Recent submissions
Now showing items 201-220 of 658
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Characterizing CDK12-Mutated Prostate Cancers.
(AMER ASSOC CANCER RESEARCH, 2020-09-28)PURPOSE: Cyclin-dependent kinase 12 (CDK12) aberrations have been reported as a biomarker of response to immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). Herein, we characterize CDK12-mutated ... -
Solution structure of the Hop TPR2A domain and investigation of target druggability by NMR, biochemical and in silico approaches.
(NATURE PORTFOLIO, 2020-09-29)Heat shock protein 90 (Hsp90) is a molecular chaperone that plays an important role in tumour biology by promoting the stabilisation and activity of oncogenic 'client' proteins. Inhibition of Hsp90 by small-molecule drugs, ... -
Mutant IDH1 Downregulates ATM and Alters DNA Repair and Sensitivity to DNA Damage Independent of TET2.
(CELL PRESS, 2016-08-08)Mutations in the isocitrate dehydrogenase-1 gene (IDH1) are common drivers of acute myeloid leukemia (AML) but their mechanism is not fully understood. It is thought that IDH1 mutants act by inhibiting TET2 to alter DNA ... -
Intracavitary 'T4 immunotherapy' of malignant mesothelioma using pan-ErbB re-targeted CAR T-cells.
(ELSEVIER IRELAND LTD, 2017-05-01)Malignant mesothelioma remains an incurable cancer. We demonstrated that mesotheliomas expressed EGFR (79.2%), ErbB4 (49.0%) and HER2 (6.3%), but lacked ErbB3. At least one ErbB family member was expressed in 88% of tumors. ... -
Current Advances in CAR T Cell Therapy for Malignant Mesothelioma.
(Scientific Archives LLC, 2020-06-22)Malignant mesothelioma is a relatively rare malignancy arising in the body's serosal surfaces, with malignant pleural mesothelioma (MPM) being the most common type. It is characterized by local spread within the thorax, ... -
Analysis and Augmentation of the Immunologic Bystander Effects of CAR T Cell Therapy in a Syngeneic Mouse Cancer Model.
(CELL PRESS, 2020-09-25)The therapeutic efficacy of adoptive transfer of T cells transduced with chimeric antigen receptors (CARs) has been limited in the treatment of solid cancers, partly due to tumor antigen heterogeneity. Overcoming lack of ... -
Glutathione Metabolism: An Achilles' Heel of ARID1A-Deficient Tumors.
(CELL PRESS, 2019-02-11)In this issue of Cancer Cell, Ogiwara et al. describe a novel link between the epigenetic regulator ARID1A and glutathione metabolism in cancer that is mediated by regulation of the cystine/glutamate transporter XCT. This ... -
Reactive oxygen species modulate macrophage immunosuppressive phenotype through the up-regulation of PD-L1.
(NATL ACAD SCIENCES, 2019-03-05)The combination of immune checkpoint blockade with chemotherapy is currently under investigation as a promising strategy for the treatment of triple negative breast cancer (TNBC). Tumor-associated macrophages (TAMs) are ... -
AhR controls redox homeostasis and shapes the tumor microenvironment in BRCA1-associated breast cancer.
(NATL ACAD SCIENCES, 2019-02-26)Cancer cells have higher reactive oxygen species (ROS) than normal cells, due to genetic and metabolic alterations. An emerging scenario is that cancer cells increase ROS to activate protumorigenic signaling while activating ... -
International Ring Trial of a High Resolution Targeted Metabolomics and Lipidomics Platform for Serum and Plasma Analysis.
(AMER CHEMICAL SOC, 2019-10-22)A challenge facing metabolomics in the analysis of large human cohorts is the cross-laboratory comparability of quantitative metabolomics measurements. In this study, 14 laboratories analyzed various blood specimens using ... -
SBDS-Deficient Cells Have an Altered Homeostatic Equilibrium due to Translational Inefficiency Which Explains their Reduced Fitness and Provides a Logical Framework for Intervention.
(PUBLIC LIBRARY SCIENCE, 2017-01-05)Ribosomopathies are a family of inherited disorders caused by mutations in genes necessary for ribosomal function. Shwachman-Diamond Bodian Syndrome (SDS) is an autosomal recessive disease caused, in most patients, by ... -
Glutathione Primes T Cell Metabolism for Inflammation.
(CELL PRESS, 2017-04-18)Activated T cells produce reactive oxygen species (ROS), which trigger the antioxidative glutathione (GSH) response necessary to buffer rising ROS and prevent cellular damage. We report that GSH is essential for T cell ... -
Immune Cell Associations with Cancer Risk.
(CELL PRESS, 2020-07-24)Proper immune system function hinders cancer development, but little is known about whether genetic variants linked to cancer risk alter immune cells. Here, we report 57 cancer risk loci associated with differences in ... -
Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma.
(AMER SOC CLINICAL INVESTIGATION INC, 2020-11-02)The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show ... -
Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma.
(ELSEVIER, 2020-09-01)BACKGROUND: In neuroblastoma, genetic alterations in ATRX, define a distinct poor outcome patient subgroup. Despite the need for new therapies, there is a lack of available models and a dearth of pre-clinical research. ... -
Multimeric antibodies with increased valency surpassing functional affinity and potency thresholds using novel formats.
(TAYLOR & FRANCIS INC, 2020-01-01)The success of therapeutic antibodies is largely attributed for their exquisite specificity, homogeneity, and functionality. There is, however, a need to engineer antibodies to extend and enhance their potency. One parameter ... -
A PI3K- and GTPase-independent Rac1-mTOR mechanism mediates MET-driven anchorage-independent cell growth but not migration.
(AMER ASSOC ADVANCEMENT SCIENCE, 2020-06-23)Receptor tyrosine kinases (RTKs) are often overexpressed or mutated in cancers and drive tumor growth and metastasis. In the current model of RTK signaling, including that of MET, downstream phosphatidylinositol 3-kinase ... -
Development of a cell-free split-luciferase biochemical assay as a tool for screening for inhibitors of challenging protein-protein interaction targets.
(F1000 Research Ltd, 2020-01-01)Targeting the interaction of proteins with weak binding affinities or low solubility represents a particular challenge for drug screening. The NanoLuc â ® Binary Technology (NanoBiT â ®) was originally developed to detect ... -
Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes.
(NATURE PUBLISHING GROUP, 2016-06-23)Receptor tyrosine kinases (RTKs) and integrins cooperate to stimulate cell migration and tumour metastasis. Here we report that an integrin influences signalling of an RTK, c-Met, from inside the cell, to promote ...