EGF content in scales or between EGF and sEGFR levels. Serum EGF concentrations reached the highest mean level (914±138pg/mL) in patients with PASI>20, and this was significantly higher than the mean of 414±82pg/mL in the group with PASI<10. Mean sEGFR serum concentrations remained significantly lower than those of controls, irrespective of disease severity. Compared with controls, patients with psoriasis had increased EGF and decreased sEGFR levels in serum. EGF and sEGFR levels correlated with disease severity.

Correlations between Carcinoembryonic Antigen, Epidermal Growth Factor and Leptin in Patients with Non-Small-Cell Lung Cancer

Objectives:Carcinoembryonic antigen (CEA), epidermal growth factor (EGF) and leptin have been reported to be intimately intertwined in lung carcinogenesis.However, few studies have simultaneously examined these proteins in lung cancer and whether a correlation exist among them remains unclear. Here, we compared the levels of CEA, EGF and leptin in non-small-cell lung cancer (NSCLC) patients and controls and evaluated the possible associations among them. Methods:97 patients ranged from 30 to 83 years of age were studied. Serum CEA, EGF and leptin levels were determined following a standard protocol. The relationships between these proteins and clinicopathological factors were evaluated by Wilcoxon rank sum or Kruskal-Wallis H test. Spearman rank-correlation were used to determine the correlations among CEA, EGF and leptin. Co-expression of these proteins in NSCLC tissues was examined by immunofluorescence. Results: Serum CEA and leptin levels in NSCLC patients were significantly higher compared to controls (both P = 0.000), but no statistically significant difference was found for EGF. CEA and EGF were not associated with the tumor-related factors, but leptin was strongly correlated with sex (P = 0.005). Significant correlations among these proteins were found when the patients were categorized into subgroups. Co-expresstion of these proteins was significantly enhanced with lung carcinogenesis. Conclusions:CEA, EGF and leptin may interplay and play vital roles in the pathogenesis of NSCLC. Besides CEA, the leptin levels were also significantly higher in NSCLC patients than in controls. Determination of preoperative leptin levels may prove useful for screening and predicting NSCLC.

Treatment for salivary gland hypofunction at both initial and advanced stages of Sjögren-like disease: a comparative study of bone marrow therapy versus spleen cell therapy with a 1-year monitoring period

Background aimsNon-obese diabetic mice (NOD) exhibit autoimmune Sjögren-like disease (SS-like). We reported previously that a combined-therapy consisting of immuno- and cell-based therapy rescued NOD from SS-like. However, therapies tested to date on NOD mice were aimed at the initial phase of SS-like. It is unknown whether therapies are effective in restoring salivary function when given at an advanced phase of SS-like. MethodsThe efficacy of two therapies (bone marrow versus spleen cells) was compared head-to-head for halting/reversing salivary hypofunction at two critical time points of SS-like (7-week-old NOD with normal saliva output and 20-week-old NOD with minimal saliva). NOD mice were divided into four groups: (i) control, (ii) complete Freund's adjuvant (CFA), (iii) bone marrow transplants with CFA or (iv) spleen cell transplants with CFA. Mice were monitored 8–12 months after therapy. ResultsBoth cell therapies were effective during the initial phase of SS-like; salivary flow rates were maintained between 80–100% of pre-symptomatic levels. Spleen cell therapy was better than bone marrow when administered in the initial phase of SS-like. When cell therapies were given at an advanced phase of SS-like (20 weeks and older), salivary flow rates improved but were at best 50% of pre-symptomatic levels. Both cell therapies decreased tumor necrosis factor-α, transforming growth factor-β1 levels and T and B cells while increasing epidermal growth factor and regulatory T cells. Elevated serum epidermal growth factor levels were measured in spleen-treated mice. ConclusionsA therapeutic effect in advanced phase disease, albeit in mice, holds promise for humans in which Sjögren syndrome is generally not diagnosed until a late stage.

