Thursday, April 10, 2014

SciBX: Science-Business eXchange Contents: April 10 2014, Volume 7 / Issue 14

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SciBX: Science-Business eXchange

TABLE OF CONTENTS

April 10 2014, Volume 7 / Issue 14

Analysis

Cover Story
Targets and Mechanisms
Tools

The Distillery: Therapeutics

Cancer
Cardiovascular disease
Endocrine/metabolic disease
Hepatic disease
Infectious disease
Inflammation

The Distillery: Techniques

Assays and screens
Disease models
Drug platforms
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Analysis

Cover Story

Top

Pre-EMP-tive strike against GBM
Michael J. Haas
doi:10.1038/scibx.2014.389
UCLA researchers have treated glioblastoma in mice by inhibiting EMP2. The findings open up a new indication for spinout Paganini, which has a mAb against the target in development for triple-negative breast cancer.
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Targets and Mechanisms

Top

Positioning properdin
Kai-Jye Lou
doi:10.1038/scibx.2014.390
Researchers at the University of Leicester have shown that a recombinant properdin produced in collaboration with The Medicines Co. has markedly higher antibacterial activity than the native protein. The researchers are now working to improve the recombinant protein's activity and homogeneity.
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Catastrophic vacuolization
Tracey Baas
doi:10.1038/scibx.2014.391
Karolinska Institute scientists have attacked glioblastoma multiforme by inducing an unconventional cell death pathway involving catastrophic vacuolization. The team identified a small molecule that prolonged survival in mouse GBM, but a combination approach with a conventional anticancer agent will likely be necessary in the clinic.
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Tools

Top

Toxic assets
C. Simone Fishburn
doi:10.1038/scibx.2014.392
A tool for in vivo detection of liver toxicity could represent a substantial improvement over in vitro methods. The litmus test for the Stanford University inventors will be to show that the nanoparticle-based method can detect toxicity in compounds that previously eluded standard analysis and later failed in the clinic.
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Distillery: Therapeutics

Cancer

Top

Epithelial membrane protein 2 (EMP2)
doi:10.1038/scibx.2014.393
Patient sample and mouse studies suggest targeting EMP2 could be used to treat glioblastoma multiforme (GBM).
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Anoctamin 1 calcium activated chloride channel (ANO1)
doi:10.1038/scibx.2014.394
In vitro studies suggest compounds that promote ANO1 degradation, as opposed to ANO1 antagonists, could be useful for treating cancer.
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Not applicable
doi:10.1038/scibx.2014.395
In vitro and mouse studies suggest the rheumatoid arthritis (RA) drug Ridauraauranofin could be used to treat CLL.
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Splice variant v6 of CD44 (CD44v6); phosphoinositide 3-kinase (PI3K)
doi:10.1038/scibx.2014.396
In vitro and mouse studies suggest inhibiting CD44v6 and PI3K could be useful for preventing metastasis in colorectal cancer.
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Jagged 1 (JAG1); notch 2 (NOTCH2); fibroblast growth factor 4 (FGF4); fibroblast growth factor receptor 1 (FGFR1; CD331)
doi:10.1038/scibx.2014.397
Cell culture and mouse studies suggest inhibiting JAG1-NOTCH2 or FGF4-FGFR1 signaling could help treat Burkitt lymphoma.
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Ubiquitin specific peptidase 1 (USP1); WD repeat domain 48 (WDR48; UAF1)
doi:10.1038/scibx.2014.398
Cell-based studies suggest inhibiting the USP1-UAF1 complex could help increase NSCLC and bone cancer sensitivity to platinum-based chemotherapies.
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Sterol O-aceyltransferase 1 (SOAT1; ACAT1)
doi:10.1038/scibx.2014.399
Studies in patient samples, mice and cell culture suggest inhibiting ACAT1 prevents cholesteryl ester (CE) synthesis and could help treat prostate cancer.
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Cardiovascular disease

Top

Peroxisome proliferation–activated receptor-γ (PPARG; PPARγ); myeloid-lymphoma or mixed-lineage 5 (MLL5); 5′-3′ exoribonuclease 2 (XRN2)
doi:10.1038/scibx.2014.400
In vitro and mouse studies suggest activating genes involved in the plasma cholesterol–lowering response could help treat atherosclerosis.
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Thrombin (factor IIa; F2)
doi:10.1038/scibx.2014.401
In vitro studies suggest an allosteric thrombin inhibitor could prevent blood clots and thrombosis.
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Endocrine/metabolic disease

