Hepatocellular carcinoma （HCC） is a major health prob- lem, being the sixth most common cancer world-wide. Dysregulation of the balance between proliferation and cell death represents a pro-tumorigenic principle in ...Hepatocellular carcinoma （HCC） is a major health prob- lem, being the sixth most common cancer world-wide. Dysregulation of the balance between proliferation and cell death represents a pro-tumorigenic principle in hu- man hepatocarcinogenesis. This review updates the recent relevant contributions reporting molecular altera- tions for HCC that induce an imbalance in the regulation of apoptosis. Alterations in the expression and/or activation of p53 are frequent in HCC cells, which confer on them resistance to chemotherapeutic drugs. Many HCCs are also insensitive to apoptosis induced either by death receptor ligands, such as FasL or TRAIL, or by transforming growth factor-beta （TGF-β）. Although the expression of some pro-apoptotic genes is decreased, the balance between death and survival is dysregulated in HCC mainly due to overactivation of anti-apoptotic pathways. Indeed, some molecules involved in counter- acting apoptosis, such as Bcl-X1, Mcl-1, c-IAP1, XIAP or survivin are over-expressed in HCC cells. Furthermore, some growth factors that mediate cell survival are upregulated in HCC, as well as the molecules involved in the machinery responsible for cleavage of their pro- forms to an active peptide. The expression and/or activation of the JAK/STAT, PI3K/AKT and RAS/ERKs path- ways are enhanced in many HCC cells, conferring on them resistance to apoptotic stimuli. Finally, recent evi- dence indicates that inflammatory processes, as well as the epithelial-mesenchymal transitions that occur in HCC cells to facilitate their dissemination, are related to cell survival. Therefore, therapeutic strategies to selectively inhibit anti-apoptotic signals in liver tumor cells have the potential to provide powerful tools to treat HCC.展开更多
Recent seismic evidence shows that basalt accumulation is widespread in the mantle transition zone(MTZ),yet its ubiquity or sporadic nature remains uncertain.To investigate this phenomenon further,we characterized the...Recent seismic evidence shows that basalt accumulation is widespread in the mantle transition zone(MTZ),yet its ubiquity or sporadic nature remains uncertain.To investigate this phenomenon further,we characterized the velocity structure across the 660-km discontinuity that separates the upper mantle from the lower mantle beneath the Sea of Okhotsk by modeling the waveform of the S660P phase,a downgoing S wave converting into a P wave at the 660-km interface.These waves were excited by two regional>410-km-deep events and were recorded by stations in central Asia.Our findings showed no need to introduce velocity anomalies at the base of the MTZ to explain the S660P waveforms because the IASP91 model adequately reproduced the waveforms.This finding indicates that the basalt accumulation has not affected the bottom of the MTZ in the study area.Instead,this discontinuity is primarily controlled by temperature or water content variations,or both.Thus,we argue that the basalt accumulation at the base of the MTZ is sporadic,not ubiquitous,reflecting its heterogeneous distribution.展开更多
AIM: To evaluate the effects of epidermal growth factor(EGF) on transforming growth factor-beta1(TGF-β1)-induced epithelial-mesenchymal transition(EMT) in human corneal epithelial cells(HCECs). METHODS: HCECs were cu...AIM: To evaluate the effects of epidermal growth factor(EGF) on transforming growth factor-beta1(TGF-β1)-induced epithelial-mesenchymal transition(EMT) in human corneal epithelial cells(HCECs). METHODS: HCECs were cultured and treated with TGF-β1 for establishing the model of EMT in vitro. Biological effect of EGF on TGF-β1-induced EMT was evaluated. Proteins and m RNAs expression changes of E-cadherin, N-cadherin and Fibronectin(EMT-relative markers) after TGF-β1 or TGF-β1 combined EGF treatment were detected by Western blot and RT-PCR, respectively. Viability and migration of HCECs were measured by CCK-8, transwell cell migration assay and cell scratch wound healing assay. Activation of Smad2, ERK, p38, JNK and Akt signaling pathways were evaluated by Western blot. Inhibitors of relevant signaling pathways were added to the HCECs to explore the key signal mechanism.RESULTS: With treatment of TGF-β1 only, three EMTrelative proteins and m RNA expression showed that EMT up-regulated in a concentration-dependent and time-dependent manner, with significantly decreasing cell viability(TGF-β1≥5 ng/m L, P<0.05) and increasing cell migration(TGF-β1≥5 ng/m L, P<0.01). The phosphorylation of Smad2 and p38 was a key process of TGF-β1-induced EMT. Meanwhile, EMT-relative proteins and m RNA expression showed that EGF inhibited TGF-β1-indued EMT, with significantly increasing cell viability(EGF≥10 ng/m L, P<0.01). It was noteworthy that EGF significantly enhanced cell migration although EMT was inhibited(EGF≥10 ng/m L, P<0.01), and the blockage of p38(by SB202190, a p38 inhibitor) was a potential mechanism of this phenomenon. CONCLUSION: EGF inhibits TGF-β1-induced EMT via suppressive p38, and promotes cells proliferation and migration in a non-EMT process by inhibiting p38 pathway.展开更多
