Objective Antibodies targeting programmed cell death protein 1(PD-1)have become the mainstay of treatment for chemotherapy-refractory gastric cancer,characterized by high levels of programmed cell death ligand-1(PDL-1...Objective Antibodies targeting programmed cell death protein 1(PD-1)have become the mainstay of treatment for chemotherapy-refractory gastric cancer,characterized by high levels of programmed cell death ligand-1(PDL-1)expression.However,the routine clinical implementation of PDL-1 testing is currently limited by the lack of robust detection methods.In this regard,the role of plasmaγ-glutamyl transpeptidase(GGT),an N-terminal nucleophilic hydrolase,as an independent predictor of the efficacy of anti-PD-1 therapy remains unknown.In this study,we aimed to assessed the prognostic role of changes in plasma GGT levels(6 weeks vs.baseline)in patients with advanced gastric cancer treated with anti-PD-1 immunotherapy.Methods We retrospectively analyzed data from 57 patients with gastric cancer treated with anti-PD-1 antibodies(camrelizumab,sintilimab,nivolumab,tislelizumab,and toripalimab)at the Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China,from July 2018 to February 2021.Results We found that after 6 weeks of treatment,there were significant differences between responders and non-responders with respect to plasma GGT levels(P<0.001).Multivariate logistic regression analysis revealed that the continuous value of the 6-week difference in GGT levels(OR=1.437,95%CI=1.116-1.849,P=0.005)and 6-week difference in GGT≥0 or<0(OR=53.675,95%CI=6.379-451.669,P<0.001)were independent predictors of disease control.Survival analysis indicated that a reduction in plasma GGT6 levels during treatment was significantly associated with a favorable progression-free survival(PFS)and overall survival(P<0.001).Consistently,univariate and multivariate Cox regression analyses revealed that a reduction in plasma GGT6 levels during treatment was an independent predictor of PFS(HR=1.033,95%CI=1.013-1.053,P=0.001).Conclusion Alterations in plasma GGT levels during treatment can be used as a predictor of disease progression and survival in patients with advanced gastric cancer undergoing treatment with anti-PD-1 antibodies.展开更多
Helicobacter pylori(H.pylori)produce an enzyme known asγ-glutamyl transpeptidase(HpGGT)that is highly conserved and common to all strains.HpGGT has been gaining increasing attention as an important virulence factor o...Helicobacter pylori(H.pylori)produce an enzyme known asγ-glutamyl transpeptidase(HpGGT)that is highly conserved and common to all strains.HpGGT has been gaining increasing attention as an important virulence factor of the bacterium,having been demonstrated to be an important colonization factor in several animal models and has also recently been strongly associated with the development of peptic ulcer disease.From the results of various independent researcher groups,it is clear that HpGGT acts through several pathways to damage gastric epithelial cells including the induction of apoptosis and cell cycle arrest,production of reactive oxygen species leading to DNA damage,promotion of inflammation by increasing cyclooxygenase-2 and interleukin-8 expression,and upregulation of heparin-binding epidermal growth factor-like growth factor resulting in cell survival and proliferation.In addition,the potential role of HpGGT in promoting gastric carcinogenesis will also be discussed in this review.Apart from affecting the gastric epithelium,HpGGT also has immunomodulatory actions on host immune cells where it displays an antiproliferative effect on T cells by inducing cell cycle arrest and also works with other H.pylori virulence factors to skew dendritic cells towards a tolerogenic phenotype,possibly contributing to the persistence of the pathogen in the gastric mucosa.展开更多
