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Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma.
(IMPACT JOURNALS LLC, 2016-10-04)
Pediatric high-grade glioma (HGG, WHO Grade III and IV) is a devastating brain tumor with a median survival of less than two years. PDGFRA is frequently mutated/ amplified in pediatric HGG, but the significance of this ...
Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors.
(NATL ACAD SCIENCES, 2016-11-29)
Myc family proteins promote cancer by inducing widespread changes in gene expression. Their rapid turnover by the ubiquitin-proteasome pathway is regulated through phosphorylation of Myc Box I and ubiquitination by the E3 ...
Heterogeneous response and progression patterns reveal phenotypic heterogeneity of tyrosine kinase inhibitor response in metastatic renal cell carcinoma.
(BIOMED CENTRAL LTD, 2016-11-14)
BACKGROUND: Molecular intratumour heterogeneity (ITH) is common in clear cell renal carcinomas (ccRCCs). However, it remains unknown whether this is mirrored by heterogeneity of drug responses between metastases in the ...
Genomic evolution and chemoresistance in germ-cell tumours.
(NATURE PUBLISHING GROUP, 2016-11-30)
Germ-cell tumours (GCTs) are derived from germ cells and occur most frequently in the testes. GCTs are histologically heterogeneous and distinctly curable with chemotherapy. Gains of chromosome arm 12p and aneuploidy are ...
Molecular or Metabolic Reprograming: What Triggers Tumor Subtypes?
(AMER ASSOC CANCER RESEARCH, 2016-09-15)
Tumor heterogeneity is reflected and influenced by genetic, epigenetic, and metabolic differences in cancer cells and their interactions with a complex microenvironment. This heterogeneity has resulted in the stratification ...
Multiple myeloma risk variant at 7p15.3 creates an IRF4-binding site and interferes with CDCA7L expression.
(NATURE PUBLISHING GROUP, 2016-11-24)
Genome-wide association studies have identified several risk loci for multiple myeloma (MM); however, the mechanisms by which they influence MM are unknown. Here by using genetic association data and functional characterization, ...
Should tissue structure suppress or amplify selection to minimize cancer risk?
(2016-08-01)
Background: It has been frequently argued that tissues evolved to suppress the accumulation of growth enhancing cancer inducing mutations. A prominent example is the hierarchical structure of tissues with high cell turnover, ...
Carcinogenic polycyclic aromatic hydrocarbons induce CYP1A1 in human cells via a p53-dependent mechanism
(Springer Science and Business Media LLC, 2016-02-01)
The tumour suppressor gene TP53 is mutated in more than 50 % of human tumours, making it one of the most important cancer genes. We have investigated the role of TP53 in cytochrome P450 (CYP)-mediated metabolic activation ...
Subcellular protein expression models for microsatellite instability in colorectal adenocarcinoma tissue images
(2016-10-01)
Background: New bioimaging techniques capable of visualising the co-location of numerous proteins within individual cells have been proposed to study tumour heterogeneity of neighbouring cells within the same tissue specimen. ...
8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors.
(AMER CHEMICAL SOC, 2016-02-25)
We report the discovery of N-substituted 4-(pyridin-2-yl)thiazole-2-amine derivatives and their subsequent optimization, guided by structure-based design, to give 8-(1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-ones, a ...