The highly conserved abundant nuclear protein poly （ADP-ribose） polymerase-1 （PARP-1） is activated by DNA damage. PARP-1 activation is associated in DNA repair, cell death and inflammation. Since oxidative stress ...The highly conserved abundant nuclear protein poly （ADP-ribose） polymerase-1 （PARP-1） is activated by DNA damage. PARP-1 activation is associated in DNA repair, cell death and inflammation. Since oxidative stress induced robust DNA damage and wide spread inflamma- tory responses are common pathologies of various CNS diseases, the attention towards PARP-1 as a therapeutic target has been amplifying. This review highlights the multiple roles of PARP- 1 in neurological diseases and po- tential of PARP- 1 inhibitors to enter clinical translation.展开更多
Poly （ADP-ribose） polymerase-1 （PARP-1） can exacerbate ischemic brain injury and lessen ischemic neuronal death, which may be associated with PARP-1 polymorphisms. The present study investigated human PARP-1 gene ...Poly （ADP-ribose） polymerase-1 （PARP-1） can exacerbate ischemic brain injury and lessen ischemic neuronal death, which may be associated with PARP-1 polymorphisms. The present study investigated human PARP-1 gene polymorphisms in various Chinese nationalities, the results of which could potentially help in the treatment and prevention of neurologic diseases. Genetic polymorphisms of seven exons in the PARP-1 gene, in 898 Chinese Han, Buyi, Shui, Miao, and Zhuang subjects, were investigated by PCR-single-strand conformation polymorphism. A single-strand conformation polymorphism variant in exons 12, 13, 16, and 17 of the PARP-1 gene was identified in 148 people, with two stationary bands showing three degenerative single strands. Results showed that the PARP-1 gene polymorphisms exist in various nationalities, and may act as a biomarker for susceptibility to disease.展开更多
The use of chemotherapeutic regimens for the treatment of pancreatic cancer is still limited because pancreatic cancer is usually diagnosed at an advanced stage as a refractory disease in which symptoms are difficult ...The use of chemotherapeutic regimens for the treatment of pancreatic cancer is still limited because pancreatic cancer is usually diagnosed at an advanced stage as a refractory disease in which symptoms are difficult to recognize in the early stages.Furthermore,at advanced stages,there are important challenges to achieve clinical benefit and symptom resolution,even with the use of an expanded spectrum of anticancer drugs.Recently,a point of reduced susceptibility to conventional chemotherapies by breast cancer susceptibility gene(BRCA)mutations led to a new perspective for overcoming the resistance of pancreatic cancer within the framework of increased genome instability.Poly(ADP-Ribose)polymerase(PARP)-1 is an enzyme that can regulate intrinsic functions,such as response to DNA damage.Therefore,in an environment where germline mutations in BRCAs(BRCAness)inhibit homologous recombination in DNA damage,resulting in a lack of DNA damage response,a key role of PARP-1 for the adaptation of the genome instability could be further emphasized.Here,we summarized the key functional role of PARP-1 in genomic instability of pancreatic cancer with the BRCAness phenotype and listed clinical applications and outcomes of PARP-1 inhibitors to highlight the importance of targeting PARP-1 activity.展开更多
Summary： Poly （ADP-ribose） polymerase-1 （PARP-1） inhibitors and histone deacetylase （HDAC） in- hibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect o...Summary： Poly （ADP-ribose） polymerase-1 （PARP-1） inhibitors and histone deacetylase （HDAC） in- hibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect of combination treatment with the PARP inhibitor P J34 and HDAC inhibitor SAHA on the proliferation of liver cancer cells. Cell proliferation and apoptosis were assessed in three human liver cancer cell lines （HepG2, Hep3B and HCC-LM3） treated with PJ34 （8 μmol/L） and SAHA （1 panol/L）, alone or combined, by Cell Counting Kit-8 assay and flow cytometry, respectively. The nude mice bear- ing subcutaneous HepG2 tumors were administered different groups of drugs （10 mg/kg PJ34, 25 mg/kg SAHA, 10 mg/kg PJ34＋25 mg/kg SAHA）, and the inhibition rates of tumor growth were compared between groups. The results showed that combined use of P J34 and SAHA could synergistically inhibit the proliferation of liver cancer cell lines HepG2, Hep3B and HCC-LM3. The apoptosis rate of HepG2 cells treated with PJ34＋SAHA was significantly higher than that of HepG2 cells treated with PJ34 or SAHA alone （P〈0.05）. In vivo, the tumor inhibition rates were 53.5%, 61.4% and 82.6% in PJ34, SAHA and PJ34＋SAHA groups, respectively. The combined use of PJ34 and SAHA could significantly inhibit the xenograft tumor growth when compared with use of P J34 or SAHA alone （P〈0.05）. It was led to conclude that P J34 and SAHA can synergistically suppress the proliferation of liver cancer cells.展开更多
