• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3705-3709
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• 2013

Background: To investigate epidermal growth factor receptor (EGFR) gene mutations in patients with non-small cell lung cancer (NSCLC) and to analyze any relationship with clinicopathological features and prognosis. Materials and Methods: EGFR gene exons 18-21 in 48 specimens of paraffin-embedded tumor tissue from NSCLC patients were amplified by PCR, followed by direct sequencing and analysis of links to clinicopathological features and prognosis. Results: EGFR mutations were detected in 18 of 48 (42.6%) patients with NSCLC. There were 9 cases of mutations in exon 20, 7 in exon 19 and 2 in exon 21. Mutations were more frequently observed in women (5/7 pts, 71.4%) than in men (13/41 pts, 31.7%) (p=0.086) and in non-smokers (5/5 pts, 100%) than smokers (13/43 pts, 30.2%). There was negative correlation of EGFR mutations with smoking status (p=0.005). EGFR mutations were more frequently observed with adenocarcinoma histology (13/32 pts, 40.6%) than in other types (5/16 pts, 31.3%) (p=0.527). The patients with EGFR mutations had better survival than those with wild-type EGFR (p=0.08). There was no association of EGFR mutations with metastatic spread. Conclusions: EGFR mutations in NSCLC were here demonstrated more frequently in females, non-smokers and adenocarcinoma histology in the western region of Turkey. Patients with EGFR mutations have a better prognosis.

• CELLMED
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• v.3 no.2
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• pp.10.1-10.8
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• 2013

Cancer is one of the major dreaded diseases causing high mortality. Lung cancer is second in position of all cancer related deaths and mainly divided into two morphologic sub-types: small-cell lung cancer and non-small cell lung cancer (NSCLC). NSCLC is an aggressive neoplasm which hardly responds to any conventional chemotherapy. Epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinase that is mainly over-expressed in NSCLC. EGFR is mainly involved in the pathogenesis and progression of different carcinoma. In vivo and in vitro studies suggest that EGFR and EGF like peptides are often over-expressed in human NSCLC and these proteins are able to induce cell transformation. The conventional therapies mostly inhibit the EGFR activity and expression level in human NSCLC with the use of some EGFR-inhibitors like HKI-272, EKB569, CL-387785 etc. and some synthetic chemotherapeutic drugs like erlotinib, gefitinib, plumbagin, docetaxel, cisplatin etc., alone or in combination of two or more drugs. These therapies selectively act by competitive inhibition of the binding of adenosine triphosphate to the tyrosine kinase domain of the EGFR, resulting in inhibition of the EGFR signaling pathway. But these chemotherapeutic drugs have some cytotoxic activities to the normal cells and have some adverse side-effects. Recent studies on some traditional alternative therapies including some herbal and plant extracts, active ingredients like curcumin, different homeopathic drugs, etc. can target EGFR-signalling in NSCLC with less toxic side-effects are being currently developed.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.785-789
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• 2016

A key drug for treatment of EGFR mutation-positive non-small cell lung cancer is epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). While the dosage of many general anti-tumor drugs is adjusted according to the patient body surface area, one uniform dose of most TKIs is recommended regardless of body size. In many cases, dose reduction or drug cessation is necessary due to adverse effects. Disease control, however, is frequently still effective, even after dose reduction. In this study, we retrospectively reviewed the characteristics of 26 patients at Fukuoka University Hospital between January 2004 and January 2015 in whom the EGFR-TKI dose was reduced with respect to progression free survival and overall survival. There were 10 and 16 patients in the gefitinib group and the erlotinib group, respectively. The median progression-free survival in the gefitinib group and the erlotinib group was 22.4 months and 14.1 months, respectively, and the median overall survival was 30.5 months and 32.4 months, respectively. After stratification of patients by body surface area, the overall median progression-free survival was significantly more prolonged in the low body surface area (<1.45 m2) group (25.6 months) compared to the high body surface area (>1.45 m2) group (9.7 months) (p=0.0131). These results indicate that low-dose EGFR-TKI may sufficiently control disease without side effects in lung cancer patients with a small body size.

