Available genetically defined cancer models are limited in genotypic and phenotypic complexity and underrepresent the heterogeneity of human cancer. Here, we describe a combinatorial genetic strategy applied to an organoid transformation assay to rapidly generate diverse, clinically relevant bladder and prostate cancer models. Importantly, the clonal architecture of the resultant tumors can be resolved using single-cell or spatially resolved next-generation sequencing to uncover polygenic drivers of cancer phenotypes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10937382 | PMC |
http://dx.doi.org/10.1038/s41588-024-01674-1 | DOI Listing |
Viruses
December 2024
Department of Rehabilitation and Regenerative Medicine, College of Physicians and Surgeons, Columbia University, HHSC-1518, 701 W. 168th Street, New York, NY 10032, USA.
This study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical cancer. Phytochemicals were tested using growth inhibition, combination, gene expression, RT PCR, and molecular docking assays.
View Article and Find Full Text PDFMolecules
January 2025
Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Epigenetic abnormalities play a critical role in colon carcinogenesis, making them a promising target for therapeutic interventions. In this study, we demonstrated that curcumin reduces colon cancer cell survival and that a decrease in lysine methylation was involved in such an effect. This correlated with the downregulation of methyltransferases EZH2, MLL1, and G9a, in both wild-type p53 (wtp53) HCT116 cells and mutant p53 (mutp53) SW480 cells, as well as SET7/9 specifically in wtp53 HCT116 cells.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78712, USA.
Glioblastoma (GBM), the most prevalent primary malignant brain tumor, remains challenging to treat due to extensive inter- and intra-tumor heterogeneity. This variability demands combination treatments to improve therapeutic outcomes. A significant obstacle in treating GBM is the expression of O-methylguanine-DNA methyltransferase, a DNA repair enzyme that reduces the efficacy of the standard alkylating agent, temozolomide, in about 50% of patients.
View Article and Find Full Text PDFStem Cell Rev Rep
January 2025
Stem Cell Institute, Department of Development and Regeneration, KU Leuven, O&N IV Herestraat 49, Leuven, 3000, Belgium.
Reliable models of the blood-brain barrier (BBB), wherein brain microvascular endothelial cells (BMECs) play a key role in maintenance of barrier function, are essential tools for developing therapeutics and disease modeling. Recent studies explored generating BMEC-like cells from human pluripotent stem cells (hPSCs) by mimicking brain-microenvironment signals or genetic reprogramming. However, due to the lack of comprehensive transcriptional studies, the exact cellular identity of most of these cells remains poorly defined.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Moderna, Inc, Cambridge, Massachusetts, USA.
The application of messenger RNA (mRNA) technology in antigen-based immuno-oncology therapies represents a significant advancement in cancer treatment. Cancer vaccines are an effective combinatorial partner to sensitize the host immune system to the tumor and boost the efficacy of immune therapies. Selecting suitable tumor antigens is the key step to devising effective vaccinations and amplifying the immune response.
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