Objective： To investigate the relationship of poly（ADP-ribose）glycohydrolase（PARG） with poly （ADP-ribose） polymerase（PARP）, vascular endothelial growth factor （VEGF） and basic fibroblast growth factor（b-FG...Objective： To investigate the relationship of poly（ADP-ribose）glycohydrolase（PARG） with poly （ADP-ribose） polymerase（PARP）, vascular endothelial growth factor （VEGF） and basic fibroblast growth factor（b-FGF） in colorectal carcinoma（CRC）. Methods： Immunohistochemical analysis was used to detect PARG, PARP, VEGF and b-FGF in human colorectal carcinoma. Flow cytometry was used to detect PARG and PARP in murine CT26 cell line. Gallotannin （GLTN） was served as PARG inhibitor. Results： The individual positive rates of PARG, PARE VEGF and b-FGF were 55.81%（24/43）, 97.67%（42/43）, 79.07%（34/43） and 81.40%（35/43）, respectively, which were significantly higher than those of control group. The positive PARG was correlated to PARP（r=0.3703, P〈0.05） and b-FGF （r=0.4838, P〈0.05）. The positive PARP was correlated to VEGF （r=0.3968, P〈0.05） and b-FGF （r=0.5610, P〈0.05）. Both PARG and PARP were expressed in CT26 cells. The positive staining rates of PARG and PARP in GLTN-treated group were 7.3% and 52.38%, respectively. They were markedly reduced than those of control group （55.41% and 95.28%, P〈0.01, n=10000）. Conclusion： The data suggest that PARG expression probably plays a role for VEGF and b-FGF expression in colorectal carcinoma.展开更多
Objective：To investigate the significance of Poly（ADP-ribose） glycolhydrolase（PARG） and membrane type 1 matrix metalloproteinase（MT1-MMP） expressions in human colorectal carcinoma.Methods：Immunohistochemical s...Objective：To investigate the significance of Poly（ADP-ribose） glycolhydrolase（PARG） and membrane type 1 matrix metalloproteinase（MT1-MMP） expressions in human colorectal carcinoma.Methods：Immunohistochemical staining for PARG and MT1-MMP was carried out on colorectal adenoma-carcinoma tissue microarrays containing normal colorectal mucosae,adenoma,adenoma with malignant transformation and adenocarcinoma（total 130 specimens）.The expressions of PARG and MT1-MMP in the GLTN [Gallotannin]-treated and GLTN-untreated lovo cells were detected by Western Blot.Results：PARG expression in adenocarcinoma（83.1%） and adenoma with malignant transformation（66.7%） was significantly higher than that in normal colorectal mucosa（10%） and adenoma（10.5%）.Expression of MT1-MMp in normal colorectal mucosa and adenoma was negative,while the expression in adenocarcinoma（80.3%） and adenoma with malignant transformation（72.2%） was high.The expressions of PARG and MT1-MMP in adenocarcinoma with metastasis and in late tumor stages were significantly higher than those in adenocarcinoma with no metastasis and in early tumor stages.Thus,PARG expression shows a positive correlation with the expression of MT1-MMP.The expressions of PARG and MT1-MMP in GLTN-treated lovo cells were weaker than that in GLTN-untreated lovo cells.Conclusion：The expression of PARG was probably related to the development of colorectal carcinoma.PARG may play an important role for the regulation of MT1-MMP expression in colorectal carcinoma.展开更多
Poly(ADP-ribose)glycosylhydrolase(PARG)is an enzyme involved in hydrolyzing the ribose–ribose bonds present in poly(ADP-ribose)(PAR),which are primarily found in the nucleus.Along with poly(ADP-ribose)polymerase,PARG...Poly(ADP-ribose)glycosylhydrolase(PARG)is an enzyme involved in hydrolyzing the ribose–ribose bonds present in poly(ADP-ribose)(PAR),which are primarily found in the nucleus.Along with poly(ADP-ribose)polymerase,PARG regulates the level of PAR in cells,playing a crucial role in DNA maintenance and repair processes.Recent studies have revealed elevated levels of PARG in various cancers,such as breast,liver,prostate,and esophageal cancers,indicating a link to unfavorable cancer outcomes.PARG is a significant molecular target for treating PAR-related cancers.This review provides a comprehensive overview of the physiological role of PARG and the development of its inhibitors,highlighting its potential as an innovative target for cancer treatment.展开更多