• Journal of Korean Neurosurgical Society
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• v.63 no.2
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• pp.163-170
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• 2020

Objective : Milk fat globule-epidermal growth factor VIII (MFG-E8) may play a key role in inflammatory responses and has the potential to function as a neuroprotective agent for ameliorating brain injury in cerebral infarction. This study aimed to determine the role of MFG-E8 in brain injury in the subacute phase of cerebral ischemia in a rat model. Methods : Focal cerebral ischemia was induced in rats by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, rats were randomly assigned to two groups and treated with either recombinant human MFG-E8 or saline. Functional outcomes were assessed using the modified Neurological Severity Score (mNSS), and infarct volumes were evaluated using histology. Anti-inflammation, angiogenesis, and neurogenesis were assessed using immunohistochemistry with antibodies against ionized calcium-binding adapter molecule 1 (Iba-1), rat endothelial cell antigen-1 (RECA-1), and bromodeoxyuridine (BrdU)/doublecortin (DCX), respectively. Results : Our results showed that intravenous MFG-E8 treatment did not reduce the infarct volume; however, the mNSS test revealed that neurobehavioral deficits were significantly improved in the MFG-E8-treated group than in the vehicle group. Immunofluorescence staining revealed a significantly lower number of Iba-1-positive cells and higher number of RECA-1 in the periinfarcted brain region, and significantly higher numbers of BrdU- and DCX-positive cells in the subventricular zone in the MFG-E8-treated group than in the vehicle group. Conclusion : Our findings suggest that MFG-E8 improves neurological function by suppressing inflammation and enhancing angiogenesis and neuronal proliferation in the subacute phase of cerebral infarction.

• YAKHAK HOEJI
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• v.40 no.4
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• pp.456-461
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• 1996

The effects of human epidermal growth factor(EGF) which was produced by recombinant DNA technique was investigated on gastric secretion, gastric lesion and ulcer models in rats. The EGF showed significant inhibition of secretion of gastric juice and total acid output, at 0.4mg/kg, id and also inhibited Shay ulceration at 0.4mg/kg, id in rats. The lesion induced by absolute ethanol was significantly reduced by oral administration of EGF at 0.4mg/kg. Likewise, EGF caused significant inhibition of indomethacin induced gastric ulcer at oral doses of 0.2 and 0.4mg/kg. The EGF produced dose-dependent inhibition of gastric ulcer induced by acidified aspirin, but showed no significant inhibition at oral doses of 0.1, 0.2 and 0.4mg/kg. The chronic gastric ulcer induced by injection of 20% acetic acid solution was significantly reduced by oral doses of 0.1 and 0.4mg/kg of EGF. Duodenal ulcer induced by mepirizole was dose-dependently inhibited by oral doses of 0.1, 0.2 and 0.4mg/kg of EGF. These data suggest that EGF possesses pronounced inhibitory action in gastric ulcer and duodenal ulcer of rats.

• Radiation Oncology Journal
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• v.32 no.3
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• pp.156-162
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• 2014

Purpose: This study was designed to evaluate the efficacy and safety of topically applied recombinant human epidermal growth factor (rhEGF) for the prevention of radiation-induced dermatitis in cancer patients. Materials and Methods: From December 2010 to April 2012, a total of 1,172 cancer patients who received radiotherapy (RT) of more than 50 Gy were prospectively enrolled and treated with EGF-based cream. An acute skin reaction classified according to the Radiation Therapy Oncology Group 6-point rating scale was the primary end point and we also assessed the occurrence of edema, dry skin, or pruritus. Results: The percentage of radiation dermatitis with maximum grade 0 and grade 1 was 19% and 58% at the time of 50 Gy, and it became 29% and 47% after completion of planned RT. This increment was observed only in breast cancer patients (from 18%/62% to 32%/49%). Adverse events related to the EGF-based cream developed in 49 patients (4%) with mild erythema the most common. Skin toxicity grade >2 was observed in 5% of the patients. Edema, dry skin, and pruritus grade ${\geq}3$ developed in 9%, 9%, and 1% of the patients, respectively. Conclusion: Prophylactic use of an EGF-based cream is effective in preventing radiation dermatitis with tolerable toxicity. Further studies comparing EGF cream with other topical agents may be necessary.

• The korean journal of orthodontics
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• v.23 no.1 s.40
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• pp.89-100
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• 1993

