Colorectal cancer(CRC) is the second most common cause of cancer-related death in western countries. Approximately one-quarter of newly diagnosed patients for CRC have metastases, and a further 40%-50% experience dise...Colorectal cancer(CRC) is the second most common cause of cancer-related death in western countries. Approximately one-quarter of newly diagnosed patients for CRC have metastases, and a further 40%-50% experience disease recurrence or develop metastases after all standard therapies. Therefore, understanding the molecular mechanisms involved in the progression of CRC and subsequently developing novel therapeutic targets is crucial to improve management of CRC and patients' long-term survival. Several tyrosine kinase receptors have been implicated in CRC development, progression and metastasis, including epidermal growth factor receptor(EGFR) and vascular EGFR. Recently, tropomyosin-related kinase B(Trk B), a tyrosine kinase receptor, has been reported in CRC and found to clearly exert several biological and clinical features, such as tumor cell growth and survival in vitro and in vivo, metastasis formation and poor prognosis. Here we review the significance of Trk B and its ligand brain derived-neurotrophic factor in CRC. We focus on their expression in CRC tumor samples, and their functional roles in CRC cell lines and in in vivo models. Finally we discuss therapeutic approaches that can lead to the development of novel therapeutic agents for treating Trk B-expressing CRC tumors.展开更多
Brain-derived neurotrophic factor was utilized in the present study to treat cell injury models induced by aggregated β-amyloid（25 35）. Methylthiazolyldiphenyl-tetrazolium bromide assay and western blot analysis sh...Brain-derived neurotrophic factor was utilized in the present study to treat cell injury models induced by aggregated β-amyloid（25 35）. Methylthiazolyldiphenyl-tetrazolium bromide assay and western blot analysis showed that brain-derived neurotrophic factor provided neuroprotection against cellular apoptosis by suppressing the decline in β-amyloid（25 35）-induced cell activity and the increasing ratio of Bax/Bcl-2. After treating pheochromocytoma cells with tyrosine kinase receptor B receptor inhibitor K252a, brain-derived neurotrophic factor reverses the above- mentioned changes. The experimental findings suggested that brain-derived neurotrophic factor prevented β-amyloid peptide-induced cellular apoptosis by modulating Bax/Bcl-2 expression, and this effect was associated with binding to the specific tyrosine kinase receptor B receptor.展开更多
BACKGROUND： Exogenous brain-derived neurotrophic factor （BDNF） promotes retinal ganglion cell survival. However, the protective mechanisms remain unclear. OBJECTIVE： To investigate changes in retinal tyrosine kina...BACKGROUND： Exogenous brain-derived neurotrophic factor （BDNF） promotes retinal ganglion cell survival. However, the protective mechanisms remain unclear. OBJECTIVE： To investigate changes in retinal tyrosine kinase receptor B （trkB） expression and effects of exogenous BDNF on trkB activation in a rat model of acute high intraocular pressure （HtOP）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Department of Anatomy and Neurobiology, Xiangya Medical School, Central South University from January 2004 to August 2006. MATERIALS： Rabbit anti-BDNF and anti-trkB.FL（full-length） polyclonal antibodies were purchased from Santa Cruz Biotechnology, USA; rabbit anti-p-trkB polyclonal antibodies were purchased from Cellsignal, USA. METHODS： A total of 48 healthy, adult, Sprague Dawiey rats were randomly assigned to acute HIOP （without BDNF pre-treatment） and BDNF pre-treated groups, with 24 animals in each group. In the BDNF pre-treated group, the left eyes were intravitreally injected with 3 pg/kg BDNF 2 days prior to HIOP. Rats in the acute HIOP group were not pre-treated with BDNE HIOP models were established by increased intraocular pressure in the left eyes until the b-wave of flash electroretinogragh disappeared and pressure was maintained for 60 minutes. The right eyes of all rats were not treated and served as the normal controls. MAIN OUTCOME MEASURES： Retinal structure and cell numbers in the ganglion cell layer （GCL） were detected by Nissl staining; expression of trkB and phosphorylated trkB in the rat retina were determined by immunohistochemistry. RESULTS： A greater number of GCL neurons were observed in the pre-treated group compared to the acute HIOP group （P 〈 0.05）. TrkB expression was significantly increased following HIOP at days 1 and 3 （P 〈 0.05）, but expression varied between retinal areas. Although trkB expression decreased at 7 days, phosphorylated trkB dramatically decreased with increasing time （P 〈 0.05）. TrkB expression in BDNF pre-treated rats was similar to the acute HIOP group at early injury time points. Nevertheless, trkB expression was significantly decreased compared to the acute HIOP group at 7 days （P 〈 0.05）, and phosphorylated trkB expression was significantly greater compared to the acute HIOP group at each time point （P〈 0.05）. CONCLUSION： TrkB expression displayed temporal and spatial changes in the rat retina following acute HIOP, and trkB up-regulation suggested that more BDNF was required for treating the injured retina. Exogenous BDNF partially ameliorated decreased expression of phosphorylated trkB and provided protection to the injured retina, to a certain degree, following HIOP.展开更多
