In China,lung cancer is a primary cancer type with high incidence and mortality.Risk factors for lung cancer include tobacco use,family history,radiation exposure,and the presence of chronic lung diseases.Most early-...In China,lung cancer is a primary cancer type with high incidence and mortality.Risk factors for lung cancer include tobacco use,family history,radiation exposure,and the presence of chronic lung diseases.Most early-stage non-small cell lung cancer(NSCLC)patients miss the optimal timing for treatment due to the lack of clinical presentations.Population-based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in China.The understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC,thus prolonging survival in patients with positive drivers.In the exploration of immune escape mechanisms,programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1)inhibitor monotherapy and PD-1/PD-L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in China.In the Chinese Society of Clinical Oncology’s guidelines for NSCLC,maintenance immunotherapy is recommended for locally advanced NSCLC after chemoradiotherapy.Adjuvant immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable NSCLC.In this review,we summarized recent advances in NSCLC in China in terms of epidemiology,biology,molecular pathology,pathogenesis,screening,diagnosis,targeted therapy,and immunotherapy。展开更多
INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 a...INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .展开更多
AIM: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also involved in the process, and to investigate the changes in NF-kB, p53, bcl-2 and caspase in the apoptosis process. METHODS: Cell culture,...AIM: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also involved in the process, and to investigate the changes in NF-kB, p53, bcl-2 and caspase in the apoptosis process. METHODS: Cell culture, MTT, Electromicroscopy, agarose gel electrophoresis, lucigenin, Western blot and electrophoretic mobility shift assay (EMSA) analysis were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanisms. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Lucigenin assay showed the generation of ROS in cells under incubation with JTE-522. The increased ROS generation might contribute to the induction of AGS cells to apoptosis. EMSA and Western blot revealed that NF-kB activity was almost completely inhibited by preventing the degradation of IkBalpha. Additionally, by using Western blot we confirmed that the level of bcl-2 was decreased, whereas p53 showed a great increase following JTE-522 treatment. Their changes were in a dose-dependent manner. CONCLUSION: These findings suggest that reactive oxygen species, NF-kB, p53, bcl-2 and caspase-3 may play an important role in the induction of apoptosis in AGS cells after treatment with JTE-522.展开更多
AIM In this study we investigated the relationship of the X protein of HBV and nuclear factor-κB(NF-κB)and the expression of NF-κB in human hepatocellular carcinoma tissues. METHODS Immunohistochemistry SP method w...AIM In this study we investigated the relationship of the X protein of HBV and nuclear factor-κB(NF-κB)and the expression of NF-κB in human hepatocellular carcinoma tissues. METHODS Immunohistochemistry SP method was used to detect the expression of NF-κB and the X protein of HBV in human hepatocellular carcinoma tissues of 52 cases.Gene transfection mediated by lipofectamine was used to transfect the eukaryotic expression vector pCDNA3.1-HBX of HBV x gene into human hepatocellular carcinoma cell line HCC-9204 and NF-κB was detected. RESULTS NF-κB was widely expressed in human hepatocellular carcinoma tissues in a total of 52 cases and its expression was related to the X protein of HBV.NF-κB was localized both in the cytoplasm and the nuclei of hepatocellular carcinoma cells in 11 cases which were positive for the X protein of HBV while in 41 cases negative for the X protein of HBV,NF-κB was only localized in the cytoplasm of hepatocellular carcinoma cells but translocated to the nuclei of hepatocellular carcinoma cells after the eukaryotic expression vector pCDNA3.1-HBX was transfected into HCC-9204 cells. CONCLUSION This study strongly suggests that the nuclear factor NF-κB is widely expressed in hepatocellular carcinoma tissues in different styles according to the expression of the X protein of HBV.NF-κB is abnormally activated in hepatocellular carcinoma,which is probably rélated to the X protein of HBV.The X protein of HBV can activate NF-κB to translocate into nuclei of hepatocellular carcinoma cells.展开更多
