- Email: [email protected]
Role of RECQ1 in cellular sensitivity to gemcitabine and overall survival of pancreatic cancer
S6
Abstracts / Pancreatology 16 (2016) S1eS63
Seipin. The mutations resulted in the changes of the fourth exons and the termination of protein translation. Conclusions: These results might lead to the change of protein function and the outbreak of the disease. In summary, the CGL patient was diagnosed from two aspects of experimental and clinical analysis. Furthermore, this study was the first report about one case of CGL complicated by severe acute pancreatitis. Taken together, these findings may shed light on the mechanism of CGL.
15029. Heparanase mRNA expression in peripheral blood mononuclear cell and heparanase activity monitor response to anticancer treatment and predict survival in pancreatic cancer
every group were killed at different time)after induction of the model. The serum amylase, lipase, Nitric oxide(NO), tumour necrosis factor alpha (TNF-a), superoxide dismutase (SOD), interleu kin-6(IL-6) were detected; Moreover, the histopathological score based on microscopic changes of pancreatic tissue were evaluated. Results: The levels of serum amylase and lipase, NO, TNF-a, IL-6 and the histopathological score (except 12h) were all decreased significantly in the Propofol-treated group than that in the SAP group at each time point (P<0.05). In contrast, the level of serum SOD was significantly elevated in the Propofol-treated group (P<0.05). Conclusion: Propofol can decrease serum amylase and lipase, reduce pancreatic tissue damage, and has therapeutic effects on the SAP in rats. Keywords: Propofol; Pancreatitis,acute necrotizing; Animal model
Wu-jun Wu, Hai-tian Hu, Yong-tian Yu, Xiao-gang Liu, Hui LI, Zhi-yong Fan, Yong Song, Zhong-jie Sun, Li-xue Du
15050.
Department of Hepatobiliary Surgery, Shaanxi Provincial People's Hospital, Xi'an City, China
Role of RECQ1 in cellular sensitivity to gemcitabine and overall survival of pancreatic cancer
Aim: Heparanase was up-regulation in pancreatic cancer and associated with a shorter survival. However, whether heparanase may serve as a useful marker to predict tumor relapse, metastasis, patients' survival, as well as their response to anticancer treatment is still unknown. Methods: Heparanase mRNA expression in peripheral blood mononuclear cell fraction (PBMC) was investigated in 31 pancreatic carcinoma patients (23 underwent surgery and 8 received chemotherapy) and ten healthy donors by real time RT-PCR. Heparanase activities in plasma and urine were also investigated using heparin-degrading enzyme assay. Patient survival time was determined according to the Kaplan-Meier method, and their difference was evaluated by the log-rank test. A P value<0.05 was considered statistically significant. Results: PBMC samples from cancer patients showed the expression of heparanase mRNA while no expression was observed for the healthy donors. Heparanase activities in blood and urine samples of the surgical group and chemotherapeutic patients were significantly higher than that of the healthy donors. Both heparanase mRNA expression and activities in the plasma and urine decreased significantly for the 17 patients that underwent R0 resection after operation (P<0.05), but increased remarkably when recurrence or metastasis occurred (P<0.05). However, which in the 6 patients who underwent R1 þ R2 resection changed slightly or remained constant. For 8 patients that received chemotherapy, heparanase mRNA and activities in the blood and urine samples of each of them decreased significantly (P<0.05). Elevated heparanase mRNA level (>a cutoff value of 1.84) in PMBC and high plasma heparanase activity (>1.30U/ml) were associated with a poor postoperativel survival in pancreatic carcinoma patients (P¼0.02 and P¼0.04). However, the high urine heparanase activity (>1.81U/ml) did not correlate with the overall survival (P¼0.10). Conclusion: The changes in heparanase mRNA expression and activity were closely associated with surgical procedure and chemotherapy, indicating that heparanase levels can be a useful diagnostic tool in monitoring patients' response to anticancer treatment and predicting their chances of survival.
