A5112453128- PI3K/AKT/mTOR signaling in cancer
- Tryptophan and brain disorders
- Peptidase Inhibition and Analysis
- Lanthanide and Transition Metal Complexes
- Polyamine Metabolism and Applications
- Mast cells and histamine
- Chemistry and Stereochemistry Studies
- Chronic Lymphocytic Leukemia Research
- Folate and B Vitamins Research
- Cancer-related Molecular Pathways
- Melanoma and MAPK Pathways
- Protein Degradation and Inhibitors
- Advanced Breast Cancer Therapies
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Protein Kinase Regulation and GTPase Signaling
- Chronic Myeloid Leukemia Treatments
- Lung Cancer Research Studies
Eli Lilly (United States)
2005-2019
Northern Kentucky University
1986
Abstract Activation of protein kinase Cβ (PKCβ) has been repeatedly implicated in tumor-induced angiogenesis. The PKCβ-selective inhibitor, Enzastaurin (LY317615.HCl), suppresses angiogenesis and was advanced for clinical development based upon this antiangiogenic activity. PKCβ now also tumor cell proliferation, apoptosis, invasiveness. Herein, we show that a direct effect on human cells, inducing apoptosis suppressing the proliferation cultured cells. treatment phosphorylation GSK3βser9,...
Expression of eukaryotic translation initiation factor 4E (eIF4E) is commonly elevated in human and experimental cancers, promoting angiogenesis tumor growth. Elevated eIF4E levels selectively increase growth factors important malignancy (e.g., VEGF, cyclin D1) thereby an attractive anticancer therapeutic target. Yet to date, no eIF4E-specific therapy has been developed. Herein we report development antisense oligonucleotides (ASOs) designed have the necessary tissue stability nuclease...
Abstract Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-dependent enzyme that catalyzes the initial and rate-limiting step of tryptophan catabolism resulting in local depletion concomitant production kynurenine, both which are immunosuppressive. Targeting IDO1 combination with PD-1/PD-L1-targeted antibodies has shown promise early phase clinical trials several cancers strongly suggests that, some patients, expression restrains checkpoint therapies. While extrinsically express response to...
Abstract PI3K/AKT/mTOR/S6K signaling pathway (AKT pathway) controls cell survival, cell-cycle progression, growth and metabolism through a cascade phosphorylation of number key substrates. This is regulated by three well characterized tumor suppressors; pten, tsc2, lkb1. Deletion these genes results in activation the AKT proliferative disorders. Similarly, activating mutations receptor tyrosine kinases or PI3 Kinase result pathway. Therefore, multiple nodes have become drug targets. As part...
Abstract Tryptophan metabolism plays a central role in immunosuppression through the local depletion of tryptophan with concomitant production and accumulation kynurenine, both which are immunosuppressive. Indoleamine 2,3-dioxygenase 1 (IDO1), heme-dependent enzyme, catalyzes initial rate-limiting step kynurenine pathway. Tumor cells selectively upregulate IDO1 as an immune-evasion mechanism either intrinsic expression IDO1, or response to IFN-γ, cytokine secreted by immune during active...
Tryptophan metabolism plays a central role in immunosuppression through the local depletion of tryptophan with concomitant production and accumulation kynurenine, both which are immunosuppressive. Indoleamine 2,3-dioxygenase 1 (IDO1), heme-dependent enzyme, catalyzes initial rate-limiting step kynurenine pathway. Tumor cells selectively upregulate IDO1 as an immune-evasion mechanism either intrinsic expression IDO1, or response to IFN-γ, cytokine secreted by immune during active response.In...
Abstract Ewing’s sarcoma (ES) is a rare but aggressive cancer typically occurring in the bone or soft tissue of children and adolescents. Current treatment regimens composed surgery, radiation, high-dose chemotherapy have improved outcomes for localized disease cases; however, ES continues to present clinical challenge recurrent metastatic setting. often characterized by chromosomal translocation that results chimeric EWS/ETS transcription factor. This fusion protein may contribute...