Cancer chemoprevention, a desirable and important facet of biomedical research, provides a practical approach to identify potentially useful inhibitors of cancer development, and offers an opporiunity to study the me...Cancer chemoprevention, a desirable and important facet of biomedical research, provides a practical approach to identify potentially useful inhibitors of cancer development, and offers an opporiunity to study the mechanism of carcinogenesis. During the recent Past a number of compounds have been tested for their anticarcinogenic potential specially constituents of our diet. The enzyme γglutamyl transpeptidase (GGT) which catalyses the transfer of glutamyl groups of peptides to other peptides and amino acid and has been proposed as a marker of cell proliferation and neoplasia. It also serves as a tool to evaluate the carcinogenic and cocarcinogenic potential of environmental toxicants. In the present investigations, CGT activity induced by careinogenic polycyclic aromatic hydmiarbons, viz. 7, 12-dimethylbenz(a) anthracene (DMBA) and benzo(a) pyrene (BaP) was significantly inhibited by diallylsulfide (DAS) and indole-3-carbnol (I3C) in mouse skin. DAS and 13C are constituents of garlic and cruciferous vegetables respectively. A significant iIthibition in GGT levels was also observed in a strong mitogen (12-o-tetradecanoyl phorbol-13-acetate) induced activity in mouse skin by pretreatment with DAS/13C. Therefore these dietary constituents seem to be strong modifiers of chemically induced carcinogenesis展开更多
Photodynamic therapy(PDT),a light triggered therapeutic mode,has been recognized as an attractive treatment for oncotherapy.The phototoxicity to normal tissues during treatment limited the development of PDT owing to ...Photodynamic therapy(PDT),a light triggered therapeutic mode,has been recognized as an attractive treatment for oncotherapy.The phototoxicity to normal tissues during treatment limited the development of PDT owing to the always“on”properties of photosensitizers.Activatable photosensitizers are of great importance for improving the selectivity of PDT.Herein,we regarded the overexpressed GGT(γ-Glutamyl transpeptidase)enzyme in tumor cells as a biomarker and developed an activatable photosensitizer Cy-GGT by decorating a specific recognition moiety of GGT,L-glutamic acid,to a hemicyanine dye based on photosensitizer Cy-NH_(2).Cy-GGT was in the“off”state with negligible fluorescence and suppressed singlet oxygen generation,but it could be specifically hydrolyzed to Cy-NH_(2) in the presence of GGT,accompanied with significant fluorescence recovery and singlet oxygen generation increase under light irradiation.The in vitro and in vivo studies indicated that Cy-GGT was suitable for precise tumor imaging and could work as an efficient photosensitizer for inhibiting tumor growth.展开更多
Helicobacter pylori(H.pylori)gamma-glutamyl transpeptidase(GGT)is a bacterial virulence factor that converts glutamine into glutamate and ammonia,and converts glutathione into glutamate and cysteinylglycine.H.pylori G...Helicobacter pylori(H.pylori)gamma-glutamyl transpeptidase(GGT)is a bacterial virulence factor that converts glutamine into glutamate and ammonia,and converts glutathione into glutamate and cysteinylglycine.H.pylori GGT causes glutamine and glutathione consumption in the host cells,ammonia production and reactive oxygen species generation.These products induce cell-cycle arrest,apoptosis,and necrosis in gastric epithelial cells.H.pylori GGT may also inhibit apoptosis and induce gastric epithelial cell proliferation through the induction of cyclooxygenase-2,epidermal growth factor-related peptides,inducible nitric oxide synthase and interleukin-8.H.pylori GGT induces immune tolerance through the inhibition of T cell-mediated immunity and dendritic cell differentiation.The effect of GGT on H.pylori colonization and gastric persistence are also discussed.展开更多
Eighteen male piglets weaned at 28 days age were randomly assigned to one of three treatments (1% glutamate. 1% and 2% glutamine supplementation). The basal diet contained 5% raw soybean. The diets were calculated to ...Eighteen male piglets weaned at 28 days age were randomly assigned to one of three treatments (1% glutamate. 1% and 2% glutamine supplementation). The basal diet contained 5% raw soybean. The diets were calculated to be isonitrogenous and isoenergetic. The level of plasma glutahione(GSH) increased markedly in piglets fed glutamine, and the response was related to dose. In treatments I and I , the levels of plasma GSH were significantly higher than that in the control at the 35 days age (P<0.05). The level of plasma GSH in treatment I was significantly higher than that in the control at 42 days age (P<0. 