Serum epidermal growth factor is associated with prognosis and hormone receptor status in patients with HER2-positive metastatic breast cancer treated with first-line trastuzumab plus taxane chemotherapy

Epidermal growth factor (EGF) is a ligand for the epidermal growth factor receptor (EGFR). Human epidermal growth factor receptor 2 (HER2) shares common signal pathways and forms a heterodimer with EGFR. In this study, we investigated the clinical and pathologic implications of serum EGF levels in patients with HER2-positive metastatic breast cancer (MBC). We analyzed serum EGF levels from baseline serum samples of consecutive patients with HER2-positive MBC who received first-line trastuzumab plus taxane chemotherapy and correlated them with treatment outcomes and pathologic features. A total of 50 women were analyzed. The median age was 47 years (range 27-72 years). Patients with high serum EGF levels (≥10.0 pg/mL) had significantly longer overall survival (47.0 months (95 % confidence interval (CI) 28.3-65.7 months) vs. 23.3 months (95 % CI 13.5-33.1 months); p = 0.009) with a tendency toward longer progression-free survival (p = 0.123). Serum EGF levels were not associated with hematologic or cardiac adverse events. Progesterone receptor-positive patients had significantly higher serum EGF levels than progesterone receptor-negative patients (24.3 pg/mL (range 9.5-69.0 pg/mL) vs. 12.3 pg/mL (range 0.0-59.5 pg/mL); p = 0.006). Our data suggest that high serum EGF levels may be associated with good prognosis in patients with HER2-positive MBC receiving trastuzumab plus taxane chemotherapy. In addition, serum EGF levels were associated with progesterone receptor positivity.

Epidermal growth factor, its receptor and transforming growth factor-β1 in the diagnosis of HCV-induced hepatocellular carcinoma

In this article, we present a study on the levels of epidermal growth factor (EGF), its phosphorylated receptor (p-EGFR) and transforming growth factor-β1 (TGF-β1) in the sera of patients with hepatocellular carcinoma (HCC) and chronic hepatitis C (CHC) infection. The results reveal significant higher serum levels of EGF and TGF-β1 in patients with HCC compared to their level in patients with CHC infection and control subjects. The levels of p-EGFR in HCC and CHC patients show a highly significant difference between patients. Based on the best cutoff value of 914pg/ml, EGF shows 63.3% sensitivity and 87.5% specificity for HCC patients where the area under the curve is 0.81. The p-EGFR shows sensitivity of 63.3% and specificity of 100% where the area under the curve is 0.87 for HCC patients based on the best cutoff value of 39U/mg protein. The best cutoff value (370pg/ml) for serum TGF-β1 displays sensitivity of 86.7% and specificity of 100%, where the area under the curve is 0.97 for HCC patients.

Serum EGF and NGF levels of patients with brain injury and limb fracture

ObjectiveTo explore the expression and significance of human epidermal growth factor (EGF) and nerve growth factor (NGF) in patients with knee osteoarthritis. MethodsRT-PCR and enzyme-linked immunosorbent assay were used to measure the serum EGF and NGF expression levels of patients with limb fracture and brain trauma injurry after 1 d, 3 d, 7 d, 14 d and the relationship between them was analyzed. The level was compared among the simple fracture group, traumatic brain injury group and the normal control group, with 40 cases in each group. ResultsThe serum NGF levels were significantly different among three groups. Serum NGF, EGF mRNA and protein levels gradually decreased with the increasing injury time in the limb fracture combined with brain injury group, traumatic brain injury group, the simple fracture group and the health control group (P<0.05). ConclusionsThe serum of NGF, EGF levels significantly increased when limb fracture combined with brain injury, so EGF and NGF may be involved in the process of fracture healing.