Tyrosine kinase receptor B （TrkB） plays an important role in long-term potentiation and memory formation.The present study used all-trans retinoic acid to induce TrkB expression in SH-SY5Y cells,and observed the eff...Tyrosine kinase receptor B （TrkB） plays an important role in long-term potentiation and memory formation.The present study used all-trans retinoic acid to induce TrkB expression in SH-SY5Y cells,and observed the effects of levetiracetam （LEV） on TrkB expression.Following exposure to 10,50,and 100 μg/mL LEV,the number of TrkB-positive cells,and average absorbance value were increased.Results demonstrated that LEV can induce TrkB expression in SH-SY5Y cells.展开更多
Electroacupuncture(EA)has been widely used for functional restoration after stroke.However,its role in post-stroke rehabilitation and the associated regulatory mechanisms remain poorly understood.In this study,we appl...Electroacupuncture(EA)has been widely used for functional restoration after stroke.However,its role in post-stroke rehabilitation and the associated regulatory mechanisms remain poorly understood.In this study,we applied EA to the Zusanli(ST36)and Quchi(LI11)acupoints in rats with middle cerebral artery occlusion and reperfusion.We found that EA effectively increased the expression of brain-derived neurotrophic factor and its receptor tyrosine kinase B,synapsin-1,postsynaptic dense protein 95,and microtubule-associated protein 2 in the ischemic penumbra of rats with middle cerebral artery occlusion and reperfusion.Moreover,EA greatly reduced the expression of myelin-related inhibitors Nogo-A and NgR in the ischemic penumbra.Tyrosine kinase B inhibitor ANA-12 weakened the therapeutic effects of EA.These findings suggest that EA can improve neurological function after middle cerebral artery occlusion and reperfusion,possibly through regulating the activity of the brain-derived neurotrophic factor/tyrosine kinase B signal pathway.All procedures and experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine,China(approval No.PZSHUTCM200110002)on January 10,2020.展开更多
Entacapone,a catechol-O-methyltransferase inhibitor,can strengthen the therapeutic effects of levodopa on the treatment of Parkinson’s disease.However,few studies are reported on whether entacapone can affect hippoca...Entacapone,a catechol-O-methyltransferase inhibitor,can strengthen the therapeutic effects of levodopa on the treatment of Parkinson’s disease.However,few studies are reported on whether entacapone can affect hippocampal neurogenesis in mice.To investigate the effects of entacapone,a modulator of dopamine,on proliferating cells and immature neurons in the mouse hippocampal dentate gyrus,60 mice(7 weeks old)were randomly divided into a vehicle-treated group and the groups treated with 10,50,or 200 mg/kg entacapone.The results showed that 50 and 200 mg/kg entacapone increased the exploration time for novel object recognition.Immunohistochemical staining results revealed that after entacapone treatment,the numbers of Ki67-positive proliferating cells,doublecortin-positive immature neurons,and phosphorylated cAMP response element-binding protein(pCREB)-positive cells were significantly increased.Western blot analysis results revealed that treatment with tyrosine kinase receptor B(TrkB)receptor antagonist significantly decreased the exploration time for novel object recognition and inhibited the expression of phosphorylated TrkB and brain-derived neurotrophic factor(BDNF).Entacapone treatment antagonized the effects of TrkB receptor antagonist.These results suggest that entacapone treatment promoted hippocampal neurogenesis and improved memory function through activating the BDNF-TrkB-pCREB pathway.This study was approved by the Institutional Animal Care and Use Committee of Seoul National University(approval No.SNU-130730-1)on February 24,2014.展开更多
基金Supported by Conseil Régional du Limousin and the CORC ComitéOrientation Recherche Cancer
文摘Colorectal cancer(CRC) is the second most common cause of cancer-related death in western countries. Approximately one-quarter of newly diagnosed patients for CRC have metastases, and a further 40%-50% experience disease recurrence or develop metastases after all standard therapies. Therefore, understanding the molecular mechanisms involved in the progression of CRC and subsequently developing novel therapeutic targets is crucial to improve management of CRC and patients' long-term survival. Several tyrosine kinase receptors have been implicated in CRC development, progression and metastasis, including epidermal growth factor receptor(EGFR) and vascular EGFR. Recently, tropomyosin-related kinase B(Trk B), a tyrosine kinase receptor, has been reported in CRC and found to clearly exert several biological and clinical features, such as tumor cell growth and survival in vitro and in vivo, metastasis formation and poor prognosis. Here we review the significance of Trk B and its ligand brain derived-neurotrophic factor in CRC. We focus on their expression in CRC tumor samples, and their functional roles in CRC cell lines and in in vivo models. Finally we discuss therapeutic approaches that can lead to the development of novel therapeutic agents for treating Trk B-expressing CRC tumors.
