ObjectiveTo detect expressions of epidermal growth factor receptor (EGFR), BRAF, and K-Ras genes in colorectal carcinoma tissues and explore pathogenesis in colorectal carcinoma. MethodThe expressions of EGFR, BRAF, and K-Ras genes were detected in these 136 colorectal carcinoma tissues and their corresponding adjacent normal colorectal tissues by immunohistochemistry. ResultsThe expressions of EGFR and BRAF in the colorectal carcinoma tissues were significantly higher than those in their corresponding adjacent normal colorectal tissues (P<0.05), but the expression of K-Ras had no significant difference between these two tissues (P>0.05). The expression of EGFR gene was related to the TNM stage, lymphatic metastasis, or degree of differentiation. The expression of BRAF gene was related to the TNM stage. The expression of K-Ras gene wasn,t related to the TNM stage, lymphatic metastasis, or degree of differentiation. The correlation analysis results showed that there was no relation among the EGFR, K-Ras, or BRAF expression. ConclusionsUp-regulated of EGFR and BRAF gene expressions might be related to development of colorectal carcinoma, and role of K-Ras is unclear. Anti EGFR and BRAF target therapy might be benefited for patients with colorectal carcinoma.
ObjectiveTo study effects of two kinds of epidermal growth factor receptor kinase inhibitors on bleomycin-induced pulmonary fibrosis in mice, and regulation mechanism on oncostatin M (OSM) and downstream signaling pathways.MethodsForty Kunming female mice were randomly divided into a control group, a fibrosis group, a gefitinib group, and an erlotinib group. The mice in the control group were administered with saline aerosol intratracheally. The mice in the fibrosis group were administered with bleomycin at a dose of 3 mg/kg aerosol intratracheally. The mice in the gefitinib group and the erlotinib group were administered with bleomycin at a dose of 3 mg/kg aerosol intratracheally and then gastrically perfused with gefitinib (20 mg·kg–1·d–1) or erlotinib (25 mg·kg–1·d–1). All mice accepted computer tomography examination 14 days after the treatment and then were sacrificed, and the lungs were collected for further detection. The lungs were stained with hematoxylin eosin and Masson’s trichrome, examined with Western blot for pathological examination and expressions of α-smooth muscle actin (α-SMA), OSM, Janus kinase 1 (JAK1), phospho-JAK1 (p-JAK1), signal transducers and activators of transcription 3 (STAT3), and phospho-STAT3 (p-STAT3) proteins.ResultsThe pathological injury of the lung in the gefitinib group and the erlotinib group was significantly relieved compared with that in the bleomycin group. The expressions of α-SMA, OSM, p-JAK1/JAK1, and p-STAT3/STAT3 proteins were also significantly reduced. There were no differences between the above-mentioned indexes between the gefitinib group and the erlotinib group.ConclusionsGefitinib and erlotinib can significantly relieve bleomycin-induced pulmonary fibrosis in mice. The underlying mechanism may be involved in inhibiting expression of OSM and downstream JAK/STAT pathways.
ObjectiveTo explore the relationship of the clinicopathological characteristics of non-small cell lung cancer (NSCLC) with the mutations of epidermal growth factor receptor (EGFR), K-ras and EML4-ALK fusion gene in cell blocks of pleural effusion (PLE). MethodsA total of 268 cytological specimens of PLE (pleural effusion), from Central Hospital of Zibo city were collected from advanced NSCLC patients between January 2012 year and June 2014 year. There were 165 male and 103 female patients at age of 53.6 (31-76) years. Qualitative diagnosis has been made in the 268 patients using PLE samples with conventional smear. Immunohistochemical staining combined with cell block section were used for further classification. There were 76 patients diagnosed as NSCLC with 39 patients of adenocarcinoma and 37 patients of squamous-cell carcinoma. In the 76 patients of lung biopsy specimens and PLE, EGFR and K-ras mutations, EML4-ALK fusions were tested. ResultsEGFR mutations rate was 34.21% (26/76). K-ras mutations rate was 6.58% (5/76). EML4-ALK fusions rate was 7.89% (6/76) at the same time. EGFR and K-ras mutations, EML4-ALK fusions were mostly found in young female adenocarcinoma patients who were non-smokers. EGFR and K-ras mutations or EML4-ALK fusions were not found in the same patient. ConclusionCytological specimens are feasible for detecting EGFR were K-ras mutations and EML4-ALK fusions. This will especially benefit to patients whose histological specimen can not be obtained.
