Trastuzumab and thyroid dysfunction: An association to be aware of.

The incidence of autoimmune thyroid disorders is higher among women with breast cancer (BC) than in other solid malignancies, while it has not a prognostic impact. Trastuzumab (T) is a humanized monoclonal antibody approved for human epidermal growth factor receptor 2 (HER2)-positive BC in the neoadjuvant, adjuvant, and metastatic scenarios. Since 2014, subcutaneous (SC) T has been employed with the same efficacy as the intravenous formulation together with an easier way of administration. To date, autoimmune thyroiditis has been linked rarely to the use of intravenous T, and no cases have been related to the SC presentation. We report two cases of HER2-positive early BC patients who developed hypothyroidism during maintenance therapy with SC T that required levothyroxine supplementation. SC T includes recombinant human hyaluronidase to facilitate tissue penetration of the drug. This enzyme may alter the thyroid gland stroma and facilitate the development of thyroid disorders. Thyroid function tests are recommended in patients on SC T.

Identification of Ezetimibe and Pranlukast as Pharmacological Chaperones for the Treatment of the Rare Disease Mucopolysaccharidosis Type IVA.

Mucopolysaccharidosis type IVA (MPS IVA) is a rare disease caused by mutations in the gene encoding the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). We report here two GALNS pharmacological chaperones, ezetimibe and pranlukast, identified by molecular docking-based virtual screening. These compounds bound to the active cavity of GALNS and increased its thermal stability as well as the production of recombinant GALNS in bacteria, yeast, and HEK293 cells. MPS IVA fibroblasts treated with these chaperones exhibited increases in GALNS protein and enzyme activity and reduced the size of enlarged lysosomes. Abnormalities in autophagy markers p62 and LC3B-II were alleviated by ezetimibe and pranlukast. Combined treatment of recombinant GALNS with ezetimibe or pranlukast produced an additive effect. Altogether, the results demonstrate that ezetimibe and pranlukast can increase the yield of recombinant GALNS and be used as a monotherapy or combination therapy to improve the therapeutic efficacy of MPS IVA enzyme replacement therapy.

Growth Factors and Astrocytes Metabolism: Possible Roles for Platelet Derived Growth Factor.

Astrocytes exert multiple functions in the brain such as the development of blood-brain barrier characteristics, the promotion of neurovascular coupling, attraction of cells through the release of chemokines, clearance of toxic substances and generation of antioxidant molecules and growth factors. In this aspect, astrocytes secrete several growth factors (BDNF, GDNF, NGF, and others) that are fundamental for cell viability, oxidant protection, genetic expression and modulation of metabolic functions. The platelet derived growth factor (PDGF), which is expressed by many SNC cells, including astrocytes, is an important molecule that has shown neuroprotective potential, improvement of wound healing, regulation of calcium metabolism and mitochondrial function. Here we explore some of these astrocyte-driven functions of growth factors and their possible therapeutic uses in the context of neurodegeneration.

37th Annual San Antonio Breast Cancer Symposium. Resumen de las aportaciones translacionales y clínicas más relevantes / 37th Annual San Antonio Breast Cancer Symposium. Summary of the most important translational and clinical contributions

En diciembre de 2014 hemos tenido la oportunidad de ampliar nuestro conocimiento en el Simposio Internacional de Cáncer de Mama, celebrado en San Antonio, resaltando: 1) en el escenario básico, la adquisición de mutaciones durante el proceso de carcinogénesis y metástasis, aumentando la clonalidad y heterogeneidad tumoral, el papel pronóstico de los neoantígenos y los linfocitos infiltrantes en el residuo tumoral tras la neoadyuvancia, así como el mayor conocimiento de alteraciones en el receptor de estrógeno asociadas a hormonorresistencia; 2) en el translacional, el empleo de xenoinjertos derivados de tumores de pacientes en modelos murinos para evitar las resistencias terapéuticas, y los biomarcadores líquidos para descartar enfermedad mínima residual en cáncer de mama precoz; y 3) en clínica los resultados tanto en prevención como en adyuvancia con hormonoterapia, la quimioterapia en triples negativos y las novedades en inmunoterapia (AU)

The 37th San Antonio Breast Cancer Symposium, held in December 2014, provided an opportunity to gain greater knowledge. Notable contributions were the following: 1) in basic research, the acquisition of mutations in carcinogenesis and metastasis, which increase with clonality and heterogeneity; the prognostic role of neoantigens and infiltrating lymphocytes in the residual tumor after neoadjuvant chemotherapy; and an increased knowledge of molecular mutations in the estrogen receptor, which explain hormonal resistance; 2) in the translational arena, the role of patient-derived xenografts to avoid therapeutic resistance; and the role of liquid biomarkers to detect minimal residual disease in early breast cancer; and 3) in the clinical scenario, advances in prevention and hormone therapy, and news on triple-negative tumors and immunotherapy (AU)