Realistic and renewable laboratory models that accurately reflect the distinct clinical features of childhood cancers have enormous potential to speed research progress. These models help us to understand disease biology, develop new research methods, advance new therapies to clinical trial, and implement personalized medicine. This chapter describes methods to generate patient-derived xenograft models of neuroblastoma and rhabdomyosarcoma, two tumor types for which children with high-risk disease have abysmal survival outcomes and survivors have lifelong-debilitating effects from treatment. Further, this protocol addresses model development from diverse clinical tumor tissue samples, subcutaneous and orthotopic engraftment, and approaches to avoid model loss.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1007/978-1-0716-3858-3_6 | DOI Listing |
Cancer Res
January 2025
Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Intrahepatic cholangiocarcinoma (iCCA) is a lethal malignancy affecting the liver and biliary system. Enhanced understanding of the pathogenic mechanisms underlying iCCA tumorigenesis and the discovery of appropriate therapeutic targets are imperative to improve patient outcomes. Here, we investigated the functions and regulations of solute carrier family 16 member 3 (SLC16A3), which has been reported to be a biomarker of poor prognosis in iCCA.
View Article and Find Full Text PDFAnimal Model Exp Med
January 2025
Cancer Institute, School of Medicine, Jianghan University, Wuhan, China.
The high morbidity and mortality of colorectal cancer (CRC) is a major challenge in clinical practice. Although a series of alternative research models of CRC have been developed, appropriate orthotopic animal models that reproduce the specific clinical response as well as pathophysiological immune features of CRC are still lacking. In the current study, we constructed a CRC orthotopic xenograft model by implanting the tumor tubes at the colorectum of mice and monitored the model development using bioluminescence imaging.
View Article and Find Full Text PDFDis Model Mech
January 2025
Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium.
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal malignancy of the gastrointestinal tract. Most GIST harbor mutations in oncogenes, such as KIT, and are treated with tyrosine kinase inhibitors (TKI), such as imatinib. Most tumors develop secondary mutations inducing drug resistance against the available TKI, which requires novel therapies.
View Article and Find Full Text PDFLeukemia
January 2025
Australian Centre for Blood Diseases (ACBD), School of Translational Medicine, Monash University, Melbourne, VIC, Australia.
Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) is an immature subtype of T-cell acute lymphoblastic leukemia (T-ALL) commonly show deregulation of the LMO2-LYL1 stem cell transcription factors, activating mutations of cytokine receptor signaling, and poor early response to intensive chemotherapy. Previously, studies of the Lmo2 transgenic mouse model of ETP-ALL identified a population of stem-like T-cell progenitors with long-term self-renewal capacity and intrinsic chemotherapy resistance linked to cellular quiescence. Here, analyses of Lmo2 transgenic mice, patient-derived xenografts, and single-cell RNA-sequencing data from primary ETP-ALL identified a rare subpopulation of leukemic stem cells expressing high levels of the cytokine receptor FLT3.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
January 2025
Department of Cancer Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Background: Despite promising preclinical studies, the application of DNA methyltransferase inhibitors in treating patients with solid cancers has thus far produced only modest outcomes. The presence of intratumoral heterogeneity in response to DNA methyltransferase inhibitors could significantly influence clinical efficacy, yet our understanding of the single-cell response to these drugs in solid tumors remains very limited.
Methods: In this study, we used cancer/testis antigen genes as a model for methylation-dependent gene expression to examine the activity of DNA methyltransferase inhibitors and their potential synergistic effect with histone deacetylase inhibitors at the single-cancer cell level.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!