Based on the evidence that hemochromatosis, an iron-overload disease, drives hepatocellular carcinoma, we hypothesized that chronic exposure to excess iron, either due to genetic or environmental causes, predisposes a...Based on the evidence that hemochromatosis, an iron-overload disease, drives hepatocellular carcinoma, we hypothesized that chronic exposure to excess iron, either due to genetic or environmental causes, predisposes an individual to cancer. Using pancreatic cancer as our primary focus, we employed cell culture studies to interrogate the connection between excess iron and cancer, and combined in vitro and in vivo studies to explore the connection further. Ferric ammonium citrate was used as an exogenous iron source. Chronic exposure to excess iron induced epithelial-mesenchymal transition(EMT) in normal and cancer cell lines, loss of p53, and suppression of p53 transcriptional activity evidenced from decreased expression of p53 target genes(p21, cyclin D1, Bax, SLC7A11). To further extrapolate our cell culture data, we generated EL-KrasG12D( EL-Kras) mouse(pancreatic neoplastic mouse model) expressing Hfe+/+ and Hfe-/- genetic background. p53 target gene expression decreased in EL-Kras/Hfe-/- mouse pancreas compared to EL-Kras/Hfe+/+ mouse pancreas. Interestingly, the incidence of acinar-to-ductal metaplasia and cystic pancreatic neoplasms(CPN) decreased in EL-Kras/Hfe-/- mice, but the CPNs that did develop were larger in these mice than in EL-Kras/Hfe+/+ mice. In conclusion, these in vitro and in vivo studies support a potential role for chronic exposure to excess iron as a promoter of more aggressive disease via p53 loss and SLC7A11 upregulation within pancreatic epithelial cells.展开更多
Since the beginning of 2017,Cancer Communications(former title:Chinese Journal of Cancer)has published a series of important questions regarding cancer research and clinical oncology,to provide an enhanced stimulus fo...Since the beginning of 2017,Cancer Communications(former title:Chinese Journal of Cancer)has published a series of important questions regarding cancer research and clinical oncology,to provide an enhanced stimulus for can-cer research,and to accelerate collaborations between institutions and investigators.In this edition,the following 8 valuable questions are presented.Question 94.The origin of tumors:time for a new paradigm?Question 95.How can we accelerate the identification of biomarkers for the early detection of pancreatic ductal adenocarcinoma?Question 96.Can we improve the treatment outcomes of metastatic pancreatic ductal adenocarcinoma through precision medicine guided by a combination of the genetic and proteomic information of the tumor?Question 97.What are the parameters that determine a competent immune system that gives a complete response to cancers after immune induction?Question 98.Is high local concentration of metformin essential for its anti-cancer activity?Question 99.How can we monitor the emergence of cancer cells anywhere in the body through plasma testing?Question 100.Can phytochemicals be more specific and efficient at targeting P-glycoproteins to overcome multi-drug resistance in cancer cells?Question 101.Is cell migration a selectable trait in the natural evolution of carcinoma?展开更多
Combining two Bose-Einstein condensates(BECs)may result in a miscible or immiscible mixture.In this study,we investigate the miscibility-immiscibility transition of binary BEC mixture trapped in an isotropic harmonic ...Combining two Bose-Einstein condensates(BECs)may result in a miscible or immiscible mixture.In this study,we investigate the miscibility-immiscibility transition of binary BEC mixture trapped in an isotropic harmonic potential,with both inter-species s-wave and p-wave scattering interaction included.The mean-field Gross-Pitaevskii equations with p-wave interaction term are numerically solved to obtain the ground-state phase diagram.Due to the pwave interaction competing with isotropic s-wave interaction,the spatial density profile of binary BEC mixtures transforming from immiscible phase to miscible phase is observed.The p-wave interaction caused miscibility can be observed in current experiments of Bose-Bose mixture tuned near a p-wave Feshbach resonance.展开更多