AIM: The goal of this study was to characterize the AFP receptor, its possible signal transduction pathway and its proliferative functions in human hepatoma cell line Bel 7402. METHODS: Cell proliferation enhanced by ...AIM: The goal of this study was to characterize the AFP receptor, its possible signal transduction pathway and its proliferative functions in human hepatoma cell line Bel 7402. METHODS: Cell proliferation enhanced by AFP was detected by MTT assay, 3H-thymidine incorporation and S-stage percentage of cell cycle analysis. With radioactive labeled 125I-AFP for receptor binding assay; cAMP accumulation, protein kinase A activity were detected by radioactive immunosorbent assay and the change of intracellular free calcium (Ca2+i) was monitored by scanning fluorescence intensity under TCS-NT confocal microscope. The expression of oncogenes N- ras, p 53, and p21( ras ) in the cultured cells in vitro were detected by Northern blotting and Western blotting respectively. RESULTS: It was demonstrated that AFP enhanced the proliferation of human hepatoma Bel 7402 cell in a dose dependent fashion as shown in MTT assay, (3)H-thymidine incorporation and S-phase percentage up to 2-fold. Two subtypes of AFP receptors were identified in the cells with Kds of 1.3 x 10(-9)mol.L(-1) and 9.9 x10(-8)mol. (-1)L respectively. Pretreatment of cells with AFP resulted in a significant increase (625%) in cAMP accumulation. The activity of protein kinase A activity were increased up to 37.5, 122.6, 73.7 and 61.2% at treatment time point 2, 6, 12 and 24 hours. The level of intracellular calcium were elevated after the treatment of alpha-fetoprotein and achieved to 204% at 4 min. The results also showed that AFP(20mg.L(-1)) could upregulate the expression of N- ras oncogenes and p 53 and p21( ras ) in Bel 7402 cells. In the later case,the alteration were 81.1%(12h) and 97.3%(12h) respectively compared with control. CONCLUSION: These results demonstrate that AFP is a potential growth factor to promote the proliferation of human hepatoma Bel 7402 cells. Its growth-regulatory effects are mediated by its specific plasma membrane receptors coupled with its transmembrane signaling transduction through the pathway of cAMP-PKA and intracellular calcium展开更多
AIM:To analyze the differences and relevance of Yes-associated protein (YAP) and survivin, and to explore the correlation and signifi cance of their expression in gastric carcinoma and precancerous lesions.METHODS: Th...AIM:To analyze the differences and relevance of Yes-associated protein (YAP) and survivin, and to explore the correlation and signifi cance of their expression in gastric carcinoma and precancerous lesions.METHODS: The PV9000 immunohistochemical method was used to detect the expression of YAP and survivin in 98 cases of normal gastric mucosa, 58 intestinal metaplasia (IM), 32 dysplasia and 98 gastric carcinoma.RESULTS: The positive rates of YAP in dysplasia (37.5%) and gastric carcinoma (48.0%) were significantly higher than that in normal gastric mucosa (13.3%), P<0.01. The positive rates of survivin in IM (53.4%), dysplasia (59.4%) and gastric carcinoma (65.3%) were significantly higher than in normal gastric mucosa (11.2%), P<0.01. Survivin expression gradually increased from 41.7% in well differentiated adenocarcinoma through 58.3% in moderately differentiated adenocarcinoma to 75.6% in poorly differentiated adenocarcinoma, with significant Rank correlation, rk=0.279, P<0.01. The positive rate of survivin in gastric carcinoma of diffused type (74.6%) was significantly higher than that in intestinal type (51.3%), P<0.05. In gastric carcinoma with lymph node metastasis (76.9%), the positive rate of survivin was signifi cantly higher than that in the group without lymph node metastasis (41.2%), P<0.01. In 98 cases of gastric carcinoma, the expression of YAP and of survivin were positively correlated, rk=0.246, P<0.01.CONCLUSION: YAP may play an important role as a carcinogenic factor and may induce survivin expression. Detecting both markers together may help in early diagnosis of gastric carcinoma.展开更多
AIM: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly. METHODS: The expression of VEGF and its receptor kinase-domain insert containing rec...AIM: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly. METHODS: The expression of VEGF and its receptor kinase-domain insert containing receptor (KDR) in human gastric cancer tissue were observed by immunohistochemical staining. VEGF levels were manipulated in human gastric cancer cell using eukaryotic expression constructs designed to express the complete VEGF(165) complimentary DNA in either the sense or antisense orientation. The biological changes of the cells were observed in which VEGF was up-regulated or down-regulated. RESULTS: VEGF-positive rate was 50%, and VEGF was mainly localized in the cytoplasm and membrane of the tumor cells, while KDR was mainly located in the membrane of vascular endothelial cells in gastric cancer tissues and peri-cancerous tissue. In 2 cases of 50 specimens, the gastric cancer cells expressed KDR, localized in both the cytoplasm and membrane. Introduction of VEGF(165) antisense into human gastric cancer cells (SGC-7901, immunofluorescence intensity, 31.6%)) resulted in a significant reduction in VEGF-specific messenger RNA and total and cell surface VEGF protein (immunofluorescence intensity, 8.9%) (P【0.05). Conversely, stable integration of VEGF(165) in the sense orientation resulted in an increase in cellular and cell surface VEGF (immunofluorescence intensity, 75.4%) (P【0.05). Lowered VEGF levels were associated with a marked decrease in the growth of nude mouse xenografted tumor (at 33 days postimplantation, tumor volume: 345.40 +/- 136.31 mm3)(P【0.05 vs control SGC-7901 group: 1534.40 +/- 362.88 mm3), whereas up-regulation of VEGF resulted in increased xenografted tumor size (at 33 days postimplantation, tumor volume: 2350.50 +/- 637.70 mm3) (P【0.05 vs control SGC-7901 group). CONCLUSION: This study provides direct evidence that VEGF plays an important role in the oncogenesis of human gastric cancer.展开更多
