Objective To investigate the role of extracellular signal-regulated kinase (ERK) in apoptosis of human colon cancer (HCT116) cells. Methods After the HCT116 cells were pretreated with specific ERK inhibitor (U012...Objective To investigate the role of extracellular signal-regulated kinase (ERK) in apoptosis of human colon cancer (HCT116) cells. Methods After the HCT116 cells were pretreated with specific ERK inhibitor (U0126) or specific siRNA and exposed to 10 mmol/L sodium butyrate (NaBT) for 24 h, their apoptosis was detected by flow cytometry, levels of SphK2 and ERK protein were measured by Western blot, and translocation of SphK2 was assayed by immunofluorescence microscopy. Results The U0126 and siRNAs specific for SphK2 blocked the export of SphK2 from nuclei to cytoplasm and increased the apoptosis of HCT116 cells following NaBT exposure. Over-expression of PKD decreased NaBT-induced apoptosis of HCT116 cells, which was reversed by U0126. Furthermore, transfection of HCT116 cells with constitutively activated PKD plasmids recovered the UO126-blocked export of SphK2. Conclusion ERK regulates the export of SphK2 and apoptosis of HCT116 cells by modulating PKD. Modulation of these molecules may help increase the sensitivity of colon cancer cells to the physiologic anti-colon cancer agent, NaBT.展开更多
Objective:Some studies have found that cholecystectomy may increase the risk of colorectal cancer(CRC),while others have reached inconsistent conclusions.We thus performed a systematic review and meta-analysis to asse...Objective:Some studies have found that cholecystectomy may increase the risk of colorectal cancer(CRC),while others have reached inconsistent conclusions.We thus performed a systematic review and meta-analysis to assess the incidence rate of CRC after cholecystectomy for patients with gallstones or gallbladder diseases,and whether the geographical location of the patients affected the results.Methods:We systematically searched PubMed,Embase,and Cochrane for studies reporting changes in the incidence rate of CRC after cholecystectomy published before January 12,2023.Our main endpoint wasthe occurrence of CRC Data were extracted and pooled,and the relative risk(RR)and 95%confidence interval(CI)were calculated.We assessed pooled data using a random-effects model.Results:In total,477 articles were identifled,and 6 articles were eligible,including 7 studies thatincluded 797,917 participants.Overall,the summarized research results showed that the risk of CRC was reduced in patients with gallbladder diseases who underwent cholecystectomy(RR:0.80,95%C:0.65 to0.99,p=0.040;I^(2)=85.0%).In the subgroup analysis based on different geographical locations,chole-cystectomy was not associated with the nisk of CRC in the Western population(RR:0.90,95%C:0.65 to 1.25.p=0.522;I^(2)=86.5%),but there was a negative corelation between cholecystectomy and the risk of CRC(RR:0,66,95%Cl:0.60 to 0,73,p=0.000)in the Chinese population Conclusions:Our findings support that for patients with gallstones or gallbladder diseases,the incidence of CRC after cholecystectomy is lower than that of patients who do not undergo cholecystectomy.展开更多
AIM: To investigate the role of nuclear translocation of calcyclin binding protein, also called Siah-1 interacting protein (CacyBP/SIP), in gastric carcinogenesis.