Top

Farnesoid X receptor (FXR; NR1H4)
doi:10.1038/scibx.2014.402
Mouse studies suggest FXR is required to mediate the effects of vertical sleeve gastrectomy—a type of bariatric surgery—on obesity.
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Hepatic disease

Top

Synoviolin (SYVN1; HRD1)
doi:10.1038/scibx.2014.403
Studies in human samples and mice suggest inhibiting HRD1 could help treat liver cirrhosis.
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Infectious disease

Top

Pannexin 1 (PANX1)
doi:10.1038/scibx.2014.404
In vitro studies suggest avoiding PANX1 inhibition could prevent the toxic side effects of some quinolone antibiotics.
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Peroxisome proliferation–activated receptor-γ (PPARG; PPARγ)
doi:10.1038/scibx.2014.405
Studies in mice and human samples suggest combining PPARγ agonists with antimalarial therapy could improve outcomes in cerebral malaria.
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Properdin
doi:10.1038/scibx.2014.406
Mouse studies suggest recombinant properdin could help protect against bacterial meningitis and pneumonia.
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Inflammation

Top

Leukotriene A4 hydrolase (LTA4H)
doi:10.1038/scibx.2014.407
Structure-based design studies led to an LTA4H inhibitor that could be useful as a lead for new anti-inflammatory agents.
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Distillery: Techniques

Assays and screens

Top

Nanoparticles for in vivo detection of drug-induced hepatotoxicity
doi:10.1038/scibx.2014.408
Mouse studies suggest semiconducting polymer nanoparticles (SPNs) could be used for real-time in vivo monitoring of drug-induced hepatotoxicity.
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Polymerized antibody–tagged magnetic beads for isolation of circulating tumor cells (CTCs)
doi:10.1038/scibx.2014.409
Magnetic beads tagged with polymerized antibodies or antibody-like molecules could help capture CTCs for cancer research purposes.
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Protein misfolding cyclic amplification (PMCA) technique to create α-synuclein (SNCA) aggregates for drug screening
doi:10.1038/scibx.2014.410
In vitro studies suggest SNCA aggregates formed using PMCA could be used to screen antiaggregating agents for Parkinson's disease (PD).
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Disease models

Top

Mice with human innate immune cells
doi:10.1038/scibx.2014.411
Humanized mice with functional human innate immune cells could be used as models to study cancer in the presence of an intact human immune system.
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Mouse model of amyotrophic lateral sclerosis (ALS) caused by partial loss of TAR DNA binding protein 43 (Tdp-43; Tardbp) function
doi:10.1038/scibx.2014.412
Mice with partial loss of Tdp-43 function could be useful as models to study and screen for new compounds to treat ALS.
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Pituitary ablation of estrogen receptor expression as a mouse model for ovarian cancer
doi:10.1038/scibx.2014.413
A genetic mouse model for estrogen-dependent ovarian cancer could be used to study disease progression and evaluate therapeutic candidates.
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Drug platforms

Top

Carbonic anhydrase IX (CAIX)-targeted small molecule–drug conjugates
doi:10.1038/scibx.2014.414
CAIX-targeted small molecule conjugates could be useful for imaging and treating cancer.
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Crystal structure of purinergic receptor P2Y G protein–coupled 12 (P2RY12; P2Y12) bound to an antagonist
doi:10.1038/scibx.2014.415
In vitro structural studies of P2RY12 bound to an antagonist could aid antithrombotic drug design.
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Enhanced antigen-specific T cell activation using nanoscale artificial antigen-presenting cells (aAPCs) in a magnetic field
doi:10.1038/scibx.2014.416
In vitro and mouse studies suggest magnetic-field culturing methods could increase activation of antigen-specific T cells by nanoscale aAPCs.
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Small molecule inhibitors of microRNA processing
doi:10.1038/scibx.2014.417
An in vitro screening system could be used to identify small molecule inhibitors of miRNAs.
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Top

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