1.Progress in human epidermal growth factor research.
Meiyu WU ; Jinghua RUAN ; Boxiong ZHONG
Chinese Journal of Biotechnology 2020;36(12):2813-2823
Human epidermal growth factor (hEGF) is a typical member of the growth factor family that activates epidermal growth factor receptors. It is synthesized and secreted by multiple tissues and organs of the human body, regulating the cell proliferation, differentiation and migration via binding to receptors and activating a series of signaling pathways. In recent years, the research on hEGF has been extended to its role in human physiology and pathology, especially in tissue regeneration and wound healing. This paper reviews the research progress of hEGF, briefly describes its gene and protein structure and characteristics, mechanisms and biological effects, with the emphasis on the roles and influences in the healing of gastrointestinal ulcers, skin wound repair and tumor pathology.
Cell Proliferation
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Epidermal Growth Factor/genetics*
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ErbB Receptors/genetics*
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Humans
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Skin
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Wound Healing
2.Risk modeling based on HER-2 related genes for bladder cancer survival prognosis assessment.
Huan Rui LIU ; Xiang PENG ; Sen Lin LI ; Xin GOU
Journal of Peking University(Health Sciences) 2023;55(5):793-801
OBJECTIVE:
To investigate the correlation between the human epidermal growth factor receptor-2-related genes (HRGs) and survival prognosis of bladder cancer and to construct a predictive model for survival prognosis of bladder cancer patients based on HRGs.
METHODS:
HRGs in bladder cancer were found by downloading bladder tumor tissue mRNA sequencing data and clinical data from the cancer genome atlas (TCGA), downloading HER-2 related genes from the molecular signatures database (MsigDB), and crossing the two databases. Further identifying HRGs associated with bladder cancer survival (P < 0.05) by using single and multi-factor Cox regression analysis and constructing HRGs risk score model (HRSM), the bladder cancer patients were categorized into high-risk and low-risk groups accor-ding to the median risk score. Survival analysis of the patients in high- and low-risk groups was conducted using R language and correlation of HRGs with clinical characteristics. A multi-factor Cox regression analysis was used to verify the independent factors affecting the prognosis of the patients with bladder cancer. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) of HRSM was calculated, and a nomogram was constructed for survival prediction of the bladder cancer patients. Analysis of HRSM and patient immune cell infiltration correlation was made using the TIMER database.
RESULTS:
A total of 13 HRGs associated with patient survival were identified in this study. Five genes (BTC, CDC37, EGF, PTPRR and EREG) were selected for HRSM by multi-factor Cox regression analysis. The 5-year survival rate of the bladder cancer patients in the high-risk group was significantly lower than that of the patients in the low-risk group. High expression of PTPRR was found to be significantly and negatively correlated with tumor grade and stage by clinical correlation analysis, while EREG was found to be the opposite; Increased expression of EGF was associated with high grade, however, the high expression ofCDC37showed the opposite result. And no significant correlation was found between BTC expression and clinical features. Correlation analysis of HRSM with immune cells revealed a positive correlation between risk score and infiltration of dendritic cells, CD8+T cells, CD4+T cells, neutrophils and macrophages.
CONCLUSION
HRGs have an important role in the prognosis of bladder cancer patients and may serve as new predictive biomarkers and potential targets for treatment.
Humans
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Epidermal Growth Factor
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Prognosis
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Urinary Bladder Neoplasms/genetics*
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Nomograms
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Urinary Bladder
3.LRIG3 gene regulates biological activity of GL15 cell line.
Gui-fa XI ; Qun WU ; Bao-feng WANG ; Dong-Sheng GUO ; Gao CHEN ; Jian-min ZHANG ; Ting LEI
Journal of Zhejiang University. Medical sciences 2008;37(5):444-450
OBJECTIVETo investigate the effects of leucine-rich repeats and immunoglobulin-like domains 3 (LRIG3) on the biological activity of glioblastoma cell line GL15.
METHODSGlioblastoma GL15 cells were cultured and transfected with LRIG3-EGFP plasmid. The location of LRIG3 in GL15 cells was observed with confocal microscopy. The proliferation and invasiveness of GL15 cells were detected with methyl thiazolyl tetrazolium (MTT) and Transwell methods respectively; the expression of epidermal growth factor receptor (EGFR) and LRIG3 mRNA and protein were detected with reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot respectively.
RESULTAfter transfection with the plasmid LRIG-EGFP, LRIG3 fusion protein was found in cytoplasm of GL15 cells and cell proliferative and invasiveness were reduced. The expression of EGFR and LRIG3 varied with the duration of EGF treatment (100 ng/ml): the expression of EGFR decreased while the expression of LRIG3 increased as time prolonged.
CONCLUSIONLRIG3 can inhibit the proliferation and invasiveness of glioblastoma cells and may be used as a target gene in gene therapy of glioblastoma.