Objective To explore the effect of membrane surface nucleolin （NCL） on activation of epidermal growth factor receptor （EGFR） signaling. Methods Immunohistochemistry was used to identify the expressions of membrane surface NCL or EGFR in pallilary thyroid carcinoma （PTC） tissues. The level of phosphorlated EGFR in TPC-1 cells was observed by Western blot. TPC-1 cells invasion capacity was detected by Transwell assay. Results The posi-tive expression rates of membrane surface NCL and EGFR in PTC tissues were 100% （56/56） and 80.4% （45/56） respe-ctively， while the expressions of NCL and EGFR were related with lymph node metastasis （P＜0.05）. There was posi-tive correlation between the expressions of NCL and EGFR （r=0.635， P＜0.01）. Western blot showed that anti-NCL or anti-EGFR of TPC-1 cells could inhibit the expression of phosphorlation EGFR （P＜0.01）. Transwell assay showed the number of membrane-invading cells were reduced significantly in anti-NCL group anti-EGFR group （P＜0.01）. Conclusions Membrane surface NCL may be a kind of indispensable component in activation of EGFR signaling， by which EGFR can participate in growth and invasion of tumors. NCL can be used as a target for developing a new field of tumor treatment.
OBJECTIVE: To explore the expressive characteristics of epidermal growth factor (EGF) and its receptor (EGFR) in tissues of fetal and adult intestines. METHODS: The expression intensity and distribution of EGF and EGFR were detected with pathological and immunohistochemical methods in 6 specimens of adult (16-54 years) intestines and 18 specimens of fetal intestines with different gestational ages (13-31 weeks). RESULTS: Positive protein particles of EGF and EGFR could be detected in tissues of fetal and adult intestines. The protein expressions of EGF and EGFR were elevated progressively with the gestational age. EGF was mainly located in the cytoplasm and extracellular matrix of intestinal villus cells, endothelial cells and tunica serosa epithelial cells, while EGFR chiefly distributed in the cellular membrane of these cells. CONCLUSION: The endogenous EGF and EGFR might be involved in the intestinal development at embryonic stage, in the structural and functional maintenance at adult stage, and in the wound healing after injury.
Objective To investigate the effect of topical external administration of recombinant human epidermal growth factor (rhEGF) when controll ing blood sugar on expression of epidermal growth factor receptor (EGFR) and EGFR mRNA of wound in diabetes mell itus (DM) combined with scald. Methods A total of 136 male Wistar rats weighing (188.57 ± 6.59) g were randamly divided into 4 groups (groups A, B, C, and D, n=34). The rats was made DM model by intraperitoneal injected 60 mg/kg streptozocin in groups A, B, and C; rats were injected buffer alone in group D as control group. After 8 weeks, the rats of 4 groups were placed in 80℃ hot water for 6 seconds for preparation of the back deep II degree scald model. In group A, the blood sugar level was controlled at the level of group D 1 week before scald model; within 24 hours after models preparation, rhEGF was sprayed on wound at 150 U/cm2 . In group B, the rats were given the same treatment as group A except not controll ing blood sugar. In group C, the blood sugar was controlled as group A and wound was suture fixation with 1% silver sulfadiazine cream at 24 hours after the model. In group D, the same treatment as group A was given after injury. The heal ing rate of the wound was detected at 3, 7, 11, 15, and 21 days after injury; the EGFR mRNA expression was determined by mRNA hybridization in situ, and the EGFR protein expression was deterimined by immunohistochemistry and Western blot at 1, 3, 5, 7, 11, 15, and 21 days. Results All the rats survived at the end of experiment. There was no significant difference in the heal ing rate of the wound among the 4 groups at 3 days (P gt; 0.05). The heal ing rate of the wound was significantly higher in groups A and D than in groups B and C (P lt; 0.05) at 7, 11, 15, and 21 days. The expession of EGFR mRNA in 4 groups was observed by hybridization in situ, which mainly distributed in the dermal fibroblasts, capillary endothel ial cells and remnants of skin and wound edge epithel ium of the subsidiary; the expessions reached the peak at 5 days in group A, at 7 days in groups B and C, and at 11 days in group D; and the peak level was significantly higher in groups A and D than in groups B and C (P lt; 0.05). Immunohistochemistry and Western blot showed that the expession of EGFR protein was observed in 4 groups and reached the peak level at 7 days in groups A and B, and at 11 days in groups C and D; showing significant difference between groups B, C and groups A, D (P lt; 0.05). Conclusion External appl ication of rhEGF when controll ing blood sugar can accelerate obviously the wound heal ing in DM combined with scald. After controll ing blood sugar, external appl ication of rhEGF can boost obviously the expressions of EGFR mRNA, EGFR, and the extending process of signal conduction.
