AIM：To clarify the expression patterns and prognostic implications of the mitotic regulator Polo-like kinase 1 （PLK1） in colon cancer. METHODS： Expression of PLK1 was investigated by immunohistochemistry （158 ca...AIM：To clarify the expression patterns and prognostic implications of the mitotic regulator Polo-like kinase 1 （PLK1） in colon cancer. METHODS： Expression of PLK1 was investigated by immunohistochemistry （158 cases） and immunoblotting in tissue of colon adenomas and adenocarcinomas. PLK1 expression patterns were correlated with clinicopathological parameters and patient prognosis. In addition, expression of PLK1 was evaluated by immunoblot and PCR in colon carcinoma cell lines, and coexpression of PLK1 with the proliferation marker Ki-67 was investigated. RESULTS： Weak PLK1 expression was observed in normal colon mucosa and adenomas. In contrast, 66.7% of carcinomas showed strong expression of PLK1. Overexpression of PLK1 correlated positively with Dukes stage （P〈0.001）, tumor stage （P = 0.001） and nodal status （P〈0.05）. Additionally, PLK1 expression was a prognostic marker in univariate survival analysis （P〈0.01） and had independent prognostic significance （RR = 3.3, P = 0.02） in patients with Iocoregional disease. Expression of PLK1 mRNA and protein was detected in all cell lines investigated. Coexpression of PLK1 and Ki-67 was observed in the majority of colon cancer cells, but a considerable proportion of cells showed PLK1 positivity without Ki-67 expression. CONCLUSION： PLK1 is a new prognostic marker for colon carcinoma patients and may be involved in tumorigenesis and progression of colon cancer. Strategies focusing on PLK1 inhibitionin vivo might therefore represent a promising new therapeutic approach for this tumor entity. 2005 The WIG Press and Elsevier Inc. All rights reserved展开更多
BACKGROUND The introduction of fine needle biopsies(FNB)to clinical practice presents a changing trend towards histology in the endoscopic ultrasound-guided tissue acquisition(EUS-TA).AIM To evaluate the clinical perf...BACKGROUND The introduction of fine needle biopsies(FNB)to clinical practice presents a changing trend towards histology in the endoscopic ultrasound-guided tissue acquisition(EUS-TA).AIM To evaluate the clinical performance of a new FNB needle,the 22-gauge(22G)Franseen needle,when sampling pancreatic solid lesions.METHODS Consecutive patients with an indication for EUS-TA for the assessment of pancreatic solid lesions were included in this prospective,single-center,singlearm trial.Each patient underwent a puncture of the lesion two times using the 22G Franseen needle and the obtained samples were directly placed into formalin for histological analysis.The primary study endpoint was the rate of high-quality obtained specimen.Secondary endpoints included the length and diameter of the core specimen,the diagnostic accuracy and the complication rate.RESULTS From June 2017 to December 2018,forty patients with pancreatic solid lesions(22 females;mean age 67.2 years)were enrolled.Tissue acquisition was achieved in all cases.High-quality histology,rated with Payne score 3,was obtained in 37/40 cases(92.5%)after two needle passes.The mean size of the acquired histological core tissue was 1.54 mm×0.39 mm.The diagnostic accuracy for the correct diagnosis was 85%(34/40).Only one adverse event was occurred,consisting of a self-limiting bleeding in the puncture site.CONCLUSION The 22G Franseen needle achieved according to our standardized protocol a high rate of histological core procurement,and a high diagnostic accuracy,with one minor adverse event reported.展开更多
Recent studies reveal a critical role of tumor cell-released extracellular vesicles(EVs)in pancreatic cancer(PC)progression.However,driver genes that direct EV function,the EV-recipient cells,and their cellular respon...Recent studies reveal a critical role of tumor cell-released extracellular vesicles(EVs)in pancreatic cancer(PC)progression.However,driver genes that direct EV function,the EV-recipient cells,and their cellular response to EV uptake remain to be identified.Therefore,we studied the role of Bcl-2-associated-anthanogene 6(BAG6),a regulator of EV biogenesis for cancer progression.We used a Cre recombinase/LoxP-based reporter system in combination with single-cell RNA sequencing to monitor in vivo EV uptake and tumor microenvironment(TME)changes in mouse models for pancreatic ductal adenocarcinoma(PDAC)in a Bag6 pro-or deficient background.In vivo data were validated using mouse and human organoids and patient samples.Our data demonstrated that Bag6-deficient subcutaneous and orthotopic PDAC tumors accelerated tumor growth dependent on EV release.Mechanistically,this was attributed to mast cell(MC)activation via EV-associated IL33.Activated MCs promoted tumor cell proliferation and altered the composition of the TME affecting fibroblast polarization and immune cell infiltration.Tumor cell proliferation and fibroblast polarization were mediated via the MC secretome containing high levels of PDGF and CD73.Patients with high BAG6 gene expression and high protein plasma level have a longer overall survival indicating clinical relevance.The current study revealed a so far unknown tumor-suppressing activity of BAG6 in PDAC.Bag6-deficiency allowed the release of EV-associated IL33 which modulate the TME via MC activation promoting aggressive tumor growth.MC depletion using imatinib diminished tumor growth providing a scientific rationale to consider imatinib for patients stratified with low BAG6 expression and high MC infiltration.展开更多