Epidermal Growth Factor Facilitates Melanoma Lymph Node Metastasis by Influencing Tumor Lymphangiogenesis

Alterations in epidermal growth factor (EGF) expression are known to be of prognostic relevance in human melanoma, but EGF-mediated effects on melanoma have not been extensively studied. As lymph node metastasis usually represents the first major step in melanoma progression, we were trying to identify a potential role of primary tumor-derived EGF in the mediation of melanoma lymph node metastases. Stable EGF knockdown (EGFkd) in EGF-high (M24met) and EGF-low (A375) expressing melanoma cells was generated. Only in EGF-high melanoma cells, EGFkd led to a significant reduction of lymph node metastasis and primary tumor lymphangiogenesis in vivo, as well as impairment of tumor cell migration in vitro. Moreover, EGF-induced sprouting of lymphatic but not of blood endothelial cells was abolished using supernatants of M24met EGFkd cells. In addition, M24met EGFkd tumors showed reduced vascular endothelial growth factor-C (VEGF-C) expression levels. Similarly, in human primary melanomas, a direct correlation between EGF/VEGF-C and EGF/Prox-1 expression levels was found. Finally, melanoma patients with lymph node micrometastases undergoing sentinel node biopsy were found to have significantly elevated EGF serum levels as compared with sentinel lymph node-negative patients. Our data indicate that tumor-derived EGF is important in mediating melanoma lymph node metastasis.

Prognostic value of circulating cytokines for stage III colon cancer

BackgroundThis study was to determine preoperative serum levels of epidermal growth factor (EGF), interleukin-6 (IL-6), and C-reactive protein (CRP) in stage III colon cancer and correlate them with disease status and prognosis. The circulating EGF in correlation with primary site epidermal growth factor receptor (EGFR) was also evaluated. MethodsSeventy-seven patients with curatively resected stage III colon cancer were selected for analysis. Enzyme-linked immunosorbent assay was used to determine EGF and IL-6 serum levels, and serum CRP levels were measured via immunoturbidimetry. EGFR expression was observed with immunohistochemical studies. ResultsThe median levels of EGFR, IL-6, and CRP were 189.4 pg/mL, 9.09 pg/mL, and 1.4 mg/mL, respectively. The factors related to recurrence with statistical significance included positive node status (P = 0.041), lymphovascular invasion (P = 0.001), and preoperative IL-6 level ≥9 pg/mL (P = 0.020). CRP and EGF levels were not significantly associated with disease-free survival rates (P = 0.438 and P = 0.309, respectively). Multivariate analysis using Cox’s proportion model revealed that lymph node status was the single independent prognostic factor for predicting time until recurrence (odds ratio, 4.99; 95% confidence interval, 1.09–22.91; P = 0.038). ConclusionIL-6 expression in stage III colon cancer patients appears to be a prognostic marker of tumor behavior. No correlations between serum EGF concentrations and tumor EGFR positivity were found in this study.

Serum Levels of Epidermal Growth Factor, Transforming Growth Factor, and c-erbB2 in Ovarian Cancer

This study aimed to investigate serum levels of epidermal growth factor (EGF), transforming growth factor α (TGF-α), and c-erbB2 in patients with ovarian cancer. In this retrospective cohort study, the study and control groups were composed of 43 women with a prediagnosis of ovarian cancer and 43 healthy women, respectively. Blood samples from all women were obtained and studied by enzyme-linked immunosorbent assay kits for EGF, TGF-α, and c-erbB2. After surgery of the study group, ovarian cancer was confirmed and compared with control group. Stage, grade, and histological types were defined after histopathologic examination, and subgroups were constructed and compared. Serum EGF, TGF-α, and c-erbB2 levels were significantly increased in study group compared with those in the control group (P < 0.001). There were no differences in serum levels of EGF, TGF-α, and c-erbB2 among all stages, grades, and histological types of ovarian cancer. If 47.90 pg/mL was selected as the cutoff value, EGF has an 80% sensitivity and a 65% specificity for detecting ovarian cancer. The cutoff value of 41,095.00 pg/mL for TGF-α has a 90% sensitivity and a 72% specificity for detecting ovarian cancer. The c-erbB2 level of 4.63 pg/mL as the cutoff value has an 83% sensitivity and a 76% specificity for predicting ovarian cancer. Serum levels of EGF, TGF-α, and c-erbB2 may be used for diagnosing ovarian cancer.

