Recent submissions
Now showing items 181-200 of 658
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A non-cell autonomous mouse model of CNS haemangioblastoma mediated by mutant KRAS.
(NATURE PORTFOLIO, 2017-03-21)Haemangioblastoma is a rare malignancy of the CNS where vascular proliferation causes lesions due to endothelial propagation. We found that conditionally expressing mutant Kras, using Rag1-Cre, gave rise to CNS haemangioblastoma ... -
Structural and functional characterization of a DARPin which inhibits Ras nucleotide exchange.
(NATURE PUBLISHING GROUP, 2017-07-14)Ras mutations are the oncogenic drivers of many human cancers and yet there are still no approved Ras-targeted cancer therapies. Inhibition of Ras nucleotide exchange is a promising new approach but better understanding ... -
Intracellular immunization against HIV infection with an intracellular antibody that mimics HIV integrase binding to the cellular LEDGF protein.
(NATURE PORTFOLIO, 2017-12-04)Preventing the protein-protein interaction of the cellular chromatin binding protein Lens Epithelium-Derived Growth Factor (LEDGF) and human immunodeficiency virus (HIV) integrase is an important possible strategy for ... -
Cloning, purification and structure determination of the HIV integrase-binding domain of lens epithelium-derived growth factor.
(INT UNION CRYSTALLOGRAPHY, 2018-03-01)Lens epithelium-derived growth factor (LEDGF)/p75 is the dominant binding partner of HIV-1 integrase in human cells. The crystal structure of the HIV integrase-binding domain (IBD) of LEDGF has been determined in the absence ... -
BRET-based RAS biosensors that show a novel small molecule is an inhibitor of RAS-effector protein-protein interactions.
(ELIFE SCIENCES PUBLICATIONS LTD, 2018-07-10)The RAS family of proteins is amongst the most highly mutated in human cancers and has so far eluded drug therapy. Currently, much effort is being made to discover mutant RAS inhibitors and in vitro screening for RAS-binding ... -
Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment.
(NATURE PORTFOLIO, 2018-08-09)Targeting specific protein-protein interactions (PPIs) is an attractive concept for drug development, but hard to implement since intracellular antibodies do not penetrate cells and most small-molecule drugs are considered ... -
Structure-based development of new RAS-effector inhibitors from a combination of active and inactive RAS-binding compounds.
(NATL ACAD SCIENCES, 2019-02-12)The RAS gene family is frequently mutated in human cancers, and the quest for compounds that bind to mutant RAS remains a major goal, as it also does for inhibitors of protein-protein interactions. We have refined ... -
Advanced Prostate Cancer with ATM Loss: PARP and ATR Inhibitors.
(ELSEVIER, 2020-11-08)BACKGROUND: Deleterious ATM alterations are found in metastatic prostate cancer (PC); PARP inhibition has antitumour activity against this subset, but only some ATM loss PCs respond. OBJECTIVE: To characterise ATM-deficient ... -
canSAR: update to the cancer translational research and drug discovery knowledgebase.
(OXFORD UNIV PRESS, 2021-01-08)canSAR (http://cansar.icr.ac.uk) is the largest, public, freely available, integrative translational research and drug discovery knowledgebase for oncology. canSAR integrates vast multidisciplinary data from across genomic, ... -
Novel Quinazolinone Inhibitors of ALK2 Flip between Alternate Binding Modes: Structure-Activity Relationship, Structural Characterization, Kinase Profiling, and Cellular Proof of Concept.
(AMER CHEMICAL SOC, 2018-08-23)Structure-activity relationship and crystallographic data revealed that quinazolinone-containing fragments flip between two distinct modes of binding to activin receptor-like kinase-2 (ALK2). We explored both binding modes ... -
Circulating tumor cells, tumor-derived extracellular vesicles and plasma cytokeratins in castration-resistant prostate cancer patients.
(Impact Journals, LLC, 2018-04-10)PURPOSE: The presence of Circulating Tumor Cells (CTCs) in Castration-Resistant Prostate Cancer (CRPC) patients is associated with poor prognosis. In this study, we evaluated the association of clinical outcome in 129 CRPC ... -
Scanning Electron Microscopy of Circulating Tumor Cells and Tumor-Derived Extracellular Vesicles.
(MDPI, 2018-10-31)To explore morphological features of circulating tumor cells (CTCs) and tumor-derived extracellular vesicles (tdEVs), we developed a protocol for scanning electron microscopy (SEM) of CTCs and tdEVs. CTCs and tdEVs were ... -
Toward a real liquid biopsy in metastatic breast and prostate cancer: Diagnostic LeukApheresis increases CTC yields in a European prospective multicenter study (CTCTrap).
(WILEY, 2018-11-15)Frequently, the number of circulating tumor cells (CTC) isolated in 7.5 mL of blood is too small to reliably determine tumor heterogeneity and to be representative as a "liquid biopsy". In the EU FP7 program CTCTrap, we ... -
Targeting Bromodomain and Extra-Terminal (BET) Family Proteins in Castration-Resistant Prostate Cancer (CRPC).
(AMER ASSOC CANCER RESEARCH, 2018-07-01)Purpose: Persistent androgen receptor (AR) signaling drives castration-resistant prostate cancer (CRPC) and confers resistance to AR-targeting therapies. Novel therapeutic strategies to overcome this are urgently required. ... -
RACK7 recognizes H3.3G34R mutation to suppress expression of MHC class II complex components and their delivery pathway in pediatric glioblastoma.
(AMER ASSOC ADVANCEMENT SCIENCE, 2020-07-01)Histone H3 point mutations have been identified in incurable pediatric brain cancers, but the mechanisms through which these mutations drive tumorigenesis are incompletely understood. Here, we provide evidence that RACK7 ... -
A potent KRAS macromolecule degrader specifically targeting tumours with mutant KRAS.
(NATURE PUBLISHING GROUP, 2020-06-26)Tumour-associated KRAS mutations are the most prevalent in the three RAS-family isoforms and involve many different amino-acids. Therefore, molecules able to interfere with mutant KRAS protein are potentially important for ... -
Unconventional role of RAC1 in MET-driven anchorage-independent tumor growth.
(TAYLOR & FRANCIS INC, 2020-08-18)We reported that RAC1 is a master regulator of cell migration and anchorage-independent growth, downstream of the oncogenic Receptor Tyrosine Kinase (RTK) MET. RAC1 growth-promoting role is guanosine triphosphatase (GTPase)- ... -
Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network.
(SPRINGERNATURE, 2020-08-19)Vaccination is one of the most successful medical interventions that has saved the life of millions of people. Vaccination is particularly important in patients with multiple myeloma, who have an increased risk of infections ... -
FGFR1 Expression and Role in Migration in Low and High Grade Pediatric Gliomas.
(Frontiers Media SA, 2019-03-13)The heterogeneous and invasive nature of pediatric gliomas poses significant treatment challenges, highlighting the importance of identifying novel chemotherapeutic targets. Recently, recurrent Fibroblast growth factor ... -
Triplet Therapy with Palbociclib, Taselisib, and Fulvestrant in PIK3CA-Mutant Breast Cancer and Doublet Palbociclib and Taselisib in Pathway-Mutant Solid Cancers.
(AMER ASSOC CANCER RESEARCH, 2021-01-01)Cyclin-dependent kinase 4/6 (CDK4/6) and PI3K inhibitors synergize in PIK3CA-mutant ER-positive HER2-negative breast cancer models. We conducted a phase Ib trial investigating the safety and efficacy of doublet CDK4/6 ...