BACKGROUND Endogenous regeneration of pancreatic isletβ-cells is a path to cure both type 1 and advanced type 2 diabetes.Pancreatic cancer cell line-1(PANC-1),a human pancreatic islet progenitor cell line,can be indu...BACKGROUND Endogenous regeneration of pancreatic isletβ-cells is a path to cure both type 1 and advanced type 2 diabetes.Pancreatic cancer cell line-1(PANC-1),a human pancreatic islet progenitor cell line,can be induced by trypsin to differentiate into insulin-secreting islet-like aggregates(ILAs).However,the underlying mechanism has not been explored.AIM To explore the mechanism and signaling pathway of trypsin-induced differentiation of islet progenitor cells into insulin-secreting cells.METHODS PANC-1 cells were induced by trypsin to form ILAs and differentiate into insulinsecreting cells.Clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9 knockout and small interfering RNA knockdown techniques were used to investigate membrane proteins and downstream signaling pathways involved in the process.RESULTS The extracellular domain of membrane receptor E-cadherin hydrolyzed by trypsin induced the aggregation of PANC-1 cells and stimulated E-cadherin-recruited casein kinase-1γ3,which specifically phosphorylated the Ser655/Thr658 site ofα-catenin in the cadherin-catenin complex,participating in the process of PANC-1 differentiation and affecting the maturation of differentiated ILAs.CONCLUSION The current study reveals the mechanism by which trypsin promotes PANC-1 cell differentiation into islet-like cells,providing a novel approach for endogenous isletβ-cell regeneration.展开更多
AIM: To investigate the changing pattern of α-catenin expression and its relationship to clinical and pathological features of colorectal cancer (CRC) patients. METHODS: Archival tumor samples were analyzed using imm...AIM: To investigate the changing pattern of α-catenin expression and its relationship to clinical and pathological features of colorectal cancer (CRC) patients. METHODS: Archival tumor samples were analyzed using immunohistochemistry (IHC) for α-catenin in 91 patients with advanced CRC. RESULTS: The values of α-catenin membrane index (MI) and cytoplasmic index (CI) were significantly related to the depth of tumor invasion (P = 0.027, P = 0.020, respectively), high indices being associated with increased depth of the primary tumor invasion (T3 and T4). Similarly, patients with high α-catenin expression had a signifi cantly increased risk of lymph node metastasis (32/39 vs 37/52 for MI and 37/45 vs 32/46 for CI) (P = 0.001, P = 0.0001, respectively, for LNN status). An altered expression (i.e., cytoplasmic pattern) was also related (P = 0.047) to the response to chemotherapy; patients with low CI were more responsive (CR: 7/46) than patients with high CI values (CR: 0/45). There was a marginal effect on survival in patients time with metastases (SWM) (P = 0.087); patients with low CI showing slightly longerSWM, but no such effect on disease free survival (DFS) or disease specifi c survival (DSS). As to co-expression with another member of the adhesion complex (β-catenin), high α-catenin/β-catenin MI index was of marginal signifi cance in predicting longer DSS (P = 0.063, log-rank). CONCLUSION: The results implicate that high α-catenin expression is intimately involved in the key regulatory mechanisms leading to invasive phenotype, lymph node metastases, and progressive disease in CRC.展开更多
This practical atlas aims to help liver and non liver pa-thologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrat...This practical atlas aims to help liver and non liver pa-thologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrate typical and atypical aspects of focal nodular hyperplasia and of hepatocellular adenoma, including hepatocel-lular adenomas subtypes with references to clinical and imaging data. Each step is important to make a correct diagnosis. The specimen including the nodule and the non-tumoral liver should be sliced, photographed and all different looking areas adequately sampled for par-affin inclusion. Routine histology includes HE, trichrome and cytokeratin 7. Immunohistochemistry includes glu-tamine synthase and according to the above results ad-ditional markers such as liver fatty acid binding protein, C reactive protein and beta catenin may be realized to differentiate focal nodular hyperplasia from hepatocel-lular adenoma subtypes. Clues for differential diagnosis and pitfalls are explained and illustrated.展开更多
基金Supported by the National Natural Science Foundation of China,No.82073908.