Objective: To study the correlation of LSD1 and PARP1 with cell proliferation and epithelial-mesenchymal transition in ovarian cancer tissue from ultrasound-guided puncture. Methods:The ovarian cancer and ovarian beni...Objective: To study the correlation of LSD1 and PARP1 with cell proliferation and epithelial-mesenchymal transition in ovarian cancer tissue from ultrasound-guided puncture. Methods:The ovarian cancer and ovarian benign lesion tissue from ultrasound-guided puncture in Pangang Group General Hospital in Panzhihua between May 2014 and March 2017 were collected to detect the mRNA expression of LSD1 and PARP1 as well as the protein levels of cell proliferation molecules and epithelial-mesenchymal transition molecules in them. Results: LSD1 and PARP1 mRNA expression in ovarian cancer tissue were significantly higher than those in benign ovarian tissue;P21, P27 and E-cadherin protein levels in ovarian cancer tissue were significantly lower than those in benign ovarian tissue while CyclinD1, E2F, Twist1, Snail, Slug and N-cadherin protein levels were significantly higher those in benign ovarian tissue;P21 and P27 protein levels in the ovarian cancer tissue with high LSD1 expression were significantly lower than those in the ovarian cancer tissue with low LSD1 expression while CyclinD1 and E2F protein levels were significantly higher than those in the ovarian cancer tissue with low LSD1 expression;Twist1, Snail, Slug and N-cadherin protein levels in the ovarian cancer tissue with high PARP1 expression were significantly higher than those in the ovarian cancer tissue with low PARP1 expression while E-cadherin protein level was significantly lower than that in the ovarian cancer tissue with low PARP1 expression. Conclusion: The LSD1 and PARP1 highly expressed in ovarian cancer tissue can promote the proliferation and epithelial-mesenchymal transition of cancer cells.展开更多
Objective:To study the correlation of serum sLAG-3, PARP-1 and CA50 levels with oncogene expression in surgically removed lesions in patients with gastric cancer.Methods: A total of 98 patients who were diagnosed with...Objective:To study the correlation of serum sLAG-3, PARP-1 and CA50 levels with oncogene expression in surgically removed lesions in patients with gastric cancer.Methods: A total of 98 patients who were diagnosed with gastric cancer in Zhouzhi County People's Hospital between June 2015 and March 2017 were selected as the gastric cancer group of the research, and 60 healthy volunteers who received physical examination during the same period were selected as control group of the research. The serum was collected from the two groups to determine sLAG-3, PARP-1 and CA50 levels;gastric cancer lesions and adjacent lesions were collected from gastric cancer group to determine the protein expression of PDCD4, RASSF1A, p16ink4a, Kiss-1, Eaf-2, CDC4, UHRF1, OCT4, Zeb-1 and c-jun.Results:Serum sLAG-3, PARP-1 and CA50 levels of gastric cancer group were significantly higher than those of control group, and the higher the TNM stage, the higher the serum sLAG-3, PARP-1 and CA50 levels;PDCD4, RASSF1A, p16ink4a, Kiss-1, Eaf-2 and CDC4 protein levels in gastric cancer lesions were significantly lower than those in adjacent lesions and negatively correlated with serum sLAG-3, PARP-1 and CA50 levels, while UHRF1, OCT4, Zeb-1 and c-jun protein levels in gastric cancer lesions were significantly higher than those in adjacent lesions and positively correlated with serum sLAG-3, PARP-1 and CA50 levels.Conclusions:The increase in serum sLAG-3, PARP-1 and CA50 levels in patients with gastric cancer is closely related to the pathological process of gastric cancer, deletion of tumor suppressor gene expression and increase of proto-oncogene expression.展开更多
文摘The highly conserved abundant nuclear protein poly （ADP-ribose） polymerase-1 （PARP-1） is activated by DNA damage. PARP-1 activation is associated in DNA repair, cell death and inflammation. Since oxidative stress induced robust DNA damage and wide spread inflamma- tory responses are common pathologies of various CNS diseases, the attention towards PARP-1 as a therapeutic target has been amplifying. This review highlights the multiple roles of PARP- 1 in neurological diseases and po- tential of PARP- 1 inhibitors to enter clinical translation.