The purpose of this study was to evaluate the effect of orthodontic force on periodontal cellular activity by immunoperoxidase stain of epidermal growth factor, one of the tissue hormone. And supplementarily, to investigate of the changes of periodontal structures, periodontium was stained by H-E, Masson's Trichrome, P. A. S. stain after orthodontic force application. The experimental animals were four young adult dogs of average 8 month old. The fixed orthodontic appliance was cemented on mandibular right 4th premolar and 1st molar of each animal as experimental site. Mandibular left 4th premolar area of the same animal was used as control. The appliance consist of two silver crown soldered with 0.030' tube, $0.018\times0.022'$ S.S. sectional arch wire, and 0.009' open coil spring for manifestating of orthodontic force for bodily tooth movement of mandibular 4th premolar toward mesial direction. Experimental group was sacrificed at 1, 2, 3, 5 weeks from beginning of the experiment, and was investigated immunohistochemically and bistochemically by several staining methods. Findings were as follows: 1. The degree of EGF staining in control group was highest in epithelium of periodontium, and osteoclasts, osteoblasts and fibroblasts around the capillary were stained at higher level in periodontium. Generally, control group shows positive distribution of EGF all around the periodontal area. 2. The degree of EGF staining in control and 5 week group were similar, and did not show the significant different level between tension and pressure side. 3. All of 1, 2, 3 week group showed the same staining degree and distribution of EGF, and the tension side was more positive reaction of EGF stain than the pressure side. 4. The features of collagen fiber and periodontal fiber arrangement observed by H-E, Masson's Trichrome and P. A. S. stain revealed that oblique periodontal fibers were strectched in tension side, compressed in pressure side of all experimental group. Some fiber group in pressure side of 5 week group recovered the regular arrangement along the capillaries.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.3009-3014
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• 2015

The epidermal growth factor (EGF) may play a pathological role in hepatocellular carcinoma (HCC). However, the conclusions of published reports on the relationship between the EGF $61^*A/G$ polymorphism and HCC risk remain controversial. To derive a more precise estimation we performed a meta-analysis based on 14 studies that together included 2,506 cases and 4,386 controls. PubMed, EMBASE, Web of Knowledge and the Chinese National Knowledge Infrastructure (CNKI) databases were used to retrieve articles up to August 1, 2014. The crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to evaluate the association. Meta-analysis results showed a significant association between the EGF $61^*A/G$ polymorphism and HCC risk in all four genetic models (allele model: OR=1.25, 95%CI=1.12-1.40; dominant model: OR=1.32, 95%CI=1.14-1.54; recessive model: OR=1.33, 95%CI=1.12-1.58; ho-mozygous model: OR=1.59, 95%CI=1.33-1.90). Moreover, significant associations were observed when stratified by ethnicity, source of controls, etiology and genotype methods. Thus, this meta-analysis suggests that the G-allele of the EGF $61^*A/G$ polymorphism is associated with an increased risk of HCC, especially in Asians and Caucasians, without influence from the source of controls or etiological diversity. Further studies with larger population sizes are needed to confirm these results.

• BMB Reports
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• v.49 no.4
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• pp.220-225
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• 2016

Cancer cells have different characteristics due to the genetic differences where these unique features may strongly influence the effectiveness of therapeutic interventions. Here, we show that the spontaneous reactivation of extracellular signalregulated kinase (ERK), distinct from conventional ERK activation, represents a potent mechanism for cancer cell survival. We studied ERK1/2 activation in vitro in SW480 colorectal cancer cells. Although ERK signaling tends to be transiently activated, we observed the delayed reactivation of ERK1/2 in epidermal growth factor (EGF)-stimulated SW480 cells. This effect was observed even after EGF withdrawal. While phosphorylated ERK1/2 translocated into the nucleus following its primary activation, it remained in the cytoplasm during late-phase activation. The inhibition of primary ERK1/2 activation or protein trafficking, blocked reactivation and concurrently increased caspase 3 activity. Our results suggest that the biphasic activation of ERK1/2 plays a role in cancer cell survival; thus, regulation of ERK1/2 activation may improve the efficacy of cancer therapies that target ERK signaling.

• Archives of Plastic Surgery
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• v.32 no.3
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• pp.314-318
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• 2005

For treatment of full thickness skin defects caused by trauma or infections, skin grafts or flaps have been the treatment of choice to date. However, in patients who are not candidates for surgery, either due to his general conditions or refusal to receive treatment, supportive methods have been the only means of care, which inherently caused psychological trauma to the patient due to uncertainties of ultimate outcome and the length of treatment. This study aimed to heal full thickness skin defects through application of topical epidermal growth factor in patients who have received 2 to 3 weeks of conservative management using medifoam $B^{(R)}$ without improvement. Six patients from March 2002 to July 2004 were enrolled. The mean size of defects was $5.4{\times}4.6cm$ in 4 patients with carcinoma and $6.4{\times}4.1cm$ in 2 patients with osmidrosis. Commercially available 0.005% EGFR solution was used, and dressing was performed once daily. All patients benefitted from the use of EGF, with closure of skin defects taking an average of 28 days in cancer patients and 22.5 days in osmidrosis cases. EGF can be used as a supportive mean of treatment in the inoperable patients with skin defects, with resultant hastening of healing shortening duration of treatment.