1464P - The Difference in the Serum Levels of BDNF, IL-6, IL-8, IL-10 and EGF in Oncology Patients Divided According to the Presence of Symptoms of Depression

ABSTRACT Objective To assess the differences in the serum levels of Brain-derived neurotrophic factor (BDNF), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10) and epidermal growth factor (EGF) in oncology patients with symptoms of depression and in oncology patients without symptoms of depression. Methods We administered the following self – report questionnaires to the hospitalized oncology patients (n = 32): Zunǵs Self-Rating Depression Scale (ZSDS) and Symptom Check List Psychiatric Rating Scale (SCL 90). We also collected blood samples from these patients for the detection of the following factors: BDNF, IL-6, IL-8, IL-10 and EGF. The procedures had been fully explained to all patients and written informed consent had been obtained. The patients were divided into two groups according to the scores in ZSDS: a group with the presence of symptoms of depression (n = 20) and a group without the symptoms of depression (n = 12). The differences in the levels of BDNF, interleukins and EGF between the groups were statistically assessed by Wilcoxon rank-sum test. Results Oncology patients with the symptoms of depression showed significantly lower levels of BDNF (medians 1452.3 vs 3229.0 pg/ml, p = 0.014). There were no significant differences in the levels of IL-6, IL-8, IL-10 and EGF between the groups. Conclusion This result supports the hypothesis of diminished neuroplasticity in oncology patients with the symptoms of depression as measured by the serum levels of BDNF. This study was supported by research project MSM 0021620819. Disclosure All authors have declared no conflicts of interest.

Serum epidermal growth factor predicts cognitive functions in early, drug-naive Parkinson’s disease patients

Epidermal growth factor (EGF) has been proposed as a candidate biomarker for cognitive impairment in Parkinson's disease (PD). We aimed to assess the relationship between serum EGF and cognitive functions in early, drug-naive PD patients and evaluate the predictive value of EGF on cognitive functions in a 2-year follow-up study. Serum EGF was measured in 65 early, drug-naive PD patients, that underwent a comprehensive neuropsychological battery. Motor symptoms were assessed by means of the Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III). Neuropsychological evaluation was repeated after 2 years. Spearman's rank correlation was used to assess the relationship between serum EGF levels and neuropsychological variables. Linear regression analysis was used to evaluate the relationship between EGF and neuropsychological scores as well as other variables (age, gender, UPDRS-III, levodopa equivalent dose, and type of treatment at follow-up) potentially affecting cognitive performance. Variation over time in cognitive scores was analyzed using repeated-measures ANOVA. At baseline, EGF was the only significant variable associated with performance on semantic fluency (R (2) = 0.131; p = 0.005). EGF levels (p = 0.025), together with UPDRS-III (p = 0.009) and age (p = 0.011), were associated with performance on frontal assessment battery (R (2) = 0.260). At 2-year follow-up, EGF was the only significant variable to predict performance on semantic fluency (R (2) = 0.147; p = 0.025) and color naming task of Stroop color-word test (R (2) = 0.121; p = 0.044). Serum EGF levels are related to frontal and temporal cognitive functions in early, drug-naive PD patients and predict performance on frontal and posterior cognitive functions at 2-year follow-up. EGF is proposed as a potential serum biomarker for early cognitive impairment in PD.

