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
Aim: To study the effect of mercuric chloride on the membrane-bound enzymes. Methods: The effect of mercuric chloride at two different doses, 1 mg/kg (low dose) and 2 mg/kg (high dose), orally for 30 days, was observe...Aim: To study the effect of mercuric chloride on the membrane-bound enzymes. Methods: The effect of mercuric chloride at two different doses, 1 mg/kg (low dose) and 2 mg/kg (high dose), orally for 30 days, was observed on the membrane-bound enzymes in the testis of adult albino rats. Results: Mercuric chloride significantly decreased the body weight and testis weight in the high dose group (P<0.05), but not in the low dose group. The activities of 5' nucleotidase and adenosine triphosphatases were markedly decreased (P<0.01) in the testis of both groups. Alkaline phosphatase and γ-glutamyl transferase activities were significantly increased (P<0.01) in both groups. However, the effect was more pronounced in the high than in the low dose groups. Conclusion: The dose dependent effect of mercuric chloride on these enzymes may affect the membrane characteristics and thereby the fertility of the animal. (Asian J Androl 2002 Dec; 4:309-311)展开更多
The objective of the present study was to evaluate the pre-clinical efficacy and toxicity of polyherbal cough syrup Linkus. Method: Animals (healthy Wistar albino rats;(150 - 250 g) of either sex) were housed under st...The objective of the present study was to evaluate the pre-clinical efficacy and toxicity of polyherbal cough syrup Linkus. Method: Animals (healthy Wistar albino rats;(150 - 250 g) of either sex) were housed under standard environmental conditions;i.e. 25°C ± 1°C and 12 h dark/light cycle. Food and water were available at libitum. The rats were treated orally with the recommended doses of the test drug (Linkus). After 15 minutes, they were individually placed in a closed Plexiglas chamber (20 × 10 × 10 cm) and exposed to citric acid (0.1 g/ml) inhalation for 7 minutes. The cough reflexes were produced and counted for the last 5 minutes and compared with those of the control animals. The following studies were conducted to evaluate the toxicity of the test drug in healthy Wistar albino rats: lethal dose50 (LD50);rats of either sex (n = 10/sex) were treated orally with doses (1 or 5 g/kg) of the test drug. Mortality and behavioral changes were observed for 1 week. Repeated dose toxicity on the healthy Wistar albino rats of both sexes (n = 5/dose/sex) was treated orally with doses of 20 mg/kg (adult human dose = ~1400 mg), 500 mg/kg (adult human dose = ~35,000 mg) and 1000 mg/kg (adult human dose = ~70,000 mg) of test drug (Linkus) for 14 days. Additionally, the control animals were treated orally with water for 14 days. Results: In female rats, the test drug (Linkus) at the dose of 300 mg/kg caused significant (p < 0.01) reduction in the cough reflexes as compared to the control. However, in male rats, a significant reduction was observed at the tested dose of 200 mg/kg (p < 0.05) and 300 mg/kg (p < 0.01). The test product did not cause mortality in rats at the given doses of 1 or 5 g/kg. Other signs of toxicity like hair loss and weight reduction were not observed. In female and male rats, the test drug (Linkus) at different doses did not show any abnormal effects on complete blood count profile of rats. Serum enzyme markers, i.e. alanine aminotransferase (ALT), alakaline phosphatase, gamma glutamyle transferase (GGT), direct bilirubin, creatinine, and proteins were also observed and found that the test drug at a higher dose did not cause any of the abnormality and had shown significant p value as compared to the control. Conclusion: The test drug (Linkus) could be an effective and safe cough syrup because it did not show any of the side effects or toxicity on experimental animals.展开更多
Hepatocellular carcinoma(HCC)is one of the most common malignant tumors with a low survival rate.The identification of mechanisms underlying the development of HCC helps uncover cellular and mo-lecular targets for the...Hepatocellular carcinoma(HCC)is one of the most common malignant tumors with a low survival rate.The identification of mechanisms underlying the development of HCC helps uncover cellular and mo-lecular targets for the diagnosis,prevention,and treatment of HCC.Golgi protein 73(GP73)level is up-regulated in HCC patients and potentially can be a therapeutic target.Despite many studies devoted to GP73 as a marker for HCC early diagnosis,there is little discussion about the function of GP73 in HCC tumorigenesis.Given the poor response to currently available HCC therapies,a better understanding of the role of GP73 in HCC may provide a new therapeutic target for HCC.The current paper summarizes the role of GP73 as a diagnostic marker as well as its roles in liver carcinogenesis.Its roles in other types of cancer are also discussed.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.