AIM: The existence and properties of alpha-fetoprotein (AFP) receptor on the surface of NIH 3T3 cells and the effects of AFP on cellular signal transduction pathway were investigated. METHODS: The effect of AFP on the...AIM: The existence and properties of alpha-fetoprotein (AFP) receptor on the surface of NIH 3T3 cells and the effects of AFP on cellular signal transduction pathway were investigated. METHODS: The effect of AFP on the proliferation of NIH 3T3 cells was measured by incorporation of 3H-TdR. Receptor-binding assay of 125I-AFP was performed to detect the properties of AFP receptor in NIH 3T3 cells. The influences of AFP on the [cAMP]i and the activities of protein kinase A (PKA) were determined. Western blot was used to detect the change of K-ras P21 protein expression. RESULTS: The proliferation of NIH 3T3 cells treated with 0-80 mg/L of AFP was significantly enhanced. The Scatchard analysis indicated that there were two classes of binding sites with KD of 2.722 x 10(-9)M (Bmax=12810 sites per cell) and 8.931 x 10(-8)M (Bmax=119700 sites per cell) respectively. In the presence of AFP (20 mg/L), the content of cAMP and activities of PKA were significantly elevated . The level of K-ras P21 protein was upregulated by AFP at the concentration of 20 mg/L. The monoclonal antibody against AFP could reverse the effects of AFP on the cAMP content, PKA activity and the expression of K-ras p21 gene. CONCLUSION: The effect of AFP on the cell proliferation was achieved by binding its receptor to trigger the signal transduction pathway of cAMP-PKA and alter the expression of K- ras p21 gene.展开更多
基金National Natural Science Foundation of China,Grant/Award Number:81871865Collaborative Innovation Program of Shanghai Municipal Health Commission,Grant/Award Number:2020CXJQ02Science and Technology Innovation Action Plan Project of Shanghai Municipal Science and Technology Commission,Grant/Award Numbers:19411950300,19411950301。
文摘In China,lung cancer is a primary cancer type with high incidence and mortality.Risk factors for lung cancer include tobacco use,family history,radiation exposure,and the presence of chronic lung diseases.Most early-stage non-small cell lung cancer(NSCLC)patients miss the optimal timing for treatment due to the lack of clinical presentations.Population-based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in China.The understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC,thus prolonging survival in patients with positive drivers.In the exploration of immune escape mechanisms,programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1)inhibitor monotherapy and PD-1/PD-L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in China.In the Chinese Society of Clinical Oncology’s guidelines for NSCLC,maintenance immunotherapy is recommended for locally advanced NSCLC after chemoradiotherapy.Adjuvant immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable NSCLC.In this review,we summarized recent advances in NSCLC in China in terms of epidemiology,biology,molecular pathology,pathogenesis,screening,diagnosis,targeted therapy,and immunotherapy。
基金Supported by the Medical Research Foundation of Guangdong Province,No.1997423
文摘INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .
基金National Natural Science Foundation of China,No.39770300,30070873the Overseas Chinese Affairs Office of the State Council Foundation,No.98-33
文摘AIM: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also involved in the process, and to investigate the changes in NF-kB, p53, bcl-2 and caspase in the apoptosis process. METHODS: Cell culture, MTT, Electromicroscopy, agarose gel electrophoresis, lucigenin, Western blot and electrophoretic mobility shift assay (EMSA) analysis were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanisms. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Lucigenin assay showed the generation of ROS in cells under incubation with JTE-522. The increased ROS generation might contribute to the induction of AGS cells to apoptosis. EMSA and Western blot revealed that NF-kB activity was almost completely inhibited by preventing the degradation of IkBalpha. Additionally, by using Western blot we confirmed that the level of bcl-2 was decreased, whereas p53 showed a great increase following JTE-522 treatment. Their changes were in a dose-dependent manner. CONCLUSION: These findings suggest that reactive oxygen species, NF-kB, p53, bcl-2 and caspase-3 may play an important role in the induction of apoptosis in AGS cells after treatment with JTE-522.
