Objective To investigate the effects of nitric oxide (NO) on reperfusion injury following pancreaticoduodenal transplanta- tion in rats. Methods The homologous male Wistar rat model of heterotopic total pancreaticoduo...Objective To investigate the effects of nitric oxide (NO) on reperfusion injury following pancreaticoduodenal transplanta- tion in rats. Methods The homologous male Wistar rat model of heterotopic total pancreaticoduodenal transplantation was used. The L-arginine (L-Arg) group received intravenous injection of L-Arg 5 minutes before and after reperfusion at a dose of 200 mg/kg while the N-Nitro-L-Arginine methyl ester (L-NAME) group received intravenous injection of L-NAME at a dose of 10mg/kg, and control group received saline. The amount of NO in the pancreas graft was measured. Serum concentration of cytokine-induced neutrophil chemoattractant (CINC) determined by enzyme-linked immunosorbant assay, expression of CINC mRNA detected by Northern blot assay, and myeloperoxidase (MPO) activity in the pancreas graft were measured. Histological observation was performed. Results The amount of NO in the L-Arg group was higher than in the control group, while in the L-NAME group was lower than in the control group (P < 0.05). The peak of serum CINC concentration occurred 3 hours after reperfusion with significant difference among groups. Expression peak of CINC mRNA in the pancreas graft occurred 3 hours after reperfusion. The expression level in the L-Arg group was lower than in the control group, the L-NAME group was higher than control group (P < 0.05). MPO activity in the L-Arg group obviously decreasd compared with other groups. The pancreas inflamma- tion was ameliorated in L-Arg group, and pancreas damage was aggravated in L-NAME group. Conclusions L-Arg can increase the amount of NO and inhibit the elevation of CINC, CINC mRNA expression, and early neutrophil accumulation in the transplanted pancreas. NO has protective effects on the ischemia/reperfusion injury of pancreaticoduodenal transplantation .展开更多
AIM：To investigate the effect and mechanism of action of erlotinib, an epidermal growth factor receptor （EGFR） small molecule tyrosine kinase inhibitor （TKI）, in the human pancreatic cancer cell line BxPC-3 both ...AIM：To investigate the effect and mechanism of action of erlotinib, an epidermal growth factor receptor （EGFR） small molecule tyrosine kinase inhibitor （TKI）, in the human pancreatic cancer cell line BxPC-3 both in vitro and in vivo.METHODS： In vitro, human pancreatic cancer cell line BxPC-3 was exposed to varying concentrations of ertotinib, and its effects on proliferation, cell cycle distribution, apoptosis and the expression of proand antiapoptotic factors such as bcl-2, bcl-xl, bax and bak, and the expression of vascular endothelial cell growth factor （VEGF） were measured with 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, flow cytometric analysis, terminal deoxynucleotidyl transferase-mediated nick end labeling assay （TUNEL）, and reverse transcriptionpolymerase chain reaction （RT-PCR）. Potential effect of erlotinib on angiogenesis was examined by tube formation assay. Tumor growth suppression was observed in xenografted nude mice with pancreatic cancer in vivo. Immunohistochemical （IHC） staining for EGFR and factor VII-related antigen was undertaken to detect the microvessel density and VEGF expression in tumor tissue in xenograft nude mice.RESULTS： Erlotinib, as a single agent, repressed BxPC-3 cell growth in a dose-dependent manner, triggered G1 arrest and induced cell apoptosis, and suppressed capillary formation of endothelium in vitro. Expressions of VEGF were significantly down-regulated at a high concentration of 200 μmol/L, however, the expressions of bcl-2 and bcl-xl were decreased at 50 μmol/L. In vivo, Erlotinib-treated mice demonstrated a reduced tumor volume, weight and microvessel density as compared to the control. IHC staining showed decreased expression of EGFR and RT-PCR had lower VEGF expression in treated mice.CONCLUSION： The in vitro and in vivo findings provide evidence that BxPC-3 cells are inhibited with erlotinib treatment. Inhibition of EGFR may be a promising adjuvant chemotherapy strategy in pancreatic cancer treatment.展开更多
