BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for h...BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for high microsatellite instability.AIM To develop methods to identify groups of patients with GC who would benefit the most from receiving the combination of a programmed cell death protein 1(PD-1)inhibitor and chemotherapy.METHODS We acquired data from 63 patients with human epidermal growth factor receptor 2(HER2)-negative GC with a histological diagnosis of GC at the Cancer Hospital,Chinese Academy of Medical Sciences between November 2020 and October 2022.All of the patients screened received a PD-1 inhibitor combined with chemotherapy as the first-line treatment.RESULTS As of July 1,2023,the objective response rate was 61.9%,and the disease control rate was 96.8%.The median progression-free survival(mPFS)for all patients was 6.3 months.The median overall survival was not achieved.Survival analysis showed that patients with a combined positive score(CPS)≥1 exhibited an extended trend in progression-free survival(PFS)when compared to patients with a CPS of 0 after receiving a PD-1 inhibitor combined with oxaliplatin and tegafur as the first-line treatment.PFS exhibited a trend for prolongation as the expression level of HER2 increased.Based on PFS,we divided patients into two groups:A treatment group with excellent efficacy and a treatment group with poor efficacy.The mPFS of the excellent efficacy group was 8 months,with a mPFS of 9.1 months after excluding a cohort of patients who received interrupted therapy due to surgery.The mPFS was 4.5 months in patients in the group with poor efficacy who did not receive surgery.Using good/poor efficacy as the endpoint of our study,univariate analysis revealed that both CPS score(P=0.004)and HER2 expression level(P=0.015)were both factors that exerted significant influence on the efficacy of treatment the combination of a PD-1 inhibitor and chemotherapy in patients with advanced GC(AGC).Finally,multivariate analysis confirmed that CPS score was a significant influencing factor.CONCLUSION CPS score and HER2 expression both impacted the efficacy of immunotherapy combined with chemotherapy in AGC patients who were non-positive for HER2.展开更多
Aim To investigate in vitro apoptosis-induction effects of oridonin on gastric tumor cells BGC-823 and its effects on cell cycle, mitochondrial membrane potential and intracellular Ca^2＋ to shed light on the mode of ...Aim To investigate in vitro apoptosis-induction effects of oridonin on gastric tumor cells BGC-823 and its effects on cell cycle, mitochondrial membrane potential and intracellular Ca^2＋ to shed light on the mode of its anticancer action. Methods The MTT method was used to investigate the inhibitory effect of oridonin on BGC-823 cells. The apoptosis-induction effect was evaluated by confocal laser microscopy and flow cytometry. The change of mitochondrial membrane potential and the increase of intracellular Ca^2＋ were assessed by fluorescence probe rhodamine123 and Fluo 3-AM, respectively, with flow cytometry. The expression of apoptosis and cell cycle related proteins was studied using western blotting. Results Oridonin inhibited BGC-823 cells growth with IC50 of 22.21 p, mol.L^-1. It induced apoptosis in a dose-dependent manner. In addition, it decreased mitochondria membrane potential, increased intracellular Ca^2＋, and activated pro-caspase 3. BGC-823 cells were arrested in G2/M cell cycle phase with lower expression of cyclin A protein. The up-regulation of p53 was observed before apoptosis and cell cycle arrest occurred. Conclusion Oridonin inhibits the proliferation of BGC-823 cells through G2/M cell cycle arrest and apoptosis induction, which is mediated by influx of Ca^2＋, up-regulation of p53, activation of caspase-3, and down-regulation of cyclin A.展开更多
Objective: Human induced pluripotent stem(i PS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human i PS cells labeled with fluorescent ...Objective: Human induced pluripotent stem(i PS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human i PS cells labeled with fluorescent magnetic nanoparticles(FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Methods: Human i PS cells were prepared and cultured for 72 h. The culture medium was collected, and then was coincubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human i PS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. Results: iP S cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iP S cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. Conclusion: FMNP-labeled human i PS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer.展开更多
