scholarly journals Toll‐DeficientDrosophilaFlies as a Fast, High‐Throughput Model for the Study of Antifungal Drug Efficacy against Invasive Aspergillosis andAspergillusVirulence

2005 ◽  
Vol 191 (7) ◽  
pp. 1188-1195 ◽  
Author(s):  
Michail S. Lionakis ◽  
Russell E. Lewis ◽  
Gregory S. May ◽  
Nathan P. Wiederhold ◽  
Nathaniel D. Albert ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
High Throughput ◽  
Drug Efficacy ◽  
Antifungal Drug ◽  
Throughput Model

scholarly journals A Microfluidic Spheroid Culture Device with a Concentration Gradient Generator for High-Throughput Screening of Drug Efficacy

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3355 ◽  
Author(s):  
Wanyoung Lim ◽  
Sungsu Park
Keyword(s):  
High Throughput ◽  
Concentration Gradient ◽  
High Throughput Screening ◽  
3D Cell Culture ◽  
Drug Efficacy ◽  
Cancer Drug ◽  
Spheroid Culture ◽  
Gradient Generator ◽  
Micro Channels

Three-dimensional (3D) cell culture is considered more clinically relevant in mimicking the structural and physiological conditions of tumors in vivo compared to two-dimensional cell cultures. In recent years, high-throughput screening (HTS) in 3D cell arrays has been extensively used for drug discovery because of its usability and applicability. Herein, we developed a microfluidic spheroid culture device (μFSCD) with a concentration gradient generator (CGG) that enabled cells to form spheroids and grow in the presence of cancer drug gradients. The device is composed of concave microwells with several serpentine micro-channels which generate a concentration gradient. Once the colon cancer cells (HCT116) formed a single spheroid (approximately 120 μm in diameter) in each microwell, spheroids were perfused in the presence of the cancer drug gradient irinotecan for three days. The number of spheroids, roundness, and cell viability, were inversely proportional to the drug concentration. These results suggest that the μFSCD with a CGG has the potential to become an HTS platform for screening the efficacy of cancer drugs.

A high-throughput model for fat graft assessment

2009 ◽  
Vol 41 (10) ◽  
pp. 738-744 ◽  
Author(s):  
Miguel A. Medina ◽  
John T. Nguyen ◽  
Michael M. McCormack ◽  
Mark A. Randolph ◽  
William G. Austen
Keyword(s):  
High Throughput ◽  
Fat Graft ◽  
Throughput Model

scholarly journals Testing Tuberculosis Drug Efficacy in a Zebrafish High-Throughput Translational Medicine Screen

2014 ◽  
Vol 59 (2) ◽  
pp. 753-762 ◽  
Author(s):  
Anita Ordas ◽  
Robert-Jan Raterink ◽  
Fraser Cunningham ◽  
Hans J. Jansen ◽  
Malgorzata I. Wiweger ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Drug Efficacy ◽  
Drug Uptake ◽  
Spectrometric Analysis ◽  
Major Advance ◽  
Zebrafish Model ◽  
Content Type ◽  
Screening Platform

ABSTRACTThe translational value of zebrafish high-throughput screens can be improved when more knowledge is available on uptake characteristics of potential drugs. We investigated reference antibiotics and 15 preclinical compounds in a translational zebrafish-rodent screening system for tuberculosis. As a major advance, we have developed a new tool for testing drug uptake in the zebrafish model. This is important, because despite the many applications of assessing drug efficacy in zebrafish research, the current methods for measuring uptake using mass spectrometry do not take into account the possible adherence of drugs to the larval surface. Our approach combines nanoliter sampling from the yolk using a microneedle, followed by mass spectrometric analysis. To date, no single physicochemical property has been identified to accurately predict compound uptake; our method offers a great possibility to monitor how any novel compound behaves within the system. We have correlated the uptake data with high-throughput drug-screening data fromMycobacterium marinum-infected zebrafish larvae. As a result, we present an improved zebrafish larva drug-screening platform which offers new insights into drug efficacy and identifies potential false negatives and drugs that are effective in zebrafish and rodents. We demonstrate that this improved zebrafish drug-screening platform can complement conventional models ofin vivoMycobacterium tuberculosis-infected rodent assays. The detailed comparison of two vertebrate systems, fish and rodent, may give more predictive value for efficacy of drugs in humans.

scholarly journals One-Step Seeding of Neural Stem Cells with Vitronectin-Supplemented Medium for High-Throughput Screening Assays

2016 ◽  
Vol 21 (10) ◽  
pp. 1112-1124 ◽  
Author(s):  
Sheng Dai ◽  
Rong Li ◽  
Yan Long ◽  
Steve Titus ◽  
Jinghua Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
High Throughput ◽  
High Throughput Screening ◽  
Neuronal Cells ◽  
Drug Efficacy ◽  
Human Stem Cells ◽  
Induced Pluripotent Cells ◽  
One Step ◽  
Human Neuronal Cells