The incidence and mortality of esophageal cancer in China rank the fifth and fourth, respectively, with squamous carcinoma accounting for more than 90%. Currently, the treatment of esophageal squamous carcinoma mainly includes surgery, chemotherapy, radiotherapy, and endoscopic treatment. However, the 5-year survival rate is only about 20%. At present, the treatment of esophageal squamous carcinoma seems to reach a plateau. Thus, it is urgent to develop new and more effective drugs and treatments. In this paper, the clinical research progresses of epidermal growth factor receptor (EGFR)- targeted therapy of esophageal squamous carcinomas were summarized, including anti-EGFR monoclonal antibodies, such as cetuximab and nimotuzumab, and EGFR-tyrosine kinase inhibitor, such as gefitinib, erlotinib, and ecclinib.
Objective To investigate the feasibility of detection of epidermal growth factor receptor ( EGFR) exon 19 deletions and exon 21 L858R mutations in pleural effusion fromnon-small-cell lung cancer ( NSCLC) patients by mutant enriched PCR assay. Methods The mutations of exon 19 and 21 of EGFR gene in pleural samples fromthirty NSCLC patients were analyzed using both the mutant-enriched PCR assay and the non-enriched PCR assay. Results Ten ( 33. 3% , 10/ 30) exon 19 deletions and five ( 16. 7% , 5/30) exon 21 L858R mutation were detected by the mutant-enriched PCR assay, while only 6 cases ( 20. 0% ) and 1 case ( 3. 3% ) were detected by the non-enriched PCR assay respectively. The difference of mutation detection rate of EGFR gene between the two methods was statistically significant ( P = 0. 032) . Mutations were detected in all of partial responders ( 2 /4) among the four patients who received gefitinib therapy. Conclusions Mutant-enriched PCR assay can detect EGFR exon 19 deletions and exon 21 L858R mutation in pleural effusion from NSCLC patients effectively, economically and accurately. It may be a valuable biomarker for gefitinib therapy in advanced NSCLC.
Objective To analyze the relationship between the epidermal growth factor receptor(EGFR) gene mutation and malignant pulmonary focal ground-glass lesion (fGGL). Methods We retrospectively collected the clinical data of 86 patients with surgical treatment in the department of cardiothoracic surgery of Changzheng Hospital from August 2012 to February 2015. There were 26 males and 60 females with a mean age of 56.14±10.55 years. We analyzed the relationship between the EGFR gene mutation and the related clinical data. Results Postoperative pathology showed atypical adenomatous hyperplasia (AAH) combined with focal adenocarcinoma in situ (AIS) or AIS in 10 patients, minimally invasive adenocarcinoma (MIA) in 15, and lepidic predominant adenocarcinoma (LPA) in 61. The EGFR gene mutation reports showed the exon 19 19-del mutation in 14 patients, exon 21 L858R mutation in 27, and exon 21 L861Q mutation in 2. There was no difference between the mutation of EGFR gene and clinical factors except age and smoking (P>0.05). Till June 30, 2015, all patients were alive and follow-up was 440.48±186.61 days. Conclusion The EGFR gene in patients with malignant pulmonary fGGL shows a higher mutation rate, which provides important clinical reference data for the basic research and the clinical treatment.
Objective To observe the effect of gefitinib on expression of epidermal growth factor receptor (EGFR) in bile duct epithelial cells, and the feasibility of inhibiting hyperplasia of bile duct epithelial cells with gefitinib. Methods Sixty-one patients with hepatolithiasis having to be in hospital for surgery from the First People’s Hospital of Shuangliu county were selected, with 25-65 years old, average 46.92 years. The patients were randomly divided into therapy group and control group. There were 30 cases in therapy group, in which fine duct was placed on lesion bile duct during operation, and through whom gefitinib solution was perfused after operation. There were 31 cases in control group with only T tube drainage after operation. The bile duct sample was obtained respectively during the operation and 6 weeks and 12 weeks after operation. The histology and expression change of EGFR were observed by HE staining, immunohistochemistry and RT-PCR method respectively. Results There were no significant differences in pathohistology changes of bile duct and the EGFR protein and mRNA expression between therapy group and control group during operation. The hyperplasia of epithelium mucosae and submucosal gland in the therapy group were obviously decreased as compared with those in control group, the EGFR mRNA and protein expression in therapy group were weaker than those of control group （Plt;0.05） 6 weeks and 12 weeks after gefitinib treatment. Conclusion EGFR is overexpressed in the chronic proliferative cholangitis, and continuously local application of gefitinib after operation can specifically interrupt the activation and expression of EFGR and then effectively inhibit the hyperplasia of bile duct epithelial cells.