AIM: To explore the inducing effect of human mutant p27 gene on the apoptosis of the human gastric cancer cell line MKN-45 and its associated mechanisms. METHODS: The recombinant adenovirus Ad-p27mt was constructed to...AIM: To explore the inducing effect of human mutant p27 gene on the apoptosis of the human gastric cancer cell line MKN-45 and its associated mechanisms. METHODS: The recombinant adenovirus Ad-p27mt was constructed to infect the human gastric cancer cell line MKN-45. Using flow cytometry, TUNEL assay and DNA fragment analysis, we measured the apoptotic effect of Ad-p27mt on the human gastric cancer cells. RESULTS: Ad-p27mt was successfully constructed and the infection efficiency reached 100%. After 18 h of infection, we observed an apoptotic hypodiploid peak on the flow cytometer before G1-S and apoptotic characteristic bands in the DNA electrophoresis. The apoptotic rate detected by TUNEL method was significantly higher in the Ad-p27mt group (89.4±3.12%)compared to the control group (3.12±0.13%, P ＜ 0.01).CONCLUSION: Human mutant p27 can induce apoptosis of the human gastric cancer cells in vitro.展开更多
AIM:To establish a cellular model correctly mimicking the gastric epithelium to overcome the limitation in the study of Helicobacter pylori(H.pylori) infection.METHODS:Aiming to overcome this limitation,clones of the ...AIM:To establish a cellular model correctly mimicking the gastric epithelium to overcome the limitation in the study of Helicobacter pylori(H.pylori) infection.METHODS:Aiming to overcome this limitation,clones of the heterogenic cancer-derived NCI-N87 cell line were isolated,by stably-transducing it with the human telomerase reverse-transcriptase(h TERT) catalytic subunit gene.The clones were first characterized regarding their cell growth pattern and phenotype.For that we measured the clones' adherence properties,expression of cell-cell junctions' markers(ZO-1 and E-cadherin) and ability to generate a sustained transepithelial electrical resistance.The gastric properties of the clones,concerning expression of mucins,zymogens and glycan contents,were then evaluated by haematoxylin and eosin staining,Periodic acid Schiff(PAS) and PAS/Alcian Blue-staining,immunocytochemistry and Western blot.In addition,we assessed the usefulness of the h TERT-expressing gastric cell line for H.pylori research,by performing co-culture assays and measuring the IL-8 secretion,by ELISA,upon infection with two H.pylori strains differing in virulence.RESULTS:Compared with the parental cell line,themost promising NCI-hT ERT-derived clones(CL5 and CL6) were composed of cells with homogenous phenotype,presented higher relative telomerase activities,better adhesion properties,ability to be maintained in culture for longer periods after confluency,and were more efficient in PAS-reactive mucins secretion.Both clones were shown to produce high amounts of MUC1,MUC2 and MUC13.NCI-hT ERT-CL5 mucins were shown to be decorated with blood group H type 2(BG-H),Lewis-x(Lex),Ley and Lea and,in a less extent,with BG-A antigens,but the former two antigens were not detected in the NCI-h TERT-CL6.None of the clones exhibited detectable levels of MUC6 nor sialylated Lex and Lea glycans.Entailing good gastric properties,both NCIhT ERT-clones were found to produce pepsinogen-5 and human gastric lipase.The progenitor-like phenotype of NCI-hT ERT-CL6 cells was highlighted by large nuclei and by the apical vesicular-like distribution of mucin 5AC and Pg5,supporting the accumulation of mucus-secreting and zymogens-chief mature cells functions.CONCLUSION:These traits,in addition to resistance to microaerobic conditions and good responsiveness to H.pylori co-culture,in a strain virulence-dependent manner,make the NCI-hT ERT-CL6 a promising model for future in vitro studies.展开更多
AIM: To investigate telomerase activity and human telomerase reverse transcriptase (hTERT) expression in normal human gastric mucosal epithelial cells (nhGMECs) and fibroblasts (nhGMFs).
