Publications by authors named "S J Sharkis"
Article Synopsis
- The study investigates the role of protein kinases, specifically c-Src, in directing the differentiation of human induced pluripotent stem cells (iPSCs) into liver cells, highlighting its importance in early liver development.
- Among 80 tested tyrosine kinase inhibitors, Src inhibitors were the only ones found to reduce endoderm formation, critical in the differentiation process.
- The research indicates that transient inhibition of c-Src can lead to the development of profibrogenic cholangiocyte-like cells, which express markers linked to liver fibrosis and inflammation, potentially shedding light on mechanisms related to biliary fibrosis in humans.
Internal tandem duplication (ITD) mutations within the FMS-like tyrosine kinase-3 (FLT3) render the receptor constitutively active driving proliferation and survival in leukemic blasts. Expression of FLT3-ITD from the endogenous promoter in a murine knockin model results in progenitor expansion and a myeloproliferative neoplasm. In this study, we show that this expansion begins with overproliferation within a compartment of normally quiescent long-term hematopoietic stem cells (LT-HSCs), which become rapidly depleted.
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- Induced pluripotent stem cell (iPSC) technology shows promise for treating various diseases, generating excitement in the medical field.
- Despite the enthusiasm, there's limited evidence supporting their effectiveness in real-world clinical scenarios.
- The text outlines potential applications for iPSCs in cancer treatment and identifies existing challenges that hinder their broader use in healthcare.
Reversal of promoter DNA hypermethylation and associated gene silencing is an attractive cancer therapy approach. The DNA methylation inhibitors decitabine and azacitidine are efficacious for hematological neoplasms at lower, less toxic, doses. Experimentally, high doses induce rapid DNA damage and cytotoxicity, which do not explain the prolonged time to response observed in patients.
View Article and Find Full Text PDFRelapse of acute myeloid leukemia (AML) is thought to reflect the failure of current therapies to adequately target leukemia stem cells (LSCs), the rare, resistant cells presumed responsible for maintenance of the leukemia and typically enriched in the CD34(+)CD38(-) cell population. Despite the considerable research on LSCs over the past 2 decades, the clinical significance of these cells remains uncertain. However, if clinically relevant, it is expected that LSCs would be enriched in minimal residual disease and predictive of relapse.
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