Objective This study aimed to analyze the relationship between the mutations in epidermal growth factor receptor(EGFR)and anaplastic lymphoma kinase(ALK)and their impact on the prognosis and treatment of lung adenocar...Objective This study aimed to analyze the relationship between the mutations in epidermal growth factor receptor(EGFR)and anaplastic lymphoma kinase(ALK)and their impact on the prognosis and treatment of lung adenocarcinoma.Methods A total of 158 cases of lung adenocarcinoma reported between January 2007 and January 2014 were retrospectively analyzed.These tumors were resected using radical pneumonectomy and underwent pathology-based diagnosis at our institution(Inner Mongolia People’s Hospital,Hohhot,China).The tissue sections were evaluated using the updated World Health Organization classification of lung adenocarcinomas(2015 version),with each histological component recorded in 5%increments.The histological subtypes were classified,and any surviving cases were followed up.The reverse transcription-polymerase chain reaction(RT-PCR)and direct DNA sequencing were used to evaluate mutations in exons 18,19,20,and 21 in the EGFR gene,and the echinoderm microtubule-associated protein-like 4 gene-ALK variant(EML4-ALK)fusions were detected using sequencing.Results Our cohort included 25 patients with pre-invasive adenocarcinoma,13 patients with lepidic,66 patients with acinar,13 patients with papillary,and 25 patients with solid infiltrative adenocarcinoma with the remaining cases presenting with a variety of pathological subtypes.The prognosis of each histological subtype was different with the 5-year disease-free survival and 5-year overall survival(OS)of pre-invasion adenocarcinoma at 100%;the 5-year OS of lepidic,acinar,and papillary adenocarcinoma patients was only 84.6%,72.7%,and 76.9%,respectively.The 5-year OS of solid and mucinous adenocarcinomas were 32.0%and 36.4%,respectively.EGFR mutation was detected in 69 cases with a mutation rate of 43.7%and majority of these mutations were found in exons 19(50.6%)and 21(37.9%),with women and non-smokers shown to experience a higher mutation rate(P<0.05).However,histological subtype analysis showed that EGFR mutations were primarily found in adenocarcinomas.Most of these mutations were found in lepidic(53.8%)or acinar adenocarcinomas(50.0%),whereas these mutations were rare in both solid(28.0%)and mucinous adenocarcinoma(27.2%).The fusion mutation rate in the EML4-ALK gene was 5.69%,and was most common in young,nonsmoking patients(P<0.05).Conclusion The prognosis of patients in each lung adenocarcinoma subtype is different,and these outcomes are likely related to mutations in the EGFR and EML4-ALK genes.EGFR mutation rates are higher in lepidic and acinar adenocarcinomas,whereas EML4-ALK gene fusion mutations are more common in solid and mucinous adenocarcinoma.EGFR mutations are more common in female and non-smoking patients,whereas EML4-ALK fusions are more common in young,non-smoking patients.展开更多
AIM： To investigate the expression of cyclooxygenase-2 （COX-2） and epithelial growth factor receptor （EGFR） throughout the progression of Barrett＇s esophagus （BE）. METHODS： COX-2 and EGFR protein expressions ...AIM： To investigate the expression of cyclooxygenase-2 （COX-2） and epithelial growth factor receptor （EGFR） throughout the progression of Barrett＇s esophagus （BE）. METHODS： COX-2 and EGFR protein expressions were detected by using immunohistochemical method. A detailed cytomorphological changes were determined. Areas of COX-2 and EGFR expression were quantified by using computer Imaging System. RESULTS： The expressions of both COX-2 and EGFR increased along with the progression from BE to esophagus adenocarcinoma （EAC）. A positive correlation was found between COX-2 expression and EGFR expression. CONCLUSION： COX-2 and EGFR may be cooperative in the stepwise progression from BE to EAC, thereby leading to carcinogenesis.展开更多
Background： Epidermal growth factor receptor（EGFR） mutation is the key predictor of EGFR tyrosine kinase inhibitors（TKIs） efficacy in non-small cell lung cancer（NSCLC）. We conducted this study to verify the fea...Background： Epidermal growth factor receptor（EGFR） mutation is the key predictor of EGFR tyrosine kinase inhibitors（TKIs） efficacy in non-small cell lung cancer（NSCLC）. We conducted this study to verify the feasibility of EGFR mutation analysis in cytological specimens and investigate the responsiveness to gefitinib treatment in patients carrying EGFR mutations.Methods： A total of 210 cytological specimens were collected for EGFR mutation detection by both direct sequencing and amplification refractory mutation system（ARMS）. We analyzed EGFR mutation status by both methods and evaluated the responsiveness to gefitinib treatment in patients harboring EGFR mutations by overall response rate（ORR）, disease control rate（DCR） and