AIM To investigate the expression of annexin II in gastric carcinoma and its role in the metastasis of gastric cancer.METHODS The expression of annexin II in 51 cases of gastric carcinoma and 24 cases of adjacent tiss...AIM To investigate the expression of annexin II in gastric carcinoma and its role in the metastasis of gastric cancer.METHODS The expression of annexin II in 51 cases of gastric carcinoma and 24 cases of adjacent tissues was detected by immunohistochemistry. The relationship between annexin II and clinical features of gastric cancer was analyzed. Annexin II specific si RNA was used to inhibit the expression of annexin II in gastric cancer HGC-27 cells, and the effects of annexin II on the migration and secretion of matrix metalloproteinases(MMPs) were observed.RESULTS The positive rate of annexin II protein was 82.4% in gastric cancer tissues and 37.5% in adjacent tissues. There was significant difference between the two groups(P < 0.01); and the positive expression of annexin II was not related to the sex and age of the patients(P > 0.05). The expression of annexin IIprotein was correlated with tumor size, histological differentiation, TNM stage, Lymph node metastasis and other clinical features were significantly correlated, the difference was statistically significant(P < 0.05). Inhibition of annexin II expression, gastric cancer HGC-27 cells migration and secretion of MMPs were significantly decreased, the difference was statistically significant(P < 0.05).CONCLUSION Annexin II is highly expressed in gastric cancer tissues, annexin II protein expression is related to tumor size, histological differentiation, TNM staging, lymph node metastasis and other clinical features were significantly correlated. Annexin II high expression can promote the invasion and metastasis of gastric cancer.展开更多
AIM： To investigate whether activin regulates the cell proliferation of human gastric cancer cell line SNU-16 through the mRNA changes in activin receptors, Smads and p21^CIP1/WAF1. METHODS： The human gastric cancer...AIM： To investigate whether activin regulates the cell proliferation of human gastric cancer cell line SNU-16 through the mRNA changes in activin receptors, Smads and p21^CIP1/WAF1. METHODS： The human gastric cancer cell lines were cultured, RNAs were purified, and RT-PCRs were carried out with specifically designed primer for each gene. Among them, the two cell lines SNU-5 and SNU-16 were cultured with activin A for 24, 48 and 72 h. The cell proliferation was measured by MTT assay. For SNU-16, changes in ActRIA, ActRIB, ActRIIA, ActRIIB, Smad2, Smad4, Smad7, and p21^CIP1/WAF1 mRNAs were detected with RT-PCR after the cells were cultured with activin A for 24, 48 and 72 h. RESULTS： The proliferation of SNU-16 cells was down regulated by activin A whereas other cells showed no change. Basal level of inhibin/activin subunits, activin receptors, Smads, and p21^CIP1/WAF1 except for activin βB mRNAs was observed to have differential expression patterns in the human gastric cancer cell lines, AGS, KATO III, SNU-1, SNU-5, SNU-16, SNU-484, SNU-601, SNU-638, SNU-668, and SNU-719. Interestingly, significantly higher expressions of ActR IIA and IIB mRNAs were observed in SNU-16 cells when compared to other cells. After activin treatment, ActR IA, IB, and IIA mRNA levels were decreased whereas ActR IIB mRNA level increased in SNU-16 cells. Smad4 mRNA increased for up to 48 h whereas Smad7 mRNA increased sharply at 24 h and returned to the initial level at 48 h in SNU-16 cells. In addition, expression of the p21^CIP1/WAF1 the mitotic inhibitor, peaked at 72 h after activin treatment in SNU-16 cells. CONCLUSION： Our results suggest that inhibition of cell growth by activin is regulated by the negative feedback effect of Smad7 on the activin signaling pathway, and is mediated through p21^CIP1/WAF1 activation in SNU-16 cells.展开更多