文摘AIM In this study we investigated the relationship of the X protein of HBV and nuclear factor-κB(NF-κB)and the expression of NF-κB in human hepatocellular carcinoma tissues. METHODS Immunohistochemistry SP method was used to detect the expression of NF-κB and the X protein of HBV in human hepatocellular carcinoma tissues of 52 cases.Gene transfection mediated by lipofectamine was used to transfect the eukaryotic expression vector pCDNA3.1-HBX of HBV x gene into human hepatocellular carcinoma cell line HCC-9204 and NF-κB was detected. RESULTS NF-κB was widely expressed in human hepatocellular carcinoma tissues in a total of 52 cases and its expression was related to the X protein of HBV.NF-κB was localized both in the cytoplasm and the nuclei of hepatocellular carcinoma cells in 11 cases which were positive for the X protein of HBV while in 41 cases negative for the X protein of HBV,NF-κB was only localized in the cytoplasm of hepatocellular carcinoma cells but translocated to the nuclei of hepatocellular carcinoma cells after the eukaryotic expression vector pCDNA3.1-HBX was transfected into HCC-9204 cells. CONCLUSION This study strongly suggests that the nuclear factor NF-κB is widely expressed in hepatocellular carcinoma tissues in different styles according to the expression of the X protein of HBV.NF-κB is abnormally activated in hepatocellular carcinoma,which is probably rélated to the X protein of HBV.The X protein of HBV can activate NF-κB to translocate into nuclei of hepatocellular carcinoma cells.
基金National Natural Science Foundation of China,No.39760077
文摘AIM: The goal of this study was to characterize the AFP receptor, its possible signal transduction pathway and its proliferative functions in human hepatoma cell line Bel 7402. METHODS: Cell proliferation enhanced by AFP was detected by MTT assay, 3H-thymidine incorporation and S-stage percentage of cell cycle analysis. With radioactive labeled 125I-AFP for receptor binding assay; cAMP accumulation, protein kinase A activity were detected by radioactive immunosorbent assay and the change of intracellular free calcium (Ca2+i) was monitored by scanning fluorescence intensity under TCS-NT confocal microscope. The expression of oncogenes N- ras, p 53, and p21( ras ) in the cultured cells in vitro were detected by Northern blotting and Western blotting respectively. RESULTS: It was demonstrated that AFP enhanced the proliferation of human hepatoma Bel 7402 cell in a dose dependent fashion as shown in MTT assay, (3)H-thymidine incorporation and S-phase percentage up to 2-fold. Two subtypes of AFP receptors were identified in the cells with Kds of 1.3 x 10(-9)mol.L(-1) and 9.9 x10(-8)mol. (-1)L respectively. Pretreatment of cells with AFP resulted in a significant increase (625%) in cAMP accumulation. The activity of protein kinase A activity were increased up to 37.5, 122.6, 73.7 and 61.2% at treatment time point 2, 6, 12 and 24 hours. The level of intracellular calcium were elevated after the treatment of alpha-fetoprotein and achieved to 204% at 4 min. The results also showed that AFP(20mg.L(-1)) could upregulate the expression of N- ras oncogenes and p 53 and p21( ras ) in Bel 7402 cells. In the later case,the alteration were 81.1%(12h) and 97.3%(12h) respectively compared with control. CONCLUSION: These results demonstrate that AFP is a potential growth factor to promote the proliferation of human hepatoma Bel 7402 cells. Its growth-regulatory effects are mediated by its specific plasma membrane receptors coupled with its transmembrane signaling transduction through the pathway of cAMP-PKA and intracellular calcium
基金Supported by National Natural Science Foundation of China,No.30371607
文摘AIM:To analyze the differences and relevance of Yes-associated protein (YAP) and survivin, and to explore the correlation and signifi cance of their expression in gastric carcinoma and precancerous lesions.METHODS: The PV9000 immunohistochemical method was used to detect the expression of YAP and survivin in 98 cases of normal gastric mucosa, 58 intestinal metaplasia (IM), 32 dysplasia and 98 gastric carcinoma.RESULTS: The positive rates of YAP in dysplasia (37.5%) and gastric carcinoma (48.0%) were significantly higher than that in normal gastric mucosa (13.3%), P<0.01. The positive rates of survivin in IM (53.4%), dysplasia (59.4%) and gastric carcinoma (65.3%) were significantly higher than in normal gastric mucosa (11.2%), P<0.01. Survivin expression gradually increased from 41.7% in well differentiated adenocarcinoma through 58.3% in moderately differentiated adenocarcinoma to 75.6% in poorly differentiated adenocarcinoma, with significant Rank correlation, rk=0.279, P<0.01. The positive rate of survivin in gastric carcinoma of diffused type (74.6%) was significantly higher than that in intestinal type (51.3%), P<0.05. In gastric carcinoma with lymph node metastasis (76.9%), the positive rate of survivin was signifi cantly higher than that in the group without lymph node metastasis (41.2%), P<0.01. In 98 cases of gastric carcinoma, the expression of YAP and of survivin were positively correlated, rk=0.246, P<0.01.CONCLUSION: YAP may play an important role as a carcinogenic factor and may induce survivin expression. Detecting both markers together may help in early diagnosis of gastric carcinoma.
