Substrate stiffness influences the outcome of antitumor drug screening in vitro

2013 ◽  
Vol 55 (1) ◽  
pp. 121-131 ◽  
Author(s):  
Jiantao Feng ◽  
Yong Tang ◽  
Yonggang Xu ◽  
Quanmei Sun ◽  
Fulong Liao ◽  
...  
Keyword(s):  
Drug Screening ◽  
Antitumor Drug ◽  
Substrate Stiffness ◽  
Screening In Vitro

scholarly journals Achievement of constitutive fluorescent pLEXSY-egfp Leishmania braziliensis and its application as an alternative method for drug screening in vitro

2017 ◽  
Vol 112 (2) ◽  
pp. 155-159 ◽  
Author(s):  
Matheus Silva e Bastos ◽  
◽  
Luciana Ângelo de Souza ◽  
Thiago Souza Onofre ◽  
Abelardo Silva Júnior ◽  
...  
Keyword(s):  
Drug Screening ◽  
Leishmania Braziliensis ◽  
Alternative Method ◽  
Screening In Vitro

scholarly journals Mass-producible microporous silicon membranes for specific leukocyte subset isolation, immunophenotyping, and personalized immunomodulatory drug screening in vitro

Lab on a Chip ◽  
2019 ◽  
Vol 19 (18) ◽  
pp. 3065-3076 ◽  
Author(s):  
Andrew Stephens ◽  
Robert Nidetz ◽  
Nicolas Mesyngier ◽  
Meng Ting Chung ◽  
Yujing Song ◽  
...  
Keyword(s):  
Microfluidic Device ◽  
Drug Screening ◽  
Leukocyte Subset ◽  
Immunomodulatory Drug ◽  
Silicon Membranes ◽  
On Chip ◽  
Leukocyte Populations ◽  
Screening In Vitro

Si micromachining processes were used to create a mass-producible immunophenotyping microfluidic device which can isolate and stimulate specific leukocyte populations, enabling measurement of secreted cytokines on-chip via a no-wash immunoassay.

Toxoplasma gondii: A simple high-throughput assay for drug screening in vitro

2009 ◽  
Vol 121 (2) ◽  
pp. 132-136 ◽  
Author(s):  
ChunMei Jin ◽  
Kusuma Kaewintajuk ◽  
JingHua Jiang ◽  
WooJin Jeong ◽  
Masaki Kamata ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
High Throughput ◽  
Drug Screening ◽  
High Throughput Assay ◽  
Screening In Vitro

scholarly journals Acanthamoeba castellanii : A new high-throughput method for drug screening in vitro

Acta Tropica ◽  
2016 ◽  
Vol 164 ◽  
pp. 95-99 ◽  
Author(s):  
Antonio Ortega-Rivas ◽  
José M. Padrón ◽  
Basilio Valladares ◽  
Hany M. Elsheikha
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Acanthamoeba Castellanii ◽  
High Throughput Method ◽  
Screening In Vitro

Simple and sensitive antimalarial drug screening in vitro and in vivo using transgenic luciferase expressing Plasmodium berghei parasites

2008 ◽  
Vol 38 (14) ◽  
pp. 1651-1662 ◽  
Author(s):  
B. Franke-Fayard ◽  
D. Djokovic ◽  
M.W. Dooren ◽  
J. Ramesar ◽  
A.P. Waters ◽  
...  
Keyword(s):  
Drug Screening ◽  
Plasmodium Berghei ◽  
Antimalarial Drug ◽  
Screening In Vitro

scholarly journals The Current Challenges for Drug Discovery in CNS Remyelination

2021 ◽  
Vol 22 (6) ◽  
pp. 2891
Author(s):  
Sonia Balestri ◽  
Alice Del Giovane ◽  
Carola Sposato ◽  
Marta Ferrarelli ◽  
Antonella Ragnini-Wilson
Keyword(s):  
Drug Screening ◽  
Myelin Sheath ◽  
Time Window ◽  
In Vitro Models ◽  
Adult Brain ◽  
Pharmacological Intervention ◽  
Cellular Models ◽  
New Findings ◽  
Myelin Injury

