Human Peripheral Blood Mononuclear Cells (hPBMCs) are essential for designing cellular models to be used in cell therapy and drug discovery research programs [1-7, 12]. Being able to access reliable and ethical sources of well-characterized hPBMCs is now becoming fundamental for running physiologically relevant cell-based assays. A good opportunity to discuss the expanding applications for hPBMCs in drug development, that Patricia Bresnahan, PhD (Global Marketing Director at HemaCare Corporation) has observed over the last years.
Which roles do IDO and TDO play in Immunotherapy? Immune evasion is one of the identifying hallmarks of cancer and researchers are investigating the complex mechanisms that enable cancer cells to evade the host’s immune system. In the context of a tumor, Tryptophan (Trp or L-Trp) catabolizing enzymes have been shown to assist cancer cells in immune evasion. [Read more…]
Peroxisome Proliferator-Activated Receptors (PPARs) are ligand-activated transcription factors of the Nuclear Receptor superfamily. PPAR active compounds are of significant interest in multiple pharmaceutical domains.
In this post, we’ll highlight a clever in vitro experimental approach to screen the PPAR-specific activity of therapeutically significant PPAR agonists or antagonists.
Lipodystrophies are disorders characterized by complete or selective loss of adipose tissue from various regions of the body. They might lead to severe metabolic disorders. The development of reliable cellular experimental models mimicking such diseases in vitro is extremely challenging (1). One of the main hurdle in the design of such in vitro cellular models is the access to reliable sources of well-qualified primary cells and the identification of optimal cell culture conditions.
Dengue Virus (DenV) is transmitted by mosquito vectors. It infects 50-100 million people each year and is at the origin of Dengue Fever and the more lethal Dengue Hemorrhagic Fever (DHF) and Shock Syndrome (DSS) leading to an estimated 500,000 cases of DHF and 22 000 deaths. The World Health Organization (WHO) estimates that 40% of the world’s population is at risk of infection.
In the June issue of Journal of Biomolecular Screening, investigators at San Diego State University (Dept of Biology) and Institute Pasteur Korea (Seoul, South Korea) developed a multiplexed cell-based assay for the identification of modulators of pre-membrane processing as a target for the discovery of DenV inhibitors. (1)
The DenV pre-membrane protein (prM) is an essential chaperone for the viral envelope protein which prevents premature fusion with vesicles during viral export. Inhibition of pre-membrane protein cleavage restricts fusion and represents, thus, a novel druggable target.
The new in vitro assay developed in this study, is the first described cell-based assay that monitors DenVprM processing within the classical secretory pathway. In a pilot screen of 1,280 small molecules on that assay, Thiostrepton, a known cyclopeptide Antibiotic and FOXM1 inhibitor, was identified as a novel positive hit in this assay (IC50=4.94 µM).
The utility of this novel assay has been proven by the identification of Thiostrepton (available at Focus Biomolecules cat. nr 10-2108) which may be a novel lead compound for the discovery of new drugs effective against Dengue Virus.
1- Stolp Z.D. et al. “A Multiplexed Cell-Based Assay for the Identification of Modulators of Pre-Membrane Processing as a Target against Dengue Virus” (2015) J. Biomol. Screen. 20:616-626. DOI: 10.1177/1087057115571247.
|Dengue Fever||Cat. Nr||Product Name||Application|
|Antibody for Dengue Virus||157MAB4043||Dengue virus Types 1,2,3,4 monoclonal antibody, clone BDI419||Dot,IF,EIA|
|Antibodies for Envelope Protein||157MAB8901||Dengue virus E-D3 monoclonal antibody, clone 5j122||ELISA,WB-Re|
|Antibodies for NS1 protein||157MAB13532||Dengue virus NS1 monoclonal antibody, clone HM026||ELISA,IF,LFIA|
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In vivo monitoring of tumor growth and metastasis provides a powerful means for studying cancer properties and development of effective therapies. Mouse models created with tumor xenografts, resulting from subcutaneous or tail vein injection of cells, have long been used for such purposes. However, without a convenient means to visualize cancer progression in these animals, invasive surgical procedures are required in order to estimate the size and weight of primary and metastatic tumors, and cannot be used for early stages in tumor development. Surgery often requires sacrificing the animals, leading to the need for large numbers of individuals and increasing the cost and risk of sampling errors.
GeneCopoeia has recently announced the introduction of pre-made cancer cell lines labeled with GFP, and pre-made cancer cell lines dual-labeled with luciferase and GFP. A new powerful and sensitive mathods to follow tumor growth & metastasis in vivo! [Read more…]
The transition from non-invasive phenotype to invasive phenotype of tumor cells marks the switch from a benign tumor to a more malignant form of cancer. Understanding the mechanisms underlying this hallmark event, which enables tumor cells to invade through Extracellular matrix, is critical for discovering pathways and new targets to develop anti-metastatic strategies. The discovery of anti-metastatic agents that inhibit cancer cell motility has been hindered by a dearth of cell motility assays that are compatible with high–throughput screening. [Read more…]
Chipman et al. (Dalhousie University, Halifax, Nova Scotia, Canada) have developed a new cell-based system “mimicking” in vitro Mature Neuromuscular Junction (NMJs). (1)
NMJs play an important role in the functionality of Motor neurons.
Their dysfunction is seen in the early stages of various Motor Neuron Diseases (MNDs) like the Amyotrophic Lateral Sclerosis (ALS), Spinal Muscular Atrophy (SMA), Primary Lateral Sclerosis (PLS), Progressive Muscular Atrophy (PMA)…
To meet these needs, Chipman et al. have created a clever co-culture system using Embryonic Stem Cell-derived Motor Neurons (ESCMNs) with primary myotubes. They also reported that NCAM-/- ESCMN/myofiber co-cultures exhibit the same phenotypes observed in NCAM-/- mice.
This work give hopes to study MNDs in vitro by using motor neurons differentiated from induced Pluripotent Stem cells (iPS) derived from individuals with ALS and SMA.
Want to know more about cell-based assays and co-culture systems?
(1) Chipman et al. “A Stem-Cell Based Bioassay to Critically Assess the Pathology of Dysfunctional Neuromuscular Junctions” (2014) PLOSone, March 13. DOI: 10.1371/journal.pone.0091643
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