AIM: There is strong evidence that tyrosine kinases are involved in the regulation of tumor progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, among...AIM: There is strong evidence that tyrosine kinases are involved in the regulation of tumor progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, among them Tie-1 and Tie-2 receptors constitute a major class.Angiopoietin (Ang)-1 is known as a ligand ofTie-2 tyrosine kinase receptor. The objective of this study was to establish a comprehensive Tie-1 and Tie-2 and Ang-1, 2 and 4expression profile in human colorectal adenocarcinomas.METHODS: We examined 96 cases of surgically resected human colorectal adenocarcinoma by immunohistochemistry and investigated the statistical correlation between the expressions of Ties and Angs and clinicopathological factors.RESULTS: Among the 96 cases of adenocarcinoma, 87(90.6%), 92 (95.8%), 83 (86.5%), 89 (92.7%), and 76cases (79.2%) showed positive staining in the cytoplasm of carcinoma cells for the Tie-1 and Tie-2 and Ang-1, 2and 4 proteins, respectively. Histologically, the expressions of Ties and Angs were variable. The expressions of Ties and Angs were correlated with several clinicopathological factors, but did not correlate with the presence of lymph node metastasis. Ties and Angs were highly expressed in human colorectal adenocarcinoma cells.CONCLUSION: These findings suggest that the Tie-Ang receptor-ligand complex is one of the factors involved in the cellular differentiation and progression of human colorectal adenocarcinoma.展开更多
Aerobic glycolysis is critical for tumor growth and metastasis.Previously,we have found that the overexpression of the inhibitor of growth 5(ING5)inhibits lung cancer aggressiveness and epithelial–mesenchymal transit...Aerobic glycolysis is critical for tumor growth and metastasis.Previously,we have found that the overexpression of the inhibitor of growth 5(ING5)inhibits lung cancer aggressiveness and epithelial–mesenchymal transition(EMT).However,whether ING5 regulates lung cancer metabolism reprogramming remains unknown.Here,by quantitative proteomics,we showed that ING5 differentially regulates protein phosphorylation and identified a new site(Y163)of the key glycolytic enzyme PDK1 whose phosphorylation was upregulated 13.847-fold.By clinical study,decreased p-PDK1Y163 was observed in lung cancer tissues and correlated with poor survival.p-PDK1Y163 represents the negative regulatory mechanism of PDK1 by causing PDHA1 dephosphorylation and activation,leading to switching from glycolysis to oxidative phosphorylation,with increasing oxygen consumption and decreasing lactate production.These effects could be impaired by PDK1Y163F mutation,which also impaired the inhibitory effects of ING5 on cancer cell EMT and invasiveness.Mouse xenograft models confirmed the indispensable role of p-PDK1Y163 in ING5-inhibited tumor growth and metastasis.By siRNA screening,ING5-upregulated TIE1 was identified as the upstream tyrosine protein kinase targeting PDK1Y163.TIE1 knockdown induced the dephosphorylation of PDK1Y163 and increased the migration and invasion of lung cancer cells.Collectively,ING5 overexpression—upregulated TIE1 phosphorylates PDK1Y163,which is critical for the inhibition of aerobic glycolysis and invasiveness of lung cancer cells.展开更多
Detailed structural and dielectric properties of Lanthanum-doped barium titanate Ba_(1-x)La_(x)Tie_(1-x/4)O_(3)ceramic powders BLTx(where x=0:00;0.10;0.20;0.30 and 0.40)/BT,BLT10,BLT20,BLT30 and BLT40,synthesized by t...Detailed structural and dielectric properties of Lanthanum-doped barium titanate Ba_(1-x)La_(x)Tie_(1-x/4)O_(3)ceramic powders BLTx(where x=0:00;0.10;0.20;0.30 and 0.40)/BT,BLT10,BLT20,BLT30 and BLT40,synthesized by the sol gel process,calcined at 900℃for 3 h and sintered at 1250○C for 6 h,have been investigated.The phase formation and crystal structure of the samples were checked by X-ray diffraction(XRD)and Raman spectroscopy.The samples crystallize in the pure perovskite structure that transforms from tetragonal to pseudocubic under doping with La;results that have been confirmed by Rietveld Refinement technique.The estimated average crystallite size of the samples was about 23 nm.Dielectric parameters(dielectric permittivity and losses)were determined in the temperature range room temperature(RT)-280℃and in the frequency range 500 Hz-2 MHz.La doping gives rise to a strong decrease of the ferro-to-paraelectric transition temperature,and the frequency dependence of the permittivity shows that the samples with x=0.00 and x=0.10 reach their resonance frequency.The frequency dependence of impedance and electric modulus properties were studied over a wide frequency range from 1 kHz to 2MHz at various temperatures to confirm the contributions from grains and grain-boundaries.The complex impedance analysis data have been presented in the Nyquist plot which is used to identify the corresponding equivalent circuit and fundamental circuit parameters;it was found that the grain boundaries resistance is dominant at room temperature.The frequency dependence of the parameters permittivity,losses and AC conductivity reveals that the relaxation process is of the Maxwell-Wagner type of interfacial polarization.展开更多
文摘AIM: There is strong evidence that tyrosine kinases are involved in the regulation of tumor progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, among them Tie-1 and Tie-2 receptors constitute a major class.Angiopoietin (Ang)-1 is known as a ligand ofTie-2 tyrosine kinase receptor. The objective of this study was to establish a comprehensive Tie-1 and Tie-2 and Ang-1, 2 and 4expression profile in human colorectal adenocarcinomas.METHODS: We examined 96 cases of surgically resected human colorectal adenocarcinoma by immunohistochemistry and investigated the statistical correlation between the expressions of Ties and Angs and clinicopathological factors.RESULTS: Among the 96 cases of adenocarcinoma, 87(90.6%), 92 (95.8%), 83 (86.5%), 89 (92.7%), and 76cases (79.2%) showed positive staining in the cytoplasm of carcinoma cells for the Tie-1 and Tie-2 and Ang-1, 2and 4 proteins, respectively. Histologically, the expressions of Ties and Angs were variable. The expressions of Ties and Angs were correlated with several clinicopathological factors, but did not correlate with the presence of lymph node metastasis. Ties and Angs were highly expressed in human colorectal adenocarcinoma cells.CONCLUSION: These findings suggest that the Tie-Ang receptor-ligand complex is one of the factors involved in the cellular differentiation and progression of human colorectal adenocarcinoma.
