Somatic mutations in solid tumors: a spectrum at the service of diagnostic armamentarium or an indecipherable puzzle? The morphological eyes looking for BRAF and somatic molecular detections on cyto-histological samples

This review article deals with the analysis and the detection of the morphological features associated with somatic mutations, mostly BRAF(V600E) mutation, on both cytological and histological samples of carcinomas. Few authors demonstrated that some architectural and specific cellular findings (i.e. polygonal eosinophilic cells defined as "plump cells" and sickle-shaped nuclei) are able to predict BRAF (V600E) mutation in both cytological and histological samples of papillary thyroid carcinoma (PTC) as well as in other carcinomas. In the current review article we evaluated the first comprehensive analysis of the morphological prediction of BRAFV600E and other somatic mutations in different malignant lesions with the description of the possible mechanisms beneath these morphologic features. The detection of predictive morphological features, mostly on FNAC, may add helpful information to the stratification of the malignant risk and personalized management of cancers. Additionally, the knowledge of the molecular mechanism of different oncogenic drivers can lead to the organ-specific triaging selection of cases and can provide significant insight for targeted therapies in different malignant lesions.info:eu-repo/semantics/publishedVersio

In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis

Methodology: We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin-dependent kinase 1 (CDK1). This compound acts by simultaneously inhibiting pro-Angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A)-mediated signaling response and CDK1-mediated mitotic entry elicits anti-Angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis

Utilizing Tissue Microarrays for Medium-Throughput Validation of Antibodies Against Immune Markers

https://openworks.mdanderson.org/sumexp21/1201/thumbnail.jp

Convergent evolutionary trajectories uncover metastatic drivers in renal cancer

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Lineage-coupled clonal capture identifies clonal evolution mechanisms and vulnerabilities of BRAF

Targeted cancer therapies have revolutionized treatment but their efficacies are limited by the development of resistance driven by clonal evolution within tumors. We developed CAPTURE , a single-cell barcoding approach to comprehensively trace clonal dynamics and capture live lineage-coupled resistant cells for in-depth multi-omics analysis and functional exploration. We demonstrate that heterogeneous clones, either preexisting or emerging from drug-tolerant persister cells, dominated resistance to vemurafenib in BRA