AIM: To investigate the effect of Mirtazapine on tumor growth, food intake, body weight, and nutritional status in gemcitabine-induced mild cachexia. METHODS: Fourteen mice with subcutaneous xenografts of a pancreatic...AIM: To investigate the effect of Mirtazapine on tumor growth, food intake, body weight, and nutritional status in gemcitabine-induced mild cachexia. METHODS: Fourteen mice with subcutaneous xenografts of a pancreatic cancer cell line (SW1990) were randomly divided into Mirtazapine and control groups. Either Mirtazapine (10 mg/kg) or saline solution was orally fed to the mice every day after tumor implantation. A model of mild cachexia was then established in both groups by intraperitoneal injection of Gemcitabine (50 mg/kg) 10 d, 13 d, and 16 d after tumor implanta- tion. Tumor size, food intake, body weight, and nutritional status were measured during the experiment. All mice were sacrificed at day 28. RESULTS: (1) After 7 d of gemcitabine administration, body-weight losses of 5%-7% which suggested mild cachexia were measured; (2) No significant difference in tumor size was detected between the Mirtazapine and control groups (P > 0.05); and (3) During the entire experimental period, food intake and body weight were slightly greater for the Mirtazapine group compared with controls (although these differences were not statistically significant). After 21 d, mice in the Mirtazapine group consumed significantly more food than control mice (3.95 ± 0.14 g vs 3.54 ± 0.10 g, P = 0.004). After 25 d, mice in the Mirtazapine group were also significantly heavier than control mice (17.24 ± 0.53 g vs 18.05 ± 0.68 g, P = 0.014). CONCLUSION: Mild cachexia model was successfully established by gemcitabine in pancreatic tumor-bearing mice. Mirtazapine can improve gemcitabine-induced mild cachexia in pancreatic tumor-bearing mice. It was believed to provide a potential therapeutic perspective for further studies on cachexia.展开更多
Objective.To investigate the difference of rejection in single versus combined pancreas and kidney transplantation in rats. Methods.Allograft models including simultaneous pancreas and kidney(SPK)transplant and pancre...Objective.To investigate the difference of rejection in single versus combined pancreas and kidney transplantation in rats. Methods.Allograft models including simultaneous pancreas and kidney(SPK)transplant and pancreas or kidney transplant alone were established in SD-Wistar rats, rejections of pancreas and kidney in different models were compared morphologically and functionally. Results.Mean survival time(MST)of pancreas was significantly prolonged in SPK than in pancreas transplant alone(PTA)(115 days vs. 92 days, P<005). Incidence of interstitial pancreatic rejection at grade Ⅱ and grade Ⅲ was much obvious in PTA than in SPK(429% vs. 125% at grade Ⅱ and 286% vs 63% at grade Ⅲ , P<005). No significant difference was found in MST between SPK and kidney transplant alone(KTA). Administration of cyclosporine A prolonged the MST of pancreas and kidney, without altering the tendency stated above. Conclusions.In SPK, the function of pancreas is protected by kidney hence the severity of rejection is reduced, whereas the function of kidney is not protected by pancreas. It suggests that different organs differ in immunoallergization and immunoregulation, and immune response tend to attack organs with greater immunoactivity, those organs with minor one could be protected. Cyclosporine A is effective on prolonging the MST of pancreas and kidney.展开更多
The present study observed the mutual benefit role of liver and pancreas in combined hepaticopan-creatic transplantation in rats. The results indicated that pancreas, when transplanted with liver, could survive for a ...The present study observed the mutual benefit role of liver and pancreas in combined hepaticopan-creatic transplantation in rats. The results indicated that pancreas, when transplanted with liver, could survive for a significant long time (13. 4±1.01 days) than it transplanted alone (9. 2±1.14 days) (P< 0. 05, t test). The interstitial rejection was mild and its rejection grade was significantly different from that of pancreas transplanted alone (P<0. 05, X2 test). The liver, when transplanted with pancreas, regenerated with strong competence and contact structure morphologically compared with liver transplanted alone. We think that pancreas could be immunologically protected against rejection and liver can be nutri-tionalized by pancreas in combined liver and pancreas transplantation.展开更多
For meeting the clinic needs in simultaneous pancreas and kidney transplantation (SPK), we success-fully establish a syngeneic SPK transplatation model in Lewis rats. The results indicate that this model isfeasible wi...For meeting the clinic needs in simultaneous pancreas and kidney transplantation (SPK), we success-fully establish a syngeneic SPK transplatation model in Lewis rats. The results indicate that this model isfeasible with a 82. 6% successful rate of operation and a 69. 6% survival rate in the first postoperativeweek. In long-term survived rats, the blood supplies are well established, function of the grafts (pancreasand kidney) maintains normal. This model is suitable for theoretical reserach in SPK transplantation for itsreasonable physiology with pancreatic juice drained into intestine and reduced postoperative complications inurinary tract and carbohydrate metabolism.展开更多
基金Supported by the Fund of Liaoning Provience Great Projection(0025001 ).