Human neuronal cells differentiated from induced pluripotent cells have emerged as a new model system for the study of disease pathophysiology and evaluation of drug efficacy. Differentiated neuronal cells are more similar in genetics and biological content to human brain cells than other animal disease models. However, culture of neuronal cells in assay plates requires a labor-intensive procedure of plate precoating, hampering its applications in high-throughput screening (HTS). We developed a simplified method with one-step seeding of neural stem cells in assay plates by supplementing the medium with a recombinant human vitronectin (VTN), thus avoiding plate precoating. Robust results were obtained from cell viability, calcium response, and neurite outgrowth assays using this new method. Our data demonstrate that this approach greatly simplifies high-throughput assays using neuronal cells differentiated from human stem cells for translational research.

scholarly journals Drosophila melanogasteras a Facile Model for Large‐Scale Studies of Virulence Mechanisms and Antifungal Drug Efficacy inCandidaSpecies

2006 ◽  
Vol 193 (7) ◽  
pp. 1014-1022 ◽  
Author(s):  
Georgios Chamilos ◽  
Michail S. Lionakis ◽  
Russell E. Lewis ◽  
Jose L. Lopez‐Ribot ◽  
Stephen P. Saville ◽  
...  
Keyword(s):  
Large Scale ◽  
Drug Efficacy ◽  
Antifungal Drug

Validation of visualized transgenic zebrafish as a high throughput model to assay bradycardia related cardio toxicity risk candidates

2012 ◽  
Vol 32 (10) ◽  
pp. 834-842 ◽  
Author(s):  
Dingsheng Wen ◽  
Aiming Liu ◽  
Feng Chen ◽  
Julin Yang ◽  
Renke Dai
Keyword(s):  
High Throughput ◽  
Transgenic Zebrafish ◽  
Throughput Model ◽  
Toxicity Risk

scholarly journals A High-Throughput Enzyme-Coupled Assay for SAMHD1 dNTPase

2015 ◽  
Vol 20 (6) ◽  
pp. 801-809 ◽  
Author(s):  
Kyle J. Seamon ◽  
James T. Stivers
Keyword(s):  
High Throughput ◽  
Colorimetric Assay ◽  
Antiviral Drug ◽  
Drug Efficacy ◽  
Nucleotide Metabolism ◽  
Zinc Salt ◽  
Inorganic Pyrophosphatase ◽  
Viral Restriction ◽  
Deoxyribonucleoside Triphosphate ◽  
Targeted Library

Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) is a recently discovered enzyme that plays a central role in nucleotide metabolism and innate immunity. SAMHD1 has deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase activity that depletes the dNTP substrates required for DNA synthesis in cells. The involvement of SAMHD1 in biological processes as varied as viral restriction, endogenous retroelement control, cancer, and modulation of anticancer/antiviral nucleoside drug efficacy makes it a valuable target for the development of small-molecule inhibitors. We report a high-throughput colorimetric assay for SAMHD1 dNTP hydrolase activity that takes advantage of Escherichia coli inorganic pyrophosphatase to convert PPPi to 3 Pi. The assay was validated by screening a library of 2653 clinically used compounds. Fifteen primary hits were obtained (0.57% hit rate); 80% of these were confirmed in a direct secondary assay for dNTP hydrolysis. The zinc salt of the antibiotic cephalosporin C was a potent inhibitor of SAMHD1 with an IC50 of 1.1 ± 0.1 µM, and this inhibition was largely attributable to the presence of zinc. The assay also screened a targeted library of nucleosides and their analogs, revealing that the antiviral drug acycloguanosine (acyclovir) is an inhibitor possessing excellent properties for future fragment-based drug development efforts.

scholarly journals A Microfluidic Spheroid Culture Device with a Concentration Gradient Generator for High-Throughput Screening of Drug Efficacy

2018 ◽  
Author(s):  
Wanyoung Lim ◽  
Sungsu Park
Keyword(s):  
High Throughput ◽  
Concentration Gradient ◽  
High Throughput Screening ◽  
3D Cell Culture ◽  
Drug Efficacy ◽  
Cancer Drug ◽  
Spheroid Culture ◽  
Gradient Generator ◽  
Micro Channels

Three-dimensional (3D) cell culture is considered more clinically relevant in mimicking the structural and physiological conditions of tumors in vivo compared to two-dimensional cell cultures. In recent years, high-throughput screening (HTS) in 3D cell arrays has been extensively used for drug discovery because of its usability and applicability. Herein, we developed a microfluidic spheroid culture device (μFSCD) with a concentration gradient generator (CGG) that enabled cells to form spheroids and grow in the presence of cancer drug gradients. The device is composed of concave microwells with several serpentine micro-channels which generate a concentration gradient. Once the colon cancer cells (HCT116) formed a single spheroid (approximately 120 μm in diameter) in each microwell, spheroids were perfused in the presence of the cancer drug gradient irinotecan for 3 days. The number of spheroids, roundness, and cell viability, were inversely proportional to the drug concentration. These results suggest that the μFSCD with a CGG has the potential to become an HTS platform for screening the efficacy of cancer drugs.

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