05). At 49 days age, there was no significantly difference of the level of GSH in plasma, liver, spleen, intestine and mes-enteric lymph node. The level of superoxide dismutase (SOD) in liver and spleen was higher than that of the control, however, the difference wasn't significant. Dietary glutamine supplementation decreased γ-glutamyl transpeptidase(γ-GT) activities in liver. The activities of γ-GT of liver protein in treatmentⅡ were significantly lower than that in the control (P<0.05). The activities ofγ-GT of duodenum in treatments I and Ⅱwere also significantly lower than that in the control (P<0.05). But there were no significant differences of the activities of γ-GT in jejunum and ileum. The results showed that dietary glutamine supplementation increased the level of plasma GSH, and decreased γ-GT activities.展开更多
γ-Glutamyl peptides can enhance basic taste sensations such as saltiness,sweetness,and umaminess,while the molecular mechanism and the difference in taste enhancement remain elusive.Thus,two complex conformations:tas...γ-Glutamyl peptides can enhance basic taste sensations such as saltiness,sweetness,and umaminess,while the molecular mechanism and the difference in taste enhancement remain elusive.Thus,two complex conformations:taste type 1 receptor 1(T1 R1)-MSG and taste type 1 receptor 2(T1 R2)-sucrose were constructed to form binding receptors.These peptides showed affinity for the two receptors,but a higher affi nity scores and more binding amino acid residues for the T1 R1-MSG receptor,implying that they may exhibit a higher umami-enhancing effect.Thereinto,γ-glutamyl alanine(γ-EA)displayed the highest affi nity for the two receptors through mobilizing multiple amino acid residues to form hydrophobic and hydrogen bonds,indicating it had the highest enhancement for umaminess and sweetness among these peptides.Sensory evaluation demonstrated the enhancement ofγ-EA on umaminess was superior to that of sweetness.Generally,γ-glutamyl peptides could enhance basic taste sensation via activating taste receptor,and exhibited a highest umami-enhancing effect.展开更多
基金Supported by a grant from the Hubei and the Huazhong University of Science and Technology Undergraduate Innovation and Entrepreneurship Training Program(No.S202110487427,DYLC2021072).
文摘Objective Antibodies targeting programmed cell death protein 1(PD-1)have become the mainstay of treatment for chemotherapy-refractory gastric cancer,characterized by high levels of programmed cell death ligand-1(PDL-1)expression.However,the routine clinical implementation of PDL-1 testing is currently limited by the lack of robust detection methods.In this regard,the role of plasmaγ-glutamyl transpeptidase(GGT),an N-terminal nucleophilic hydrolase,as an independent predictor of the efficacy of anti-PD-1 therapy remains unknown.In this study,we aimed to assessed the prognostic role of changes in plasma GGT levels(6 weeks vs.baseline)in patients with advanced gastric cancer treated with anti-PD-1 immunotherapy.Methods We retrospectively analyzed data from 57 patients with gastric cancer treated with anti-PD-1 antibodies(camrelizumab,sintilimab,nivolumab,tislelizumab,and toripalimab)at the Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China,from July 2018 to February 2021.Results We found that after 6 weeks of treatment,there were significant differences between responders and non-responders with respect to plasma GGT levels(P<0.001).Multivariate logistic regression analysis revealed that the continuous value of the 6-week difference in GGT levels(OR=1.437,95%CI=1.116-1.849,P=0.005)and 6-week difference in GGT≥0 or<0(OR=53.675,95%CI=6.379-451.669,P<0.001)were independent predictors of disease control.Survival analysis indicated that a reduction in plasma GGT6 levels during treatment was significantly associated with a favorable progression-free survival(PFS)and overall survival(P<0.001).Consistently,univariate and multivariate Cox regression analyses revealed that a reduction in plasma GGT6 levels during treatment was an independent predictor of PFS(HR=1.033,95%CI=1.013-1.053,P=0.001).Conclusion Alterations in plasma GGT levels during treatment can be used as a predictor of disease progression and survival in patients with advanced gastric cancer undergoing treatment with anti-PD-1 antibodies.
