Publications by authors named "R A Kopher"
Article Synopsis
- Metastatic castration-resistant prostate cancer (mCRPC) often shows loss of sensitivity to androgen receptors and activation of the PI3K/AKT/mTOR pathway, making treatment difficult due to feedback mechanisms that lead to drug resistance.
- The study suggests that gedatolisib, a potent multi-target inhibitor of the PI3K pathway and mTORC1/2, is more effective than single-node PAM inhibitors for treating prostate cancer cells, regardless of their PTEN/PIK3CA status.
- Gedatolisib's superior effectiveness arises from its ability to impact critical cell functions, and it is currently in a clinical trial combined with darolutamide for patients with mCRPC.
Article Synopsis
- The PAM pathway, often disrupted in breast cancer, involves interlinked signaling that supports tumor growth, and current treatments typically target only one part of this pathway.
- Researchers propose that gedatolisib, a pan-PI3K/mTOR inhibitor, could be more effective than single-node PAM inhibitors by addressing multiple targets, potentially reducing drug resistance in breast cancer cells.
- In laboratory tests, gedatolisib showed superior anti-cancer effects compared to other PAM inhibitors by decreasing cell survival and invasive behavior across various breast cancer cell lines, leading to further clinical evaluation in a Phase 3 study.
We generated a RUNX2-yellow fluorescent protein (YFP) reporter system to study osteogenic development from human embryonic stem cells (hESCs). Our studies demonstrate the fidelity of YFP expression with expression of RUNX2 and other osteogenic genes in hESC-derived osteoprogenitor cells, as well as the osteogenic specificity of YFP signal. In vitro studies confirm that the hESC-derived YFP(+) cells have similar osteogenic phenotypes to osteoprogenitor cells generated from bone-marrow mesenchymal stem cells.
View Article and Find Full Text PDFTo evaluate hematopoietic niche cell populations isolated from human embryonic stem cells (hESCs), we tested the ability of hESC-derived stromal lines to support CD34(+) umbilical cord blood (UCB)- and hESC-derived CD34(+)45(+) cells in long-term culture initiating cell (LTC-IC) assays. Specifically, these hematopoietic populations were cocultured with hESC-derived mesenchymal stromal cells (hESC-MSCs) and hESC-derived endothelial cells (hESC-ECs), and then assessed for their LTC-IC potential in comparison to coculture with bone marrow (BM)-derived MSCs and the mouse stromal line M2-10B4. We found that the hESC-derived stromal lines supported LTC-ICs from UCB similar to M2-10B4 cells and better than BM-MSCs.
View Article and Find Full Text PDFDevelopment of novel therapeutic approaches to repair fracture non-unions remains a critical clinical necessity. We evaluated the capacity of human embryonic stem cell (hESC)-derived mesenchymal stem/stromal cells (MSCs) to induce healing in a fracture non-union model in rats. In addition, we placed these findings in the context of parallel studies using human bone marrow MSCs (hBM-MSCs) or a no cell control group (n = 10-12 per group).
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