文摘AIM：To clarify the expression patterns and prognostic implications of the mitotic regulator Polo-like kinase 1 （PLK1） in colon cancer. METHODS： Expression of PLK1 was investigated by immunohistochemistry （158 cases） and immunoblotting in tissue of colon adenomas and adenocarcinomas. PLK1 expression patterns were correlated with clinicopathological parameters and patient prognosis. In addition, expression of PLK1 was evaluated by immunoblot and PCR in colon carcinoma cell lines, and coexpression of PLK1 with the proliferation marker Ki-67 was investigated. RESULTS： Weak PLK1 expression was observed in normal colon mucosa and adenomas. In contrast, 66.7% of carcinomas showed strong expression of PLK1. Overexpression of PLK1 correlated positively with Dukes stage （P〈0.001）, tumor stage （P = 0.001） and nodal status （P〈0.05）. Additionally, PLK1 expression was a prognostic marker in univariate survival analysis （P〈0.01） and had independent prognostic significance （RR = 3.3, P = 0.02） in patients with Iocoregional disease. Expression of PLK1 mRNA and protein was detected in all cell lines investigated. Coexpression of PLK1 and Ki-67 was observed in the majority of colon cancer cells, but a considerable proportion of cells showed PLK1 positivity without Ki-67 expression. CONCLUSION： PLK1 is a new prognostic marker for colon carcinoma patients and may be involved in tumorigenesis and progression of colon cancer. Strategies focusing on PLK1 inhibitionin vivo might therefore represent a promising new therapeutic approach for this tumor entity. 2005 The WIG Press and Elsevier Inc. All rights reserved
文摘BACKGROUND The introduction of fine needle biopsies(FNB)to clinical practice presents a changing trend towards histology in the endoscopic ultrasound-guided tissue acquisition(EUS-TA).AIM To evaluate the clinical performance of a new FNB needle,the 22-gauge(22G)Franseen needle,when sampling pancreatic solid lesions.METHODS Consecutive patients with an indication for EUS-TA for the assessment of pancreatic solid lesions were included in this prospective,single-center,singlearm trial.Each patient underwent a puncture of the lesion two times using the 22G Franseen needle and the obtained samples were directly placed into formalin for histological analysis.The primary study endpoint was the rate of high-quality obtained specimen.Secondary endpoints included the length and diameter of the core specimen,the diagnostic accuracy and the complication rate.RESULTS From June 2017 to December 2018,forty patients with pancreatic solid lesions(22 females;mean age 67.2 years)were enrolled.Tissue acquisition was achieved in all cases.High-quality histology,rated with Payne score 3,was obtained in 37/40 cases(92.5%)after two needle passes.The mean size of the acquired histological core tissue was 1.54 mm×0.39 mm.The diagnostic accuracy for the correct diagnosis was 85%(34/40).Only one adverse event was occurred,consisting of a self-limiting bleeding in the puncture site.CONCLUSION The 22G Franseen needle achieved according to our standardized protocol a high rate of histological core procurement,and a high diagnostic accuracy,with one minor adverse event reported.
基金This work was supported by grants from Deutsche Forschungsgemeinschaft(KFO325,project 329116008 and GRK2573,project 416910386 to EPvS)Hessisches Ministerium fur Wissenschaft und Kunst(LOEWE iCANx to EPvS)+1 种基金from von Behring-RontgenStiftung(66-0024 to VP and BD)Open Access funding enabled and organized by Projekt DEAL.
文摘Recent studies reveal a critical role of tumor cell-released extracellular vesicles(EVs)in pancreatic cancer(PC)progression.However,driver genes that direct EV function,the EV-recipient cells,and their cellular response to EV uptake remain to be identified.Therefore,we studied the role of Bcl-2-associated-anthanogene 6(BAG6),a regulator of EV biogenesis for cancer progression.We used a Cre recombinase/LoxP-based reporter system in combination with single-cell RNA sequencing to monitor in vivo EV uptake and tumor microenvironment(TME)changes in mouse models for pancreatic ductal adenocarcinoma(PDAC)in a Bag6 pro-or deficient background.In vivo data were validated using mouse and human organoids and patient samples.Our data demonstrated that Bag6-deficient subcutaneous and orthotopic PDAC tumors accelerated tumor growth dependent on EV release.Mechanistically,this was attributed to mast cell(MC)activation via EV-associated IL33.Activated MCs promoted tumor cell proliferation and altered the composition of the TME affecting fibroblast polarization and immune cell infiltration.Tumor cell proliferation and fibroblast polarization were mediated via the MC secretome containing high levels of PDGF and CD73.Patients with high BAG6 gene expression and high protein plasma level have a longer overall survival indicating clinical relevance.The current study revealed a so far unknown tumor-suppressing activity of BAG6 in PDAC.Bag6-deficiency allowed the release of EV-associated IL33 which modulate the TME via MC activation promoting aggressive tumor growth.MC depletion using imatinib diminished tumor growth providing a scientific rationale to consider imatinib for patients stratified with low BAG6 expression and high MC infiltration.