基金Supported by Singapore National Medical Research Council,No.R182000180213
文摘Helicobacter pylori(H.pylori)produce an enzyme known asγ-glutamyl transpeptidase(HpGGT)that is highly conserved and common to all strains.HpGGT has been gaining increasing attention as an important virulence factor of the bacterium,having been demonstrated to be an important colonization factor in several animal models and has also recently been strongly associated with the development of peptic ulcer disease.From the results of various independent researcher groups,it is clear that HpGGT acts through several pathways to damage gastric epithelial cells including the induction of apoptosis and cell cycle arrest,production of reactive oxygen species leading to DNA damage,promotion of inflammation by increasing cyclooxygenase-2 and interleukin-8 expression,and upregulation of heparin-binding epidermal growth factor-like growth factor resulting in cell survival and proliferation.In addition,the potential role of HpGGT in promoting gastric carcinogenesis will also be discussed in this review.Apart from affecting the gastric epithelium,HpGGT also has immunomodulatory actions on host immune cells where it displays an antiproliferative effect on T cells by inducing cell cycle arrest and also works with other H.pylori virulence factors to skew dendritic cells towards a tolerogenic phenotype,possibly contributing to the persistence of the pathogen in the gastric mucosa.
文摘Cancer chemoprevention, a desirable and important facet of biomedical research, provides a practical approach to identify potentially useful inhibitors of cancer development, and offers an opporiunity to study the mechanism of carcinogenesis. During the recent Past a number of compounds have been tested for their anticarcinogenic potential specially constituents of our diet. The enzyme γglutamyl transpeptidase (GGT) which catalyses the transfer of glutamyl groups of peptides to other peptides and amino acid and has been proposed as a marker of cell proliferation and neoplasia. It also serves as a tool to evaluate the carcinogenic and cocarcinogenic potential of environmental toxicants. In the present investigations, CGT activity induced by careinogenic polycyclic aromatic hydmiarbons, viz. 7, 12-dimethylbenz(a) anthracene (DMBA) and benzo(a) pyrene (BaP) was significantly inhibited by diallylsulfide (DAS) and indole-3-carbnol (I3C) in mouse skin. DAS and 13C are constituents of garlic and cruciferous vegetables respectively. A significant iIthibition in GGT levels was also observed in a strong mitogen (12-o-tetradecanoyl phorbol-13-acetate) induced activity in mouse skin by pretreatment with DAS/13C. Therefore these dietary constituents seem to be strong modifiers of chemically induced carcinogenesis
基金This work was supported by the National Natural Science Foundation of China(21925802,21878039,21822804,21808028,22022803,22078046)and the Natural Science Foundation of China-Liaoning Joint Fund(U1908202).
文摘Photodynamic therapy(PDT),a light triggered therapeutic mode,has been recognized as an attractive treatment for oncotherapy.The phototoxicity to normal tissues during treatment limited the development of PDT owing to the always“on”properties of photosensitizers.Activatable photosensitizers are of great importance for improving the selectivity of PDT.Herein,we regarded the overexpressed GGT(γ-Glutamyl transpeptidase)enzyme in tumor cells as a biomarker and developed an activatable photosensitizer Cy-GGT by decorating a specific recognition moiety of GGT,L-glutamic acid,to a hemicyanine dye based on photosensitizer Cy-NH_(2).Cy-GGT was in the“off”state with negligible fluorescence and suppressed singlet oxygen generation,but it could be specifically hydrolyzed to Cy-NH_(2) in the presence of GGT,accompanied with significant fluorescence recovery and singlet oxygen generation increase under light irradiation.The in vitro and in vivo studies indicated that Cy-GGT was suitable for precise tumor imaging and could work as an efficient photosensitizer for inhibiting tumor growth.
基金Supported by Italian Ministry for University and Research(Progetto di Ricerca di Interesse Nazionale No.2009A37C8C_002,to Ricci V)Fondazione Cariplo Grant(No.2011-0485 to Ricci V)+2 种基金Second University of Naples(CIRANAD to Romano M)University of Naples "Federico Ⅱ"(Fondo d’Ateneo per la Ricercato Zarrilli R)
文摘Helicobacter pylori(H.pylori)gamma-glutamyl transpeptidase(GGT)is a bacterial virulence factor that converts glutamine into glutamate and ammonia,and converts glutathione into glutamate and cysteinylglycine.H.pylori GGT causes glutamine and glutathione consumption in the host cells,ammonia production and reactive oxygen species generation.These products induce cell-cycle arrest,apoptosis,and necrosis in gastric epithelial cells.H.pylori GGT may also inhibit apoptosis and induce gastric epithelial cell proliferation through the induction of cyclooxygenase-2,epidermal growth factor-related peptides,inducible nitric oxide synthase and interleukin-8.H.pylori GGT induces immune tolerance through the inhibition of T cell-mediated immunity and dendritic cell differentiation.The effect of GGT on H.pylori colonization and gastric persistence are also discussed.
