The incidence of hepatocellular carcinoma (HCC) is 750,000 new cases globally, it is the second leading cause of cancer-related death and represents a major health problem. When identified at early stages, curative treatments such as resection, transplantation and percutaneous ablation are feasible. Surveillance programs established in developed countries allow for early detection in 50% of cases. Candidates for entering surveillance are mostly cirrhotic patients that account for 1% of the human population. Around half of the nodules identified in the setting of these programs are ultimately malignant. In fact, small
Background: Two families of transcriptional regulators, members of the “signal transducers and activators of transcription” (STAT) and “interferon regulatory factor” (IRF) families, work in conjunction to establish a cascade of gene regulation and signal transduction events that lead to transcriptional activation of interferon-stimulated genes (ISGs). Proteins encoded by such ISGs have potent antiviral properties, which include disruption of the viral replicative life cycle, blockage of cell cycle progression, and apoptosis.
Researchers at the Icahn School of Medicine at Mount Sinai have made novel fusion proteins that induce interferon expression for use
Intracellular signaling pathways mediate cellular responses to a variety of extracellular signals and dysregulation of such pathways, especially those involved in cell growth and differentiation, is the main cause of cancer. The RAS family of proteins plays key roles in signal transduction, and mutations in RAS proto-oncogenes are involved in about 20% to 30% of all human tumors.
PTPN11 is a cytoplasmic Src homology-2 (SH2) domain-containing protein tyrosine phosphatase that is critical for RAS signaling. Specifically, PTPN11 positively controls RAS function, and is required for the activation of the mitogen-activated protein
Scientists in Drs. Hoffman and Chaurasia’s laboratories have developed a novel approach to substantially expand the numbers of functional Cord blood (CB) hematopoietic stem cells (HSCs) while maintaining true stem cell engraftment capability. Cord blood (CB) cells that express CD34 have extensive hematopoietic capacity and rapidly divide ex-vivo in the presence of cytokine combinations. However, many of these CB CD34+ cells lose their marrow-repopulating potential.
To overcome this functional decline, dividing CB-CD34+ cells were treated with histone deacetylase inhibitors (HDACI) valproic acid (VPA) for seven days using a serum-free (SF) culture
Protein ubiquitination, a multi-step process utilizing a cascade of three enzyme classes (E1, E2 and E3), tightly regulates cellular protein turnover. It plays a key role in cellular proliferation and inflammation and is associated with a multitude of diseases, including cancer, metabolic disorders, and muscle and nerve degeneration.
Dr. Pan and colleagues developed a novel high throughput functional screen to identify small molecule inhibitors of the ubiquitin system. They reconstituted the enzymatic cascade in vitro, using E1, E2 and E3 together with fluorescently labeled ubiquitin (Ub). Formation of lysine 48 linked
LOW DOSE PROTEASOME INHIBITOR SENSITIZES PI3K RESISTANT CANCERS TO TREATMENT WITH PI3K PATHWAY INHIBITORS
Resistance to PI3 kinase pathway inhibitors can occur through changes in cancer signaling pathways. “Priming” with subtherapeutic doses bortezomib leads to activation of and reliance on the PI3 kinase pathway, making cancers susceptible to PI3 kinase pathway inhibitors.
Dr. Ross Cagan and members of his laboratory at Mount Sinai’s Center for Personalized Cancer Therapeutics, using a unique high-throughput screening method in drosophila, demonstrated the use of low dose bortezomib permitted effective treatment with multiple dual PI3K/mTOR inhibitors in flies with mutations in the ras, p53, pten, and apc pathways. These findings were
Dr. Chris Basler and colleagues have developed a stable cell line with enhanced virus replication and production efficiency. The Vero 76 cell line (ATCC No. CCL-1587) has been widely used for cell-based research and product development (1, 2, 4). Several characteristics of Vero 76 cells make them particularly suited for vaccine development and production, including their ability to support large-scale growth of many virus types, a lack of interferon response, and their subsequent susceptibility to viral infection (2, 3, 5). However, despite the absence of IFN genes, Vero 76 cells
Bromodomain-containing proteins function as chromatin modifiers and mediators of protein-protein interactions, controlling gene expression. BRDs have been functionally implicated in numerous disease processes, including cancer, and small molecule inhibitors have been developed with some advancing to early clinical trials in cancer. BRD4 is a member of the BET (Bromodomain and extra terminal domain) family proteins containing two tandem bromodomains and is the target of drug discovery efforts by Mount Sinai researchers who have developed novel composition of matter inhibitors of BRD4.
Current Development Status
Significant in vitro studies completed
Mouse xenografts of Triple Negative