15049. The effects of propofol on severe acute pancreatitis in rats Jing-yi Wu, Yi-sheng Zhang, Xiao-ju Jin, Guo-hai Zhao The Yijishan Hospital of Wannan Medical College, Wuhu 241001, China Objective: To investigate the therapeutic effects and mechanisms of propofol on severe acute pancreatitis(SAP) in rats. Methods: The 54 male Sprague-Dawley rats were randomized into three groups with 18 rats in each group: the Sham-operation group, the SAP group, the Propofol-treated group.After models were induced, the rats in the Propofol-treated group were injected continually propofol by dorsal vein of penis. The rats in all groups were killed at 3, 6, 12 hours (six rats in
Chang Liu 1, 3, Yanan Li 1, Jijiang Zhu 1, Huamin Wang 2, Ping Chang 1, Jianjun Shen 1, Fangyu Wang 3, **, Donghui Li 1, * 1
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 2 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 3 Department of Gastroenterology and Hepatology, Jinling Hospital, Southern Medical University, Nanjing 210002, China E-mail address: [email protected], [email protected]
Grant Support: Supported by the National Institutes of Health (NIH) R01 grant CA098380 (D.L.), NIH Cancer Center Core grant CA16672, and the Lockton Research Funds (D.L.) Abstract Aims: DNA helicases play an important role in DNA replication, recombination and repair. We have previously shown a significant association of RecQ1 A159C polymorphic variant with a poor prognosis in patients with pancreatic cancer. The purpose of the current study is to explore the role of RecQ1 gene in cellular response to gemcitabine and in patient survival. Methods: RecQ1 protein expression was measured in tumor tissues of 67 patients with pancreatic cancer using immunohistochemistry and the protein expression level was analyzed in relation to overall survival. RecQ1 gene expression was knocked down by siRNA in pancreatic adenocarcinoma cell lines. Cell proliferation, apoptosis and cell cycle distribution as well as mRNA expression of DNA repair and cell cycle regulating genes were compared in cells treated with or without gemcitabine in vector control and RecQ1 knockdown cells.. Results: RecQ1 knockdown resulted in increased sensitivity (decreased proliferation and increased apoptosis) to gemcitabine treatment. RecQ1deficient cells had reduced S-Phase distribution in cells with or without gemcitabine treatment. RecQ1 knockdown down-regulated the expression of cell cycle check point signal transducers CHK1, CHK2 and RAD9, and many genes involved in S phase DNA replication and M phase regulation. Conclusions: These observations suggest that RecQ1 plays an important role in DNA repair and cell cycle regulation, which in turn affect the cellular sensitivity to gemcitabine. Keywords: RecQ1, pancreatic cancer, gemcitabine, DNA repair, cell cycle regulation.
* Corresponding author. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX 77030, USA. Tel.: þ1 713 834 6690; fax: þ1 713 834 6153. ** Corresponding author. Department of Gastroenterology, Jinling Hospital, Southern Medical University, 305 East Zhongshan Road, Nanjing 21002, China. Tel.: þ86 025 80861051.
Abstracts / Pancreatology 16 (2016) S1eS63
Seipin. The mutations resulted in the changes of the fourth exons and the termination of protein translation. Conclusions: These results might lead to the change of protein function and the outbreak of the disease. In summary, the CGL patient was diagnosed from two aspects of experimental and clinical analysis. Furthermore, this study was the first report about one case of CGL complicated by severe acute pancreatitis. Taken together, these findings may shed light on the mechanism of CGL.
15029. Heparanase mRNA expression in peripheral blood mononuclear cell and heparanase activity monitor response to anticancer treatment and predict survival in pancreatic cancer
every group were killed at different time)after induction of the model. The serum amylase, lipase, Nitric oxide(NO), tumour necrosis factor alpha (TNF-a), superoxide dismutase (SOD), interleu kin-6(IL-6) were detected; Moreover, the histopathological score based on microscopic changes of pancreatic tissue were evaluated. Results: The levels of serum amylase and lipase, NO, TNF-a, IL-6 and the histopathological score (except 12h) were all decreased significantly in the Propofol-treated group than that in the SAP group at each time point (P<0.05). In contrast, the level of serum SOD was significantly elevated in the Propofol-treated group (P<0.05). Conclusion: Propofol can decrease serum amylase and lipase, reduce pancreatic tissue damage, and has therapeutic effects on the SAP in rats. Keywords: Propofol; Pancreatitis,acute necrotizing; Animal model
Wu-jun Wu, Hai-tian Hu, Yong-tian Yu, Xiao-gang Liu, Hui LI, Zhi-yong Fan, Yong Song, Zhong-jie Sun, Li-xue Du
15050.