文摘Aim: To study the effect of mercuric chloride on the membrane-bound enzymes. Methods: The effect of mercuric chloride at two different doses, 1 mg/kg (low dose) and 2 mg/kg (high dose), orally for 30 days, was observed on the membrane-bound enzymes in the testis of adult albino rats. Results: Mercuric chloride significantly decreased the body weight and testis weight in the high dose group (P<0.05), but not in the low dose group. The activities of 5' nucleotidase and adenosine triphosphatases were markedly decreased (P<0.01) in the testis of both groups. Alkaline phosphatase and γ-glutamyl transferase activities were significantly increased (P<0.01) in both groups. However, the effect was more pronounced in the high than in the low dose groups. Conclusion: The dose dependent effect of mercuric chloride on these enzymes may affect the membrane characteristics and thereby the fertility of the animal. (Asian J Androl 2002 Dec; 4:309-311)
文摘The objective of the present study was to evaluate the pre-clinical efficacy and toxicity of polyherbal cough syrup Linkus. Method: Animals (healthy Wistar albino rats;(150 - 250 g) of either sex) were housed under standard environmental conditions;i.e. 25°C ± 1°C and 12 h dark/light cycle. Food and water were available at libitum. The rats were treated orally with the recommended doses of the test drug (Linkus). After 15 minutes, they were individually placed in a closed Plexiglas chamber (20 × 10 × 10 cm) and exposed to citric acid (0.1 g/ml) inhalation for 7 minutes. The cough reflexes were produced and counted for the last 5 minutes and compared with those of the control animals. The following studies were conducted to evaluate the toxicity of the test drug in healthy Wistar albino rats: lethal dose50 (LD50);rats of either sex (n = 10/sex) were treated orally with doses (1 or 5 g/kg) of the test drug. Mortality and behavioral changes were observed for 1 week. Repeated dose toxicity on the healthy Wistar albino rats of both sexes (n = 5/dose/sex) was treated orally with doses of 20 mg/kg (adult human dose = ~1400 mg), 500 mg/kg (adult human dose = ~35,000 mg) and 1000 mg/kg (adult human dose = ~70,000 mg) of test drug (Linkus) for 14 days. Additionally, the control animals were treated orally with water for 14 days. Results: In female rats, the test drug (Linkus) at the dose of 300 mg/kg caused significant (p < 0.01) reduction in the cough reflexes as compared to the control. However, in male rats, a significant reduction was observed at the tested dose of 200 mg/kg (p < 0.05) and 300 mg/kg (p < 0.01). The test product did not cause mortality in rats at the given doses of 1 or 5 g/kg. Other signs of toxicity like hair loss and weight reduction were not observed. In female and male rats, the test drug (Linkus) at different doses did not show any abnormal effects on complete blood count profile of rats. Serum enzyme markers, i.e. alanine aminotransferase (ALT), alakaline phosphatase, gamma glutamyle transferase (GGT), direct bilirubin, creatinine, and proteins were also observed and found that the test drug at a higher dose did not cause any of the abnormality and had shown significant p value as compared to the control. Conclusion: The test drug (Linkus) could be an effective and safe cough syrup because it did not show any of the side effects or toxicity on experimental animals.
基金This study was supported bygrants funded by the USA National Institutes of Health(NIH)R01CA222490 to Y.-J.Y.Wanalong with grants from the National Natural Science Foundation of China Project number 81602456financial sup-port from the China Scholarship Council(CSC)to Y.Wang.
文摘Hepatocellular carcinoma(HCC)is one of the most common malignant tumors with a low survival rate.The identification of mechanisms underlying the development of HCC helps uncover cellular and mo-lecular targets for the diagnosis,prevention,and treatment of HCC.Golgi protein 73(GP73)level is up-regulated in HCC patients and potentially can be a therapeutic target.Despite many studies devoted to GP73 as a marker for HCC early diagnosis,there is little discussion about the function of GP73 in HCC tumorigenesis.Given the poor response to currently available HCC therapies,a better understanding of the role of GP73 in HCC may provide a new therapeutic target for HCC.The current paper summarizes the role of GP73 as a diagnostic marker as well as its roles in liver carcinogenesis.Its roles in other types of cancer are also discussed.