文摘Eighteen male piglets weaned at 28 days age were randomly assigned to one of three treatments (1% glutamate. 1% and 2% glutamine supplementation). The basal diet contained 5% raw soybean. The diets were calculated to be isonitrogenous and isoenergetic. The level of plasma glutahione(GSH) increased markedly in piglets fed glutamine, and the response was related to dose. In treatments I and I , the levels of plasma GSH were significantly higher than that in the control at the 35 days age (P<0.05). The level of plasma GSH in treatment I was significantly higher than that in the control at 42 days age (P<0. 05). At 49 days age, there was no significantly difference of the level of GSH in plasma, liver, spleen, intestine and mes-enteric lymph node. The level of superoxide dismutase (SOD) in liver and spleen was higher than that of the control, however, the difference wasn't significant. Dietary glutamine supplementation decreased γ-glutamyl transpeptidase(γ-GT) activities in liver. The activities of γ-GT of liver protein in treatmentⅡ were significantly lower than that in the control (P<0.05). The activities ofγ-GT of duodenum in treatments I and Ⅱwere also significantly lower than that in the control (P<0.05). But there were no significant differences of the activities of γ-GT in jejunum and ileum. The results showed that dietary glutamine supplementation increased the level of plasma GSH, and decreased γ-GT activities.
基金financial support by the National Natural Science Foundation of China(31901814)Guangzhou Science and Technology program key project(202104020028)the Major State Basic Reasearch Development Program Of China(2018YFD0901003)。
文摘γ-Glutamyl peptides can enhance basic taste sensations such as saltiness,sweetness,and umaminess,while the molecular mechanism and the difference in taste enhancement remain elusive.Thus,two complex conformations:taste type 1 receptor 1(T1 R1)-MSG and taste type 1 receptor 2(T1 R2)-sucrose were constructed to form binding receptors.These peptides showed affinity for the two receptors,but a higher affi nity scores and more binding amino acid residues for the T1 R1-MSG receptor,implying that they may exhibit a higher umami-enhancing effect.Thereinto,γ-glutamyl alanine(γ-EA)displayed the highest affi nity for the two receptors through mobilizing multiple amino acid residues to form hydrophobic and hydrogen bonds,indicating it had the highest enhancement for umaminess and sweetness among these peptides.Sensory evaluation demonstrated the enhancement ofγ-EA on umaminess was superior to that of sweetness.Generally,γ-glutamyl peptides could enhance basic taste sensation via activating taste receptor,and exhibited a highest umami-enhancing effect.
文摘目的探讨γ-谷氨酰转肽酶(γ-glutamyl transpeptidase,GGT)与嗜酸性粒细胞(eosinophils,EOS)等检验指标联合B超检查对肝吸虫病的诊断价值。方法选取粪便寄生虫检查找到肝吸虫卵的病例175例为观察组,另选取同期肝吸虫抗体检测及粪便寄生虫卵检查均阴性的健康体检人员171例为对照组。分析比较两组间总胆红素(total bilirubin,TBIL)、直接胆红素(direct bilirubin,DBIL)、GGT、EOS及B超检查结果的差异,筛选出有统计学意义的检查指标,运用logistic回归分析建立肝吸虫病联合诊断模型。结果两组GGT和EOS比较差异有统计学意义(P<0.001)。两组间B超检查结果对比,观察组胆囊病变、胆管病变以及肝脏病变分别为31例(17.7%)、36例(20.6%)、70例(40.0%);对照组胆囊病变、胆管病变以及肝脏病变分别为11例(6.4%)、3例(1.8%)、64例(37.4%)。经逐步回归分析,GGT、EOS、胆囊异常、胆管异常4项指标入选模型。GGT与EOS联合B超检查建立回归方程,得到联合诊断模型logitP。logitP的受试者工作特性曲线(receiver operator characteristic curve,ROC)的曲线下面积(the area under curve,AUC)为0.784,敏感性为0.669,特异性为0.801。结论GGT和EOS联合B超检查在肝吸虫病诊断中具有较好的诊断效能。