The mortality of ovarian cancer is higher than any other female genital malignant tumors, while there exists a strong correlation between early-stage detection and cure for it. CA125 and HE4 are two most common and ef...The mortality of ovarian cancer is higher than any other female genital malignant tumors, while there exists a strong correlation between early-stage detection and cure for it. CA125 and HE4 are two most common and effective serum markers in recent screening research of ovarian cancer. This paper derives a sequential screening strategy for ovarian cancer by jointly modeling the longitudinal profiles of CA125 and HE4. We construct a Bayesian hierarchical mixture model with changepoint, and propose two approaches for diagnosis: the risk of cancer index and the hypothesis test on the true incidence time. We simulated a 7-year sequential screening research and compared with the standard approach based on a fixed cutoff level. Our approach achieves a 15% higher sensitivity for a fixed specificity, indicating that the sequential strategy combining multiple markers is more effective in the early-stage detection of ovarian cancer.展开更多
Objective To investigate whether the apoptosis is involved in the mechanism of cytotoxicity of trichosanthin to gastric cancer cells. Methods Morphologic studies and TL]AIEL stainning were used to ex-plore qualitative...Objective To investigate whether the apoptosis is involved in the mechanism of cytotoxicity of trichosanthin to gastric cancer cells. Methods Morphologic studies and TL]AIEL stainning were used to ex-plore qualitatively and quantitatively the apoptotic status of gastric cancer cells before and after treatment with trichosanthin. Results In the experiment in vitro , when gastric cancer cells SGC-7901 were treated by trichosanthin (0. 1μg/ml, 36h), some typical apoptotic morphologic changes occured. A significant increase of apoptotic index (AI) was from (3.78±1.11)%, (3.98±1.12)% and (3.85±1.08)%at 36, 42, 48h to (11.30±2.33)%,(10.22±2.00)% and (11.18±1.85)%,respectively(P<0.01). In the experiment in vivo, nude mice with SGC-7901 xenografted tumor were treated by trichosanthin (0. 3mg kg-1 d -1, × 5d, intraperitoneal injection), some typical apoptotic morphologic changes were observed. These apoptotic cells were limited only in xenografted tumor. Al increased significantly from (4.95± 1 .94) % to (8. 75± 1 .38 )%, (P <0.01). Conclusion The apoptosis would be involved in the mechanism of cytotoxicity of trichosanthin to gastric cancer cells.展开更多
Ovarian cancer is one of the most deadly female genital malignant tumors in many regions while an effective early screening strategy can save numerous lives.CA125 and HE4 are tumor markers validated efficacious as wel...Ovarian cancer is one of the most deadly female genital malignant tumors in many regions while an effective early screening strategy can save numerous lives.CA125 and HE4 are tumor markers validated efficacious as well as most commonly used in recent screening research of ovarian cancer.In this paper,the authors construct a change-point and mixture model on the basis of longitudinal CA125 and HE4 levels and estimated parameters using maximum likelihood method with the preclinical duration assumed right-censored,which is more adaptive and yields comparable results in comparison to the Bayesian approach raised by Skates.Consistency of estimators is proved.The authors also run a 5-year simulation of sequential screening by calculating the risk of cancer and hypothesis testing the true incidence time respectively.Results show that diagnosis based on hypothesis test performs better in early detection.展开更多
Objective: The aim of this study was to explore the correlation between epithelial to mesenchymal transition (EMT) and chemoresistance of non-small-cell lung cancer (NSCLC). Methods: In vitro, the drug resistanc...Objective: The aim of this study was to explore the correlation between epithelial to mesenchymal transition (EMT) and chemoresistance of non-small-cell lung cancer (NSCLC). Methods: In vitro, the drug resistance index of cisplatin resistant lung adenocarcinoma cell line (A549/DDP) was detected by CCK-8 assay; the morphological change between A549/ DDP cells and lung adenocarcinoma cells (A549) was observed by phase contrast microscope; expression of EMT markers (including E-cadherin and vimentin) and resistance protein, excision repair cross-complementing 1 (ERCC1) was detected by immunocytochemistry. The expression of E-cadherin, vimentin and ERCC1 was investigated by immunohistochemistry in 120 cases of NSCLC, half of that were treated with pre-operative neoadjuvant chemotherapy (neoadjuvant chemotherapy group), and the other underwent surgery alone (simple surgery group). Results: There was a significant difference between the ICso (half maximal inhibitory concentration) of A549/DDP cells (5.20) and A549 cells (1.88) (P 〈 0.05), and the drug resistance index of A549/DDP cells was 2.77. Compared with A549 cells, A549/DDP