Objective To preliminarily explore the effects of human microRNA-181a on migration of gastric cancer cells and its mechanism.Methods The expression of miRNA-181a-5p in gastric cancer cell line GC9811 and peritoneal hi...Objective To preliminarily explore the effects of human microRNA-181a on migration of gastric cancer cells and its mechanism.Methods The expression of miRNA-181a-5p in gastric cancer cell line GC9811 and peritoneal high metastasis gastric cancer cell line GC9811-P were tested by quantitative real-time polymerase chain reaction(qRT-PCR).GC9811 cell line was展开更多
Malabaricone C （1）, isolated from the seeds ofMyristicafragrans Houtt., belongs to a kind of diarylnonanoid compounds that are only found in Myristicaceae till now. In this study, biotransformation of 1 was investig...Malabaricone C （1）, isolated from the seeds ofMyristicafragrans Houtt., belongs to a kind of diarylnonanoid compounds that are only found in Myristicaceae till now. In this study, biotransformation of 1 was investigated using rat hepatic microsomes for the first time and the main biotransformation product was elucidated as malabaricone B （2） according to the spectroscopic data. Further evaluation on human gastric cancer cell lines showed that the cytotoxic effects of malabaricone C and its metabolite malabaricone B were comparable to those of vinorelbine, with the values of IC50 of （42.62±3.10） and （19.80±1.70） μg/mL on NCI-N87, and （22.94±1.33） and （19.60±2.21） μg/mL on MGC803, respectively. Statistical analysis revealed that malabaricone B had significantly stronger cytotoxicity than the parent compound （P〈0.01 on NCI-N87 and P〈0.05 on MGC803）, which may indicate a bioactivation of malabaricone C by hepatic microsomes. These results suggest that malabaricone C has a simple biotransformation pathway by hepatic microsomes and provide valuable information for further investigation on both the parent compound and its biotransformation product as anti-gastric cancer agents or lead compounds.展开更多
AIM:To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis.METHODS:Cell transplantation into mouse livers was conducted using alpha-fetoprotein(AFP)-producing hu-...AIM:To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis.METHODS:Cell transplantation into mouse livers was conducted using alpha-fetoprotein(AFP)-producing hu-man gastric cancer cells(h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing urokinase-type plasminogen activator(uPA) driven by the albumin enhancer/promoter crossed with a severe combined immunodeficient(SCID) mouse line(uPA/SCID mice).Host mice were divided into two groups(A and B).Group A mice were transplanted with h-GCCs alone,and group B mice were transplanted with h-GCCs and h-hepatocytes together.The replacement index(RI),which is the ratio of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a histological section,was estimated by measuring h-AFP and h-albumin concentrations in sera,respectively,as well as by immunohistochemical analyses of h-AFP and human cytokeratin 18 in histological sections.RESULTS:The h-GCCs successfully engrafted,repopulated,and colonized the livers of mice in group A(RI = 22.0% ± 2.6%).These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures,which is a characteristics feature of gastric cancers.The serum h-AFP level reached 211.0 ± 142.2 g/mL(range,7.1-324.2 g/mL).In group B mice,the h-GCCs and h-hepatocytes independently engrafted,repopulated the host liver,and developed colonies(RI = 12.0% ± 6.8% and 66.0% ± 12.3%,respectively).h-GCC colonies also showed typical adenocarcinomatous glandular structures around the h-hepatocyte-colonies.These mice survived for the full 56 day-study and did not exhibit any metastasis of h-GCCs in the extrahepatic regions during the observational period.The mice with an h-hepatocyte-repopulated liver possessed metastasized h-GCCs and therefore could be a useful humanized liver animal model for studying liver cancer metastasis in vivo.CONCLUSION:A novel animal model of human liver cancer metastasis was established using the uPA/SCID mouse line.This model could be useful for in vivo testing of anti-cancer drugs and for studying the mechanisms of human liver cancer metastasis.展开更多