Genetic testing for hepatocellular carcinoma: An ambitious goal still to achieve

Background & Aims: A single nucleotide polymorphism 61⁄G (rs4444903) in the epidermal growth factor (EGF) gene has been associated, in two case–control studies, with hepatocellular carcinoma (HCC). We tested associations between demographic, clinical, and genetic data and development of HCC, and developed a simple predictive model in a cohort of patients with chronic hepatitis C and advanced fibrosis. Methods: Black and white subjects from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial (n = 816) were followed up prospectively for development of a definite or presumed case of HCC for a median time period of 6.1 years. We used the Cox proportional hazards regression model to determine the hazard ratio for risk of HCC and to develop prediction models. Results: Subjects with EGF genotype G/G had a higher adjusted risk for HCC than those with genotype A/A (hazard ratio, 2.10; 95% confidence interval, 1.05–4.23; P = .03). After adjusting for EGF genotype, blacks had no increased risk of HCC risk compared with whites. Higher serum levels of EGF were observed among subjects with at least one G allele (P = .08); the subset of subjects with EGF G/G genotype and above-median serum levels of EGF had the highest risk of HCC. We developed a simple prediction model that included the EGF genotype to identify patients at low, intermediate, and high risk for HCC; 6-year cumulative HCC incidences were 2.3%, 10.4%, and 26%, respectively. Conclusions: We associated the EGF genotype G/G with increased risk for HCC; differences in its frequency among black and white subjects might account for differences in HCC incidence between these Journal of Hepatology 20

Risperidone-Related Improvement of Irritability in Children with Autism Is not Associated with Changes in Serum of Epidermal Growth Factor and Interleukin-13

Risperidone has been shown to improve serious behavioral problems in children with autism. Here we asked whether risperidone-associated improvement was related to changes in concentrations of inflammatory molecules in the serum of these subjects. Seven molecules were identified as worthy of further assessment by performing a pilot analysis of 31 inflammatory markers in 21 medication-free subjects with autism versus 15 healthy controls: epidermal growth factor (EGF), interferon-γ (IFN-γ), interleukin (IL)-13, IL-17, monocyte chemoattractant protein-1 (MCP-1), IL-1 and IL-1-receptor antagonist. Serum concentrations of these markers were then established in a different set of subjects that participated in a double-blind, clinical trial and an expanded group of healthy subjects. In the first analysis, samples obtained from subjects with autism at baseline visits were compared to visits after 8-week treatment with placebo (n=37) or risperidone (n=40). The cytokine concentrations remained stable over the 8-week period for both risperidone and placebo groups. In the second analysis, we explored further the differences between medication-free subjects with autism (n=77) and healthy controls (recruited independently; n=19). Serum levels of EGF were elevated in subjects with autism (median=103 pg/mL, n=75) in comparison to healthy controls (75 pg/mL, n=19; p<0.05), and levels of IL-13 were decreased in autism (median=0.8 pg/mL, n=77) in comparison to controls (9.8 pg/mL, n=19; p=0.0003). These changes did not correlate with standardized measures used for a diagnosis of autism. In summary, risperidone-induced clinical improvement in subjects with autism was not associated with changes in the serum inflammatory markers measured. Whether altered levels of EGF and IL-13 play a role in the pathogenesis or phenotype of autism requires further investigation.

Healthy ageing through regulated proteostasis

During metazoan life, protein homeostasis (proteostasis) declines with age due to impaired proteasome activity. The signalling pathways activated by growth factors that regulate proteostasis and their importance to ageing are just emerging. In this issue, Liu et al report a crucial role of epidermal growth factor (EGF) in regulating Caenorhabditis elegans lifespan through the RAF/MAPK pathway. EGF signalling activates the ubiquitin–proteosome system (UPS) and represses the chaperone machinery by modulating the expression of several ageing‐related genes (gerontogenes). This strategic switch in controlling global protein turnover provides novel insights into the molecular mechanisms driving ageing in multi‐cellular organisms.

Autonomic nervous system dysfunction and serum levels of neurotoxic and neurotrophic cytokines in patients with cobalamin deficiency.