文摘BACKGROUND Endogenous regeneration of pancreatic isletβ-cells is a path to cure both type 1 and advanced type 2 diabetes.Pancreatic cancer cell line-1(PANC-1),a human pancreatic islet progenitor cell line,can be induced by trypsin to differentiate into insulin-secreting islet-like aggregates(ILAs).However,the underlying mechanism has not been explored.AIM To explore the mechanism and signaling pathway of trypsin-induced differentiation of islet progenitor cells into insulin-secreting cells.METHODS PANC-1 cells were induced by trypsin to form ILAs and differentiate into insulinsecreting cells.Clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9 knockout and small interfering RNA knockdown techniques were used to investigate membrane proteins and downstream signaling pathways involved in the process.RESULTS The extracellular domain of membrane receptor E-cadherin hydrolyzed by trypsin induced the aggregation of PANC-1 cells and stimulated E-cadherin-recruited casein kinase-1γ3,which specifically phosphorylated the Ser655/Thr658 site ofα-catenin in the cadherin-catenin complex,participating in the process of PANC-1 differentiation and affecting the maturation of differentiated ILAs.CONCLUSION The current study reveals the mechanism by which trypsin promotes PANC-1 cell differentiation into islet-like cells,providing a novel approach for endogenous isletβ-cell regeneration.
基金Partly the Special Government Funding (EVO)allocated to Turku University Central Hospital and CancerSociety of South-West Finland (Turku), No. 13687
文摘AIM: To investigate the changing pattern of α-catenin expression and its relationship to clinical and pathological features of colorectal cancer (CRC) patients. METHODS: Archival tumor samples were analyzed using immunohistochemistry (IHC) for α-catenin in 91 patients with advanced CRC. RESULTS: The values of α-catenin membrane index (MI) and cytoplasmic index (CI) were significantly related to the depth of tumor invasion (P = 0.027, P = 0.020, respectively), high indices being associated with increased depth of the primary tumor invasion (T3 and T4). Similarly, patients with high α-catenin expression had a signifi cantly increased risk of lymph node metastasis (32/39 vs 37/52 for MI and 37/45 vs 32/46 for CI) (P = 0.001, P = 0.0001, respectively, for LNN status). An altered expression (i.e., cytoplasmic pattern) was also related (P = 0.047) to the response to chemotherapy; patients with low CI were more responsive (CR: 7/46) than patients with high CI values (CR: 0/45). There was a marginal effect on survival in patients time with metastases (SWM) (P = 0.087); patients with low CI showing slightly longerSWM, but no such effect on disease free survival (DFS) or disease specifi c survival (DSS). As to co-expression with another member of the adhesion complex (β-catenin), high α-catenin/β-catenin MI index was of marginal signifi cance in predicting longer DSS (P = 0.063, log-rank). CONCLUSION: The results implicate that high α-catenin expression is intimately involved in the key regulatory mechanisms leading to invasive phenotype, lymph node metastases, and progressive disease in CRC.
基金Supported by Association pour la Recherche sur le Cancer,No.3194
文摘This practical atlas aims to help liver and non liver pa-thologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrate typical and atypical aspects of focal nodular hyperplasia and of hepatocellular adenoma, including hepatocel-lular adenomas subtypes with references to clinical and imaging data. Each step is important to make a correct diagnosis. The specimen including the nodule and the non-tumoral liver should be sliced, photographed and all different looking areas adequately sampled for par-affin inclusion. Routine histology includes HE, trichrome and cytokeratin 7. Immunohistochemistry includes glu-tamine synthase and according to the above results ad-ditional markers such as liver fatty acid binding protein, C reactive protein and beta catenin may be realized to differentiate focal nodular hyperplasia from hepatocel-lular adenoma subtypes. Clues for differential diagnosis and pitfalls are explained and illustrated.
