BACKGROUND:Acinar cell carcinoma (ACC) is a rare malignancy of the pancreas arising from acinar cells.Unlike ductal adenocarcinoma,this tumor rarely presents with pancreatitis.METHODS:We present a case of ACC associat...BACKGROUND:Acinar cell carcinoma (ACC) is a rare malignancy of the pancreas arising from acinar cells.Unlike ductal adenocarcinoma,this tumor rarely presents with pancreatitis.METHODS:We present a case of ACC associated with chronic calcifying pancreatitis,and a review of the literature focusing on diagnosis and management.RESULTS:A 43-year-old man was proposed for Wirsungojejunal derivation for chronic pancreatitis.Histopathological examination of the tissue extracted revealed an ACC.Duodenopancreatectomy was performed.Six months postoperatively,the patient developed hepatic metastasis and was treated with gemcitabine as palliative chemotherapy.CONCLUSIONS:The clinical presentation of ACC of the pancreas is not specific and the tumor can be underdiagnosed when associated with chronic pancreatitis.Data regarding course,treatment,and prognosis of this tumor are generally lacking.展开更多
AIM To elucidate the underlying mechanism that microRNA-22(miR-22) promotes the apoptosis of rat pancreatic acinar cells(AR42 J) and the elements that regulate the expression of miR-22.METHODS One hundred nanomoles pe...AIM To elucidate the underlying mechanism that microRNA-22(miR-22) promotes the apoptosis of rat pancreatic acinar cells(AR42 J) and the elements that regulate the expression of miR-22.METHODS One hundred nanomoles per liter of caerulein(Cae)was administrated to induce the apoptosis of AR42 J cells and the apoptosis rate was detected by flow cytometry analysis. An amylase assay kit was used to measure the amylase expression level in the supernatant. Quantitative real-time PCR(qRT-PCR)was adopted to measure miR-22 expression. We used online tools to predict the potential transcription promoter of miR-22 and the binding sites, which was further identified by using luciferase reporter analysis,chromatin immunoprecipitation(ChIP) and ChIPqP CR assays. Then, a mimic of miR-22, Nr3 c1 plasmid encoding the glucocorticoid receptor(GR), and siNr3 c1 were used to transfect AR42 J cells, respectively.The mRNA expression of miR-22, Nr3 c1, and Erb-b2 receptor tyrosine kinase 3(ErbB3) was confirmed by qRT-PCR and the apoptosis rate of AR42 J cells was detected by flow cytometry analysis. Western blot was used to detect the expression of ErbB3, GR, PI3 k, PI3 kp85α, Akt, p-Akt, Bad, Bax, Bcl-xl, Bcl-2, and cleaved caspase3.RESULTS After inducing apoptosis of AR42 J cells in vitro, the expression of miR-22 was significantly increased by2.20 ± 0.26 and 4.19 ± 0.54 times, respectively, at3 h and 6 h in comparison with the control group.As revealed by qRT-PCR assay, the expression of miR-22 was 78.25 ± 6.61 times higher in the miR-22 mimic group relative to the miRNA control group,accompanied with an obviously increased acinar cell apoptosis rate(32.53 ± 1.15 vs 18.07 ± 0.89, P =0.0006). The upregulation of miR-22 could suppress its target gene, ErbB3, and the phosphorylation of PI3 k and Akt. Furthermore, we predicted the potential transcription promoter of miR-22 and the binding sites using online tools. Luciferase reporter analysis and sitedirected mutagenesis indicated that the binding site(GACAGCCATGTACA) of the GR, which is encoded by the Nr3 c1 gene. Downregulation of the expression of GR could upregulate the expression of miR-22, which further promoted the apoptosis of AR42 J cells.CONCLUSION GR transcriptionally represses the expression of miR-22,which further promotes the apoptosis of pancreatic acinar cells by downregulating the downstream signaling pathway.展开更多
Objectives:To observe the protective effect of cathepsin B inhibition against apoptosis of acinar cells in the early management of pancreatic contusion and laceration in rats,which would provide evidence of a potentia...Objectives:To observe the protective effect of cathepsin B inhibition against apoptosis of acinar cells in the early management of pancreatic contusion and laceration in rats,which would provide evidence of a potential early therapeutic for pancreatic contusion and laceration.Methods:Twenty-four rats were assigned to 2 groups:1)Model(n=12)with an induced pancreatic injury of severity I-II and 2)CA074-V(n=12):an induced pancreatic injury,severity I-II treated with the cathepsin B inhibitor CA074-me(0.01mg/g)by intravenous administration through the caudal vein at 5minutes post model establishment.The mice in these two groups were further randomly divided into 4 subgroups containing 3 rats each that were sacrificed for quantitation of apoptosis,immunohistochemistry of cathepsin B,and serum amylase and lipase measurements at different time points after model establishment(0,3,6,and 12hours).Results:The percentage of apoptotic pancreatic acinar cells collected from the injured tissues were much lower in the CA074-V group than the Model group at 3hours[9.25±3.94%vs.64.76±26.47%,P<0.10]and 6hours[14.71±8.22%vs.66.60±13.54%,P<0.10]post model establishment.The percentage of cathepsin B-positive pancreatic acinar cells were much lower in the CA074-V group than in the Model group at 3hours[31.07±12.02%vs.69.16±5.71%,P<0.10],6hours[24.84±0.93%vs.47.06±0.91%,P<0.10],and 12hours[28.33±9.14%vs.52.72±1.25%,P<0.10]post model establishment.Conclusions:Early cathepsin B inhibition effectively blocked acinar cell apoptosis in an experimental rat model of pancreatic contusion and laceration.展开更多
文摘BACKGROUND:Acinar cell carcinoma (ACC) is a rare malignancy of the pancreas arising from acinar cells.Unlike ductal adenocarcinoma,this tumor rarely presents with pancreatitis.METHODS:We present a case of ACC associated with chronic calcifying pancreatitis,and a review of the literature focusing on diagnosis and management.RESULTS:A 43-year-old man was proposed for Wirsungojejunal derivation for chronic pancreatitis.Histopathological examination of the tissue extracted revealed an ACC.Duodenopancreatectomy was performed.Six months postoperatively,the patient developed hepatic metastasis and was treated with gemcitabine as palliative chemotherapy.CONCLUSIONS:The clinical presentation of ACC of the pancreas is not specific and the tumor can be underdiagnosed when associated with chronic pancreatitis.Data regarding course,treatment,and prognosis of this tumor are generally lacking.
