Glioblastoma is the most common and deadly primary brain malignancy. Despite advances in precision medicine oncology (PMO) allowing the identification of molecular vulnerabilities in glioblastoma, treatment options remain limited, and molecular assays guided by genomic and expression profiling to inform patient enrollment in life-saving trials are lacking. Here, we generate four-dimensional (4D) cell-culture arrays for rapid assessment of drug responses in glioblastoma patient-derived models. The arrays are 3D printed with thermo-responsive shape memory polymer (SMP). Upon heating, the SMP arrays self-transform in time from 3D cell-culture inserts into histological cassettes. We assess the utility of these arrays with glioblastoma cells, gliospheres, and patient derived organoid-like (PDO) models and demonstrate their use with glioblastoma PDOs for assessing drug sensitivity, on-target activity, and synergy in drug combinations. When including genomic and drug testing assays, this platform is poised to offer rapid functional drug assessments for future selection of therapies in PMO.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393526 | PMC |
http://dx.doi.org/10.1016/j.isci.2020.101365 | DOI Listing |
Nanoscale
January 2025
Department of Anaesthesiology, Perioperative and Pain Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 211101, China.
Through transcriptomic analysis of patient-derived glioblastoma tissues, we identify an overactivation of inflammatory pathways that contribute to the development of a tumor-promoting microenvironment and therapeutic resistance. To address this critical mechanism, we present NanoAid, a biomimetic nanoplatform designed to target inflammatory pro-tumor processes to advance glioblastoma chemotherapy. NanoAid employs macrophage-membrane-liposome hybrids to optimize the delivery of COX-2 inhibitor parecoxib and paclitaxel.
View Article and Find Full Text PDFAttempts to activate an anti-tumor immune response in glioblastoma (GBM) have been met with many challenges due to its inherently immunosuppressive tumor microenvironment. The degree and mechanisms by which molecularly and phenotypically diverse tumor-propagating glioma stem cells (GSCs) contribute to this state are poorly defined. In this study, our multifaceted approach combining bioinformatics analyses of clinical and experimental datasets, single-cell sequencing, and molecular and pharmacologic manipulation of patient-derived cells identified GSCs expressing immunosuppressive effectors mimicking regulatory T cells (Tregs).
View Article and Find Full Text PDFACS Omega
January 2025
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States.
Protein arginine methyltransferase 5 (PRMT5), which symmetrically dimethylates cytosolic and nuclear proteins, has been demonstrated as an important cancer therapeutic target. In recent years, many advanced achievements in PRMT5 inhibitor development have been made. Most PRMT5 inhibitors in the clinical trial focus on targeting the C-terminal catalytic domain, whereas developing small molecules to interrupt the PRMT5/pICLn (methylosome subunit) protein-protein interface is also of great importance for inhibiting PRMT5.
View Article and Find Full Text PDFCell Death Dis
January 2025
Division of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.
The association of necrosis in tumors with poor prognosis implies a potential tumor-promoting role. However, the mechanisms underlying cell death in this context and how damaged tissue contributes to tumor progression remain unclear. Here, we identified p38 mitogen-activated protein kinases (p38 MAPK, a.
View Article and Find Full Text PDFActa Biomater
January 2025
Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia 30322, USA; Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA. Electronic address:
Pro-tumoral M2 tumor-associated macrophages (TAMs) play a critical role in the tumor immune microenvironment (TIME), making them an important therapeutic target for cancer treatment. Approaches for imaging and monitoring M2 TAMs, as well as tracking their changes in response to tumor progression or treatment are highly sought-after but remain underdeveloped. Here, we report an M2-targeted magnetic resonance imaging (MRI) probe based on sub-5 nm ultrafine iron oxide nanoparticles (uIONP), featuring an anti-biofouling coating to prevent non-specific macrophage uptake and an M2-specific peptide ligand (M2pep) for active targeting of M2 TAMs.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!