progression free survival（PFS）.Results： Of all patients, EGFR mutation rate was 28.6%（60/210） by direct sequencing and 45.2%（95/210） by ARMS（P〈0.001） respectively. Among the EGFR wild type patients tested by direct sequencing, 26.7% of them were positive by ARMS. For the 72 EGFR mutation positive patients treated with gefitinib, the ORR, DCR and median PFS were 69.4%, 90.2% and 9.3 months respectively. The patients whose EGFR mutation status was negative by direct sequencing but positive by ARMS had lower ORR（48.0% vs. 80.9%, P=0.004） and shorter median PFS（7.4 vs. 10.5 months, P=0.009） as compared with that of EGFR mutation positive patients by both detection methods. Conclusions： Our study verified the feasibility of EGFR analysis in cytological specimens in advanced NSCLC. ARMS is more sensitive than direct sequencing in EGFR mutation detection. EGFR Mutation status tested on cytological samples is applicable for predicting the response to gefitinib. Abundance of EGFR mutations might have an influence on TKIs efficacy.展开更多
Epidermal growth factor receptor(EGFR)signaling has become an importanttarget for drug development becauseEGFR signaling enhances tumor cell proliferation,migration,and invasion and inhibits apoptosis.However,theresul...Epidermal growth factor receptor(EGFR)signaling has become an importanttarget for drug development becauseEGFR signaling enhances tumor cell proliferation,migration,and invasion and inhibits apoptosis.However,theresults of clinical trials using EGFR inhibitors in patients with solid tumors have been disappointing.Here,wereport a protective effect of the EGFR inhibitors AG1478 and PD153035 against cell death induced by acute hy-poxia,which contrasts with their proapoptotic effects under normoxia.Under hypoxic conditions,both agents re-展开更多
（-）-Epigallocatechin gallate （EGCG）, a major polyphenolic constituent of green tea, can inhibit activity of specific receptor tyrosine kinases （RTKs） and related downstream signal transduction pathways, resultin...（-）-Epigallocatechin gallate （EGCG）, a major polyphenolic constituent of green tea, can inhibit activity of specific receptor tyrosine kinases （RTKs） and related downstream signal transduction pathways, resulting in the control of unwanted cell proliferation. The epidermal growth factor receptor （EGFR） signaling pathway is one of the most important pathways that regulates growth, survival,proliferation and differentiation in mammalian cells. This review addresses the effects of EGCG on some protein factors involved in the EGFR signaling pathway in a direct or indirect manner. Based on our understanding of the interaction between EGCG and these factors, and based on their structures, EGCG could be used as a lead compound for designing and synthesizing novel drugs with significant biological activity.展开更多
Objective： The plasma fibrinogen levels had not only been used as an independent prognostic parameter for the patients with non-small cell lung cancer （NSCLC）, but also as a promising biomarker for evaluating the e...Objective： The plasma fibrinogen levels had not only been used as an independent prognostic parameter for the patients with non-small cell lung cancer （NSCLC）, but also as a promising biomarker for evaluating the efficacy of chemotherapy. This study aimed to investigate the correlation between the plasma fibrinogen levels and epidermal growth factor receptor （EGFR） gene mutation and clinical-pathological characteristics of Chinese patients with NSCLC. Methods： In this retrospective study, NSCLC specimens collected from 352 patients between November 2009 and November 2011 were selected to detect EGFR gene mutation with real-time polymerase chain reaction （RT-PCR）. In these specimens, 308 ones were also detected EGFR gene copy number with fluorescence in situ hybridization （FISH）. Coagulation makers were examined prior to the operations. The association between the plasma fibrinogen levels and EGFR gene mutation and clinical-pathological characteristics were analyzed using SPSS 16.0 software. Results： The median pre-operation plasma fibrinogen level was 3.55 g/L （109/352） patients with higher plasma fibrinogen level （〉 4.0 g/L）. The lower plasma fibrinogen levels correlated significantly with EGFR gene mutations （P 〈 0.001）, the similar result was seen in platelet counts （P = 0.026）. A linear correlation was found between the plasma fibrinogen levels and the platelet counts in NSCLC patients （R^2 = 0.209, P 〈 0.001）. Pre-peration plasma fibrinogen levels correlated with gender （P 〈 0.001）, smoking status （P 〈 0.001 ）, and histology （P 〈 0.001 ）. There were significant link between the above clinical-pathological characteristics and EGFR gene mutations. In addition, EGFR gene mutation was correlated with FISH-positive status （P 〈 0.001）. Moreover, both plasma fibrinogen level （P = 0.024） and the EGFR gene copy number （P = 0.040） had significant relationships with the pathological TNM stage. Conclusion： This study showed that a significant relevance between plasma fibrinogen levels and EGFR gene mutations. The plasma fibrinogen level might be as a clinical decision parameter for evaluating the efficacy of anti-EGFR tyrosine kinase inhibitors （TKIs） in NSCLC. The patients of NSCLC had higher indicate have poor benefits from anti-EFGR TKIs. In addition, pre-operation plasma fibrinogen level could be used as an indepedent prognostic biomarker for the patients with NSCLC.展开更多
