The use of in vitro cell culture models for mechanistic studies and as permeability screens for the blood–brain barrier in the pharmaceutical industry—Background and current status in the drug discovery process

2002 ◽  
Vol 38 (6) ◽  
pp. 355-364 ◽  
Author(s):  
Stefan Lundquist ◽  
Mila Renftel
Keyword(s):  
Cell Culture ◽  
Drug Discovery ◽  
Pharmaceutical Industry ◽  
Current Status ◽  
Discovery Process ◽  
Mechanistic Studies ◽  
Drug Discovery Process ◽  
Culture Models ◽  
Cell Culture Models

Conditionally immortalized cell lines as model systems for high-throughput biology in drug discovery

2002 ◽  
Vol 30 (4) ◽  
pp. 800-802 ◽  
Author(s):  
N. Daniele ◽  
R. Halse ◽  
E. Grinyo ◽  
S.J. Yeaman ◽  
P. R. Shepherd
Keyword(s):  
Cell Culture ◽  
Drug Discovery ◽  
Cell Lines ◽  
High Throughput ◽  
Biological Data ◽  
Model Systems ◽  
Drug Discovery Process ◽  
Culture Models ◽  
Immortalized Cell ◽  
Cell Culture Models

There is an increasing emphasis on the need for high-quality biological data much earlier in the drug-discovery process. This has led to the development of high-throughput approaches to biology, many of which rely on the use of cell-culture models. Unfortunately, available cell-culture models often reflect poorly the characteristics of the tissue they are supposed to represent. However, the conditional-immortalization approach as applied by Xcellsyz offers the possibility of producing human cell lines on demand, which are truly representative of the tissue from which they derive.

scholarly journals Turnover of the Active Fraction of IRS1 Involves Raptor-mTOR- and S6K1-Dependent Serine Phosphorylation in Cell Culture Models of Tuberous Sclerosis

2006 ◽  
Vol 26 (17) ◽  
pp. 6425-6434 ◽  
Author(s):  
O. Jameel Shah ◽  
Tony Hunter
Keyword(s):  
Cell Culture ◽  
Tuberous Sclerosis ◽  
High Speed ◽  
Serine Phosphorylation ◽  
Feedback Signal ◽  
Insulin Receptor Substrates ◽  
Igf I ◽  
Culture Models ◽  
Cell Culture Models

ABSTRACT The TSC1-TSC2/Rheb/Raptor-mTOR/S6K1 cell growth cassette has recently been shown to regulate cell autonomous insulin and insulin-like growth factor I (IGF-I) sensitivity by transducing a negative feedback signal that targets insulin receptor substrates 1 and 2 (IRS1 and -2). Using two cell culture models of the familial hamartoma syndrome, tuberous sclerosis, we show here that Raptor-mTOR and S6K1 are required for phosphorylation of IRS1 at a subset of serine residues frequently associated with insulin resistance, including S307, S312, S527, S616, and S636 (of human IRS1). Using loss- and gain-of-function S6K1 constructs, we demonstrate a requirement for the catalytic activity of S6K1 in both direct and indirect regulation of IRS1 serine phosphorylation. S6K1 phosphorylates IRS1 in vitro on multiple residues showing strong preference for RXRXXS/T over S/T,P sites. IRS1 is preferentially depleted from the high-speed pellet fraction in TSC1/2-deficient mouse embryo fibroblasts or in HEK293/293T cells overexpressing Rheb. These studies suggest that, through serine phosphorylation, Raptor-mTOR and S6K1 cell autonomously promote the depletion of IRS1 from specific intracellular pools in pathological states of insulin and IGF-I resistance and thus potentially in lesions associated with tuberous sclerosis.

scholarly journals Conjunctival melanoma and electrochemotherapy: preliminary results using 2D and 3D cell culture models in vitro

2018 ◽  
Vol 97 (4) ◽  
pp. e632-e640 ◽  
Author(s):  
Miltiadis Fiorentzis ◽  
Periklis Katopodis ◽  
Helen Kalirai ◽  
Berthold Seitz ◽  
Arne Viestenz ◽  
...  
Keyword(s):  
Cell Culture ◽  
3D Cell Culture ◽  
Conjunctival Melanoma ◽  
Preliminary Results ◽  
Culture Models ◽  
2D And 3D ◽  
Cell Culture Models

scholarly journals Applying phasor approach analysis of multiphoton FLIM measurements to probe the metabolic activity of three-dimensional in vitro cell culture models

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Pirmin H. Lakner ◽  
Michael G. Monaghan ◽  
Yvonne Möller ◽  
Monilola A. Olayioye ◽  
Katja Schenke-Layland
Keyword(s):  
Cell Culture ◽  
Metabolic Activity ◽  
Three Dimensional ◽  
In Vitro Cell Culture ◽  
Culture Models ◽  
Cell Culture Models

scholarly journals In vitro models of the blood–brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use

2016 ◽  
Vol 36 (5) ◽  
pp. 862-890 ◽  
Author(s):  
Hans C Helms ◽  
N Joan Abbott ◽  
Malgorzata Burek ◽  
Romeo Cecchelli ◽  
Pierre-Olivier Couraud ◽  
...  
Keyword(s):  
Cell Culture ◽  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Blood Brain ◽  
Culture Models ◽  
Cell Culture Models ◽  
The Brain

The endothelial cells lining the brain capillaries separate the blood from the brain parenchyma. The endothelial monolayer of the brain capillaries serves both as a crucial interface for exchange of nutrients, gases, and metabolites between blood and brain, and as a barrier for neurotoxic components of plasma and xenobiotics. This “blood-brain barrier” function is a major hindrance for drug uptake into the brain parenchyma. Cell culture models, based on either primary cells or immortalized brain endothelial cell lines, have been developed, in order to facilitate in vitro studies of drug transport to the brain and studies of endothelial cell biology and pathophysiology. In this review, we aim to give an overview of established in vitro blood–brain barrier models with a focus on their validation regarding a set of well-established blood–brain barrier characteristics. As an ideal cell culture model of the blood–brain barrier is yet to be developed, we also aim to give an overview of the advantages and drawbacks of the different models described.

In Vitro Human Lung Cell Culture Models to Study the Toxic Potential of Nanoparticles

Nanotoxicity ◽  
2009 ◽  
pp. 379-395 ◽  
Author(s):  
Fabian Blank ◽  
Peter Gehr ◽  
Barbara Rothen-Rutishauser
Keyword(s):  
Cell Culture ◽  
Human Lung ◽  
Culture Models ◽  
Toxic Potential ◽  
Cell Culture Models

Drug Discovery

2018 ◽  
pp. 399-404
Author(s):  
S. Nassir Ghaemi
Keyword(s):  
Drug Discovery ◽  
Pharmaceutical Industry ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
New Approach ◽  
The Past ◽  
Scientific Exploration ◽  
Clinical Indications ◽  
The Future ◽  
Clinical Diagnoses

Newer and better medications are obtained as part of the drug discovery process, which occurs mainly in the pharmaceutical industry. This process is hampered by excessive attention to marketing demands, as opposed to scientific exploration. It also is impaired by the psychiatric profession’s mistaken ideologies, whether psychoanalytic orthodoxy in the past or DSM beliefs of the present. Wrong clinical phenotypes impair finding new pharmacological mechanisms and targeting them well to the write clinical indications. Perhaps as a consequence, no treatments have been developed in the last few decades, since DSM-III, that are more effective than prior agents. Progress for the future in drug discovery will require not just better neurobiological work, but also a new approach to clinical diagnoses in psychiatry.

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