文摘Hepatocellular carcinoma （HCC） is a major health prob- lem, being the sixth most common cancer world-wide. Dysregulation of the balance between proliferation and cell death represents a pro-tumorigenic principle in hu- man hepatocarcinogenesis. This review updates the recent relevant contributions reporting molecular altera- tions for HCC that induce an imbalance in the regulation of apoptosis. Alterations in the expression and/or activation of p53 are frequent in HCC cells, which confer on them resistance to chemotherapeutic drugs. Many HCCs are also insensitive to apoptosis induced either by death receptor ligands, such as FasL or TRAIL, or by transforming growth factor-beta （TGF-β）. Although the expression of some pro-apoptotic genes is decreased, the balance between death and survival is dysregulated in HCC mainly due to overactivation of anti-apoptotic pathways. Indeed, some molecules involved in counter- acting apoptosis, such as Bcl-X1, Mcl-1, c-IAP1, XIAP or survivin are over-expressed in HCC cells. Furthermore, some growth factors that mediate cell survival are upregulated in HCC, as well as the molecules involved in the machinery responsible for cleavage of their pro- forms to an active peptide. The expression and/or activation of the JAK/STAT, PI3K/AKT and RAS/ERKs path- ways are enhanced in many HCC cells, conferring on them resistance to apoptotic stimuli. Finally, recent evi- dence indicates that inflammatory processes, as well as the epithelial-mesenchymal transitions that occur in HCC cells to facilitate their dissemination, are related to cell survival. Therefore, therapeutic strategies to selectively inhibit anti-apoptotic signals in liver tumor cells have the potential to provide powerful tools to treat HCC.
基金support from the National Natural Science Foundation of China(Grant No.42276049)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB42020103).
文摘Recent seismic evidence shows that basalt accumulation is widespread in the mantle transition zone(MTZ),yet its ubiquity or sporadic nature remains uncertain.To investigate this phenomenon further,we characterized the velocity structure across the 660-km discontinuity that separates the upper mantle from the lower mantle beneath the Sea of Okhotsk by modeling the waveform of the S660P phase,a downgoing S wave converting into a P wave at the 660-km interface.These waves were excited by two regional>410-km-deep events and were recorded by stations in central Asia.Our findings showed no need to introduce velocity anomalies at the base of the MTZ to explain the S660P waveforms because the IASP91 model adequately reproduced the waveforms.This finding indicates that the basalt accumulation has not affected the bottom of the MTZ in the study area.Instead,this discontinuity is primarily controlled by temperature or water content variations,or both.Thus,we argue that the basalt accumulation at the base of the MTZ is sporadic,not ubiquitous,reflecting its heterogeneous distribution.
基金Supported by the 63th Postdoctoral Science Foundation of China(No.2018M632487)General Natural Science ProjectsDepartment of Education,Zhejiang Province,China(No.Y201636718)
文摘AIM: To evaluate the effects of epidermal growth factor(EGF) on transforming growth factor-beta1(TGF-β1)-induced epithelial-mesenchymal transition(EMT) in human corneal epithelial cells(HCECs). METHODS: HCECs were cultured and treated with TGF-β1 for establishing the model of EMT in vitro. Biological effect of EGF on TGF-β1-induced EMT was evaluated. Proteins and m RNAs expression changes of E-cadherin, N-cadherin and Fibronectin(EMT-relative markers) after TGF-β1 or TGF-β1 combined EGF treatment were detected by Western blot and RT-PCR, respectively. Viability and migration of HCECs were measured by CCK-8, transwell cell migration assay and cell scratch wound healing assay. Activation of Smad2, ERK, p38, JNK and Akt signaling pathways were evaluated by Western blot. Inhibitors of relevant signaling pathways were added to the HCECs to explore the key signal mechanism.RESULTS: With treatment of TGF-β1 only, three EMTrelative proteins and m RNA expression showed that EMT up-regulated in a concentration-dependent and time-dependent manner, with significantly decreasing cell viability(TGF-β1≥5 ng/m L, P<0.05) and increasing cell migration(TGF-β1≥5 ng/m L, P<0.01). The phosphorylation of Smad2 and p38 was a key process of TGF-β1-induced EMT. Meanwhile, EMT-relative proteins and m RNA expression showed that EGF inhibited TGF-β1-indued EMT, with significantly increasing cell viability(EGF≥10 ng/m L, P<0.01). It was noteworthy that EGF significantly enhanced cell migration although EMT was inhibited(EGF≥10 ng/m L, P<0.01), and the blockage of p38(by SB202190, a p38 inhibitor) was a potential mechanism of this phenomenon. CONCLUSION: EGF inhibits TGF-β1-induced EMT via suppressive p38, and promotes cells proliferation and migration in a non-EMT process by inhibiting p38 pathway.