基金Supported by Beijing CSCO Clinical Oncology Research Foundation,No.Y-HH202102-0314。
文摘BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for high microsatellite instability.AIM To develop methods to identify groups of patients with GC who would benefit the most from receiving the combination of a programmed cell death protein 1(PD-1)inhibitor and chemotherapy.METHODS We acquired data from 63 patients with human epidermal growth factor receptor 2(HER2)-negative GC with a histological diagnosis of GC at the Cancer Hospital,Chinese Academy of Medical Sciences between November 2020 and October 2022.All of the patients screened received a PD-1 inhibitor combined with chemotherapy as the first-line treatment.RESULTS As of July 1,2023,the objective response rate was 61.9%,and the disease control rate was 96.8%.The median progression-free survival(mPFS)for all patients was 6.3 months.The median overall survival was not achieved.Survival analysis showed that patients with a combined positive score(CPS)≥1 exhibited an extended trend in progression-free survival(PFS)when compared to patients with a CPS of 0 after receiving a PD-1 inhibitor combined with oxaliplatin and tegafur as the first-line treatment.PFS exhibited a trend for prolongation as the expression level of HER2 increased.Based on PFS,we divided patients into two groups:A treatment group with excellent efficacy and a treatment group with poor efficacy.The mPFS of the excellent efficacy group was 8 months,with a mPFS of 9.1 months after excluding a cohort of patients who received interrupted therapy due to surgery.The mPFS was 4.5 months in patients in the group with poor efficacy who did not receive surgery.Using good/poor efficacy as the endpoint of our study,univariate analysis revealed that both CPS score(P=0.004)and HER2 expression level(P=0.015)were both factors that exerted significant influence on the efficacy of treatment the combination of a PD-1 inhibitor and chemotherapy in patients with advanced GC(AGC).Finally,multivariate analysis confirmed that CPS score was a significant influencing factor.CONCLUSION CPS score and HER2 expression both impacted the efficacy of immunotherapy combined with chemotherapy in AGC patients who were non-positive for HER2.
基金Program for Changjiang Scholar and Innova-tive Team in University(Grant No.985-2-063-112).
文摘Aim To investigate in vitro apoptosis-induction effects of oridonin on gastric tumor cells BGC-823 and its effects on cell cycle, mitochondrial membrane potential and intracellular Ca^2＋ to shed light on the mode of its anticancer action. Methods The MTT method was used to investigate the inhibitory effect of oridonin on BGC-823 cells. The apoptosis-induction effect was evaluated by confocal laser microscopy and flow cytometry. The change of mitochondrial membrane potential and the increase of intracellular Ca^2＋ were assessed by fluorescence probe rhodamine123 and Fluo 3-AM, respectively, with flow cytometry. The expression of apoptosis and cell cycle related proteins was studied using western blotting. Results Oridonin inhibited BGC-823 cells growth with IC50 of 22.21 p, mol.L^-1. It induced apoptosis in a dose-dependent manner. In addition, it decreased mitochondria membrane potential, increased intracellular Ca^2＋, and activated pro-caspase 3. BGC-823 cells were arrested in G2/M cell cycle phase with lower expression of cyclin A protein. The up-regulation of p53 was observed before apoptosis and cell cycle arrest occurred. Conclusion Oridonin inhibits the proliferation of BGC-823 cells through G2/M cell cycle arrest and apoptosis induction, which is mediated by influx of Ca^2＋, up-regulation of p53, activation of caspase-3, and down-regulation of cyclin A.
