scholarly journals Cetuximab-mediated ADCC activity is correlated with the cell surface expression level of EGFR but not with the KRAS/BRAF mutational status in colorectal cancer

2014 ◽  
Vol 31 (5) ◽  
pp. 2115-2122 ◽  
Author(s):  
YUKI SEO ◽  
YOSHIYUKI ISHII ◽  
HIROKI OCHIAI ◽  
KAZUMASA FUKUDA ◽  
SHINGO AKIMOTO ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Surface ◽  
Surface Expression ◽  
Expression Level ◽  
Cell Surface Expression ◽  
Adcc Activity ◽  
Mutational Status

scholarly journals Immune Monitoring Assay for Extracorporeal Photopheresis Treatment Optimization After Heart Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Maja-Theresa Dieterlen ◽  
Kristin Klaeske ◽  
Alexander A. Bernhardt ◽  
Michael A. Borger ◽  
Sara Klein ◽  
...  
Keyword(s):  
Cell Surface ◽  
Heart Transplantation ◽  
Immune Cells ◽  
Surface Expression ◽  
Immune Monitoring ◽  
Expression Level ◽  
Cell Surface Expression ◽  
Patient Specific ◽  
Extracorporeal Photopheresis ◽  
Treatment Optimization

BackgroundExtracorporeal photopheresis (ECP) induces immunological changes that lead to a reduced risk of transplant rejection. The aim of the present study was to determine optimum conditions for ECP treatment by analyzing a variety of tolerance-inducing immune cells to optimize the treatment.MethodsTen ECP treatments were applied to each of 17 heart-transplant patients from month 3 to month 9 post-HTx. Blood samples were taken at baseline, three times during treatment, and four months after the last ECP treatment. The abundance of subsets of tolerance-inducing regulatory T cells (Tregs) and dendritic cells (DCs) in the samples was determined by flow cytometry. A multivariate statistical model describing the immunological status of rejection-free heart transplanted patients was used to visualize the patient-specific immunological improvement induced by ECP.ResultsAll BDCA+ DC subsets (BDCA1+ DCs: p < 0.01, BDCA2+ DCs: p < 0.01, BDCA3+ DCs: p < 0.01, BDCA4+ DCs: p < 0.01) as well as total Tregs(p < 0.01) and CD39+ Tregs(p < 0.01) increased during ECP treatment, while CD62L+ Tregs decreased (p < 0.01). The cell surface expression level of BDCA1 (p < 0.01) and BDCA4 (p < 0.01) on DCs as well as of CD120b (p < 0.01) on Tregs increased during the study period, while CD62L expression on Tregs decreased significantly (p = 0.04). The cell surface expression level of BDCA2 (p = 0.47) and BDCA3 (p = 0.22) on DCs as well as of CD39 (p = 0.14) and CD147 (p = 0.08) on Tregs remained constant during the study period. A cluster analysis showed that ECP treatment led to a sustained immunological improvement.ConclusionsWe developed an immune monitoring assay for ECP treatment after heart transplantation by analyzing changes in tolerance-inducing immune cells. This assay allowed differentiation of patients who did and did not show immunological improvement. Based on these results, we propose classification criteria that may allow optimization of the duration of ECP treatment.

Abstract 468: Identification of a New Component of the Na v 1.5 Complex: αB-crystallin Interacts with Na v 1.5 and Regulates Ubiquitination and Internalization of Cell Surface Na v 1.5

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Yuan Huang ◽  
Zhijie Wang ◽  
Yinan Liu ◽  
Qiuyun Chen ◽  
Qing k. Wang
Keyword(s):  
Cell Surface ◽  
Protein Interactions ◽  
Sodium Current ◽  
Surface Expression ◽  
Expression Level ◽  
Cell Surface Expression ◽  
Protein Protein Interactions ◽  
Interacting Protein ◽  
Binding Partner ◽  
Αb Crystallin

Mutations in cardiac Na + channel Na v 1.5 cause cardiac arrhythmias and sudden death. The cardiac Na + channel functions as a protein complex, however, its complete components remain to be fully elucidated. A yeast two-hybrid screen identified a new candidate Na v 1.5-interacting protein, αB-crystallin. GST-pull-down, co-immunoprecipitation and immunostaining analyses validated the interaction between Na v 1.5 and αB-crystallin. Overexpression of αB-crystallin significantly increased peak sodium current ( I Na ) density, and the underlying molecular mechanism is the increased cell surface expression level of Na v 1.5 via reduced internalization of cell surface Na v 1.5 and ubiquitination of Na v 1.5. Knockout of αB-crystallin expression significantly decreased the cell-surface expression level of Na v 1.5. αB-crystallin interacted with Nedd4-2, however, a catalytically inactive Nedd4-2-C801S mutant reduced the interaction between αB-crystallin and Nedd4-2 and also blocked the increase of peak I Na density by αB-crystallin. Na v 1.5 mutation V1980A at the interaction site for Nedd4-2 eliminated the effect of αB-crystallin on reduction of Na v 1.5 ubiquitination and increases of I Na density. The data suggest that the interactions between αB-crystallin and functionally active Nedd4-2 and between αB-crystallin and Na v 1.5 are critical to increased I Na density by αB-crystallin. Multiple mutations in αB-crystallin have been associated with human diseases. Two mutations, R109H and R151X, eliminated the effect of αB-crystallin on I Na . This study identifies αB-crystallin as a new binding partner for Na v 1.5. αB-crystallin interacts with Na v 1.5 and increases I Na by modulating the expression level and internalization of cell surface Na v 1.5 and ubiquitination of Na v 1.5, which requires the protein-protein interactions between αB-crystallin and Na v 1.5 and between αB-crystallin and functionally active Nedd4-2.

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