文摘Brain-derived neurotrophic factor was utilized in the present study to treat cell injury models induced by aggregated β-amyloid（25 35）. Methylthiazolyldiphenyl-tetrazolium bromide assay and western blot analysis showed that brain-derived neurotrophic factor provided neuroprotection against cellular apoptosis by suppressing the decline in β-amyloid（25 35）-induced cell activity and the increasing ratio of Bax/Bcl-2. After treating pheochromocytoma cells with tyrosine kinase receptor B receptor inhibitor K252a, brain-derived neurotrophic factor reverses the above- mentioned changes. The experimental findings suggested that brain-derived neurotrophic factor prevented β-amyloid peptide-induced cellular apoptosis by modulating Bax/Bcl-2 expression, and this effect was associated with binding to the specific tyrosine kinase receptor B receptor.
基金the National Natural Science Foundation of China, No. 30100098, 30570979
文摘BACKGROUND： Exogenous brain-derived neurotrophic factor （BDNF） promotes retinal ganglion cell survival. However, the protective mechanisms remain unclear. OBJECTIVE： To investigate changes in retinal tyrosine kinase receptor B （trkB） expression and effects of exogenous BDNF on trkB activation in a rat model of acute high intraocular pressure （HtOP）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Department of Anatomy and Neurobiology, Xiangya Medical School, Central South University from January 2004 to August 2006. MATERIALS： Rabbit anti-BDNF and anti-trkB.FL（full-length） polyclonal antibodies were purchased from Santa Cruz Biotechnology, USA; rabbit anti-p-trkB polyclonal antibodies were purchased from Cellsignal, USA. METHODS： A total of 48 healthy, adult, Sprague Dawiey rats were randomly assigned to acute HIOP （without BDNF pre-treatment） and BDNF pre-treated groups, with 24 animals in each group. In the BDNF pre-treated group, the left eyes were intravitreally injected with 3 pg/kg BDNF 2 days prior to HIOP. Rats in the acute HIOP group were not pre-treated with BDNE HIOP models were established by increased intraocular pressure in the left eyes until the b-wave of flash electroretinogragh disappeared and pressure was maintained for 60 minutes. The right eyes of all rats were not treated and served as the normal controls. MAIN OUTCOME MEASURES： Retinal structure and cell numbers in the ganglion cell layer （GCL） were detected by Nissl staining; expression of trkB and phosphorylated trkB in the rat retina were determined by immunohistochemistry. RESULTS： A greater number of GCL neurons were observed in the pre-treated group compared to the acute HIOP group （P 〈 0.05）. TrkB expression was significantly increased following HIOP at days 1 and 3 （P 〈 0.05）, but expression varied between retinal areas. Although trkB expression decreased at 7 days, phosphorylated trkB dramatically decreased with increasing time （P 〈 0.05）. TrkB expression in BDNF pre-treated rats was similar to the acute HIOP group at early injury time points. Nevertheless, trkB expression was significantly decreased compared to the acute HIOP group at 7 days （P 〈 0.05）, and phosphorylated trkB expression was significantly greater compared to the acute HIOP group at each time point （P〈 0.05）. CONCLUSION： TrkB expression displayed temporal and spatial changes in the rat retina following acute HIOP, and trkB up-regulation suggested that more BDNF was required for treating the injured retina. Exogenous BDNF partially ameliorated decreased expression of phosphorylated trkB and provided protection to the injured retina, to a certain degree, following HIOP.