基金supported by National Natural Science Foundation of China (Grant No. 81225010, 20803040, 81028009, and 31170961)National Key Basic Research Program of China (973 Program) (Grant No. 2010CB933902 and 2015CB931802)+1 种基金National Key Technology Research and Development Program (863 Program) (Grant No. 2012AA022703 and 2014AA020700)Shanghai Science and Technology Fund (Grant No.13NM1401500)
文摘Objective: Human induced pluripotent stem(i PS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human i PS cells labeled with fluorescent magnetic nanoparticles(FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Methods: Human i PS cells were prepared and cultured for 72 h. The culture medium was collected, and then was coincubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human i PS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. Results: iP S cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iP S cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. Conclusion: FMNP-labeled human i PS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer.
基金Supported by the Natural Science Foundation of Shanghai,No. 04ZB14072
文摘AIM: To explore the inducing effect of human mutant p27 gene on the apoptosis of the human gastric cancer cell line MKN-45 and its associated mechanisms. METHODS: The recombinant adenovirus Ad-p27mt was constructed to infect the human gastric cancer cell line MKN-45. Using flow cytometry, TUNEL assay and DNA fragment analysis, we measured the apoptotic effect of Ad-p27mt on the human gastric cancer cells. RESULTS: Ad-p27mt was successfully constructed and the infection efficiency reached 100%. After 18 h of infection, we observed an apoptotic hypodiploid peak on the flow cytometer before G1-S and apoptotic characteristic bands in the DNA electrophoresis. The apoptotic rate detected by TUNEL method was significantly higher in the Ad-p27mt group (89.4±3.12%)compared to the control group (3.12±0.13%, P ＜ 0.01).CONCLUSION: Human mutant p27 can induce apoptosis of the human gastric cancer cells in vitro.
基金Supported by Grants from the Fundao para a Ciência e a Tecnologia(FCT,Portugal),No.PPCDT/SAL-IMI/57297/2004 and No.PTDC/BIM-MEC/1051/2012The Swedish Cancer foundation+2 种基金The Swedish Research Council,No.K2010-79X-21372-01-3Forska utan djurfrsk,Animal Free ResearchResearch fellowship 2011 from the Sociedade Portuguesa de Gastrenterologia(Portugal)
文摘AIM:To establish a cellular model correctly mimicking the gastric epithelium to overcome the limitation in the study of Helicobacter pylori(H.pylori) infection.METHODS:Aiming to overcome this limitation,clones of the heterogenic cancer-derived NCI-N87 cell line were isolated,by stably-transducing it with the human telomerase reverse-transcriptase(h TERT) catalytic subunit gene.The clones were first characterized regarding their cell growth pattern and phenotype.For that we measured the clones' adherence properties,expression of cell-cell junctions' markers(ZO-1 and E-cadherin) and ability to generate a sustained transepithelial electrical resistance.The gastric properties of the clones,concerning expression of mucins,zymogens and glycan contents,were then evaluated by haematoxylin and eosin staining,Periodic acid Schiff(PAS) and PAS/Alcian Blue-staining,immunocytochemistry and Western blot.In addition,we assessed the usefulness of the h TERT-expressing gastric cell line for H.pylori research,by performing co-culture assays and measuring the IL-8 secretion,by ELISA,upon infection with two H.pylori strains differing in virulence.RESULTS:Compared with the parental cell line,themost promising NCI-hT ERT-derived clones(CL5 and CL6) were composed of cells with homogenous phenotype,presented higher relative telomerase activities,better adhesion properties,ability to be maintained in culture for longer periods after confluency,and were more efficient in PAS-reactive mucins secretion.Both clones were shown to produce high amounts of MUC1,MUC2 and MUC13.NCI-hT ERT-CL5 mucins were shown to be decorated with blood group H type 2(BG-H),Lewis-x(Lex),Ley and Lea and,in a less extent,with BG-A antigens,but the former two antigens were not detected in the NCI-h TERT-CL6.None of the clones exhibited detectable levels of MUC6 nor sialylated Lex and Lea glycans.Entailing good gastric properties,both NCIhT ERT-clones were found to produce pepsinogen-5 and human gastric lipase.The progenitor-like phenotype of NCI-hT ERT-CL6 cells was highlighted by large nuclei and by the apical vesicular-like distribution of mucin 5AC and Pg5,supporting the accumulation of mucus-secreting and zymogens-chief mature cells functions.CONCLUSION:These traits,in addition to resistance to microaerobic conditions and good responsiveness to H.pylori co-culture,in a strain virulence-dependent manner,make the NCI-hT ERT-CL6 a promising model for future in vitro studies.
