The Epidermal Growth Factor system is present in human organs and plays an important role in cell proliferation, differentiation and apoptosis during embryogenesis and postnatal development. It has four receptors (EGF...The Epidermal Growth Factor system is present in human organs and plays an important role in cell proliferation, differentiation and apoptosis during embryogenesis and postnatal development. It has four receptors (EGFR, ErbB-2, ErbB-3 and ErbB-4) and numerous ligands. Dysregulation of the Epidermal Growth Factor signaling network is implicated in the pathogenesis of various disorders. Especially in cancer, the Epidermal Growth Factor system becomes hyperactivated with various mechanisms (ligand overproduction, receptor overproduction, constitutive receptor activation). EGFR overexpression may have a dual role in endometrial cancer. It seems that in type I endometrial cancer, EGFR overexpression did not affect disease progression. However in type II endometrial cancer, EGFR overexpression associated with high grade disease and adverse clinical outcome. Moreover ΕrbB-2 overexpression especially in type II endometrial cancer, is an indicator of a highly aggressive disease with poor overall survival. The potential role of ErbB receptors (especially EGFR and ErbB-2) as targets for cancer therapy has been investigated for over 20 years. There are 2 major classes of ErbB targeted therapies: anti-ErbB monoclonal antibodies (MoAbs) and ErbB-specific tyrosine kinase inhibitors (TKIs). ErbB targeted therapies have still shown modest effect in unselected endometrial cancer patients. However, they may be clinically active as adjuvant therapy in well-defined subgroups of type II endometrial cancer patients with EGFR and ErbB-2 overexpression.展开更多
Background Mesenchymal stem cells are a promising cell type for cell transplantation in myocardial infarction. Type I neuregulins-1, also known as heregulin, can promote the survival of cardiomyocytes and stimulate an...Background Mesenchymal stem cells are a promising cell type for cell transplantation in myocardial infarction. Type I neuregulins-1, also known as heregulin, can promote the survival of cardiomyocytes and stimulate angiogenesis. The purpose of this study was to investigate the expression of heregulin and ErbB receptors in mesenchymal stem cells, then further detect the secretion of heregulin and the changes in expression of heregulin and ErbB receptors under conditions of serum deprivation and hvooxia. Methods Mesenchymal stem cells isolated from bone marrow of 180 g male Sprague-Dawley rats were cultured. Passage 3 cells were detected experimentally by regular reverse transcriptase-polymerase chain reaction （RT-PCR）, quantitative real time PCR and Western blotting.Results Heregulin and ErbB receptors were expressed in mesenchymal stem cells, and all three ErbB receptors mRNA expressions were significantly down-regulated by serum deprivation and hypoxia, but serum deprivation and hypoxia significantly increased the protein expression of heregulin. Serum deprivation and hypoxia more than 12 hours could induce the secretion of heregulin.Conclusions Mesenchymal stem cells can express all three ErbB receptors and heregulin. Serum deprivation and hypoxia decrease the mRNA expression of ErbB receptors, increase the expression of heregulin, and activate the secretion of heregulin.展开更多
Cytologic locailzation of epidermai growth factor receptor (EGF-R) and C-erbB2oncogene product in normal developing placenta ovas studied by avidin/biotin immunoperoxidase techniques.Both proteins were predominantly e...Cytologic locailzation of epidermai growth factor receptor (EGF-R) and C-erbB2oncogene product in normal developing placenta ovas studied by avidin/biotin immunoperoxidase techniques.Both proteins were predominantly expressed in the villous syncytiotrophoblasts but not in the cytotrophoblasts.The immunoreactive intensity for EGF-R decreased with the development of pregnancy.Concerning the intermediate trophoblasts in cell islands and cell columns,both proteins were more easily detected in the cells distal to the villous stroma than in the juxtastromal cells.These findings suggest that EGF-R and C-erbB-2 may play a significant role in the induction and regulation of differentiated trophoblast function展开更多
It is first reported here that estrogen occupied receptor(EoR)and progesterone occupied receptor (RoR)expressed in cancerous tissues (59.57% and 82.98% respectively)and morphologically normal epithlium(50 77.78% and ...It is first reported here that estrogen occupied receptor(EoR)and progesterone occupied receptor (RoR)expressed in cancerous tissues (59.57% and 82.98% respectively)and morphologically normal epithlium(50 77.78% and 70-88.89%respectively) in nasoplharyngeal carcinomas(NPCs)with insignificant difference(P>0.05).Positive rates of EoR and PoR increased greatly in clinical stage Ⅲ and Ⅳ, compared with in Ⅱ(P<0.05), and exhibited insignificant difference between female cases and male ones(P>0.05).Positive rate of C-erbB-2 was 19.15% in cancerous cells, and 9.68% in stage Ⅲand 66.67% in Ⅳin NPCs(P<0.05).Significant difference of C-erbB-2expression was observed between bilateral cervical lymph node metastasis(BCLM)and unilateral ones(P<0.05)but not for EoR or PoR(P>0.05)These findings suggest that EoR or PoR may be correlated with aggravation but not genesis and node metastasis in NPCs and that C-erbB-2may be correlated with aggravation and promotion of formation of node metastasis in NPCs.展开更多