基金the National Natural Science Foundation of China, No. 30972500the Natural Science Foundation of Guangdong Province, No. 7301507
文摘Poly （ADP-ribose） polymerase-1 （PARP-1） can exacerbate ischemic brain injury and lessen ischemic neuronal death, which may be associated with PARP-1 polymorphisms. The present study investigated human PARP-1 gene polymorphisms in various Chinese nationalities, the results of which could potentially help in the treatment and prevention of neurologic diseases. Genetic polymorphisms of seven exons in the PARP-1 gene, in 898 Chinese Han, Buyi, Shui, Miao, and Zhuang subjects, were investigated by PCR-single-strand conformation polymorphism. A single-strand conformation polymorphism variant in exons 12, 13, 16, and 17 of the PARP-1 gene was identified in 148 people, with two stationary bands showing three degenerative single strands. Results showed that the PARP-1 gene polymorphisms exist in various nationalities, and may act as a biomarker for susceptibility to disease.
文摘The use of chemotherapeutic regimens for the treatment of pancreatic cancer is still limited because pancreatic cancer is usually diagnosed at an advanced stage as a refractory disease in which symptoms are difficult to recognize in the early stages.Furthermore,at advanced stages,there are important challenges to achieve clinical benefit and symptom resolution,even with the use of an expanded spectrum of anticancer drugs.Recently,a point of reduced susceptibility to conventional chemotherapies by breast cancer susceptibility gene(BRCA)mutations led to a new perspective for overcoming the resistance of pancreatic cancer within the framework of increased genome instability.Poly(ADP-Ribose)polymerase(PARP)-1 is an enzyme that can regulate intrinsic functions,such as response to DNA damage.Therefore,in an environment where germline mutations in BRCAs(BRCAness)inhibit homologous recombination in DNA damage,resulting in a lack of DNA damage response,a key role of PARP-1 for the adaptation of the genome instability could be further emphasized.Here,we summarized the key functional role of PARP-1 in genomic instability of pancreatic cancer with the BRCAness phenotype and listed clinical applications and outcomes of PARP-1 inhibitors to highlight the importance of targeting PARP-1 activity.
基金supported by grants from the National Natural Science Foundation of China(No.81172293)the New Century Excellent Talent Foundation of Ministry of Education of China(No.NCET-04-0701)
文摘Summary： Poly （ADP-ribose） polymerase-1 （PARP-1） inhibitors and histone deacetylase （HDAC） in- hibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect of combination treatment with the PARP inhibitor P J34 and HDAC inhibitor SAHA on the proliferation of liver cancer cells. Cell proliferation and apoptosis were assessed in three human liver cancer cell lines （HepG2, Hep3B and HCC-LM3） treated with PJ34 （8 μmol/L） and SAHA （1 panol/L）, alone or combined, by Cell Counting Kit-8 assay and flow cytometry, respectively. The nude mice bear- ing subcutaneous HepG2 tumors were administered different groups of drugs （10 mg/kg PJ34, 25 mg/kg SAHA, 10 mg/kg PJ34＋25 mg/kg SAHA）, and the inhibition rates of tumor growth were compared between groups. The results showed that combined use of P J34 and SAHA could synergistically inhibit the proliferation of liver cancer cell lines HepG2, Hep3B and HCC-LM3. The apoptosis rate of HepG2 cells treated with PJ34＋SAHA was significantly higher than that of HepG2 cells treated with PJ34 or SAHA alone （P〈0.05）. In vivo, the tumor inhibition rates were 53.5%, 61.4% and 82.6% in PJ34, SAHA and PJ34＋SAHA groups, respectively. The combined use of PJ34 and SAHA could significantly inhibit the xenograft tumor growth when compared with use of P J34 or SAHA alone （P〈0.05）. It was led to conclude that P J34 and SAHA can synergistically suppress the proliferation of liver cancer cells.