基金Supported by National Natural Science Foundation of China,No.30270609
文摘AIM: To investigate telomerase activity and human telomerase reverse transcriptase (hTERT) expression in normal human gastric mucosal epithelial cells (nhGMECs) and fibroblasts (nhGMFs).
文摘AIM To investigate the expression of annexin II in gastric carcinoma and its role in the metastasis of gastric cancer.METHODS The expression of annexin II in 51 cases of gastric carcinoma and 24 cases of adjacent tissues was detected by immunohistochemistry. The relationship between annexin II and clinical features of gastric cancer was analyzed. Annexin II specific si RNA was used to inhibit the expression of annexin II in gastric cancer HGC-27 cells, and the effects of annexin II on the migration and secretion of matrix metalloproteinases(MMPs) were observed.RESULTS The positive rate of annexin II protein was 82.4% in gastric cancer tissues and 37.5% in adjacent tissues. There was significant difference between the two groups(P < 0.01); and the positive expression of annexin II was not related to the sex and age of the patients(P > 0.05). The expression of annexin IIprotein was correlated with tumor size, histological differentiation, TNM stage, Lymph node metastasis and other clinical features were significantly correlated, the difference was statistically significant(P < 0.05). Inhibition of annexin II expression, gastric cancer HGC-27 cells migration and secretion of MMPs were significantly decreased, the difference was statistically significant(P < 0.05).CONCLUSION Annexin II is highly expressed in gastric cancer tissues, annexin II protein expression is related to tumor size, histological differentiation, TNM staging, lymph node metastasis and other clinical features were significantly correlated. Annexin II high expression can promote the invasion and metastasis of gastric cancer.
基金Supported by the Research Fund 2003 from the Catholic University of Korea
文摘AIM： To investigate whether activin regulates the cell proliferation of human gastric cancer cell line SNU-16 through the mRNA changes in activin receptors, Smads and p21^CIP1/WAF1. METHODS： The human gastric cancer cell lines were cultured, RNAs were purified, and RT-PCRs were carried out with specifically designed primer for each gene. Among them, the two cell lines SNU-5 and SNU-16 were cultured with activin A for 24, 48 and 72 h. The cell proliferation was measured by MTT assay. For SNU-16, changes in ActRIA, ActRIB, ActRIIA, ActRIIB, Smad2, Smad4, Smad7, and p21^CIP1/WAF1 mRNAs were detected with RT-PCR after the cells were cultured with activin A for 24, 48 and 72 h. RESULTS： The proliferation of SNU-16 cells was down regulated by activin A whereas other cells showed no change. Basal level of inhibin/activin subunits, activin receptors, Smads, and p21^CIP1/WAF1 except for activin βB mRNAs was observed to have differential expression patterns in the human gastric cancer cell lines, AGS, KATO III, SNU-1, SNU-5, SNU-16, SNU-484, SNU-601, SNU-638, SNU-668, and SNU-719. Interestingly, significantly higher expressions of ActR IIA and IIB mRNAs were observed in SNU-16 cells when compared to other cells. After activin treatment, ActR IA, IB, and IIA mRNA levels were decreased whereas ActR IIB mRNA level increased in SNU-16 cells. Smad4 mRNA increased for up to 48 h whereas Smad7 mRNA increased sharply at 24 h and returned to the initial level at 48 h in SNU-16 cells. In addition, expression of the p21^CIP1/WAF1 the mitotic inhibitor, peaked at 72 h after activin treatment in SNU-16 cells. CONCLUSION： Our results suggest that inhibition of cell growth by activin is regulated by the negative feedback effect of Smad7 on the activin signaling pathway, and is mediated through p21^CIP1/WAF1 activation in SNU-16 cells.