The imbalance between neurotoxic cytokine tumor necrosis factor-α (TNF-α) and neurotrophic cytokines epidermal growth factor (EGF) and interleukin-6 (IL-6) plays a role in the pathogenesis of cobalamin (Cbl) deficiency-induced neuropathy. The aim of this study was to evaluate autonomic nervous system dysfunction and to look for any relationship between autonomic nervous system disturbances and serum cytokine levels (TNF-α, EGF, IL-6) in patients with Cbl deficiency. Serum levels of TNF-α, EGF and IL-6 were studied in patients with Cbl deficiency (n=41) and a healthy control group (n=17) and after 3 months in patients who underwent Cbl replacement therapy (n=22). All patients with Cbl deficiency underwent electrophysiological studies (EPS) for the diagnosis of neuropathy. Statistical analysis was performed using SPSS for Windows 11.5 software. With EPS, 29 of 41 Cbl-deficient patients (70.73%) demonstrated neurological dysfunction [3 (7.32%), 19 (46.34%) and 7 (17.07%) patients with sensorimotor peripheral neuropathy, parasympathetic, and sympathetic autonomic dysfunction, respectively]. Although there was no significant difference in serum levels of EGF and IL-6 between patients with versus without autonomic dysfunction, levels were significantly lower in Cbl- deficient patients than healthy controls. Presence of autonomic dysfunction seems to be a frequent neurological finding in patients with Cbl deficiency. However, we could not find any relationship between serum cytokine levels and autonomic dysfunction by EPS.

Downregulation of serum epidermal growth factor in patients with inflammatory bowel disease. Is there a link with mucosal damage?

Background: Epidermal growth factor (EGF) is a multipotent peptide which contributes to epithelial development, inhibition of gastric acid secretion, acceleration of wound healing, and promotion of angiogenesis. The aim of this study is to evaluate serum EGF concentrations in inflammatory bowel disease (IBD) patients, with regard to disease and patients’ characteristics.Methods: EGF determination was performed by a commercially available enzyme-linked immunosorbent assay. Fifty-two patients with ulcerative colitis (UC), 59 with Crohn's disease (CD), and 55 healthy controls (HC) were included in the study.Results: Mean ( ± SEM) serum EGF levels were 217.2 ( ± 30.40) pg/mL in UC patients, 324.6 ( ± 37.29) pg/mL in CD patients, and 453.1 ( ± 39.44) pg/mL in HC. Serum EGF levels were significantly lower in UC and CD patients compared to HC (P < 0.0001 and P = 0.0199, respectively). Lower serum EGF levels were observed in UC compared to CD patients (P = 0.0277). Extent of the disease was found to affect serum EGF levels in UC, demonstrating significant reduction in patients with left-sided colitis and pancolitis in comparison with those with proctitis (P = 0.0190 and P = 0.0024, respectively). EGF concentration was not influenced by other characteristics of patients and disease.Conclusions: Significantly, lower levels of serum EGF are observed in IBD patients compared to HC, while disease extent plays a key role in regulation of serum EGF in UC. Downregulation of serum EGF may be correlated with different patterns of bowel inflammation, epithelial development, and wound healing in IBD.

Increased Serum Levels of Epidermal Growth Factor in Children with Autism

The etiology of autism is unclear, however autism is considered as a multifactorial disorder that is influenced by neurological, environmental, immunological and genetic factors. Growth factors, including epidermal growth factor (EGF), play an important role in the cellular proliferation and the differentiation of the central and peripheral nervous system. In this study we hypothesized that EGF may play a role in the pathophysiology of autism and examined serum EGF levels in children with autism. We measured serum levels of EGF in the 27 autistic children and 28 age- matched normal controls. The serum levels of EGF in the subjects with autism were significantly higher than those of normal control subjects. However, there were no correlations between serum EGF levels and clinical variables in the subjects with autism. This is the first report demonstrating the increased serum levels of EGF in children with autism. This study suggests that increased levels of EGF might have an importance in the pathophysiology of autism.