文摘Objective To investigate the effects of nitric oxide (NO) on reperfusion injury following pancreaticoduodenal transplanta- tion in rats. Methods The homologous male Wistar rat model of heterotopic total pancreaticoduodenal transplantation was used. The L-arginine (L-Arg) group received intravenous injection of L-Arg 5 minutes before and after reperfusion at a dose of 200 mg/kg while the N-Nitro-L-Arginine methyl ester (L-NAME) group received intravenous injection of L-NAME at a dose of 10mg/kg, and control group received saline. The amount of NO in the pancreas graft was measured. Serum concentration of cytokine-induced neutrophil chemoattractant (CINC) determined by enzyme-linked immunosorbant assay, expression of CINC mRNA detected by Northern blot assay, and myeloperoxidase (MPO) activity in the pancreas graft were measured. Histological observation was performed. Results The amount of NO in the L-Arg group was higher than in the control group, while in the L-NAME group was lower than in the control group (P < 0.05). The peak of serum CINC concentration occurred 3 hours after reperfusion with significant difference among groups. Expression peak of CINC mRNA in the pancreas graft occurred 3 hours after reperfusion. The expression level in the L-Arg group was lower than in the control group, the L-NAME group was higher than control group (P < 0.05). MPO activity in the L-Arg group obviously decreasd compared with other groups. The pancreas inflamma- tion was ameliorated in L-Arg group, and pancreas damage was aggravated in L-NAME group. Conclusions L-Arg can increase the amount of NO and inhibit the elevation of CINC, CINC mRNA expression, and early neutrophil accumulation in the transplanted pancreas. NO has protective effects on the ischemia/reperfusion injury of pancreaticoduodenal transplantation .
文摘AIM：To investigate the effect and mechanism of action of erlotinib, an epidermal growth factor receptor （EGFR） small molecule tyrosine kinase inhibitor （TKI）, in the human pancreatic cancer cell line BxPC-3 both in vitro and in vivo.METHODS： In vitro, human pancreatic cancer cell line BxPC-3 was exposed to varying concentrations of ertotinib, and its effects on proliferation, cell cycle distribution, apoptosis and the expression of proand antiapoptotic factors such as bcl-2, bcl-xl, bax and bak, and the expression of vascular endothelial cell growth factor （VEGF） were measured with 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, flow cytometric analysis, terminal deoxynucleotidyl transferase-mediated nick end labeling assay （TUNEL）, and reverse transcriptionpolymerase chain reaction （RT-PCR）. Potential effect of erlotinib on angiogenesis was examined by tube formation assay. Tumor growth suppression was observed in xenografted nude mice with pancreatic cancer in vivo. Immunohistochemical （IHC） staining for EGFR and factor VII-related antigen was undertaken to detect the microvessel density and VEGF expression in tumor tissue in xenograft nude mice.RESULTS： Erlotinib, as a single agent, repressed BxPC-3 cell growth in a dose-dependent manner, triggered G1 arrest and induced cell apoptosis, and suppressed capillary formation of endothelium in vitro. Expressions of VEGF were significantly down-regulated at a high concentration of 200 μmol/L, however, the expressions of bcl-2 and bcl-xl were decreased at 50 μmol/L. In vivo, Erlotinib-treated mice demonstrated a reduced tumor volume, weight and microvessel density as compared to the control. IHC staining showed decreased expression of EGFR and RT-PCR had lower VEGF expression in treated mice.CONCLUSION： The in vitro and in vivo findings provide evidence that BxPC-3 cells are inhibited with erlotinib treatment. Inhibition of EGFR may be a promising adjuvant chemotherapy strategy in pancreatic cancer treatment.
