Geometrical and Mechanical Nanoarchitectonics at Interfaces Bridging Molecules with Cell Phenotypes

Author(s):  
Jun Nakanishi ◽  
Shota Yamamoto
Keyword(s):  
2008 ◽  
Vol 31 (4) ◽  
pp. 22
Author(s):  
Jonathan So ◽  
Kelly Elder ◽  
Anna Dai ◽  
Claus Jorgensen ◽  
Rune Linding ◽  
...  

Networks of kinases play a role in the transmission and integration of signals from the membrane to the nucleus. We aim to elucidate kinase phosphorylation and interaction partners in these networks through the immuno-precipitation and mass spectrometric analysis of a representative set of 100 Flag-tagged kinases stably expressed in human colorectal cancer cells. The goal is to generate a comprehensive set of interactions and dynamic phosphorylation sites which correlate with cell phenotypes such as apoptosis and proliferation. The techniques of mass-spectrometry have allowed for the identification of proteins and their phosphorylation sites in complex samples. Various labeling methods such as iTRAQ has enabled the relative quantification of these sites as afunction of time (White et al. PNAS, 2007). However, kinases usually work in the context of particular signaling stimuli. We aim to characterize the role of these over-expressed kinases in the context of Trail-induced apoptosis. This isparticularly relevant to tumorigenesis in that many cancers are resistant to apoptosis and recombinant Trail therapies are currently undergoing clinical trials. We present assays to correlate the proliferative ability and sensitivity to apoptosis of various stable cell lines with kinase expression levels through flow cytometry. We also present efforts to trace downstream signaling through the monitoring of MAP kinase phosphorylation using a high-throughput bead array.


2018 ◽  
Vol 25 (35) ◽  
pp. 4507-4517 ◽  
Author(s):  
Mauro Rigato ◽  
Gian Paolo Fadini

Background: Circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) are immature cells involved in vascular repair and related to many aspects of macro and microvascular disease. <p> Objective: We aimed to review studies reporting the prognostic role of CPCs/EPCs measurement on development of cardiovascular disease and microangiopathy. <p> Methods and Results: We reviewed the English language literature for prospective observational studies reporting the future development of cardiovascular disease or microangiopathy in patients having a baseline determination of CPCs/EPCs. We retrieved 34 studied reporting on cardiovascular outcomes and 2 studies reporting on microvascular outcomes. Overall, a reduced baseline level of CPCs/EPCs was associated with a significant increased risk of cardiovascular events, all-cause death, and onset/progression of microangiopathy. The most predictive phenotypes were CD34+ and CD34+CD133+. The main limitation was related to the high heterogeneity among studies in terms of patient characteristics and cell phenotypes. <p> Conclusion: The present review shows that a reduced level of circulating progenitor cells is a risk factor for the development of future cardiovascular events and death. In addition, low CPCs/EPCs levels predict the onset or worsening of microalbuminuria and retinopathy in diabetic patients.


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