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Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity.
(AMER ASSOC CANCER RESEARCH, 2015-08-01)
Neuroblastoma is the most common extracranial solid tumor of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not ...
Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity.
(ELSEVIER SCIENCE INC, 2014-09-01)
Apremilast, an oral small molecule inhibitor of phosphodiesterase 4 (PDE4), is in development for chronic inflammatory disorders, and has shown efficacy in psoriasis, psoriatic arthropathies, and Behçet's syndrome. In March ...
Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness.
(NATURE PUBLISHING GROUP, 2016-01-18)
Stromal fibroblast recruitment to tumours and activation to a cancer-associated fibroblast (CAF) phenotype has been implicated in promoting primary tumour growth and progression to metastatic disease. However, the mechanisms ...
Mouse mammary stem cells express prognostic markers for triple-negative breast cancer.
(BMC, 2015-03-04)
INTRODUCTION: Triple-negative breast cancer (TNBC) is a heterogeneous group of tumours in which chemotherapy, the current mainstay of systemic treatment, is often initially beneficial but with a high risk of relapse and ...
The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma.
(IMPACT JOURNALS LLC, 2016-01-19)
CCT245737 is the first orally active, clinical development candidate CHK1 inhibitor to be described. The IC50 was 1.4 nM against CHK1 enzyme and it exhibited>1,000-fold selectivity against CHK2 and CDK1. CCT245737 potently ...
Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent Neuroblastoma.
(AMER ASSOC CANCER RESEARCH, 2015-11-15)
PURPOSE: MYCN-dependent neuroblastomas have low cure rates with current multimodal treatment regimens and novel therapeutic drugs are therefore urgently needed. In previous preclinical studies, we have shown that targeted ...
Cdc42EP3/BORG2 and Septin Network Enables Mechano-transduction and the Emergence of Cancer-Associated Fibroblasts.
(CELL PRESS, 2015-12-29)
Cancer-associated fibroblasts (CAFs) are non-cancerous cells found in solid tumors that remodel the tumor matrix and promote cancer invasion and angiogenesis. Here, we demonstrate that Cdc42EP3/BORG2 is required for the ...
Reactivation of p53 by a Cytoskeletal Sensor to Control the Balance Between DNA Damage and Tumor Dissemination.
(OXFORD UNIV PRESS INC, 2015-10-13)
BACKGROUND: Abnormal cell migration and invasion underlie metastasis, and actomyosin contractility is a key regulator of tumor invasion. The links between cancer migratory behavior and DNA damage are poorly understood. ...
Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation.
(AMER ASSOC CANCER RESEARCH, 2016-06-01)
PI3K plays a key role in cellular metabolism and cancer. Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines, and ...
Co-option of Liver Vessels and Not Sprouting Angiogenesis Drives Acquired Sorafenib Resistance in Hepatocellular Carcinoma.
(OXFORD UNIV PRESS INC, 2016-04-08)
BACKGROUND: The anti-angiogenic Sorafenib is the only approved systemic therapy for advanced hepatocellular carcinoma (HCC). However, acquired resistance limits its efficacy. An emerging theory to explain intrinsic resistance ...