Katarzyna Kuryłowicz
A5081025581- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Cancer, Lipids, and Metabolism
- Lung Cancer Treatments and Mutations
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
- Chronic Myeloid Leukemia Treatments
- Autophagy in Disease and Therapy
- interferon and immune responses
- Immune Cell Function and Interaction
- Renin-Angiotensin System Studies
- Retinopathy of Prematurity Studies
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Phagocytosis and Immune Regulation
- Drug Transport and Resistance Mechanisms
- Cardiac Fibrosis and Remodeling
- Zebrafish Biomedical Research Applications
- Eicosanoids and Hypertension Pharmacology
- Eosinophilic Disorders and Syndromes
- Acute Myeloid Leukemia Research
- Cell death mechanisms and regulation
- Retinoids in leukemia and cellular processes
- NF-κB Signaling Pathways
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer Research and Treatments
University of Chicago
2021-2025
Oklahoma Medical Research Foundation
2020-2023
May Institute
2023
Jagiellonian University
2020
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...
Abstract Approximately 20% of patients with myeloproliferative neoplasms (MPN) harbor mutations in the gene calreticulin (CALR), 80% those classified as either type I or II. While II CALR-mutant proteins retain many Ca2+ binding sites present wild-type protein, lose these residues. The functional consequences this differential loss remain unexplored. Here, we show that residues mutant CALR protein directly impairs its ability, which turn leads to depleted endoplasmic reticulum (ER) and...
<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...
BACKGROUND: During infectious diseases, proinflammatory cytokines transiently destabilize interactions between adjacent vascular endothelial cells (ECs) to facilitate the passage of immune molecules and into tissues. However, in lung, resulting hyperpermeability can lead organ dysfunction. Previous work identified transcription factor ERG (erythroblast transformation-specific–related gene) as a master regulator homeostasis. Here we investigate whether sensitivity pulmonary blood vessels...
Significance Premature babies and diabetic patients can become blind when too many blood vessels develop in their eyes, therapeutic strategies are needed for eliminating those extra vessels. We studied newborn mice that naturally undergo loss of some eye to identify ways promote vessel regression elimination. identified a class proteins called E-26 transformation-specific transcription factors downregulated during normal regression, especially with slow flow. Importantly, we found drug...
The receptor-interacting protein kinase 3 (RIPK3) is a multi-functional best known for facilitating cellular necroptosis and inflammation. Recent evidence from our lab indicates that RIPK3 expression must be tightly regulated in endothelial cells to promote angiogenesis, maintain vascular integrity during embryogenesis, provide protection postnatal atherosclerosis. activity stability are by post-translational modifications caspase-dependent cleavage. However, less about the transcriptional...
In the present study, we investigated influence of resveratrol on PhIP treated human colon cancer cells and compared effect to HaCaT considered as normal, keratinocytes. Our results show that decreases DNA damage in both cell types, it increases sensitivity LoVo apoptosis has no PhIP-treated cells. We confirm PhIP-induced is p53 caspase 3/7 dependent. Interestingly, normal such HaCaT, which lack functional are more resistant treatment.