Department of Hepatobiliary Surgery, Shaanxi Provincial People's Hospital, Xi'an City, China
Role of RECQ1 in cellular sensitivity to gemcitabine and overall survival of pancreatic cancer
Aim: Heparanase was up-regulation in pancreatic cancer and associated with a shorter survival. However, whether heparanase may serve as a useful marker to predict tumor relapse, metastasis, patients' survival, as well as their response to anticancer treatment is still unknown. Methods: Heparanase mRNA expression in peripheral blood mononuclear cell fraction (PBMC) was investigated in 31 pancreatic carcinoma patients (23 underwent surgery and 8 received chemotherapy) and ten healthy donors by real time RT-PCR. Heparanase activities in plasma and urine were also investigated using heparin-degrading enzyme assay. Patient survival time was determined according to the Kaplan-Meier method, and their difference was evaluated by the log-rank test. A P value<0.05 was considered statistically significant. Results: PBMC samples from cancer patients showed the expression of heparanase mRNA while no expression was observed for the healthy donors. Heparanase activities in blood and urine samples of the surgical group and chemotherapeutic patients were significantly higher than that of the healthy donors. Both heparanase mRNA expression and activities in the plasma and urine decreased significantly for the 17 patients that underwent R0 resection after operation (P<0.05), but increased remarkably when recurrence or metastasis occurred (P<0.05). However, which in the 6 patients who underwent R1 þ R2 resection changed slightly or remained constant. For 8 patients that received chemotherapy, heparanase mRNA and activities in the blood and urine samples of each of them decreased significantly (P<0.05). Elevated heparanase mRNA level (>a cutoff value of 1.84) in PMBC and high plasma heparanase activity (>1.30U/ml) were associated with a poor postoperativel survival in pancreatic carcinoma patients (P¼0.02 and P¼0.04). However, the high urine heparanase activity (>1.81U/ml) did not correlate with the overall survival (P¼0.10). Conclusion: The changes in heparanase mRNA expression and activity were closely associated with surgical procedure and chemotherapy, indicating that heparanase levels can be a useful diagnostic tool in monitoring patients' response to anticancer treatment and predicting their chances of survival.
15049. The effects of propofol on severe acute pancreatitis in rats Jing-yi Wu, Yi-sheng Zhang, Xiao-ju Jin, Guo-hai Zhao The Yijishan Hospital of Wannan Medical College, Wuhu 241001, China Objective: To investigate the therapeutic effects and mechanisms of propofol on severe acute pancreatitis(SAP) in rats. Methods: The 54 male Sprague-Dawley rats were randomized into three groups with 18 rats in each group: the Sham-operation group, the SAP group, the Propofol-treated group.After models were induced, the rats in the Propofol-treated group were injected continually propofol by dorsal vein of penis. The rats in all groups were killed at 3, 6, 12 hours (six rats in
Chang Liu 1, 3, Yanan Li 1, Jijiang Zhu 1, Huamin Wang 2, Ping Chang 1, Jianjun Shen 1, Fangyu Wang 3, **, Donghui Li 1, * 1
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 2 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 3 Department of Gastroenterology and Hepatology, Jinling Hospital, Southern Medical University, Nanjing 210002, China E-mail address: [email protected], [email protected]
Grant Support: Supported by the National Institutes of Health (NIH) R01 grant CA098380 (D.L.), NIH Cancer Center Core grant CA16672, and the Lockton Research Funds (D.L.) Abstract Aims: DNA helicases play an important role in DNA replication, recombination and repair. We have previously shown a significant association of RecQ1 A159C polymorphic variant with a poor prognosis in patients with pancreatic cancer. The purpose of the current study is to explore the role of RecQ1 gene in cellular response to gemcitabine and in patient survival. Methods: RecQ1 protein expression was measured in tumor tissues of 67 patients with pancreatic cancer using immunohistochemistry and the protein expression level was analyzed in relation to overall survival. RecQ1 gene expression was knocked down by siRNA in pancreatic adenocarcinoma cell lines. Cell proliferation, apoptosis and cell cycle distribution as well as mRNA expression of DNA repair and cell cycle regulating genes were compared in cells treated with or without gemcitabine in vector control and RecQ1 knockdown cells.. Results: RecQ1 knockdown resulted in increased sensitivity (decreased proliferation and increased apoptosis) to gemcitabine treatment. RecQ1deficient cells had reduced S-Phase distribution in cells with or without gemcitabine treatment. RecQ1 knockdown down-regulated the expression of cell cycle check point signal transducers CHK1, CHK2 and RAD9, and many genes involved in S phase DNA replication and M phase regulation. Conclusions: These observations suggest that RecQ1 plays an important role in DNA repair and cell cycle regulation, which in turn affect the cellular sensitivity to gemcitabine. Keywords: RecQ1, pancreatic cancer, gemcitabine, DNA repair, cell cycle regulation.
* Corresponding author. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX 77030, USA. Tel.: þ1 713 834 6690; fax: þ1 713 834 6153. ** Corresponding author. Department of Gastroenterology, Jinling Hospital, Southern Medical University, 305 East Zhongshan Road, Nanjing 21002, China. Tel.: þ86 025 80861051.