Distinct genomic and immunologic tumor evolution in germline TP53-driven breast cancers.

Pathogenic germline TP53 alterations cause Li-Fraumeni Syndrome (LFS), and breast cancer is the most common cancer in LFS females. We performed first of its kind multimodal analysis of LFS breast cancer (LFS-BC) compared to sporadic premenopausal BC. Nearly all LFS-BC underwent biallelic loss of TP53 with no recurrent oncogenic variants except ERBB2 (HER2) amplification. Compared to sporadic BC, in situ and invasive LFS-BC exhibited a high burden of short amplified aneuploid segments (SAAS). Pro-apoptotic p53 target genes BAX and TP53I3 failed to be up-regulated in LFS-BC as was seen in sporadic BC compared to normal breast tissue. LFS-BC had lower CD8+ T-cell infiltration compared to sporadic BC yet higher levels of proliferating cytotoxic T-cells. Within LFS-BC, progression from in situ to invasive BC was marked by an increase in chromosomal instability with a decrease in proliferating cytotoxic T-cells. Our study uncovers critical events in mutant p53-driven tumorigenesis in breast tissue.

Anomalías de las arterias coronarias: una revisión de la literatura y propuesta de una nueva clasificación / Coronary artery anomalies: a review of the literature and a proposal for a new classification

Resumen Las anomalías de las arterias coronarias son alteraciones anatómicas, usualmente congénitas, que afectan el origen, el curso y la terminación de alguna de las arterias coronarias epicárdicas principales. Estas pueden llevar a desenlaces adversos, como isquemia miocárdica, falla cardiaca, enfermedad coronaria o muerte súbita. Desde sus primeras descripciones hasta la actualidad, y gracias al desarrollo de nuevas tecnologías, se ha obtenido más información y mejor caracterización de estas anomalías, lo que hace necesario revisar y actualizar las clasificaciones originales. Este artículo se propone plantear una posible nueva clasificación que combina las características anatómicas y el grado de significado clínico para intentar lograr un mayor entendimiento, y así facilitar la decisión clínica para la elección del tratamiento. Se realizó una revisión narrativa y se incluyen casos de nuestra experiencia.

Abstract Coronary artery anomalies (CAA) are anatomical abnormalities, usually congenital, that affect the origin, course, and termination of one of the three main epicardical coronary arteries. These may lead to adverse outcomes such as myocardial ischemia, heart failure, coronary artery disease and/or sudden death. Since their first descriptions to the present day, and thanks to the development of new technologies, more information and better characterization of these anomalies has been obtained, requiring that the original classifications be revised and updated. The aim of this article is to propose a possible new classification that combines anatomical features and the degree of clinical significance to try to achieve a better understanding, and thus facilitate the clinical choice of treatment. A narrative review was performed and cases from our experience are included.

Correction: Escudero-Flórez et al. Dengue Virus Infection Alters Inter-Endothelial Junctions and Promotes Endothelial-Mesenchymal-Transition-like Changes in Human Microvascular Endothelial Cells. Viruses 2023, 15, 1437.

Ryan L [...].

Dengue Virus Infection Alters Inter-Endothelial Junctions and Promotes Endothelial-Mesenchymal-Transition-Like Changes in Human Microvascular Endothelial Cells.

Dengue virus (DENV) is a pathogenic arbovirus that causes human disease. The most severe stage of the disease (severe dengue) is characterized by vascular leakage, hypovolemic shock, and organ failure. Endothelial dysfunction underlies these phenomena, but the causal mechanisms of endothelial dysfunction are poorly characterized. This study investigated the role of c-ABL kinase in DENV-induced endothelial dysfunction. Silencing c-ABL with artificial miRNA or targeting its catalytic activity with imatinib revealed that c-ABL is required for the early steps of DENV infection. DENV-2 infection and conditioned media from DENV-infected cells increased endothelial expression of c-ABL and CRKII phosphorylation, promoted expression of mesenchymal markers, e.g., vimentin and N-cadherin, and decreased the levels of endothelial-specific proteins, e.g., VE-cadherin and ZO-1. These effects were reverted by silencing or inhibiting c-ABL. As part of the acquisition of a mesenchymal phenotype, DENV infection and treatment with conditioned media from DENV-infected cells increased endothelial cell motility in a c-ABL-dependent manner. In conclusion, DENV infection promotes a c-ABL-dependent endothelial phenotypic change that leads to the loss of intercellular junctions and acquisition of motility.

Glossolomamagenticristatum (Gesneriaceae), a new species from the Cordillera Oriental of the Colombian Andes.

A narrowly endemic new species of Glossoloma is described from the Cordillera Oriental of the northern Andes, in the Colombian departments of Caquetá and Huila. Glossolomamagenticristatum J.L.Clark, D.Hoyos & Clavijo, sp. nov. differs from most other congeners by a habit that is usually epiphytic with elongate scandent subwoody shoots, the presence of a magenta corolla tube, and a creased calyx formed by tightly appressed adjacent lobes. A brief summary of Gesneriaceae diversity in the Colombia departments of Caquetá and Huila is discussed with an emphasis on the old highway between Florencia and Guadalupe. The conservation status of G.magenticristatum is assessed as Endangered (EN) based on IUCN Criteria.

ResumenSe describe una especie de Glossoloma endémica de la Cordillera Oriental de los Andes del norte, en los departamentos de Caquetá y Huila. Glossolomamagenticristatum J.L.Clark, D.Hoyos & Clavijo, sp. nov. se diferencia de otras especies en el género por el hábito usualmente epífito con ramas alargadas, escandentes y subleñosas, el tubo de la corola magenta, y un cáliz con los lóbulos estrechamente adpresos y con margen ondulada. Se presenta una breve síntesis de la diversidad de Gesneriaceae en los departamentos de Caquetá y Huila, con un énfasis en la vieja carretera entre Florencia y Guadalupe. Se evalúa el estado de conservación de G.magenticristatum y se propone que se debería categorizar como En Peligro (EN), de acuerdo a los criterios de la UICN.

Response of Leptomeningeal Metastases in EGFR-Mutated Non-Small-Cell Lung Cancer to Afatinib in the Absence of Radiotherapy.

Palliative radiotherapy is currently the medical standard of care for non-small-cell lung cancer (NSCLC) patients with symptomatic CNS and leptomeningeal disease. We report the case of a 62-year-old male patient with EGFR mutation (del19+) NSLC with symptomatic lymph node, bone, CNS, and leptomeningeal metastases. Taking into account on one hand the response to tyrosine kinase inhibitors (TKIs) and on the other hand the short- to medium-term side effects of radiotherapy and the lack of timely availability in our healthcare system, the patient was treated with afatinib (40 mg daily) and exhibited a rapid response with improvement of neurological symptoms. The patient presented partial response of extracranial, CNS, and leptomeningeal lesions at 3, 6, and 12 months of treatment, currently completing 16 months of progression-free survival despite presenting mild dermatological and gastrointestinal toxicities. Afatinib is an effective and safe option in patients with NSLC EGFR mutation del19+ with CNS and leptomeningeal compromise avoiding or delaying radiotherapy and its side effects, especially in countries where there is a lack of access to this kind of therapy.