文摘Objective: To study the correlation of LSD1 and PARP1 with cell proliferation and epithelial-mesenchymal transition in ovarian cancer tissue from ultrasound-guided puncture. Methods:The ovarian cancer and ovarian benign lesion tissue from ultrasound-guided puncture in Pangang Group General Hospital in Panzhihua between May 2014 and March 2017 were collected to detect the mRNA expression of LSD1 and PARP1 as well as the protein levels of cell proliferation molecules and epithelial-mesenchymal transition molecules in them. Results: LSD1 and PARP1 mRNA expression in ovarian cancer tissue were significantly higher than those in benign ovarian tissue;P21, P27 and E-cadherin protein levels in ovarian cancer tissue were significantly lower than those in benign ovarian tissue while CyclinD1, E2F, Twist1, Snail, Slug and N-cadherin protein levels were significantly higher those in benign ovarian tissue;P21 and P27 protein levels in the ovarian cancer tissue with high LSD1 expression were significantly lower than those in the ovarian cancer tissue with low LSD1 expression while CyclinD1 and E2F protein levels were significantly higher than those in the ovarian cancer tissue with low LSD1 expression;Twist1, Snail, Slug and N-cadherin protein levels in the ovarian cancer tissue with high PARP1 expression were significantly higher than those in the ovarian cancer tissue with low PARP1 expression while E-cadherin protein level was significantly lower than that in the ovarian cancer tissue with low PARP1 expression. Conclusion: The LSD1 and PARP1 highly expressed in ovarian cancer tissue can promote the proliferation and epithelial-mesenchymal transition of cancer cells.
文摘Objective:To study the correlation of serum sLAG-3, PARP-1 and CA50 levels with oncogene expression in surgically removed lesions in patients with gastric cancer.Methods: A total of 98 patients who were diagnosed with gastric cancer in Zhouzhi County People's Hospital between June 2015 and March 2017 were selected as the gastric cancer group of the research, and 60 healthy volunteers who received physical examination during the same period were selected as control group of the research. The serum was collected from the two groups to determine sLAG-3, PARP-1 and CA50 levels;gastric cancer lesions and adjacent lesions were collected from gastric cancer group to determine the protein expression of PDCD4, RASSF1A, p16ink4a, Kiss-1, Eaf-2, CDC4, UHRF1, OCT4, Zeb-1 and c-jun.Results:Serum sLAG-3, PARP-1 and CA50 levels of gastric cancer group were significantly higher than those of control group, and the higher the TNM stage, the higher the serum sLAG-3, PARP-1 and CA50 levels;PDCD4, RASSF1A, p16ink4a, Kiss-1, Eaf-2 and CDC4 protein levels in gastric cancer lesions were significantly lower than those in adjacent lesions and negatively correlated with serum sLAG-3, PARP-1 and CA50 levels, while UHRF1, OCT4, Zeb-1 and c-jun protein levels in gastric cancer lesions were significantly higher than those in adjacent lesions and positively correlated with serum sLAG-3, PARP-1 and CA50 levels.Conclusions:The increase in serum sLAG-3, PARP-1 and CA50 levels in patients with gastric cancer is closely related to the pathological process of gastric cancer, deletion of tumor suppressor gene expression and increase of proto-oncogene expression.
