Background： Circulating tumor cells （CTCs） are often undetected through the immunomagnetic epithelial cell adhesion molecule （EpCAM）-based CellSearch~ System in breast and colorectal cancer （CRC） patients treat...Background： Circulating tumor cells （CTCs） are often undetected through the immunomagnetic epithelial cell adhesion molecule （EpCAM）-based CellSearch~ System in breast and colorectal cancer （CRC） patients treated with bevacizumab （BEV）, where low CTC numbers have been reported even in patients with evidence of progression of disease. To date, the reasons for this discrepancy have not been clarified. This study was carried out to investigate the molecular and phenotypic changes in CRC cells after chronic exposure to BEV in vitro. Methods： The human CRC cell line WiDr was exposed to a clinically relevant dose of BEV for 3 months in vitro. The expression of epithelial and mesenchymal markers and EpCAM isoforms was determined by western blotting and immunofluorescence. To evaluate the impact of EpCAM variant isoforms expression on CTC enumeration by CellSearch, untreated and treated colon cancer cells were spiked into 7.5 mL of blood from a healthy donor and enumerated by CellSearch. Results： Chronic exposure of CRC cell line to BEV induced decreased expression of EpCAM 40 kDa isoform and increased expression EpCAM 42 kDa isoform, together with a decreased expression of cytokeratins （CK）, while no evidence of epithelial to mesenchymal transition （EMT） in treated cells was observed. The recovery rate of cells through CellSearch was gradually reduced in course of treatment with BEV, being 84% , 70% and 40% at l, 2 and 3 months, respectively. Conclusions： We hypothesize that BEV may prevent CellSearch from capturing CTCs through altering EpCAM isoforms.展开更多
This contribution shows an analysis of vibration measurement on large floor-mounted traction batteries of Battery Electric Vehicles(BEV).The focus lies on the requirements for a realistic replication of the mechanical...This contribution shows an analysis of vibration measurement on large floor-mounted traction batteries of Battery Electric Vehicles(BEV).The focus lies on the requirements for a realistic replication of the mechanical environments in a testing laboratory.Especially the analysis on global bending transfer functions and local corner bending coherence indicate that neither a fully stiff fixation of the battery nor a completely independent movement on the four corners yields a realistic and conservative test scenario.The contribution will further show what implication these findings have on future vibration&shock testing equipment for large traction batteries.Additionally,it will cover an outlook on how vibration behavior of highly integrated approaches(cell2car)changes the mechanical loads on the cells.展开更多
文摘Background： Circulating tumor cells （CTCs） are often undetected through the immunomagnetic epithelial cell adhesion molecule （EpCAM）-based CellSearch~ System in breast and colorectal cancer （CRC） patients treated with bevacizumab （BEV）, where low CTC numbers have been reported even in patients with evidence of progression of disease. To date, the reasons for this discrepancy have not been clarified. This study was carried out to investigate the molecular and phenotypic changes in CRC cells after chronic exposure to BEV in vitro. Methods： The human CRC cell line WiDr was exposed to a clinically relevant dose of BEV for 3 months in vitro. The expression of epithelial and mesenchymal markers and EpCAM isoforms was determined by western blotting and immunofluorescence. To evaluate the impact of EpCAM variant isoforms expression on CTC enumeration by CellSearch, untreated and treated colon cancer cells were spiked into 7.5 mL of blood from a healthy donor and enumerated by CellSearch. Results： Chronic exposure of CRC cell line to BEV induced decreased expression of EpCAM 40 kDa isoform and increased expression EpCAM 42 kDa isoform, together with a decreased expression of cytokeratins （CK）, while no evidence of epithelial to mesenchymal transition （EMT） in treated cells was observed. The recovery rate of cells through CellSearch was gradually reduced in course of treatment with BEV, being 84% , 70% and 40% at l, 2 and 3 months, respectively. Conclusions： We hypothesize that BEV may prevent CellSearch from capturing CTCs through altering EpCAM isoforms.
基金We acknowledge support for the article processing charge by the Open Access Publication Fund of Hamburg University of Applied Sciences.
文摘This contribution shows an analysis of vibration measurement on large floor-mounted traction batteries of Battery Electric Vehicles(BEV).The focus lies on the requirements for a realistic replication of the mechanical environments in a testing laboratory.Especially the analysis on global bending transfer functions and local corner bending coherence indicate that neither a fully stiff fixation of the battery nor a completely independent movement on the four corners yields a realistic and conservative test scenario.The contribution will further show what implication these findings have on future vibration&shock testing equipment for large traction batteries.Additionally,it will cover an outlook on how vibration behavior of highly integrated approaches(cell2car)changes the mechanical loads on the cells.