文摘Tyrosine kinase receptor B （TrkB） plays an important role in long-term potentiation and memory formation.The present study used all-trans retinoic acid to induce TrkB expression in SH-SY5Y cells,and observed the effects of levetiracetam （LEV） on TrkB expression.Following exposure to 10,50,and 100 μg/mL LEV,the number of TrkB-positive cells,and average absorbance value were increased.Results demonstrated that LEV can induce TrkB expression in SH-SY5Y cells.
基金supported by the National Key R&D Program of China,No.2018YFC2001600(to JGX)the National Natural Science Foundation of China,No.81902301(to JJW)+3 种基金Budgetary Project of Shanghai University of Traditional Chinese Medicine of China,No.2019LK024(to JJW)Intelligent Medical Program of Shanghai(Municipal)Health Commission of China,No.2018ZHYL0216(to CLS)Clinical Science and Technology Innovation Project of Shanghai Shen Kang Hospital Development Center of China,No.SHDC12018126(to CLS)Accelerated the Development of Traditional Chinese Medicine Three-Year Action Plan Project(of Shanghai Health Commission)of China,Nos.ZY(2018-2020)-CCCX-2001-06(to JGX and CLS)and ZY(2018-2020)-CCCX-2004-05(to JGX and CLS)。
文摘Electroacupuncture(EA)has been widely used for functional restoration after stroke.However,its role in post-stroke rehabilitation and the associated regulatory mechanisms remain poorly understood.In this study,we applied EA to the Zusanli(ST36)and Quchi(LI11)acupoints in rats with middle cerebral artery occlusion and reperfusion.We found that EA effectively increased the expression of brain-derived neurotrophic factor and its receptor tyrosine kinase B,synapsin-1,postsynaptic dense protein 95,and microtubule-associated protein 2 in the ischemic penumbra of rats with middle cerebral artery occlusion and reperfusion.Moreover,EA greatly reduced the expression of myelin-related inhibitors Nogo-A and NgR in the ischemic penumbra.Tyrosine kinase B inhibitor ANA-12 weakened the therapeutic effects of EA.These findings suggest that EA can improve neurological function after middle cerebral artery occlusion and reperfusion,possibly through regulating the activity of the brain-derived neurotrophic factor/tyrosine kinase B signal pathway.All procedures and experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine,China(approval No.PZSHUTCM200110002)on January 10,2020.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea Government(MSIP)(NRF-2016R1A2B4009156)the Promising-Pioneering Researcher Program through Seoul National University(SNU)in 2015 and by the Research Institute for Veterinary Science,Seoul National University.
文摘Entacapone,a catechol-O-methyltransferase inhibitor,can strengthen the therapeutic effects of levodopa on the treatment of Parkinson’s disease.However,few studies are reported on whether entacapone can affect hippocampal neurogenesis in mice.To investigate the effects of entacapone,a modulator of dopamine,on proliferating cells and immature neurons in the mouse hippocampal dentate gyrus,60 mice(7 weeks old)were randomly divided into a vehicle-treated group and the groups treated with 10,50,or 200 mg/kg entacapone.The results showed that 50 and 200 mg/kg entacapone increased the exploration time for novel object recognition.Immunohistochemical staining results revealed that after entacapone treatment,the numbers of Ki67-positive proliferating cells,doublecortin-positive immature neurons,and phosphorylated cAMP response element-binding protein(pCREB)-positive cells were significantly increased.Western blot analysis results revealed that treatment with tyrosine kinase receptor B(TrkB)receptor antagonist significantly decreased the exploration time for novel object recognition and inhibited the expression of phosphorylated TrkB and brain-derived neurotrophic factor(BDNF).Entacapone treatment antagonized the effects of TrkB receptor antagonist.These results suggest that entacapone treatment promoted hippocampal neurogenesis and improved memory function through activating the BDNF-TrkB-pCREB pathway.This study was approved by the Institutional Animal Care and Use Committee of Seoul National University(approval No.SNU-130730-1)on February 24,2014.
