A5076242741- Nonmelanoma Skin Cancer Studies
- Cancer and Skin Lesions
- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- CNS Lymphoma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Salivary Gland Tumors Diagnosis and Treatment
- CAR-T cell therapy research
- Iron Metabolism and Disorders
- Medical Imaging Techniques and Applications
- Melanoma and MAPK Pathways
- PI3K/AKT/mTOR signaling in cancer
- Breast Cancer Treatment Studies
- Head and Neck Cancer Studies
- Cytokine Signaling Pathways and Interactions
- Immune cells in cancer
- Cancer-related Molecular Pathways
- Cancer, Hypoxia, and Metabolism
- Pregnancy and preeclampsia studies
- Hemoglobinopathies and Related Disorders
- Cancer Mechanisms and Therapy
- Glioma Diagnosis and Treatment
- Coenzyme Q10 studies and effects
- Hippo pathway signaling and YAP/TAZ
University of California, Los Angeles
2010-2024
University of California System
2024
UCLA Medical Center
2020
Institute for Molecular Medicine
2011-2018
Memorial Sloan Kettering Cancer Center
2011-2017
UCLA Health
2015
Cornell University
2011
UCLA Jonsson Comprehensive Cancer Center
2011
Loss-of-function mutations in JAK1/2 can lead to acquired resistance anti-programmed death protein 1 (PD-1) therapy. We reasoned that they may also be involved primary anti-PD-1 JAK1/2-inactivating were noted tumor biopsies of 23 patients with melanoma and 16 mismatch repair-deficient colon cancer treated PD-1 blockade. Both cases had a high mutational load but did not respond Two out 48 human cell lines mutations, which led lack PD-L1 expression upon interferon gamma exposure mediated by an...
The recent discovery of mutations in metabolic enzymes has rekindled interest harnessing the altered metabolism cancer cells for therapy. One potential drug target is isocitrate dehydrogenase 1 (IDH1), which mutated multiple human cancers. Here, we examine role mutant IDH1 fully transformed with endogenous mutations. A selective R132H-IDH1 inhibitor (AGI-5198) identified through a high-throughput screen blocked, dose-dependent manner, ability enzyme (mIDH1) to produce R-2-hydroxyglutarate...
Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial ibrutinib, first-in-class inhibitor, for patients relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred 10 13 (77%) PCNSL, including five complete responses. only PCNSL resistance harbored mutation within coiled-coil domain CARD11, known...
Abstract In contrast to normal cells, cancer cells avidly take up glucose and metabolize it lactate even when oxygen is abundant, a phenomenon referred as the Warburg effect. This fundamental alteration in metabolism enables their specific detection by positron emission tomography (PET) following i.v. injection of analogue 18F-fluorodeoxy-glucose (18FDG). However, this useful imaging technique limited fact that not all cancers FDG. To identify molecular determinants 18FDG retention, we...
The phosphatase and tensin homolog (PTEN) is a tumor suppressor that inactivated in many human cancers. PTEN loss has been associated with resistance to inhibitors of the epidermal growth factor receptor (EGFR), but molecular basis this unclear. It believed unopposed phosphatidylinositol-3-kinase (PI3K) activation through multiple tyrosine kinases (RTKs) can relieve PTEN-deficient cancers from their “dependence” on EGFR or any other single RTK for survival. Here we report distinct mechanism...
Copy number alteration (CNA) profiling of human tumors has revealed recurrent patterns DNA amplifications and deletions across diverse cancer types. These are suggestive conserved selection pressures during tumor evolution but cannot be fully explained by known oncogenes suppressor genes. Using a pan-cancer analysis CNA data from patient experimental systems, here we show that principal component analysis-defined signatures predictive glycolytic phenotypes, including 18F-fluorodeoxy-glucose...
AKT, a critical effector of the phosphoinositide 3-kinase (PI3K) signalling cascade, is an intensely pursued therapeutic target in oncology. Two distinct classes AKT inhibitors have been clinical development, ATP-competitive and allosteric. Class-specific differences drug activity are likely result differential structural conformational requirements governing efficient binding, which ultimately determine isoform-specific potency, selectivity profiles against clinically relevant mutant variants.
Abstract Metabolic obstacles of the tumor microenvironment remain a challenge to T-cell-mediated cancer immunotherapies. To better understand interplay immune checkpoint signaling and metabolism, this study developed used an optimized metabolite extraction protocol for non-adherent primary human T-cells, broadly profile in vitro metabolic changes effected by PD-1 mass spectrometry-based metabolomics isotopomer analysis. Inhibitory reduced aerobic glycolysis glutaminolysis. A general scarcity...
In plasma, iron is normally bound to transferrin, the principal protein in blood responsible for binding and transporting throughout body. However, conditions of overload when iron-binding capacity transferrin exceeded, non-transferrin-bound (NTBI) appears plasma. NTBI taken up by hepatocytes other parenchymal cells via transporters can cause cellular damage promoting generation reactive oxygen species. how affects endothelial cells, most proximal cell type exposed circulating NTBI, has not...
Iron is essential for a healthy pregnancy, and iron supplementation nearly universally recommended, regardless of maternal status. A signal potential harm the U-shaped association between ferritin, marker stores, risk adverse pregnancy outcomes. However, ferritin also induced by inflammation may overestimate stores during or infection. In this study, we use mouse models to determine whether loading, inflammation, their interaction cause poor Only exposure both excess but not either condition...
Meeting abstracts PD-L1-negative tumors assessed by immunohistochemistry often still respond to PD-1 blockade. PD-L1 is inducible interferon, therefore, absolute negative are the ones unable up-regulate in response interferons. Genetic mutations interferon receptor
Abstract Centriole and/or cilia defects are characteristic of cancer cells and have been linked to cell invasion. However, the mechanistic basis these effects is unknown. Spindle assembly abnormal protein 6 homolog (SAS-6) essential for centriole biogenesis formation. In cycling cells, SAS-6 undergoes APC Cdh1 -mediated targeted degradation by 26S proteasome at end mitosis. Little known about function outside centrosome biogenesis. To examine this, we expressed a non-degradable mutant...
Abstract Background: PMD-026 is a first in class, reversible, oral small molecule inhibitor of p90 ribosomal S6 kinase (RSK), family activated by the MAPK and PDK-1 pathways, which regulate substrates involved cancer cell proliferation drug resistance. Both pathways are implicated HR+ triple negative breast (TNBC). RSK2 can modulate growth (BC) promoting cycle progression through G2/M, specifically pYB-1S102 nucleates spindle pole formation M-phase cells. This mechanism action (MOA) for be...
Abstract Introduction. The role of PD-L1 as a predictive biomarker for response to PD-1 blockade is unclear. Emerging evidence, including our findings reported here, suggests that expression important only when induced by the presence T cells producing interferons, in what termed adaptive immune resistance (Tumeh, Nature 2014). Therefore, studying or not interferons may define molecular mechanisms select patients whose tumors are incapable respond cell infiltration upregulating PD-L1....
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Supplementary Figure Legends 1-4, Methods from <sup>18</sup>F-Fluorodeoxy-glucose Positron Emission Tomography Marks MYC-Overexpressing Human Basal-Like Breast Cancers
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