Brain Neoplasms ; pathology ; Cell Proliferation ; Epidermal Growth Factor ; genetics ; Glioblastoma ; pathology ; Humans ; Membrane Proteins ; genetics ; metabolism ; Neoplasm Invasiveness ; Plasmids ; genetics ; RNA, Messenger ; genetics ; metabolism ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Recombinant Fusion Proteins ; genetics ; metabolism ; Transfection ; Tumor Cells, Cultured
4.Epidermal growth factor receptor mutations detected in tumors from Chinese "never smokers" with lung adenocarcinoma.
Guo-ping REN ; Theresa Y WANG ; Qiu-lu PAN ; William PAO ; Jing HUAI
Chinese Medical Journal 2005;118(9):769-771
Adenocarcinoma
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genetics
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Adult
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Aged
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Female
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Humans
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Lung Neoplasms
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genetics
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Male
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Middle Aged
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Mutation
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Receptor, Epidermal Growth Factor
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genetics
5.Effects of electroacupuncture at points "Weibingfang" on EGF and EGFR mRNA expressions in rats with lesion of gastric mucosa.
Lai-Xi JI ; Li-Ping YAN ; Hai-Jun WANG ; Bo WANG ; Xia-Yi ZHANG ; Tian-Sheng ZHANG ; Xiao-Fei JIN
Chinese Acupuncture & Moxibustion 2008;28(10):757-759
OBJECTIVETo probe the mechanism of electroacupuncture at points "Weibingfang" in treatment of acute gastric mucosal lesion.
METHODSForty Wistar rats of sanitary degree were randomly divided into 4 groups, normal group, model group, sham-model group and Weibingfang group, 10 rats in each group. The acute gastric mucosal lesion model was made by intragastric perfusion of anhydrous alcohol. The Weibingfang group were treated by electroacupuncture at "Neiguan" (PC 6), "Zhongwan" (CV 12) and "Zusanli" (ST 36) with sparse-dense wave, frequency of 10-30 Hz, current intensity of 2 mA, for 20 min. One hour after the treatment, the blood from the abdominal aorta and the gastric mucosa tissue were taken, and serum epidermal growth factor (EGF) level and epidermic growth factor receptor mRNA (EGFR mRNA) expression in the gastric mucosa were detected with enzyme linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) respectively.
RESULTSThere were significant differences in blood EGF level (41.62 +/- 12.58) ng/L and EGFR mRNA expression (0.78 +/- 0.03) in the model group were significantly different from [(60.37 +/- 12.01) ng/L and 0.55 +/- 0.04] in the normal group and [(61.21 +/- 13.46) ng/L and 0.53 +/- 0.05] in the sham-model group (P < 0.05); after electroacupuncture, blood EGF level (70.59 +/- 10.14) ng/L increased and the EGFR mRNA expression (1.18 +/- 0.02) in the gastric mucosa was up-regulated with a significant differences as compared with those in the model group (P < 0.05).
CONCLUSIONPoint "Weibingfang" can promote proliferation, differentiation and migration of the gastric mucosal epidermic cells to repair the gastric mucosal lesion.
Acupuncture Points ; Animals ; Electroacupuncture ; Epidermal Growth Factor ; blood ; genetics ; Female ; Gastric Mucosa ; metabolism ; Gene Expression ; Humans ; Male ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Stomach Diseases ; genetics ; metabolism ; therapy
6.Construction and expression of an anti-EGFR/anti-KDR bispecific single-chain diabody.
Ya-qiong ZHOU ; Juan ZHANG ; Hai-zhen JIN ; Yuan HE ; Tong WANG ; Min WANG
Acta Pharmaceutica Sinica 2012;47(10):1317-1322
Bispecific antibodies have been exploited as both cancer immunodiagnostics and cancer therapeutics, which have shown promises in clinical trials in cancer imaging and therapy. To improve the anti-tumor effect, an scDb (bispecific single-chain diabody) was constructed from the variable domain genes of two scFvs (single-chain variable fragment antibodies) directed against human EGFR (epidermal growth factor receptor) and VEGFR2 (vascular endothelial growth factor receptor 2) extracellular domains. The anti-EGFR/ anti-KDR scDb was constructed into pHEN2 plasmid and expressed in Escherichia coli HB2151 host. After purification by one-step affinity chromatography of IMAC, scDb protein was characterized by Western blotting. The yield of scDb protein was 570 microg per liter medium. scDb bound to EGFR as efficiently as the parental antibody scFv-E10, while a little bit weaker than the parental antibody scFv-AK404R when bound to KDR. In conclusion, the scDb protein could bind both EGFR and KDR specifically and could be applied for further anti-tumor research.
Antibodies, Bispecific
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biosynthesis
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genetics
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Escherichia coli
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metabolism
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Humans
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Plasmids
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Protein Binding
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Receptor, Epidermal Growth Factor
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immunology
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Single-Chain Antibodies
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biosynthesis
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genetics
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Vascular Endothelial Growth Factor Receptor-2
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immunology
7.Expression, purification and refolding of extracellular domain of mouse epidermal growth factor receptor.
