Hannah E. Crentsil
A5107533893- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Lung Cancer Treatments and Mutations
- Immune cells in cancer
- Neuroblastoma Research and Treatments
- Phagocytosis and Immune Regulation
- Chromatin Remodeling and Cancer
- Axon Guidance and Neuronal Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Glioma Diagnosis and Treatment
- Nuclear Receptors and Signaling
The University of Texas Southwestern Medical Center
2025
Children's Medical Center
2025
University of Pittsburgh
2024
Abstract In patients with non–small cell lung cancer (NSCLC), the relationship between tumor metabolism and clinical outcomes is unknown. Here, 13C-labeled nutrients were intraoperatively infused into more than 90 surgically resectable pulmonary lesions, metabolic properties of resected tumors correlated survival. NSCLCs 13C-glucose, high 13C enrichment in tricarboxylic acid (TCA) cycle intermediates conferred a HR 3.8 for early death, typically metastasis. To test whether these features...
<div>Abstract<p>In patients with non–small cell lung cancer (NSCLC), the relationship between tumor metabolism and clinical outcomes is unknown. Here, <sup>13</sup>C-labeled nutrients were intraoperatively infused into more than 90 surgically resectable pulmonary lesions, metabolic properties of resected tumors correlated survival. In NSCLCs <sup>13</sup>C-glucose, high <sup>13</sup>C enrichment in tricarboxylic acid (TCA) cycle intermediates...
<p>(Related to Figure 1). TCA cycle labeling and metabolite abundance in tumors lungs from NSCLC patents.</p>
<p>(Related to Figure 4). Development of patient-derived xenografts from malignant tumors in the lung.</p>
<p>(Related to Figure 3). TCA cycle metabolite abundance does not correlate with overall survival.</p>
<p>Increased <sup>13</sup>C enrichment in the TCA cycle predicts reduced survival. <b>A,</b><sup>13</sup>C adjacent lung and tumors with high or low labeling. Fractional enrichments of glycolytic (M+3) (M+2) metabolites are normalized to glucose (M+6) within tissue. <b>B</b> <b>C,</b> Overall (<b>B</b>) recurrence-free (<b>C</b>) survival patients whose have The groups include above below median for...
<p>Inhibition of complex I with IACS-010759 limits metastasis in NSCLC PDXs. <b>A</b> and <b>B,</b> Tumor-bearing mice were treated daily DMSO or (5 mg/kg) by oral gavage for 3–4 weeks then infused [U-<sup>13</sup>C]glucose 3 hours. Overall TCA cycle enrichment was calculated as the sum isotopologues citrate, malate, glutamate compared between DMSO- IACS-010759–treated groups. <b>C</b> <b>D,</b> Subcutaneous tumor volume (L ×...
<p>PDXs derived from primary NSCLC retain histological, molecular, and metabolic characteristics. <b>A</b> <b>B,</b> Summary of histological molecular characterization donor tumors (<b>A</b>) PDX models (<b>B</b>). <b>C,</b> H&E staining PDXs. <b>D,</b> Engraftment success NSCLCs lung metastases considering the phenotype patient’s tumor. “High” “low” TCA cycle enrichment was defined in <a href="#fig3"...
<p>PDXs generated from primary NSCLCs spontaneously metastasize in NSG mice. <b>A,</b> Flow cytometry analysis of lung tissue a mouse engrafted with mx73. Cells were stained lineage markers (CD45, CD31, and TER119) HLA. <b>B,</b> Bioluminescence lungs bearing metastases <b>C,</b> IHC staining for Ki67-positive cells metastasis mx148. <b>D,</b> Percentage HLA-ABC–expressing detected the mice NSCLC PDXs. Each dot represents one mouse. Data...
<p>(Related to Figure 2). Epithelial and myeloid cell contributions gene expression 13C labeling features.</p>
<p>(Related to Figure 3). Relationships between TCA cycle labeling and clinical factors.</p>
<p>(Related to Figures 5 and 6): Treatment with IACS-010759 reduces distant metastasis.</p>
<p>Cancer cells drive an OXPHOS expression signature in tumors. <b>A,</b> Heatmap of TCA cycle and ETC transcript differences between primary NSCLC adjacent lung samples. <b>B,</b> RNA scores comparing matched tumor for the pathways indicated. <b>C,</b> Single-cell RNA-seq data from GSE131907. were calculated as mean genes each cell type, derived samples (red) or (blue). <b>D,</b> GSE123902. <b>C</b> nonmalignant tissue...
<p><sup>13</sup>C enrichment in the TCA cycle distinguishes tumors but not benign pulmonary lesions from adjacent lung. <b>A,</b> Summary of patients with lesions. <b>B,</b> Schematic labeling [U-<sup>13</sup>C]glucose, including glycolysis and multiple turns cycle. <b>C–E,</b><sup>13</sup>C comparisons between each lesion type The sum isotopologues metabolite is normalized to corresponding Each dot represents one...
Abstract MALT1 protease is an intracellular signaling molecule that promotes tumor progression via cancer cell-intrinsic and cell-extrinsic mechanisms. has been mostly studied in lymphocytes, little known about its role tumor-associated macrophages. Here, we show plays a key glioblastoma (GBM)-associated Mechanistically, GBM cells induce MALT1-NF-κB axis within macrophages, leading to macrophage migration polarization toward immunosuppressive phenotype. Inactivation of transcriptional...
Abstract BACKGROUND Glioblastoma (GBM), one of the deadliest primary tumors central nervous system, is characterized by a highly immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages and microglia (TAMs) are dominant population immune cells in GBM TME substantially contribute to immunosuppression, progression, treatment resistance. Elucidating molecular mechanisms underlying TAM behavior crucial development effective immuno-therapeutic strategies for treating GBM. The...