The myelin sheath wraps around axons, allowing saltatory currents to be transmitted along neurons. Several genetic, viral, or environmental factors can damage the central nervous system (CNS) myelin sheath during life. Unless the myelin sheath is repaired, these insults will lead to neurodegeneration. Remyelination occurs spontaneously upon myelin injury in healthy individuals but can fail in several demyelination pathologies or as a consequence of aging. Thus, pharmacological intervention that promotes CNS remyelination could have a major impact on patient’s lives by delaying or even preventing neurodegeneration. Drugs promoting CNS remyelination in animal models have been identified recently, mostly as a result of repurposing phenotypical screening campaigns that used novel oligodendrocyte cellular models. Although none of these have as yet arrived in the clinic, promising candidates are on the way. Many questions remain. Among the most relevant is the question if there is a time window when remyelination drugs should be administrated and why adult remyelination fails in many neurodegenerative pathologies. Moreover, a significant challenge in the field is how to reconstitute the oligodendrocyte/axon interaction environment representative of healthy as well as disease microenvironments in drug screening campaigns, so that drugs can be screened in the most appropriate disease-relevant conditions. Here we will provide an overview of how the field of in vitro models developed over recent years and recent biological findings about how oligodendrocytes mature after reactivation of their staminal niche. These data have posed novel questions and opened new views about how the adult brain is repaired after myelin injury and we will discuss how these new findings might change future drug screening campaigns for CNS regenerative drugs.

scholarly journals Substrate Stiffness and Stretch Regulate Profibrotic Mechanosignaling in Pulmonary Arterial Adventitial Fibroblasts

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1000
Author(s):  
Ariel Wang ◽  
Shulin Cao ◽  
Jennifer C. Stowe ◽  
Daniela Valdez-Jasso
Keyword(s):  
Transforming Growth Factor ◽  
Substrate Stiffness ◽  
Messenger Rnas ◽  
Ang Ii ◽  
Integrin Β3 ◽  
Custom Made ◽  
Adventitial Fibroblasts ◽  
Pulmonary Arterial ◽  
Six Genes

Pulmonary arterial adventitial fibroblasts (PAAFs) are important regulators of fibrotic vascular remodeling during the progression of pulmonary arterial hypertension (PAH), a disease that currently has no effective anti-fibrotic treatments. We conducted in-vitro experiments in PAAFs cultured on hydrogels attached to custom-made equibiaxial stretchers at 10% stretch and substrate stiffnesses representing the mechanical conditions of mild and severe stages of PAH. The expression of collagens α(1)I and α(1)III and elastin messenger RNAs (Col1a1, Col3a1, Eln) were upregulated by increased stretch and substrate stiffness, while lysyl oxidase-like 1 and α-smooth muscle actin messenger RNAs (Loxl1, Acta2) were only significantly upregulated when the cells were grown on matrices with an elevated stiffness representative of mild PAH but not on a stiffness representative of severe PAH. Fibronectin messenger RNA (Fn1) levels were significantly induced by increased substrate stiffness and transiently upregulated by stretch at 4 h, but was not significantly altered by stretch at 24 h. We modified our published computational network model of the signaling pathways that regulate profibrotic gene expression in PAAFs to allow for differential regulation of mechanically-sensitive nodes by stretch and stiffness. When the model was modified so that stiffness activated integrin β3, the Macrophage Stimulating 1 or 2 (MST1\2) kinases, angiotensin II (Ang II), transforming growth factor-β (TGF-β), and syndecan-4, and stretch-regulated integrin β3, MST1\2, Ang II, and the transient receptor potential (TRP) channel, the model correctly predicted the upregulation of all six genes by increased stiffness and the observed responses to stretch in five out of six genes, although it could not replicate the non-monotonic effects of stiffness on Loxl1 and Acta2 expression. Blocking Ang II Receptor Type 1 (AT1R) with losartan in-vitro uncovered an interaction between the effects of stretch and stiffness and angiotensin-independent activation of Fn1 expression by stretch in PAAFs grown on 3-kPa matrices. This novel combination of in-vitro and in-silico models of PAAF profibrotic cell signaling in response to altered mechanical conditions may help identify regulators of vascular adventitial remodeling due to changes in stretch and matrix stiffness that occur during the progression of PAH in-vivo.

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