文摘AIM: To investigate the effect of Mirtazapine on tumor growth, food intake, body weight, and nutritional status in gemcitabine-induced mild cachexia. METHODS: Fourteen mice with subcutaneous xenografts of a pancreatic cancer cell line (SW1990) were randomly divided into Mirtazapine and control groups. Either Mirtazapine (10 mg/kg) or saline solution was orally fed to the mice every day after tumor implantation. A model of mild cachexia was then established in both groups by intraperitoneal injection of Gemcitabine (50 mg/kg) 10 d, 13 d, and 16 d after tumor implanta- tion. Tumor size, food intake, body weight, and nutritional status were measured during the experiment. All mice were sacrificed at day 28. RESULTS: (1) After 7 d of gemcitabine administration, body-weight losses of 5%-7% which suggested mild cachexia were measured; (2) No significant difference in tumor size was detected between the Mirtazapine and control groups (P > 0.05); and (3) During the entire experimental period, food intake and body weight were slightly greater for the Mirtazapine group compared with controls (although these differences were not statistically significant). After 21 d, mice in the Mirtazapine group consumed significantly more food than control mice (3.95 ± 0.14 g vs 3.54 ± 0.10 g, P = 0.004). After 25 d, mice in the Mirtazapine group were also significantly heavier than control mice (17.24 ± 0.53 g vs 18.05 ± 0.68 g, P = 0.014). CONCLUSION: Mild cachexia model was successfully established by gemcitabine in pancreatic tumor-bearing mice. Mirtazapine can improve gemcitabine-induced mild cachexia in pancreatic tumor-bearing mice. It was believed to provide a potential therapeutic perspective for further studies on cachexia.
文摘Objective.To investigate the difference of rejection in single versus combined pancreas and kidney transplantation in rats. Methods.Allograft models including simultaneous pancreas and kidney(SPK)transplant and pancreas or kidney transplant alone were established in SD-Wistar rats, rejections of pancreas and kidney in different models were compared morphologically and functionally. Results.Mean survival time(MST)of pancreas was significantly prolonged in SPK than in pancreas transplant alone(PTA)(115 days vs. 92 days, P<005). Incidence of interstitial pancreatic rejection at grade Ⅱ and grade Ⅲ was much obvious in PTA than in SPK(429% vs. 125% at grade Ⅱ and 286% vs 63% at grade Ⅲ , P<005). No significant difference was found in MST between SPK and kidney transplant alone(KTA). Administration of cyclosporine A prolonged the MST of pancreas and kidney, without altering the tendency stated above. Conclusions.In SPK, the function of pancreas is protected by kidney hence the severity of rejection is reduced, whereas the function of kidney is not protected by pancreas. It suggests that different organs differ in immunoallergization and immunoregulation, and immune response tend to attack organs with greater immunoactivity, those organs with minor one could be protected. Cyclosporine A is effective on prolonging the MST of pancreas and kidney.
文摘The present study observed the mutual benefit role of liver and pancreas in combined hepaticopan-creatic transplantation in rats. The results indicated that pancreas, when transplanted with liver, could survive for a significant long time (13. 4±1.01 days) than it transplanted alone (9. 2±1.14 days) (P< 0. 05, t test). The interstitial rejection was mild and its rejection grade was significantly different from that of pancreas transplanted alone (P<0. 05, X2 test). The liver, when transplanted with pancreas, regenerated with strong competence and contact structure morphologically compared with liver transplanted alone. We think that pancreas could be immunologically protected against rejection and liver can be nutri-tionalized by pancreas in combined liver and pancreas transplantation.
文摘For meeting the clinic needs in simultaneous pancreas and kidney transplantation (SPK), we success-fully establish a syngeneic SPK transplatation model in Lewis rats. The results indicate that this model isfeasible with a 82. 6% successful rate of operation and a 69. 6% survival rate in the first postoperativeweek. In long-term survived rats, the blood supplies are well established, function of the grafts (pancreasand kidney) maintains normal. This model is suitable for theoretical reserach in SPK transplantation for itsreasonable physiology with pancreatic juice drained into intestine and reduced postoperative complications inurinary tract and carbohydrate metabolism.
