Novel Uveal Melanoma Patient-Derived Organoid Models Recapitulate Human Disease to Support Translational Research.

Purpose: A lack of representative human disease models has limited the translation of new and more effective treatments in uveal melanoma (UM), the most common primary adult intraocular malignancy. To fill this critical need, we developed and characterized a multicenter biobank of UM patient-derived organoids (PDOs).

Methods: UM patients requiring enucleation from 2019 to 2024 donated tumor tissue for PDO generation.

Effect of Detraining on Muscle Strength, Functional Capacity, Mental Health, and Body Composition in Individuals with Spinal Cord Injury.

Spinal cord injury (SCI) is a condition that significantly affects the quality of life (QoL) of individuals, causing motor, physiological, social, and psychological impairments. Physical exercise plays a crucial role in maintaining the health and functional capacity of these individuals, helping to minimize the negative impacts of SCI. The aim of this study was to evaluate the effect of detraining (DT) (reduction or cessation of physical exercise) during the pandemic on five individuals with thoracic SCI.

KRAS Promotes GLI2-Dependent Transcription during Pancreatic Carcinogenesis.

Aberrant activation of GLI transcription factors has been implicated in the pathogenesis of different tumor types including pancreatic ductal adenocarcinoma. However, the mechanistic link with established drivers of this disease remains in part elusive. In this study, using a new genetically engineered mouse model overexpressing constitutively active mouse form of GLI2 and a combination of genome-wide assays, we provide evidence of a novel mechanism underlying the interplay between KRAS, a major driver of pancreatic ductal adenocarcinoma development, and GLI2 to control oncogenic gene expression.

SUFU promotes GLI activity in a Hedgehog-independent manner in pancreatic cancer.

Aberrant activation of the Hedgehog (Hh) signaling pathway, through which the GLI family of transcription factors (TF) is stimulated, is commonly observed in cancer cells. One well-established mechanism of this increased activity is through the inactivation of Suppressor of Fused (SUFU), a negative regulator of the Hh pathway. Relief from negative regulation by SUFU facilitates GLI activity and induction of target gene expression.