scholarly journals Novel Phenotypic Fluorescent Three-Dimensional Platforms for High-throughput Drug Screening and Personalized Chemotherapy

2013 ◽  
Vol 4 (5) ◽  
pp. 402-415 ◽  
Author(s):  
Changge Fang ◽  
Ingalill Avis ◽  
David Salomon ◽  
Frank Cuttitta
2019 ◽  
Author(s):  
Sang-Cheol Lee ◽  
Young Saing Kim ◽  
In Gyu Hwang ◽  
Su Jin Lee ◽  
Se Hoon Park

2019 ◽  
Author(s):  
Sang-Cheol Lee ◽  
Young Saing Kim ◽  
In Gyu Hwang ◽  
Su Jin Lee ◽  
Se Hoon Park

2018 ◽  
Vol 12 (4) ◽  
Author(s):  
Christopher Uhl ◽  
Wentao Shi ◽  
Yaling Liu

As a necessary pathway to man-made organs, organ-on-chips (OOC), which simulate the activities, mechanics, and physiological responses of real organs, have attracted plenty of attention over the past decade. As the maturity of three-dimensional (3D) cell-culture models and microfluidics advances, the study of OOCs has made significant progress. This review article provides a comprehensive overview and classification of OOC microfluidics. Specifically, the review focuses on OOC systems capable of being used in preclinical drug screening and development. Additionally, the review highlights the strengths and weaknesses of each OOC system toward the goal of improved drug development and screening. The various OOC systems investigated throughout the review include, blood vessel, lung, liver, and tumor systems and the potential benefits, which each provides to the growing challenge of high-throughput drug screening. Published OOC systems have been reviewed over the past decade (2007–2018) with focus given mainly to more recent advances and improvements within each organ system. Each OOC system has been reviewed on how closely and realistically it is able to mimic its physiological counterpart, the degree of information provided by the system toward the ultimate goal of drug development and screening, how easily each system would be able to transition to large scale high-throughput drug screening, and what further improvements to each system would help to improve the functionality, realistic nature of the platform, and throughput capacity. Finally, a summary is provided of where the broad field of OOCs appears to be headed in the near future along with suggestions on where future efforts should be focused for optimized performance of OOC systems in general.


2019 ◽  
Author(s):  
Philip Tatman ◽  
Anthony Fringuello ◽  
Denise Damek ◽  
Samy Youssef ◽  
Randy Jensn ◽  
...  

2019 ◽  
Author(s):  
Michael Gerckens ◽  
Hani Alsafadi ◽  
Darcy Wagner ◽  
Katharina Heinzelmann ◽  
Kenji Schorpp ◽  
...  

2020 ◽  
Author(s):  
S Bhatia ◽  
H Ahlert ◽  
N Dienstbier ◽  
J Schliehe-Diecks ◽  
M Sönnichsen ◽  
...  

2021 ◽  
Vol 11 (7) ◽  
Author(s):  
Ruochen Jia ◽  
Leon Kutzner ◽  
Anna Koren ◽  
Kathrin Runggatscher ◽  
Peter Májek ◽  
...  

AbstractMutations of calreticulin (CALR) are the second most prevalent driver mutations in essential thrombocythemia and primary myelofibrosis. To identify potential targeted therapies for CALR mutated myeloproliferative neoplasms, we searched for small molecules that selectively inhibit the growth of CALR mutated cells using high-throughput drug screening. We investigated 89 172 compounds using isogenic cell lines carrying CALR mutations and identified synthetic lethality with compounds targeting the ATR-CHK1 pathway. The selective inhibitory effect of these compounds was validated in a co-culture assay of CALR mutated and wild-type cells. Of the tested compounds, CHK1 inhibitors potently depleted CALR mutated cells, allowing wild-type cell dominance in the co-culture over time. Neither CALR deficient cells nor JAK2V617F mutated cells showed hypersensitivity to ATR-CHK1 inhibition, thus suggesting specificity for the oncogenic activation by the mutant CALR. CHK1 inhibitors induced replication stress in CALR mutated cells revealed by elevated pan-nuclear staining for γH2AX and hyperphosphorylation of RPA2. This was accompanied by S-phase cell cycle arrest due to incomplete DNA replication. Transcriptomic and phosphoproteomic analyses revealed a replication stress signature caused by oncogenic CALR, suggesting an intrinsic vulnerability to CHK1 perturbation. This study reveals the ATR-CHK1 pathway as a potential therapeutic target in CALR mutated hematopoietic cells.


Sign in / Sign up

Export Citation Format

Share Document