Patient-derived tumor organoids mimic treatment-induced DNA damage response in glioblastoma.

Glioblastoma (GB) is the most common primary malignant brain tumor, characterized by resistance to therapy. Despite aggressive treatment options, GB remains an incurable disease. Invasiveness and heterogeneity are key GB features that cannot be studied in preclinical models.

New Insights in ATP Synthesis as Therapeutic Target in Cancer and Angiogenic Ocular Diseases.

Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion.

Infiltrating natural killer cells bind, lyse and increase chemotherapy efficacy in glioblastoma stem-like tumorospheres.

Glioblastomas remain the most lethal primary brain tumors. Natural killer (NK) cell-based therapy is a promising immunotherapeutic strategy in the treatment of glioblastomas, since these cells can select and lyse therapy-resistant glioblastoma stem-like cells (GSLCs). Immunotherapy with super-charged NK cells has a potential as antitumor approach since we found their efficiency to kill patient-derived GSLCs in 2D and 3D models, potentially reversing the immunosuppression also seen in the patients.

Upregulation of Cathepsin X in Glioblastoma: Interplay with γ-Enolase and the Effects of Selective Cathepsin X Inhibitors.

Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Understanding GBM pathobiology and discovering novel therapeutic targets are critical to finding efficient treatments. Upregulation of the lysosomal cysteine carboxypeptidase cathepsin X has been linked to immune dysfunction and neurodegenerative diseases, but its role in cancer and particularly in GBM progression in patients is unknown.

Proteases Regulate Cancer Stem Cell Properties and Remodel Their Microenvironment.

Proteolytic activity is perturbed in tumors and their microenvironment, and proteases also affect cancer stem cells (CSCs). CSCs are the therapy-resistant subpopulation of cancer cells with tumor-initiating capacity that reside in specialized tumor microenvironment niches. In this review, we briefly summarize the significance of proteases in regulating CSC activities with a focus on brain tumor glioblastoma.

Genetic Variations of Ultraconserved Elements in the Human Genome.

Ultraconserved elements (UCEs) are among the most popular DNA markers for phylogenomic analysis. In at least three of five placental mammalian genomes (human, dog, cow, mouse, and rat), 2189 UCEs of at least 200 bp in length that are identical have been identified. Most of these regions have not yet been functionally annotated, and their associations with diseases remain largely unknown.