文摘Objective To preliminarily explore the effects of human microRNA-181a on migration of gastric cancer cells and its mechanism.Methods The expression of miRNA-181a-5p in gastric cancer cell line GC9811 and peritoneal high metastasis gastric cancer cell line GC9811-P were tested by quantitative real-time polymerase chain reaction(qRT-PCR).GC9811 cell line was
基金National Natural Science Foundation of China(Grant No.30973863.81161120429)National Key Technology R&D Program of China(Grant No.2011BAI07B08)
文摘Malabaricone C （1）, isolated from the seeds ofMyristicafragrans Houtt., belongs to a kind of diarylnonanoid compounds that are only found in Myristicaceae till now. In this study, biotransformation of 1 was investigated using rat hepatic microsomes for the first time and the main biotransformation product was elucidated as malabaricone B （2） according to the spectroscopic data. Further evaluation on human gastric cancer cell lines showed that the cytotoxic effects of malabaricone C and its metabolite malabaricone B were comparable to those of vinorelbine, with the values of IC50 of （42.62±3.10） and （19.80±1.70） μg/mL on NCI-N87, and （22.94±1.33） and （19.60±2.21） μg/mL on MGC803, respectively. Statistical analysis revealed that malabaricone B had significantly stronger cytotoxicity than the parent compound （P〈0.01 on NCI-N87 and P〈0.05 on MGC803）, which may indicate a bioactivation of malabaricone C by hepatic microsomes. These results suggest that malabaricone C has a simple biotransformation pathway by hepatic microsomes and provide valuable information for further investigation on both the parent compound and its biotransformation product as anti-gastric cancer agents or lead compounds.
基金Supported by CLUSTER-Yoshizato Project and the National Hospital Organization Nagasaki Medical Center
文摘AIM:To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis.METHODS:Cell transplantation into mouse livers was conducted using alpha-fetoprotein(AFP)-producing hu-man gastric cancer cells(h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing urokinase-type plasminogen activator(uPA) driven by the albumin enhancer/promoter crossed with a severe combined immunodeficient(SCID) mouse line(uPA/SCID mice).Host mice were divided into two groups(A and B).Group A mice were transplanted with h-GCCs alone,and group B mice were transplanted with h-GCCs and h-hepatocytes together.The replacement index(RI),which is the ratio of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a histological section,was estimated by measuring h-AFP and h-albumin concentrations in sera,respectively,as well as by immunohistochemical analyses of h-AFP and human cytokeratin 18 in histological sections.RESULTS:The h-GCCs successfully engrafted,repopulated,and colonized the livers of mice in group A(RI = 22.0% ± 2.6%).These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures,which is a characteristics feature of gastric cancers.The serum h-AFP level reached 211.0 ± 142.2 g/mL(range,7.1-324.2 g/mL).In group B mice,the h-GCCs and h-hepatocytes independently engrafted,repopulated the host liver,and developed colonies(RI = 12.0% ± 6.8% and 66.0% ± 12.3%,respectively).h-GCC colonies also showed typical adenocarcinomatous glandular structures around the h-hepatocyte-colonies.These mice survived for the full 56 day-study and did not exhibit any metastasis of h-GCCs in the extrahepatic regions during the observational period.The mice with an h-hepatocyte-repopulated liver possessed metastasized h-GCCs and therefore could be a useful humanized liver animal model for studying liver cancer metastasis in vivo.CONCLUSION:A novel animal model of human liver cancer metastasis was established using the uPA/SCID mouse line.This model could be useful for in vivo testing of anti-cancer drugs and for studying the mechanisms of human liver cancer metastasis.