基金The authors acknowledge the financial support received from the National Institute of Health(CA223271)The authors would also like to thank Dr.Ming Tsao(Ontario Cancer Institute)for the human pancreatic ductal epithelial(HPDE)cell line.
文摘Based on the evidence that hemochromatosis, an iron-overload disease, drives hepatocellular carcinoma, we hypothesized that chronic exposure to excess iron, either due to genetic or environmental causes, predisposes an individual to cancer. Using pancreatic cancer as our primary focus, we employed cell culture studies to interrogate the connection between excess iron and cancer, and combined in vitro and in vivo studies to explore the connection further. Ferric ammonium citrate was used as an exogenous iron source. Chronic exposure to excess iron induced epithelial-mesenchymal transition(EMT) in normal and cancer cell lines, loss of p53, and suppression of p53 transcriptional activity evidenced from decreased expression of p53 target genes(p21, cyclin D1, Bax, SLC7A11). To further extrapolate our cell culture data, we generated EL-KrasG12D( EL-Kras) mouse(pancreatic neoplastic mouse model) expressing Hfe+/+ and Hfe-/- genetic background. p53 target gene expression decreased in EL-Kras/Hfe-/- mouse pancreas compared to EL-Kras/Hfe+/+ mouse pancreas. Interestingly, the incidence of acinar-to-ductal metaplasia and cystic pancreatic neoplasms(CPN) decreased in EL-Kras/Hfe-/- mice, but the CPNs that did develop were larger in these mice than in EL-Kras/Hfe+/+ mice. In conclusion, these in vitro and in vivo studies support a potential role for chronic exposure to excess iron as a promoter of more aggressive disease via p53 loss and SLC7A11 upregulation within pancreatic epithelial cells.
文摘Since the beginning of 2017,Cancer Communications(former title:Chinese Journal of Cancer)has published a series of important questions regarding cancer research and clinical oncology,to provide an enhanced stimulus for can-cer research,and to accelerate collaborations between institutions and investigators.In this edition,the following 8 valuable questions are presented.Question 94.The origin of tumors:time for a new paradigm?Question 95.How can we accelerate the identification of biomarkers for the early detection of pancreatic ductal adenocarcinoma?Question 96.Can we improve the treatment outcomes of metastatic pancreatic ductal adenocarcinoma through precision medicine guided by a combination of the genetic and proteomic information of the tumor?Question 97.What are the parameters that determine a competent immune system that gives a complete response to cancers after immune induction?Question 98.Is high local concentration of metformin essential for its anti-cancer activity?Question 99.How can we monitor the emergence of cancer cells anywhere in the body through plasma testing?Question 100.Can phytochemicals be more specific and efficient at targeting P-glycoproteins to overcome multi-drug resistance in cancer cells?Question 101.Is cell migration a selectable trait in the natural evolution of carcinoma?
基金supported in part by the Top-Notch Academic Programs Project of Jiangsu Higher Education Institutions(TAPP)the Startup Fund of Nanjing University of Aeronautics and Astronautics(No.1008-0280YAT21004)
文摘Combining two Bose-Einstein condensates(BECs)may result in a miscible or immiscible mixture.In this study,we investigate the miscibility-immiscibility transition of binary BEC mixture trapped in an isotropic harmonic potential,with both inter-species s-wave and p-wave scattering interaction included.The mean-field Gross-Pitaevskii equations with p-wave interaction term are numerically solved to obtain the ground-state phase diagram.Due to the pwave interaction competing with isotropic s-wave interaction,the spatial density profile of binary BEC mixtures transforming from immiscible phase to miscible phase is observed.The p-wave interaction caused miscibility can be observed in current experiments of Bose-Bose mixture tuned near a p-wave Feshbach resonance.