cells increased expression of ERCC1 (P 〈 0.05). Moreover, A549/DDP cells showed morphological and phenotypic changes consistent with EMT: with spindle-shaped morphology, and decreased expression of E-cadherin and increased expression of vimentin. Immunohistochemistry showed significant positive correlation between the expression of ERCCI and vimentin (r = 0.496, 0.332, P 〈 0.05), and significant negative correlation between the ERCCI and E-cadherin (r = -0.403, -0.295, P 〈 0.05) in neoadjuvant chemotherapy group and simple surgery group. In addition, compared with simple surgery group, the expression of ERCC1 (P = 0.003) and vimentin (P = 0.004) was significantly increased, and the expression of E-cadherin was decreased in neoadjuvant chemotherapy group (P = 0.032). Cenclusion: A549/DDP cells acquired cis展开更多
基金supported by National Natural Science Foundation of China(81272180)National Basic Research Program of China(2012CB518200)
文摘Objective To investigate the role of extracellular signal-regulated kinase (ERK) in apoptosis of human colon cancer (HCT116) cells. Methods After the HCT116 cells were pretreated with specific ERK inhibitor (U0126) or specific siRNA and exposed to 10 mmol/L sodium butyrate (NaBT) for 24 h, their apoptosis was detected by flow cytometry, levels of SphK2 and ERK protein were measured by Western blot, and translocation of SphK2 was assayed by immunofluorescence microscopy. Results The U0126 and siRNAs specific for SphK2 blocked the export of SphK2 from nuclei to cytoplasm and increased the apoptosis of HCT116 cells following NaBT exposure. Over-expression of PKD decreased NaBT-induced apoptosis of HCT116 cells, which was reversed by U0126. Furthermore, transfection of HCT116 cells with constitutively activated PKD plasmids recovered the UO126-blocked export of SphK2. Conclusion ERK regulates the export of SphK2 and apoptosis of HCT116 cells by modulating PKD. Modulation of these molecules may help increase the sensitivity of colon cancer cells to the physiologic anti-colon cancer agent, NaBT.
文摘Objective:Some studies have found that cholecystectomy may increase the risk of colorectal cancer(CRC),while others have reached inconsistent conclusions.We thus performed a systematic review and meta-analysis to assess the incidence rate of CRC after cholecystectomy for patients with gallstones or gallbladder diseases,and whether the geographical location of the patients affected the results.Methods:We systematically searched PubMed,Embase,and Cochrane for studies reporting changes in the incidence rate of CRC after cholecystectomy published before January 12,2023.Our main endpoint wasthe occurrence of CRC Data were extracted and pooled,and the relative risk(RR)and 95%confidence interval(CI)were calculated.We assessed pooled data using a random-effects model.Results:In total,477 articles were identifled,and 6 articles were eligible,including 7 studies thatincluded 797,917 participants.Overall,the summarized research results showed that the risk of CRC was reduced in patients with gallbladder diseases who underwent cholecystectomy(RR:0.80,95%C:0.65 to0.99,p=0.040;I^(2)=85.0%).In the subgroup analysis based on different geographical locations,chole-cystectomy was not associated with the nisk of CRC in the Western population(RR:0.90,95%C:0.65 to 1.25.p=0.522;I^(2)=86.5%),but there was a negative corelation between cholecystectomy and the risk of CRC(RR:0,66,95%Cl:0.60 to 0,73,p=0.000)in the Chinese population Conclusions:Our findings support that for patients with gallstones or gallbladder diseases,the incidence of CRC after cholecystectomy is lower than that of patients who do not undergo cholecystectomy.
基金Supported by National Natural Science Foundation of China,No.81072040
文摘AIM: To investigate the role of nuclear translocation of calcyclin binding protein, also called Siah-1 interacting protein (CacyBP/SIP), in gastric carcinogenesis.
基金Supported by the the National Natural Science Foundation of China(Grant No.11171007)Ph.D. Programs Foundation of Ministry of Education of China(No.20090001110005)
文摘The mortality of ovarian cancer is higher than any other female genital malignant tumors, while there exists a strong correlation between early-stage detection and cure for it. CA125 and HE4 are two most common and effective serum markers in recent screening research of ovarian cancer. This paper derives a sequential screening strategy for ovarian cancer by jointly modeling the longitudinal profiles of CA125 and HE4. We construct a Bayesian hierarchical mixture model with changepoint, and propose two approaches for diagnosis: the risk of cancer index and the hypothesis test on the true incidence time. We simulated a 7-year sequential screening research and compared with the standard approach based on a fixed cutoff level. Our approach achieves a 15% higher sensitivity for a fixed specificity, indicating that the sequential strategy combining multiple markers is more effective in the early-stage detection of ovarian cancer.