基金National Natural Science Foundation of China,No.31671440
文摘AIM To elucidate the underlying mechanism that microRNA-22(miR-22) promotes the apoptosis of rat pancreatic acinar cells(AR42 J) and the elements that regulate the expression of miR-22.METHODS One hundred nanomoles per liter of caerulein(Cae)was administrated to induce the apoptosis of AR42 J cells and the apoptosis rate was detected by flow cytometry analysis. An amylase assay kit was used to measure the amylase expression level in the supernatant. Quantitative real-time PCR(qRT-PCR)was adopted to measure miR-22 expression. We used online tools to predict the potential transcription promoter of miR-22 and the binding sites, which was further identified by using luciferase reporter analysis,chromatin immunoprecipitation(ChIP) and ChIPqP CR assays. Then, a mimic of miR-22, Nr3 c1 plasmid encoding the glucocorticoid receptor(GR), and siNr3 c1 were used to transfect AR42 J cells, respectively.The mRNA expression of miR-22, Nr3 c1, and Erb-b2 receptor tyrosine kinase 3(ErbB3) was confirmed by qRT-PCR and the apoptosis rate of AR42 J cells was detected by flow cytometry analysis. Western blot was used to detect the expression of ErbB3, GR, PI3 k, PI3 kp85α, Akt, p-Akt, Bad, Bax, Bcl-xl, Bcl-2, and cleaved caspase3.RESULTS After inducing apoptosis of AR42 J cells in vitro, the expression of miR-22 was significantly increased by2.20 ± 0.26 and 4.19 ± 0.54 times, respectively, at3 h and 6 h in comparison with the control group.As revealed by qRT-PCR assay, the expression of miR-22 was 78.25 ± 6.61 times higher in the miR-22 mimic group relative to the miRNA control group,accompanied with an obviously increased acinar cell apoptosis rate(32.53 ± 1.15 vs 18.07 ± 0.89, P =0.0006). The upregulation of miR-22 could suppress its target gene, ErbB3, and the phosphorylation of PI3 k and Akt. Furthermore, we predicted the potential transcription promoter of miR-22 and the binding sites using online tools. Luciferase reporter analysis and sitedirected mutagenesis indicated that the binding site(GACAGCCATGTACA) of the GR, which is encoded by the Nr3 c1 gene. Downregulation of the expression of GR could upregulate the expression of miR-22, which further promoted the apoptosis of AR42 J cells.CONCLUSION GR transcriptionally represses the expression of miR-22,which further promotes the apoptosis of pancreatic acinar cells by downregulating the downstream signaling pathway.
基金The experimental protocol was approved on Nov.26th,2020 by the General Hospital of the People’s Liberation Army(PLA)and the registration number is S2020-418-01We thank the support from the Chinese PLA General Hospital(2020-YQPY-002,ZH19016,2018XXFC-20)from the National Natural Science Fund(81701961,82072200).
文摘Objectives:To observe the protective effect of cathepsin B inhibition against apoptosis of acinar cells in the early management of pancreatic contusion and laceration in rats,which would provide evidence of a potential early therapeutic for pancreatic contusion and laceration.Methods:Twenty-four rats were assigned to 2 groups:1)Model(n=12)with an induced pancreatic injury of severity I-II and 2)CA074-V(n=12):an induced pancreatic injury,severity I-II treated with the cathepsin B inhibitor CA074-me(0.01mg/g)by intravenous administration through the caudal vein at 5minutes post model establishment.The mice in these two groups were further randomly divided into 4 subgroups containing 3 rats each that were sacrificed for quantitation of apoptosis,immunohistochemistry of cathepsin B,and serum amylase and lipase measurements at different time points after model establishment(0,3,6,and 12hours).Results:The percentage of apoptotic pancreatic acinar cells collected from the injured tissues were much lower in the CA074-V group than the Model group at 3hours[9.25±3.94%vs.64.76±26.47%,P<0.10]and 6hours[14.71±8.22%vs.66.60±13.54%,P<0.10]post model establishment.The percentage of cathepsin B-positive pancreatic acinar cells were much lower in the CA074-V group than in the Model group at 3hours[31.07±12.02%vs.69.16±5.71%,P<0.10],6hours[24.84±0.93%vs.47.06±0.91%,P<0.10],and 12hours[28.33±9.14%vs.52.72±1.25%,P<0.10]post model establishment.Conclusions:Early cathepsin B inhibition effectively blocked acinar cell apoptosis in an experimental rat model of pancreatic contusion and laceration.
