SciBX: Science-Business eXchange Contents: August 29 2013, Volume 6 / Issue 33

TABLE OF CONTENTS August 29 2013, Volume 6 / Issue 33 Analysis Cover Story Translational Notes Targets and Mechanisms Tools The Distillery: Therapeutics Autoimmune disease Cancer Cardiovascular disease Endocrine/metabolic disease Hematology Infectious disease Inflammation Neurology Various The Distillery: Techniques Assays and screens Disease models Drug delivery Drug platforms Nature Publishing Group and Relay Technology Management present: The Epigenetics Target Explorer  Click here to access this free online tool and the accompanying article in Nature Reviews Drug Discovery.    Analysis Cover Story Top Sleuthing for toxicity Tracey Baas doi:10.1038/scibx.2013.879 Immunocore, Adaptimmune and UPenn researchers have determined that off-target toxicity most likely caused the two fatalities in a cancer trial of affinity-enhanced T cell receptors. The results highlight the need for using biologically appropriate disease models and deep molecular analyses to minimize cross-reactivity–related toxicity in future adoptive immunotherapy trials. Full Text | PDF Translational Notes Top Collaborating against diabetes complications Michael J. Haas doi:10.1038/scibx.2013.880 Pfizer's deal with the Sanford-Burnham Medical Research Institute to identify and validate new drug targets to prevent and treat insulin resistance and organ damage in obesity-related diabetes could help reverse a trend that has seen the pharma arriving late—or not at all—to the party with new targets for the indication. Full Text | PDF Targets and Mechanisms Top Going stromal with docetaxel Chris Cain doi:10.1038/scibx.2013.881 Ontario Institute for Cancer Research scientists have developed glycopolymer-conjugated docetaxel nanoparticles that target the tumor stroma and outperform Abraxane in mouse models of breast cancer. The institution is now backing the program with $1.5 million to bring it to the clinic. Full Text | PDF Tools Top DISCerning schizophrenia in mice C. Simone Fishburn doi:10.1038/scibx.2013.882 A team at The Johns Hopkins University has created a transgenic mouse model of prefrontal dysfunction involving disrupted networks of neurons that cause behavioral changes similar to those seen in patients with schizophrenia or mood disorders. Full Text | PDF Distillery: Therapeutics Autoimmune disease Top Natural killer p30 receptor (NKp30;NCR3; CD337) doi:10.1038/scibx.2013.883 Patient studies suggest inhibiting NKp30 could help treat the autoimmune disease primary Sjögren's syndrome (pSS). Full Text | PDF Phosphoinositide kinase FYVE finger containing (PIKFYVE) doi:10.1038/scibx.2013.884 Cell culture studies identified the molecular target of apilimod as PIKFYVE, suggesting the target could be inhibited to treat autoimmune diseases. Full Text | PDF Cancer Top Actin α2 smooth aorta muscle (ACTA2; α-SMA) doi:10.1038/scibx.2013.885 Mouse studies suggest a polyethylene glycol formulation of docetaxel conjugated to acetylated carboxymethylcellulose could help treat breast cancer. Full Text | PDF Mediator of cell motility 1 (MEMO1; MEMO) doi:10.1038/scibx.2013.886 Mouse and cell culture studies suggest inhibiting MEMO could help treat estrogen-dependent breast cancers. Full Text | PDF Androgen receptor; cyclin D1 (CCND1; BCL1) doi:10.1038/scibx.2013.887 In vitro and mouse studies identified acetamide analog small molecules that could help treat prostate and other cancers. Full Text | PDF Cyclic adenosine monophosphate (cAMP); cell division cycle 25B (CDC25B); melanocortin 1 receptor (MC1R) doi:10.1038/scibx.2013.888 Cell culture studies suggest targeting the MC1R-cAMP-CDC25B signaling pathway could help treat melanoma. Full Text | PDF Proteasome doi:10.1038/scibx.2013.889 In vitro and mouse studies identified a homopiperazine proteasome inhibitor that could help treat drug-resistant MM. Full Text | PDF Regenerating islet-derived 3β (REG3B) doi:10.1038/scibx.2013.890 Mouse studies suggest inhibiting REG3B could help treat pancreatic cancer. Full Text | PDF Cardiovascular disease Top Potassium channel K2p3.1 (KCNK3); phospholipase A2 (PLA2) doi:10.1038/scibx.2013.891 Studies in patient samples and cell culture suggest activating KCNK3 could help treat pulmonary arterial hypertension (PAH). Full Text | PDF Endocrine/metabolic disease Top IL-15; IL-15 receptor α-chain (IL-15RA) doi:10.1038/scibx.2013.892 Studies in mice and human samples suggest inhibiting IL-15 or IL-15RA could help treat type 1 diabetes. Full Text | PDF Hematology Top Not applicable doi:10.1038/scibx.2013.893 Mouse studies suggest the nucleotide sugar uridine diphosphate glucose (UDP-glucose) could be