文摘Objective To investigate whether the apoptosis is involved in the mechanism of cytotoxicity of trichosanthin to gastric cancer cells. Methods Morphologic studies and TL]AIEL stainning were used to ex-plore qualitatively and quantitatively the apoptotic status of gastric cancer cells before and after treatment with trichosanthin. Results In the experiment in vitro , when gastric cancer cells SGC-7901 were treated by trichosanthin (0. 1μg/ml, 36h), some typical apoptotic morphologic changes occured. A significant increase of apoptotic index (AI) was from (3.78±1.11)%, (3.98±1.12)% and (3.85±1.08)%at 36, 42, 48h to (11.30±2.33)%,(10.22±2.00)% and (11.18±1.85)%,respectively(P<0.01). In the experiment in vivo, nude mice with SGC-7901 xenografted tumor were treated by trichosanthin (0. 3mg kg-1 d -1, × 5d, intraperitoneal injection), some typical apoptotic morphologic changes were observed. These apoptotic cells were limited only in xenografted tumor. Al increased significantly from (4.95± 1 .94) % to (8. 75± 1 .38 )%, (P <0.01). Conclusion The apoptosis would be involved in the mechanism of cytotoxicity of trichosanthin to gastric cancer cells.
基金supported by the Ph.D. Programs Foundation of Ministry of Education of China under Grant No.20090001110005the National Natural Science Foundation of China under Grant No.11171007
文摘Ovarian cancer is one of the most deadly female genital malignant tumors in many regions while an effective early screening strategy can save numerous lives.CA125 and HE4 are tumor markers validated efficacious as well as most commonly used in recent screening research of ovarian cancer.In this paper,the authors construct a change-point and mixture model on the basis of longitudinal CA125 and HE4 levels and estimated parameters using maximum likelihood method with the preclinical duration assumed right-censored,which is more adaptive and yields comparable results in comparison to the Bayesian approach raised by Skates.Consistency of estimators is proved.The authors also run a 5-year simulation of sequential screening by calculating the risk of cancer and hypothesis testing the true incidence time respectively.Results show that diagnosis based on hypothesis test performs better in early detection.
文摘Objective: The aim of this study was to explore the correlation between epithelial to mesenchymal transition (EMT) and chemoresistance of non-small-cell lung cancer (NSCLC). Methods: In vitro, the drug resistance index of cisplatin resistant lung adenocarcinoma cell line (A549/DDP) was detected by CCK-8 assay; the morphological change between A549/ DDP cells and lung adenocarcinoma cells (A549) was observed by phase contrast microscope; expression of EMT markers (including E-cadherin and vimentin) and resistance protein, excision repair cross-complementing 1 (ERCC1) was detected by immunocytochemistry. The expression of E-cadherin, vimentin and ERCC1 was investigated by immunohistochemistry in 120 cases of NSCLC, half of that were treated with pre-operative neoadjuvant chemotherapy (neoadjuvant chemotherapy group), and the other underwent surgery alone (simple surgery group). Results: There was a significant difference between the ICso (half maximal inhibitory concentration) of A549/DDP cells (5.20) and A549 cells (1.88) (P 〈 0.05), and the drug resistance index of A549/DDP cells was 2.77. Compared with A549 cells, A549/DDP cells increased expression of ERCC1 (P 〈 0.05). Moreover, A549/DDP cells showed morphological and phenotypic changes consistent with EMT: with spindle-shaped morphology, and decreased expression of E-cadherin and increased expression of vimentin. Immunohistochemistry showed significant positive correlation between the expression of ERCCI and vimentin (r = 0.496, 0.332, P 〈 0.05), and significant negative correlation between the ERCCI and E-cadherin (r = -0.403, -0.295, P 〈 0.05) in neoadjuvant chemotherapy group and simple surgery group. In addition, compared with simple surgery group, the expression of ERCC1 (P = 0.003) and vimentin (P = 0.004) was significantly increased, and the expression of E-cadherin was decreased in neoadjuvant chemotherapy group (P = 0.032). Cenclusion: A549/DDP cells acquired cis