The epidermal growth factor receptor （EGFR） is a member of the ErbB/EGFR family, including EGFR/Herl, ErbB2/Her2, ErbB-3/Her3, and ErbB-4/Her4. EGFR exerts its effects through the receptor tyrosine kinase phosphoryl...The epidermal growth factor receptor （EGFR） is a member of the ErbB/EGFR family, including EGFR/Herl, ErbB2/Her2, ErbB-3/Her3, and ErbB-4/Her4. EGFR exerts its effects through the receptor tyrosine kinase phosphorylation and activation of important downstream signaling pathways in normal and neoplastic cells, mainly the Ras GTPase/MAP kinase （MAPK）, STAT3, and phosphatidylinositide 3 kinase-AKT pathways. EGFR deregulation is common in malignant glioma, especially primary glioblastoma, and exists in three forms： gene overexpression （amplification）, autocrine effects of EGFR activation, and activating receptor mutation （EGFRvlII）. However, some EGFR abnormalities have also been found in low-grade gliomas, including the nuclear localization of EGFR, expression in the microfoci of anaplastic transformation, and association with neovascularization in the mesenchyma of the glioma, which suggests that some unknown EGFR-related mechanisms are possibly responsible for its central role in the initiation and progression of malignant glioma. Uncovering these mechanisms will have potential value in the development of radio- therapy, chemotherapy, and EGFR-targeted therapy for glioma.展开更多
Objectives Epidermal growth factor receptor （EGFR）is a receptor protein tyrosine kinase and plays a critical role in the development and function of the heart.Previous studies have demonstrated that EGFR is involved...Objectives Epidermal growth factor receptor （EGFR）is a receptor protein tyrosine kinase and plays a critical role in the development and function of the heart.Previous studies have demonstrated that EGFR is involved in regulating electrical excitability of the heart.The present study was designed to investigate whether EGFR activation would mediate myocardial arrhythmias induced by ischemia/reperfu- sion in anaesthetized rats.Methods and results Myocardial ischemia/reperfusion arrhythmias were induced by 10 min ligation of the left anterior descending coronary artery,followed by a 30 min reperfusion in anaesthetized rats.Incidence and severity of cardiac arrhythmias were significantly reduced by pretreatment with the EGFR kinase inhibitor AG556.Phosphorylation level of myocardial EGFR was increased during ischemia and at early reperfusion.Intramyocardial transfection of EGFR siRNA reduced EGFR mRNA and protein,and decreased the incidence of ventricular fibrillation induced by reperfusion.Interestingly,tyrosine phosphorylation levels of cardiac Na<sup>+</sup> channel(I<sub>Na</sub>) and L-type Ca<sup>2+</sup> channel(I<sub>Ca.l</sub>) were significantly increased at corresponding time points to the alteration of phosphorylated EGFR level during reperfusion.AG556 pretreatment countered the increased tyrosine phosphorylation level of Na<sup>+</sup> and L-type Ca<sup>2+</sup> channels induced by reperfusion.No significant alteration was observed in tyrosine phosphorylation levels of cardiac Kv4.2 and Kir2.1 channels during the cardiac ischemia/reperfusion. Conclusions These results demonstrate for the first time that EGFR plays an important role in the genesis of myocardial ischemia/reperfusion arrhythmias,which is likely mediated at least in part by enhancing tyrosine phosphorylation of cardiac Na<sup>+</sup> and L-type Ca<sup>2+</sup> channels.展开更多
In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussiv...In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori.The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury(ALI).A lipopolysaccharide(LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting,co-immunoprecipitation,and quantitative real time-PCR analysis.The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA(Pla2g2a)-epidermal growth factor receptor(EGFR).The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation.In addition,M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and m TOR via the inhibition of Pla2g2a-EGFR.Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury,which may represent a promising strategy to treat ALI.展开更多
基金Supported by a grant from the Sciences Foundation of Health Commission of Inner Mongolia Autonomous Region(No.201701008).