基金supported by the National Natural Science Foundation of China (No 30870946)Natural Science Foundation of CQ CSTC(CSTC, 2006BB5288)
文摘Objective： To investigate the relationship of poly（ADP-ribose）glycohydrolase（PARG） with poly （ADP-ribose） polymerase（PARP）, vascular endothelial growth factor （VEGF） and basic fibroblast growth factor（b-FGF） in colorectal carcinoma（CRC）. Methods： Immunohistochemical analysis was used to detect PARG, PARP, VEGF and b-FGF in human colorectal carcinoma. Flow cytometry was used to detect PARG and PARP in murine CT26 cell line. Gallotannin （GLTN） was served as PARG inhibitor. Results： The individual positive rates of PARG, PARE VEGF and b-FGF were 55.81%（24/43）, 97.67%（42/43）, 79.07%（34/43） and 81.40%（35/43）, respectively, which were significantly higher than those of control group. The positive PARG was correlated to PARP（r=0.3703, P〈0.05） and b-FGF （r=0.4838, P〈0.05）. The positive PARP was correlated to VEGF （r=0.3968, P〈0.05） and b-FGF （r=0.5610, P〈0.05）. Both PARG and PARP were expressed in CT26 cells. The positive staining rates of PARG and PARP in GLTN-treated group were 7.3% and 52.38%, respectively. They were markedly reduced than those of control group （55.41% and 95.28%, P〈0.01, n=10000）. Conclusion： The data suggest that PARG expression probably plays a role for VEGF and b-FGF expression in colorectal carcinoma.
基金supported by the National Natural Science Foundation of China(No.30870946)Research Foundation of Chongqing Medical University(XB0536)
文摘Objective：To investigate the significance of Poly（ADP-ribose） glycolhydrolase（PARG） and membrane type 1 matrix metalloproteinase（MT1-MMP） expressions in human colorectal carcinoma.Methods：Immunohistochemical staining for PARG and MT1-MMP was carried out on colorectal adenoma-carcinoma tissue microarrays containing normal colorectal mucosae,adenoma,adenoma with malignant transformation and adenocarcinoma（total 130 specimens）.The expressions of PARG and MT1-MMP in the GLTN [Gallotannin]-treated and GLTN-untreated lovo cells were detected by Western Blot.Results：PARG expression in adenocarcinoma（83.1%） and adenoma with malignant transformation（66.7%） was significantly higher than that in normal colorectal mucosa（10%） and adenoma（10.5%）.Expression of MT1-MMp in normal colorectal mucosa and adenoma was negative,while the expression in adenocarcinoma（80.3%） and adenoma with malignant transformation（72.2%） was high.The expressions of PARG and MT1-MMP in adenocarcinoma with metastasis and in late tumor stages were significantly higher than those in adenocarcinoma with no metastasis and in early tumor stages.Thus,PARG expression shows a positive correlation with the expression of MT1-MMP.The expressions of PARG and MT1-MMP in GLTN-treated lovo cells were weaker than that in GLTN-untreated lovo cells.Conclusion：The expression of PARG was probably related to the development of colorectal carcinoma.PARG may play an important role for the regulation of MT1-MMP expression in colorectal carcinoma.
基金supported by grants from the National Natural Science Foundation of China(32271485)the Natural Science Foundation of Zhejiang Province(YXD23H0302)to J.J.+3 种基金as well as grants from the National Natural Science Foundation of China(82473195)the Natural Science Foundation of Zhejiang Province(LTGY23H160018)the Zhejiang Medical and Health Science and Technology Program(2024KY789)the Beijing Science and Technology Innovation Medical Development Foundation(KC2023-JX-0270-07)to Z.Y.
文摘Poly(ADP-ribose)glycosylhydrolase(PARG)is an enzyme involved in hydrolyzing the ribose–ribose bonds present in poly(ADP-ribose)(PAR),which are primarily found in the nucleus.Along with poly(ADP-ribose)polymerase,PARG regulates the level of PAR in cells,playing a crucial role in DNA maintenance and repair processes.Recent studies have revealed elevated levels of PARG in various cancers,such as breast,liver,prostate,and esophageal cancers,indicating a link to unfavorable cancer outcomes.PARG is a significant molecular target for treating PAR-related cancers.This review provides a comprehensive overview of the physiological role of PARG and the development of its inhibitors,highlighting its potential as an innovative target for cancer treatment.