文摘形成血管和淋巴管内层的内皮细胞是脉管系统的重要组成部分,并参与血管和淋巴系统疾病的发病机制。内皮细胞上的血管生成素(Angiopoietin,Ang)-具有免疫球蛋白和表皮生长因子同源性结构域的酪氨酸蛋白激酶(Tyrosine kinase receptors with immunoglobulin and EGF homology domains,Tie)轴是除了血管内皮生长因子受体途径外胚胎心血管和淋巴发育所必需的第二种内皮细胞特异性配体-受体信号传导系统。Ang-Tie轴参与调节产后血管生成与重塑、血管通透性和炎症,以维持血管平衡,因此,该系统在许多血管和淋巴系统疾病中发挥重要的作用。针对近年来Ang-Tie轴在血管和淋巴系统相关疾病中作用的研究进展,文中系统论述了Ang-Tie轴在炎症诱导的血管通透性、血管重塑、眼部新生脉管、剪切应力反应、动脉粥样硬化和肿瘤血管生成和转移中的作用,并总结了涉及Ang-Tie轴的相关治疗性抗体、重组蛋白和小分子药物。
基金supported by the National Natural Science Foundation of China(Nos.81672269,81272587,and 81172223).
文摘Aerobic glycolysis is critical for tumor growth and metastasis.Previously,we have found that the overexpression of the inhibitor of growth 5(ING5)inhibits lung cancer aggressiveness and epithelial–mesenchymal transition(EMT).However,whether ING5 regulates lung cancer metabolism reprogramming remains unknown.Here,by quantitative proteomics,we showed that ING5 differentially regulates protein phosphorylation and identified a new site(Y163)of the key glycolytic enzyme PDK1 whose phosphorylation was upregulated 13.847-fold.By clinical study,decreased p-PDK1Y163 was observed in lung cancer tissues and correlated with poor survival.p-PDK1Y163 represents the negative regulatory mechanism of PDK1 by causing PDHA1 dephosphorylation and activation,leading to switching from glycolysis to oxidative phosphorylation,with increasing oxygen consumption and decreasing lactate production.These effects could be impaired by PDK1Y163F mutation,which also impaired the inhibitory effects of ING5 on cancer cell EMT and invasiveness.Mouse xenograft models confirmed the indispensable role of p-PDK1Y163 in ING5-inhibited tumor growth and metastasis.By siRNA screening,ING5-upregulated TIE1 was identified as the upstream tyrosine protein kinase targeting PDK1Y163.TIE1 knockdown induced the dephosphorylation of PDK1Y163 and increased the migration and invasion of lung cancer cells.Collectively,ING5 overexpression—upregulated TIE1 phosphorylates PDK1Y163,which is critical for the inhibition of aerobic glycolysis and invasiveness of lung cancer cells.
文摘Detailed structural and dielectric properties of Lanthanum-doped barium titanate Ba_(1-x)La_(x)Tie_(1-x/4)O_(3)ceramic powders BLTx(where x=0:00;0.10;0.20;0.30 and 0.40)/BT,BLT10,BLT20,BLT30 and BLT40,synthesized by the sol gel process,calcined at 900℃for 3 h and sintered at 1250○C for 6 h,have been investigated.The phase formation and crystal structure of the samples were checked by X-ray diffraction(XRD)and Raman spectroscopy.The samples crystallize in the pure perovskite structure that transforms from tetragonal to pseudocubic under doping with La;results that have been confirmed by Rietveld Refinement technique.The estimated average crystallite size of the samples was about 23 nm.Dielectric parameters(dielectric permittivity and losses)were determined in the temperature range room temperature(RT)-280℃and in the frequency range 500 Hz-2 MHz.La doping gives rise to a strong decrease of the ferro-to-paraelectric transition temperature,and the frequency dependence of the permittivity shows that the samples with x=0.00 and x=0.10 reach their resonance frequency.The frequency dependence of impedance and electric modulus properties were studied over a wide frequency range from 1 kHz to 2MHz at various temperatures to confirm the contributions from grains and grain-boundaries.The complex impedance analysis data have been presented in the Nyquist plot which is used to identify the corresponding equivalent circuit and fundamental circuit parameters;it was found that the grain boundaries resistance is dominant at room temperature.The frequency dependence of the parameters permittivity,losses and AC conductivity reveals that the relaxation process is of the Maxwell-Wagner type of interfacial polarization.