文摘Objective This study aimed to analyze the relationship between the mutations in epidermal growth factor receptor(EGFR)and anaplastic lymphoma kinase(ALK)and their impact on the prognosis and treatment of lung adenocarcinoma.Methods A total of 158 cases of lung adenocarcinoma reported between January 2007 and January 2014 were retrospectively analyzed.These tumors were resected using radical pneumonectomy and underwent pathology-based diagnosis at our institution(Inner Mongolia People’s Hospital,Hohhot,China).The tissue sections were evaluated using the updated World Health Organization classification of lung adenocarcinomas(2015 version),with each histological component recorded in 5%increments.The histological subtypes were classified,and any surviving cases were followed up.The reverse transcription-polymerase chain reaction(RT-PCR)and direct DNA sequencing were used to evaluate mutations in exons 18,19,20,and 21 in the EGFR gene,and the echinoderm microtubule-associated protein-like 4 gene-ALK variant(EML4-ALK)fusions were detected using sequencing.Results Our cohort included 25 patients with pre-invasive adenocarcinoma,13 patients with lepidic,66 patients with acinar,13 patients with papillary,and 25 patients with solid infiltrative adenocarcinoma with the remaining cases presenting with a variety of pathological subtypes.The prognosis of each histological subtype was different with the 5-year disease-free survival and 5-year overall survival(OS)of pre-invasion adenocarcinoma at 100%;the 5-year OS of lepidic,acinar,and papillary adenocarcinoma patients was only 84.6%,72.7%,and 76.9%,respectively.The 5-year OS of solid and mucinous adenocarcinomas were 32.0%and 36.4%,respectively.EGFR mutation was detected in 69 cases with a mutation rate of 43.7%and majority of these mutations were found in exons 19(50.6%)and 21(37.9%),with women and non-smokers shown to experience a higher mutation rate(P<0.05).However,histological subtype analysis showed that EGFR mutations were primarily found in adenocarcinomas.Most of these mutations were found in lepidic(53.8%)or acinar adenocarcinomas(50.0%),whereas these mutations were rare in both solid(28.0%)and mucinous adenocarcinoma(27.2%).The fusion mutation rate in the EML4-ALK gene was 5.69%,and was most common in young,nonsmoking patients(P<0.05).Conclusion The prognosis of patients in each lung adenocarcinoma subtype is different,and these outcomes are likely related to mutations in the EGFR and EML4-ALK genes.EGFR mutation rates are higher in lepidic and acinar adenocarcinomas,whereas EML4-ALK gene fusion mutations are more common in solid and mucinous adenocarcinoma.EGFR mutations are more common in female and non-smoking patients,whereas EML4-ALK fusions are more common in young,non-smoking patients.
基金Supported by the University of Louisville Hospital the Society for Surgery of the Alimentary Tract Career Development Award
文摘AIM： To investigate the expression of cyclooxygenase-2 （COX-2） and epithelial growth factor receptor （EGFR） throughout the progression of Barrett＇s esophagus （BE）. METHODS： COX-2 and EGFR protein expressions were detected by using immunohistochemical method. A detailed cytomorphological changes were determined. Areas of COX-2 and EGFR expression were quantified by using computer Imaging System. RESULTS： The expressions of both COX-2 and EGFR increased along with the progression from BE to esophagus adenocarcinoma （EAC）. A positive correlation was found between COX-2 expression and EGFR expression. CONCLUSION： COX-2 and EGFR may be cooperative in the stepwise progression from BE to EAC, thereby leading to carcinogenesis.
