AIM: Activated pancreatic stellate cells (PSCs) have been implicated in the pathogenesis of pancreatic fibrosis and inflammation. Primary PSCs can be subcultured only several times because of their limited growth pote...AIM: Activated pancreatic stellate cells (PSCs) have been implicated in the pathogenesis of pancreatic fibrosis and inflammation. Primary PSCs can be subcultured only several times because of their limited growth potential. A continuous cell line may therefore be valuable in studying molecular mechanisms of these pancreatic disorders. The aim of this study was to establish a cell line of rat PSCs by spontaneous immortalization.METHODS: PSCs were isolated from the pancreas of male Wistar rats, and conventional subcultivation was performed repeatedly. Telomerase activity was measured using the telomere repeat amplification protocol. Activation of transcription factors was assessed by electrophoretic mobility shift assay.Activation of mitogen-activated protein (MAP) kinases was examined by Western blotting using anti-phosphospecific antibodies. Expression of cytokine-induced neutrophil chemoattractant-1 was determined by enzyme immunoassay.RESULTS: Conventional subcultivation yielded actively growing cells. One clone was obtained after limiting dilution,and designated as SIPS. This cell line has been passaged repeatedly more than 2 years, and is thus likely immortalized.SIPS cells retained morphological characteristics of primary,culture-activated PSCs. SIPS expressed α-smooth muscle actin, glial acidic fibrillary protein, vimentin, desmin, type Ⅰ collagen, fibronectin, and prolyl hydroxylases. Telomerase activity and p53 expression were negative. Proliferation of SIPS cells was serum-dependent, and stimulated with platelet-derived growth factor-BB through the activation of extracellular signal-regulated kinase. Interleukin-1β activated nuclear factor-κB, activator protein-1, and MAP kinases.Interleukin-1β induced cytokine-induced neutrophil chemoattractant-1 expression through the activation of nuclear factor-κB and MAP kinases.CONCLUSION: SIPS cells can be useful for in vitro studies of cell biology and signal transduction of PSCs.展开更多
BACKGROUND There is no standard therapy for second-line treatment of gemcitabine-refractory pancreatic cancer patients with poor performance status.A combination of chemotherapy drugs 5-fluorouracil(5-FU),leucovorin,i...BACKGROUND There is no standard therapy for second-line treatment of gemcitabine-refractory pancreatic cancer patients with poor performance status.A combination of chemotherapy drugs 5-fluorouracil(5-FU),leucovorin,irinotecan,and oxaliplatin(FOLFIRINOX)or 5-fluorouracil/leucovorin plus nanoliposomal irinotecan can be considered as second-line treatment for such patients;however,due to toxicity,none of the regimens are recommended for patients with poor performance.Capecitabine or S-1 has relatively low toxicity and can be considered a treatment option for gemcitabine-refractory pancreatic cancer.AIM To investigate the efficacy and toxicity of oral chemotherapy as second-line treatment in patients with pancreatic cancer.METHODS Patients who had progressive disease after first-line gemcitabine-based chemotherapy were retrospectively analyzed between January 2011 and December 2018.They were treated with capecitabine or S-1 as the second-line treatment.Capecitabine was administered as a 2500 mg/m2 divided dose on days 1-14,followed by a 1-wk rest.S-1 was taken orally based on the patient’s body surface area for 28 d,followed by 2-wk of rest.Progression-free survival and overall survival were used to compare efficacy of capecitabine and S-1.RESULTS Of the 81 patients,41 were treated with capecitabine and 40 with S-1.The median time to treatment failure in both groups was 1.5 mo(P=0.425).The objective response rate was similar in the two groups:9.8%with capecitabine and 2.5%with S-1(P=0.359).Median progression-free survival was longer in the S-1 group than in the capecitabine group(S-12.7 mo,capecitabine 2.0 mo,P=0.003).There was no significant difference in the median overall survival between the capecitabine and S-1 groups(4.3 mo vs 5.0 mo,P=0.092).Grade 3 or 4 hand-foot syndrome was significantly more common in the capecitabine group than in the S-1 group(14.6%vs 0%,P=0.026).CONCLUSION Capecitabine or S-1 can be used as a second-line treatment for patients with advanced pancreatic cancer with poor performance status after progression to a gemcitabine-based regimen.展开更多
基于多阶低通滤波匹配网络和渐变式宽带匹配结构,设计和加工了一款面向5G通信的S波段的高效率非对称Doherty功率放大器(DPA)。与传统设计方法不同,移除了主功放匹配网络后端的1/4波长线,采用改进式输出合路网络的方法,并用谐波后匹配来...基于多阶低通滤波匹配网络和渐变式宽带匹配结构,设计和加工了一款面向5G通信的S波段的高效率非对称Doherty功率放大器(DPA)。与传统设计方法不同,移除了主功放匹配网络后端的1/4波长线,采用改进式输出合路网络的方法,并用谐波后匹配来抑制谐波,既大大简化了匹配网络,又提高了功放的带宽。经过连续波信号测试,在3.5 GHz处,Doherty功放的饱和输出功率为48.5 d Bm,最大功率附加效率(PAE)为68.5%,7.5 d B回退量的PAE效率达到了52%;在3.4~3.6 GHz频带内,饱和输出功率大于48.3 d Bm,饱和PAE大于55.7%,7.5 d B回退量的PAE效率大于48.1%。同时,采用20 MHz的LTE信号对DPA进行测试,获得了较好的线性度,7.5 d B回退量的PAE为50.2%,邻信道功率比(ACPR)为-51 d Bc。测试结果验证了该高效率宽带网络的可行性和有效性,该设计在5 G通信中具有广阔的应用前景。展开更多
基金Grant-in-Aid for Encouragement of Young Scientists from Japan Society for the Promotion of Science(to A.M.)Pancreas Research Foundation of Japan(to A.M.)