Bing HU ; Ling TIAN ; You LU ; Li YANG ; Xia ZHAO ; Jiyan LIU ; Yuquan WEI
Journal of Biomedical Engineering 2003;20(2):264-267
A DNA fragment encoding extracellular domain of mouse epidermal growth factor receptor (EGFR) was obtained by PCR from a previous recombinant plasmid. The DNA fragment was then ligated into prokaryotic expression vector, and expressed in Escherichia Coli. The recombinant protein was purified under denature conditions by affinity chromatography, and refolded with gradient dialysis. The recombinant protein could produce antibodies to recognize extracellular domain and full-length of mouse EGFR, and form homodimer in the presence of EGF detected by western blot analysis. These findings provide evidence that the renatured recombinant extracellular domain of mouse epidermal growth factor receptor is immunogenetic and may be important for further application of this protein in functional and immunological research.
Animals
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Escherichia coli
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genetics
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metabolism
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Genetic Vectors
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Mice
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Plasmids
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Receptor, Epidermal Growth Factor
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biosynthesis
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chemistry
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genetics
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isolation & purification
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Transfection
8.Evolving Molecular Genetics of Glioblastoma.
Qiu-Ju LI ; Jin-Quan CAI ; Cheng-Yin LIU
Chinese Medical Journal 2016;129(4):464-471
OBJECTIVETo summary the recent advances in molecular research of glioblastoma (GBM) and current trends in personalized therapy of this disease.
DATA SOURCESData cited in this review were obtained mainly from PubMed in English up to 2015, with keywords "molecular", "genetics", "GBM", "isocitrate dehydrogenase", "telomerase reverse transcriptase", "epidermal growth factor receptor", "PTPRZ1-MET", and "clinical treatment".
STUDY SELECTIONArticles regarding the morphological pathology of GBM, the epidemiology of GBM, genetic alteration of GBM, and the development of treatment for GBM patients were identified, retrieved, and reviewed.
RESULTSThere is a large amount of data supporting the view that these recurrent genetic aberrations occur in a specific context of cellular origin, co-oncogenic hits and are present in distinct patient populations. Primary and secondary GBMs are distinct disease entities that affect different age groups of patients and develop through distinct genetic aberrations. These differences are important, especially because they may affect sensitivity to radio- and chemo-therapy and should thus be considered in the identification of targets for novel therapeutic approaches.
CONCLUSIONThis review highlights the molecular and genetic alterations of GBM, indicating that they are of potential value in the diagnosis and treatment for patients with GBM.
Brain Neoplasms ; genetics ; pathology ; Glioblastoma ; genetics ; pathology ; Humans ; Isocitrate Dehydrogenase ; genetics ; Mutation ; PTEN Phosphohydrolase ; genetics ; Receptor, Epidermal Growth Factor ; genetics ; Telomerase ; genetics
9.Recent advances in gene change of pancreatic cancer.
Acta Academiae Medicinae Sinicae 2004;26(1):79-82
A large number of data derived from molecular analyses support the hypothesis that human cancer is a genetic disease and a distinct subset of genes have been found to be genetically changed in most tumors. Molecular alterations in pancreatic cancer include: (1) oncogenes such as K-ras, c-myc, c-fos, and c-erbB-2; (2) tumor suppressor genes such as p53, p16, DPC4/SMAD4, and DCC; and (3) growth factors such as EGF, FGF, HGF, PDGF, VEGF, TGF-beta. Genetic alterations of K-ras and p53 are common in human pancreatic cancer, but the occurrence of pancreatic cancer is a multi-step phenomenon in which the accumulation of genetic changes is extremely important.
Epidermal Growth Factor
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genetics
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Fibroblast Growth Factors
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genetics
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Genes, Tumor Suppressor
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Genes, myc
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genetics
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Genes, p16
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Genes, p53
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genetics
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Genes, ras
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genetics
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Growth Substances
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genetics
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metabolism
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Humans
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Oncogenes
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genetics
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Pancreatic Neoplasms
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genetics
10.Effects of IL-10 and PDGF-BB on expression of EGF and bFGF mRNA in hepatic stellate cells.
Yue-Hong HUANG ; Xiao-Zhong WANG ; Yun-Xin CHEN ; Zhi-Xin CHEN ; Li-Juan ZHANG
Chinese Journal of Hepatology 2004;12(9):562-563
Cell Line
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Epidermal Growth Factor
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biosynthesis
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genetics
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Fibroblast Growth Factor 2
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biosynthesis
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genetics
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Hepatocytes
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metabolism
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Humans
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Interleukin-10
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pharmacology
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Platelet-Derived Growth Factor
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pharmacology
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Proto-Oncogene Proteins c-sis
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RNA, Messenger
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biosynthesis
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genetics