文摘Background： Epidermal growth factor receptor（EGFR） mutation is the key predictor of EGFR tyrosine kinase inhibitors（TKIs） efficacy in non-small cell lung cancer（NSCLC）. We conducted this study to verify the feasibility of EGFR mutation analysis in cytological specimens and investigate the responsiveness to gefitinib treatment in patients carrying EGFR mutations.Methods： A total of 210 cytological specimens were collected for EGFR mutation detection by both direct sequencing and amplification refractory mutation system（ARMS）. We analyzed EGFR mutation status by both methods and evaluated the responsiveness to gefitinib treatment in patients harboring EGFR mutations by overall response rate（ORR）, disease control rate（DCR） and progression free survival（PFS）.Results： Of all patients, EGFR mutation rate was 28.6%（60/210） by direct sequencing and 45.2%（95/210） by ARMS（P〈0.001） respectively. Among the EGFR wild type patients tested by direct sequencing, 26.7% of them were positive by ARMS. For the 72 EGFR mutation positive patients treated with gefitinib, the ORR, DCR and median PFS were 69.4%, 90.2% and 9.3 months respectively. The patients whose EGFR mutation status was negative by direct sequencing but positive by ARMS had lower ORR（48.0% vs. 80.9%, P=0.004） and shorter median PFS（7.4 vs. 10.5 months, P=0.009） as compared with that of EGFR mutation positive patients by both detection methods. Conclusions： Our study verified the feasibility of EGFR analysis in cytological specimens in advanced NSCLC. ARMS is more sensitive than direct sequencing in EGFR mutation detection. EGFR Mutation status tested on cytological samples is applicable for predicting the response to gefitinib. Abundance of EGFR mutations might have an influence on TKIs efficacy.
文摘Epidermal growth factor receptor(EGFR)signaling has become an importanttarget for drug development becauseEGFR signaling enhances tumor cell proliferation,migration,and invasion and inhibits apoptosis.However,theresults of clinical trials using EGFR inhibitors in patients with solid tumors have been disappointing.Here,wereport a protective effect of the EGFR inhibitors AG1478 and PD153035 against cell death induced by acute hy-poxia,which contrasts with their proapoptotic effects under normoxia.Under hypoxic conditions,both agents re-
文摘（-）-Epigallocatechin gallate （EGCG）, a major polyphenolic constituent of green tea, can inhibit activity of specific receptor tyrosine kinases （RTKs） and related downstream signal transduction pathways, resulting in the control of unwanted cell proliferation. The epidermal growth factor receptor （EGFR） signaling pathway is one of the most important pathways that regulates growth, survival,proliferation and differentiation in mammalian cells. This review addresses the effects of EGCG on some protein factors involved in the EGFR signaling pathway in a direct or indirect manner. Based on our understanding of the interaction between EGCG and these factors, and based on their structures, EGCG could be used as a lead compound for designing and synthesizing novel drugs with significant biological activity.
基金Supported by a grant from the Ministry of Science and Technology ofChina(No.2012AA021502)
文摘Objective： The plasma fibrinogen levels had not only been used as an independent prognostic parameter for the patients with non-small cell lung cancer （NSCLC）, but also as a promising biomarker for evaluating the efficacy of chemotherapy. This study aimed to investigate the correlation between the plasma fibrinogen levels and epidermal growth factor receptor （EGFR） gene mutation and clinical-pathological characteristics of Chinese patients with NSCLC. Methods： In this retrospective study, NSCLC specimens collected from 352 patients between November 2009 and November 2011 were selected to detect EGFR gene mutation with real-time polymerase chain reaction （RT-PCR）. In these specimens, 308 ones were also detected EGFR gene copy number with fluorescence in situ hybridization （FISH）. Coagulation makers were examined prior to the operations. The association between the plasma fibrinogen levels and EGFR gene mutation and clinical-pathological characteristics were analyzed using SPSS 16.0 software. Results： The median pre-operation plasma fibrinogen level was 3.55 g/L （109/352） patients with higher plasma fibrinogen level （〉 4.0 g/L）. The lower plasma fibrinogen levels correlated significantly with EGFR gene mutations （P 〈 0.001）, the similar result was seen in platelet counts （P = 0.026）. A linear correlation was found between the plasma fibrinogen levels and the platelet counts in NSCLC patients （R^2 = 0.209, P 〈 0.001）. Pre-peration plasma fibrinogen levels correlated with gender （P 〈 0.001）, smoking status （P 〈 0.001 ）, and histology （P 〈 0.001 ）. There were significant link between the above clinical-pathological characteristics and EGFR gene mutations. In addition, EGFR gene mutation was correlated with FISH-positive status （P 〈 0.001）. Moreover, both plasma fibrinogen level （P = 0.024） and the EGFR gene copy number （P = 0.040） had significant relationships with the pathological TNM stage. Conclusion： This study showed that a significant relevance between plasma fibrinogen levels and EGFR gene mutations. The plasma fibrinogen level might be as a clinical decision parameter for evaluating the efficacy of anti-EGFR tyrosine kinase inhibitors （TKIs） in NSCLC. The patients of NSCLC had higher indicate have poor benefits from anti-EFGR TKIs. In addition, pre-operation plasma fibrinogen level could be used as an indepedent prognostic biomarker for the patients with NSCLC.