文摘AIM: Activated pancreatic stellate cells (PSCs) have been implicated in the pathogenesis of pancreatic fibrosis and inflammation. Primary PSCs can be subcultured only several times because of their limited growth potential. A continuous cell line may therefore be valuable in studying molecular mechanisms of these pancreatic disorders. The aim of this study was to establish a cell line of rat PSCs by spontaneous immortalization.METHODS: PSCs were isolated from the pancreas of male Wistar rats, and conventional subcultivation was performed repeatedly. Telomerase activity was measured using the telomere repeat amplification protocol. Activation of transcription factors was assessed by electrophoretic mobility shift assay.Activation of mitogen-activated protein (MAP) kinases was examined by Western blotting using anti-phosphospecific antibodies. Expression of cytokine-induced neutrophil chemoattractant-1 was determined by enzyme immunoassay.RESULTS: Conventional subcultivation yielded actively growing cells. One clone was obtained after limiting dilution,and designated as SIPS. This cell line has been passaged repeatedly more than 2 years, and is thus likely immortalized.SIPS cells retained morphological characteristics of primary,culture-activated PSCs. SIPS expressed α-smooth muscle actin, glial acidic fibrillary protein, vimentin, desmin, type Ⅰ collagen, fibronectin, and prolyl hydroxylases. Telomerase activity and p53 expression were negative. Proliferation of SIPS cells was serum-dependent, and stimulated with platelet-derived growth factor-BB through the activation of extracellular signal-regulated kinase. Interleukin-1β activated nuclear factor-κB, activator protein-1, and MAP kinases.Interleukin-1β induced cytokine-induced neutrophil chemoattractant-1 expression through the activation of nuclear factor-κB and MAP kinases.CONCLUSION: SIPS cells can be useful for in vitro studies of cell biology and signal transduction of PSCs.
文摘BACKGROUND There is no standard therapy for second-line treatment of gemcitabine-refractory pancreatic cancer patients with poor performance status.A combination of chemotherapy drugs 5-fluorouracil(5-FU),leucovorin,irinotecan,and oxaliplatin(FOLFIRINOX)or 5-fluorouracil/leucovorin plus nanoliposomal irinotecan can be considered as second-line treatment for such patients;however,due to toxicity,none of the regimens are recommended for patients with poor performance.Capecitabine or S-1 has relatively low toxicity and can be considered a treatment option for gemcitabine-refractory pancreatic cancer.AIM To investigate the efficacy and toxicity of oral chemotherapy as second-line treatment in patients with pancreatic cancer.METHODS Patients who had progressive disease after first-line gemcitabine-based chemotherapy were retrospectively analyzed between January 2011 and December 2018.They were treated with capecitabine or S-1 as the second-line treatment.Capecitabine was administered as a 2500 mg/m2 divided dose on days 1-14,followed by a 1-wk rest.S-1 was taken orally based on the patient’s body surface area for 28 d,followed by 2-wk of rest.Progression-free survival and overall survival were used to compare efficacy of capecitabine and S-1.RESULTS Of the 81 patients,41 were treated with capecitabine and 40 with S-1.The median time to treatment failure in both groups was 1.5 mo(P=0.425).The objective response rate was similar in the two groups:9.8%with capecitabine and 2.5%with S-1(P=0.359).Median progression-free survival was longer in the S-1 group than in the capecitabine group(S-12.7 mo,capecitabine 2.0 mo,P=0.003).There was no significant difference in the median overall survival between the capecitabine and S-1 groups(4.3 mo vs 5.0 mo,P=0.092).Grade 3 or 4 hand-foot syndrome was significantly more common in the capecitabine group than in the S-1 group(14.6%vs 0%,P=0.026).CONCLUSION Capecitabine or S-1 can be used as a second-line treatment for patients with advanced pancreatic cancer with poor performance status after progression to a gemcitabine-based regimen.
文摘基于多阶低通滤波匹配网络和渐变式宽带匹配结构,设计和加工了一款面向5G通信的S波段的高效率非对称Doherty功率放大器(DPA)。与传统设计方法不同,移除了主功放匹配网络后端的1/4波长线,采用改进式输出合路网络的方法,并用谐波后匹配来抑制谐波,既大大简化了匹配网络,又提高了功放的带宽。经过连续波信号测试,在3.5 GHz处,Doherty功放的饱和输出功率为48.5 d Bm,最大功率附加效率(PAE)为68.5%,7.5 d B回退量的PAE效率达到了52%;在3.4~3.6 GHz频带内,饱和输出功率大于48.3 d Bm,饱和PAE大于55.7%,7.5 d B回退量的PAE效率大于48.1%。同时,采用20 MHz的LTE信号对DPA进行测试,获得了较好的线性度,7.5 d B回退量的PAE为50.2%,邻信道功率比(ACPR)为-51 d Bc。测试结果验证了该高效率宽带网络的可行性和有效性,该设计在5 G通信中具有广阔的应用前景。
