An overview of cell phenotypes in HCS: limitations and advantages

@article{Gasparri2009AnOO,
  title={An overview of cell phenotypes in HCS: limitations and advantages},
  author={Fabio Gasparri},
  journal={Expert Opinion on Drug Discovery},
  year={2009},
  volume={4},
  pages={643 - 657}
}
  • F. Gasparri
  • Published 21 May 2009
  • Biology
  • Expert Opinion on Drug Discovery
Background: High-content screening (HCS) defines a series of cell-based multiparametric approaches for analysis at the single-cell level. In recent years, HCS has been increasingly pursued in the drug discovery field, adding to the repertoire of assay type, or increasing throughput in applications such as compound screening and mechanism of action studies, as well as for target identification/validation (siRNA screening). Obviously, as cells represent the objects of high-content assays, the… 

The development of high-content screening (HCS) technology and its importance to drug discovery

TLDR
The authors highlight the importance of high-content screening in drug discovery, as testified by its numerous applications in a variety of therapeutic areas: oncology, infective diseases, cardiovascular and neurodegenerative diseases, and the role of HCS technology in different phases of the drug discovery pipeline.

Phenotypic Screens Targeting Neurodegenerative Diseases

TLDR
This review will summarize the progress of compound screening using phenotypic-based strategies for neurodegenerative diseases, with a highlight on unique considerations for disease models, assays, and screening methodologies.

Components of the Linker of the Nucleo-and Cytoskeletal Complex ( LINC ) as Novel Molecular Targets for Small Cell Lung Cancer

TLDR
An overview of the putative source cell for SCLC, the neuroepithelial cell, will be presented to aid in the selection of novel drug targets, and it would be expected that the components of signal transduction pathways active in such functions are intimately connected to cell survival, these proteins are potential drug candidates.

Establishing an Infrastructure for High-Throughput Short-Interfering RNA Screening.

TLDR
This chapter describes the infrastructure requirements needed to successfully perform HT-RNAi screening and information on the methodology, instrumentation, experimental design, and workflow aspects is provided, as well as insights on how to successfully implement a high-throughput RNAi screen.

Approaches to Assess Biased Signaling at the CB1R Receptor.

Discovery of autophagy modulators through the construction of a high-content screening platform via monitoring of lipid droplets

TLDR
The construction of a high-content screening platform for the discovery of autophagy modulators via monitoring of cellular lipid droplets as a late-stage marker of Autophagy is reported, which allows the simultaneous identification of completely different types of autophile regulators in a single operation.

Computational Systems Toxicology

TLDR
An interdisciplinary approach including apical and molecular measurements, computational, and modeling efforts is currently being one of the most promising approaches to ensure AOPs become the useful framework they were designed to be.

References

SHOWING 1-10 OF 168 REFERENCES

Past, present, and future of high content screening and the field of cellomics.

TLDR
HCS integrates the instrumentation, application software, reagents, sample preparation, and informatics/bioinformatics required to rapidly flow from producing data, generating information, and ultimately creating new cellular knowledge.

High-content analysis of kinase activity in cells.

TLDR
The application of HCA to the discovery of small molecule inhibitors targeting kinases which are implicated in Oncology is discussed, including primary HTS on compound collections.

Requirements, features, and performance of high content screening platforms.

TLDR
The requirements for HCS and the systems that have been designed to meet these application needs are discussed and new applications, improved software, better data visualization tools, and new detection methods such as multispectral imaging and fluorescence lifetime are predicted to drive the development of future HCS platforms.

Cell-cycle inhibitor profiling by high-content analysis.

TLDR
This approach allows monitoring of compound-induced cell-cycle perturbations by analyzing specific cellular markers such as nuclear morphology, DNA content or histone H3 phosphorylation and indicates the induction of DNA damage response or apoptosis in osteosarcoma U-2 OS adherent cell cultures.

High-content imaging characterization of cell cycle therapeutics through in vitro and in vivo subpopulation analysis

TLDR
Cutting the eukaryotic cell cycle into individual cellular subpopulations using HCI in conjunction with unsupervised K-means clustering allows for a more accurate means of assessing compound selectivity and leads to more meaningful comparisons between so-called targeted therapeutics.

High-content analysis in preclinical drug discovery.

TLDR
High-Content Analysis once more has demonstrated its outstanding potential to significantly support establishing effective pharmaceutical research processes in order to both advance research projects and cut costs.

High-Content Screening: A New Approach to Easing Key Bottlenecks in the Drug Discovery Process

TLDR
A high-content screen designed to measure the drug-induced transport of a green fluorescent protein-human glucocorticoid receptor chimeric protein from the cytoplasm to the nucleus of human tumor cells and a multiparametric measurement of apoptosis is described.

The use of high-content screening for the discovery and characterization of compounds that modulate mitotic index and cell cycle progression by differing mechanisms of action.

TLDR
An approach for characterizing inhibitors of Aurora kinase family members using high-content screening is validated by determining compound effects on the levels of the mitotic marker phospho-histone H3 (Ser10), indicating a block of cell cycle progression at M-phase.

High-content single-cell drug screening with phosphospecific flow cytometry.

TLDR
A high-content, cell-based drug discovery platform based on phosphospecific flow cytometry, or phosphoflow, that enabled screening for inhibitors against multiple endogenous kinase signaling pathways in heterogeneous primary cell populations at the single-cell level is described.

Cell-based high content screening using an integrated microfluidic device.

TLDR
The established platform is able to rapidly extract the maximum of information from tumor cells in response to several drugs varying in concentration, with minimal sample and less time, which is very useful for basic biomedical research and cancer treatment.
...