文摘The epidermal growth factor receptor （EGFR） is a member of the ErbB/EGFR family, including EGFR/Herl, ErbB2/Her2, ErbB-3/Her3, and ErbB-4/Her4. EGFR exerts its effects through the receptor tyrosine kinase phosphorylation and activation of important downstream signaling pathways in normal and neoplastic cells, mainly the Ras GTPase/MAP kinase （MAPK）, STAT3, and phosphatidylinositide 3 kinase-AKT pathways. EGFR deregulation is common in malignant glioma, especially primary glioblastoma, and exists in three forms： gene overexpression （amplification）, autocrine effects of EGFR activation, and activating receptor mutation （EGFRvlII）. However, some EGFR abnormalities have also been found in low-grade gliomas, including the nuclear localization of EGFR, expression in the microfoci of anaplastic transformation, and association with neovascularization in the mesenchyma of the glioma, which suggests that some unknown EGFR-related mechanisms are possibly responsible for its central role in the initiation and progression of malignant glioma. Uncovering these mechanisms will have potential value in the development of radio- therapy, chemotherapy, and EGFR-targeted therapy for glioma.
文摘Objectives Epidermal growth factor receptor （EGFR）is a receptor protein tyrosine kinase and plays a critical role in the development and function of the heart.Previous studies have demonstrated that EGFR is involved in regulating electrical excitability of the heart.The present study was designed to investigate whether EGFR activation would mediate myocardial arrhythmias induced by ischemia/reperfu- sion in anaesthetized rats.Methods and results Myocardial ischemia/reperfusion arrhythmias were induced by 10 min ligation of the left anterior descending coronary artery,followed by a 30 min reperfusion in anaesthetized rats.Incidence and severity of cardiac arrhythmias were significantly reduced by pretreatment with the EGFR kinase inhibitor AG556.Phosphorylation level of myocardial EGFR was increased during ischemia and at early reperfusion.Intramyocardial transfection of EGFR siRNA reduced EGFR mRNA and protein,and decreased the incidence of ventricular fibrillation induced by reperfusion.Interestingly,tyrosine phosphorylation levels of cardiac Na<sup>+</sup> channel(I<sub>Na</sub>) and L-type Ca<sup>2+</sup> channel(I<sub>Ca.l</sub>) were significantly increased at corresponding time points to the alteration of phosphorylated EGFR level during reperfusion.AG556 pretreatment countered the increased tyrosine phosphorylation level of Na<sup>+</sup> and L-type Ca<sup>2+</sup> channels induced by reperfusion.No significant alteration was observed in tyrosine phosphorylation levels of cardiac Kv4.2 and Kir2.1 channels during the cardiac ischemia/reperfusion. Conclusions These results demonstrate for the first time that EGFR plays an important role in the genesis of myocardial ischemia/reperfusion arrhythmias,which is likely mediated at least in part by enhancing tyrosine phosphorylation of cardiac Na<sup>+</sup> and L-type Ca<sup>2+</sup> channels.
基金the National Natural Science Foundation(81773982,82003937)Youth Academic leaders of the Qinglan Project in Jiangsu province for financial support。
文摘In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori.The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury(ALI).A lipopolysaccharide(LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting,co-immunoprecipitation,and quantitative real time-PCR analysis.The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA(Pla2g2a)-epidermal growth factor receptor(EGFR).The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation.In addition,M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and m TOR via the inhibition of Pla2g2a-EGFR.Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury,which may represent a promising strategy to treat ALI.