useful for stem cell mobilization in potential bone marrow donors. Full Text | PDF Infectious disease Top Not applicable doi:10.1038/scibx.2013.894 Rat studies suggest decreasing mitochondrial reactive oxygen species could help prevent kidney damage in acute infectious pyelonephritis. Full Text | PDF Inflammation Top Transforming growth factor-β1 (TGFB1); transforming growth factor-β receptor 1 (TGFBR1; ALK5); TGFBR2 (TGFβ-RII) doi:10.1038/scibx.2013.895 Studies in human samples suggest inhibiting TGFBR1 or TGFBR2 could help treat allergy-related conditions. Full Text | PDF Heparan sulfate glycosaminoglycan (HSGAG) doi:10.1038/scibx.2013.896 In vitro studies identified heparan sulfate mimetics that could help treat inflammatory diseases. Full Text | PDF Neurology Top β-Amyloid (Aβ) doi:10.1038/scibx.2013.897 In silico and in vitro studies identified Aβ fiber–binding compounds that could help treat AD. Full Text | PDF Liver X receptor-β (NR1H2; LXR-β) doi:10.1038/scibx.2013.898 SAR and mouse studies suggest flavonoid LXR-β agonists could be useful for treating AD. Full Text | PDF Fusion (involved in t(12;16) in malignant liposarcoma) (FUS; TLS) doi:10.1038/scibx.2013.899 Mouse studies suggest inhibiting FUS aggregation could help treat ALS. Full Text | PDF Microtubule-associated protein-τ (MAPT; TAU; FTDP-17) doi:10.1038/scibx.2013.900 Mouse studies suggest inhibiting TAU protein could help prevent seizures. Full Text | PDF Low-density lipoprotein-related protein 1 α-2-macroglobulin receptor (LRP1; CD91); neurotrophic tyrosine kinase receptor 3 (NTRK3; TrkC) doi:10.1038/scibx.2013.901 Cell culture and rat studies suggest targeting LRP1 could promote neuronal regeneration. Full Text | PDF Various Top Tumor necrosis factor-α (TNF-α) doi:10.1038/scibx.2013.902 Biochemical and cell culture studies identified a bicyclic peptide inhibitor of TNF-α that could help treat cachexia and autoimmune disease. Full Text | PDF Distillery: Techniques Assays and screens Top Nanometer-scale thermometry in living cells doi:10.1038/scibx.2013.903 Nanometer-scale thermometry in living cells could be useful for monitoring cellular activity in response to stimuli and could aid the development of temperature-sensitive therapeutics. Full Text | PDF Phenotypic neuronal assays to screen for small molecules that decrease β-amyloid (Aβ) doi:10.1038/scibx.2013.904 Phenotypic screening of embryonic stem cell (ESC)-derived neurons could help identify small molecules that decrease Aβ to treat Alzheimer's disease (AD). Full Text | PDF Strategy to decrease off-target peptide recognition by affinity-enhanced, T cell receptor (TCR)-based T cell therapies doi:10.1038/scibx.2013.905 Amino acid scanning and cell culture screens could be used to decrease the risk of off-target toxicity from TCR-based T cell therapies to treat cancer. Full Text | PDF Disease models Top Mouse model of fibroblast growth factor 9 (Fgf9; Gaf)-driven lung cancer doi:10.1038/scibx.2013.906 Transgenic mice with inducible expression of Fgf9 in lung epithelium could be useful as a model to help identify new treatments for lung cancer. Full Text | PDF Mouse model of methylmalonic acidemia–associated renal pathology doi:10.1038/scibx.2013.907 A mouse model of methylmalonic acidemia–associated renal pathology could help identify new treatments for the condition, which is a metabolic disorder caused primarily by mutations in methylmalonyl CoA mutase (MUT). Full Text | PDF Mouse models of idiopathic basal ganglia calcification (IBGC) doi:10.1038/scibx.2013.908 Mouse models of IBGC could be useful for studying associations between brain lesions and cognitive, motor and psychiatric symptoms. Full Text | PDF Rat model of Roux-en-Y gastric bypass doi:10.1038/scibx.2013.909 Roux-en-Y gastric bypass–treated rats could be used to study the mechanisms underlying the efficacy of the procedure and could help develop new treatments for metabolic diseases. Full Text | PDF Drug delivery Top Lentiviral vectors targeting endoglin (CD105; ENG) for endothelial cell–targeted therapy doi:10.1038/scibx.2013.910 In vitro and mouse studies suggest lentiviral vectors targeting CD105 could be used for endothelium-targeted gene delivery. Full Text | PDF Drug platforms Top Crystal structure of glucagon receptor (GCGR) doi:10.1038/scibx.2013.911 A crystal structure of GCGR could help drug discovery efforts targeting class B GPCRs. Full Text | PDF Photoreceptor replacement therapy for degenerative retinal disease doi:10.1038/scibx.2013.912 Embryonic stem cell (ESC)-derived photoreceptors could help treat degenerative retinal diseases. Full Text | PDF Top

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