目的考察多柔比星对中枢神经系统的致抑郁作用,并探究其潜在的毒性作用机制。方法 SD大鼠随机分为3组:对照组、多柔比星短期给药组(DoxS)、多柔比星长期给药组(DoxL)。DoxS组腹腔注射DOX(2.5 mg·kg^(-1)),2 d 1次,共3次;DoxL组腹...目的考察多柔比星对中枢神经系统的致抑郁作用,并探究其潜在的毒性作用机制。方法 SD大鼠随机分为3组:对照组、多柔比星短期给药组(DoxS)、多柔比星长期给药组(DoxL)。DoxS组腹腔注射DOX(2.5 mg·kg^(-1)),2 d 1次,共3次;DoxL组腹腔注射DOX(2.5 mg·kg^(-1)),2 d 1次,共7次;对照组给予相同体积的生理盐水。同时检测给药前后体重变化、糖水偏好度,考察强迫游泳行为学,PCR和免疫印迹方法对NRG1/ErbB通路mRNA及相关蛋白水平,及下游信号通路Akt、ERK蛋白水平进行检测。结果 DoxS组大鼠糖水偏好度及强迫游泳不动时间与对照组相比无明显差别,短期给予多柔比星增加了NRG1/ErbB mRNA及相关蛋白磷酸化的表达;DoxL组大鼠表现出较低的糖水偏好度及增加的强迫游泳不动时间,长期给予多柔比星降低NRG1/ErbB mRNA及相关蛋白磷酸化水平。结论短期给予多柔比星代偿性的激活了NRG1/ErbB通路,而长期给予多柔比星则会抑制该通路并诱导大鼠抑郁样行为,这些证据表明多柔比星对NRG1/ErbB通路的抑制作用与其神经毒性有关。展开更多
文摘The Epidermal Growth Factor system is present in human organs and plays an important role in cell proliferation, differentiation and apoptosis during embryogenesis and postnatal development. It has four receptors (EGFR, ErbB-2, ErbB-3 and ErbB-4) and numerous ligands. Dysregulation of the Epidermal Growth Factor signaling network is implicated in the pathogenesis of various disorders. Especially in cancer, the Epidermal Growth Factor system becomes hyperactivated with various mechanisms (ligand overproduction, receptor overproduction, constitutive receptor activation). EGFR overexpression may have a dual role in endometrial cancer. It seems that in type I endometrial cancer, EGFR overexpression did not affect disease progression. However in type II endometrial cancer, EGFR overexpression associated with high grade disease and adverse clinical outcome. Moreover ΕrbB-2 overexpression especially in type II endometrial cancer, is an indicator of a highly aggressive disease with poor overall survival. The potential role of ErbB receptors (especially EGFR and ErbB-2) as targets for cancer therapy has been investigated for over 20 years. There are 2 major classes of ErbB targeted therapies: anti-ErbB monoclonal antibodies (MoAbs) and ErbB-specific tyrosine kinase inhibitors (TKIs). ErbB targeted therapies have still shown modest effect in unselected endometrial cancer patients. However, they may be clinically active as adjuvant therapy in well-defined subgroups of type II endometrial cancer patients with EGFR and ErbB-2 overexpression.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30670868） and the Provincial Natural Science Foundation of Zhejiang （No. R206007）.
文摘Background Mesenchymal stem cells are a promising cell type for cell transplantation in myocardial infarction. Type I neuregulins-1, also known as heregulin, can promote the survival of cardiomyocytes and stimulate angiogenesis. The purpose of this study was to investigate the expression of heregulin and ErbB receptors in mesenchymal stem cells, then further detect the secretion of heregulin and the changes in expression of heregulin and ErbB receptors under conditions of serum deprivation and hvooxia. Methods Mesenchymal stem cells isolated from bone marrow of 180 g male Sprague-Dawley rats were cultured. Passage 3 cells were detected experimentally by regular reverse transcriptase-polymerase chain reaction （RT-PCR）, quantitative real time PCR and Western blotting.Results Heregulin and ErbB receptors were expressed in mesenchymal stem cells, and all three ErbB receptors mRNA expressions were significantly down-regulated by serum deprivation and hypoxia, but serum deprivation and hypoxia significantly increased the protein expression of heregulin. Serum deprivation and hypoxia more than 12 hours could induce the secretion of heregulin.Conclusions Mesenchymal stem cells can express all three ErbB receptors and heregulin. Serum deprivation and hypoxia decrease the mRNA expression of ErbB receptors, increase the expression of heregulin, and activate the secretion of heregulin.
文摘Cytologic locailzation of epidermai growth factor receptor (EGF-R) and C-erbB2oncogene product in normal developing placenta ovas studied by avidin/biotin immunoperoxidase techniques.Both proteins were predominantly expressed in the villous syncytiotrophoblasts but not in the cytotrophoblasts.The immunoreactive intensity for EGF-R decreased with the development of pregnancy.Concerning the intermediate trophoblasts in cell islands and cell columns,both proteins were more easily detected in the cells distal to the villous stroma than in the juxtastromal cells.These findings suggest that EGF-R and C-erbB-2 may play a significant role in the induction and regulation of differentiated trophoblast function
文摘It is first reported here that estrogen occupied receptor(EoR)and progesterone occupied receptor (RoR)expressed in cancerous tissues (59.57% and 82.98% respectively)and morphologically normal epithlium(50 77.78% and 70-88.89%respectively) in nasoplharyngeal carcinomas(NPCs)with insignificant difference(P>0.05).Positive rates of EoR and PoR increased greatly in clinical stage Ⅲ and Ⅳ, compared with in Ⅱ(P<0.05), and exhibited insignificant difference between female cases and male ones(P>0.05).Positive rate of C-erbB-2 was 19.15% in cancerous cells, and 9.68% in stage Ⅲand 66.67% in Ⅳin NPCs(P<0.05).Significant difference of C-erbB-2expression was observed between bilateral cervical lymph node metastasis(BCLM)and unilateral ones(P<0.05)but not for EoR or PoR(P>0.05)These findings suggest that EoR or PoR may be correlated with aggravation but not genesis and node metastasis in NPCs and that C-erbB-2may be correlated with aggravation and promotion of formation of node metastasis in NPCs.