文摘AIM: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly. METHODS: The expression of VEGF and its receptor kinase-domain insert containing receptor (KDR) in human gastric cancer tissue were observed by immunohistochemical staining. VEGF levels were manipulated in human gastric cancer cell using eukaryotic expression constructs designed to express the complete VEGF(165) complimentary DNA in either the sense or antisense orientation. The biological changes of the cells were observed in which VEGF was up-regulated or down-regulated. RESULTS: VEGF-positive rate was 50%, and VEGF was mainly localized in the cytoplasm and membrane of the tumor cells, while KDR was mainly located in the membrane of vascular endothelial cells in gastric cancer tissues and peri-cancerous tissue. In 2 cases of 50 specimens, the gastric cancer cells expressed KDR, localized in both the cytoplasm and membrane. Introduction of VEGF(165) antisense into human gastric cancer cells (SGC-7901, immunofluorescence intensity, 31.6%)) resulted in a significant reduction in VEGF-specific messenger RNA and total and cell surface VEGF protein (immunofluorescence intensity, 8.9%) (P【0.05). Conversely, stable integration of VEGF(165) in the sense orientation resulted in an increase in cellular and cell surface VEGF (immunofluorescence intensity, 75.4%) (P【0.05). Lowered VEGF levels were associated with a marked decrease in the growth of nude mouse xenografted tumor (at 33 days postimplantation, tumor volume: 345.40 +/- 136.31 mm3)(P【0.05 vs control SGC-7901 group: 1534.40 +/- 362.88 mm3), whereas up-regulation of VEGF resulted in increased xenografted tumor size (at 33 days postimplantation, tumor volume: 2350.50 +/- 637.70 mm3) (P【0.05 vs control SGC-7901 group). CONCLUSION: This study provides direct evidence that VEGF plays an important role in the oncogenesis of human gastric cancer.
基金This work was supported by National NaturalScience Fundation of China(No.39760077).
文摘AIM: The existence and properties of alpha-fetoprotein (AFP) receptor on the surface of NIH 3T3 cells and the effects of AFP on cellular signal transduction pathway were investigated. METHODS: The effect of AFP on the proliferation of NIH 3T3 cells was measured by incorporation of 3H-TdR. Receptor-binding assay of 125I-AFP was performed to detect the properties of AFP receptor in NIH 3T3 cells. The influences of AFP on the [cAMP]i and the activities of protein kinase A (PKA) were determined. Western blot was used to detect the change of K-ras P21 protein expression. RESULTS: The proliferation of NIH 3T3 cells treated with 0-80 mg/L of AFP was significantly enhanced. The Scatchard analysis indicated that there were two classes of binding sites with KD of 2.722 x 10(-9)M (Bmax=12810 sites per cell) and 8.931 x 10(-8)M (Bmax=119700 sites per cell) respectively. In the presence of AFP (20 mg/L), the content of cAMP and activities of PKA were significantly elevated . The level of K-ras P21 protein was upregulated by AFP at the concentration of 20 mg/L. The monoclonal antibody against AFP could reverse the effects of AFP on the cAMP content, PKA activity and the expression of K-ras p21 gene. CONCLUSION: The effect of AFP on the cell proliferation was achieved by binding its receptor to trigger the signal transduction pathway of cAMP-PKA and alter the expression of K- ras p21 gene.
