Changes in HER2 Amplification Status for Breast Cancer Patients After Immunohistochemistry Directed In Situ Hybridization.

The 2018 ASCO/CAP guidelines for HER2 testing for breast cancer implemented the addition of immunohistochemistry (IHC) directed in situ hybridization (ISH) recount to resolve equivocal results. The implementation of an additional 2+ IHC-directed ISH recount adds additional complexity to the testing workflow for an unclear impact on HER2 results. A retrospective review of all equivocal ISH cases (groups 2, 3, and 4) that underwent 2+ IHC-directed ISH, since the 2018 guidelines, which were finalized as either amplified or not amplified, was performed.

Developing Allosteric Chaperones for -Associated Disorders-An Integrated Computational and Experimental Approach.

Mutations in the gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase), are associated with Gaucher disease and increased risk of Parkinson's disease. This study describes the discovery and characterization of novel allosteric pharmacological chaperones for GCase through an innovative computational approach combined with experimental validation. Utilizing virtual screening and structure-activity relationship optimization, researchers identified several compounds that significantly enhance GCase activity and stability across various cellular models, including patient-derived fibroblasts and neuronal cells harboring mutations.

Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice.

Fostamatinib, a recently approved Syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here, 138 patients with ITP (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively.

Pilot study to evaluate isolation by size of circulating tumour cells in canine oral melanoma.

Liquid biopsy for circulating tumour cell (CTC) detection is generally unexplored in veterinary medicine. Dogs with highly aggressive and heterogeneous tumours, such as oral malignant melanoma (OMM), could benefit from studies involving size-based isolation methods for CTCs, as they do not depend on specific antibodies. This pilot study aimed to detect CTCs from canine OMM using Isolation by Size of Epithelial Tumor Cells (ISET), a microfiltration methodology, followed by immunocytochemistry (ICC) with Melan-A, PNL2, and S100 antibodies.

Discovery of allosteric regulators with clinical potential to stabilize alpha-L-iduronidase in mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal disease caused by lowered activity of the enzyme alpha-L-iduronidase (IDUA). Current therapeutic options show limited efficacy and do not treat some important aspects of the disease. Therefore, it may be advantageous to identify strategies that could improve the efficacy of existing treatments.