Massar Alsamraae
A5036051548- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Cancer, Lipids, and Metabolism
- Lung Cancer Treatments and Mutations
- Prostate Cancer Treatment and Research
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA modifications and cancer
- Cancer, Stress, Anesthesia, and Immune Response
- Bone health and treatments
- PARP inhibition in cancer therapy
- Redox biology and oxidative stress
- Lung Cancer Research Studies
- Chemical Reactions and Isotopes
- Blood disorders and treatments
- Tryptophan and brain disorders
- Sulfur Compounds in Biology
- Bone and Dental Protein Studies
- Metabolomics and Mass Spectrometry Studies
- Cancer-related molecular mechanisms research
- Inflammatory Biomarkers in Disease Prognosis
University of Chicago
2024-2025
University of Chicago Medicine Comprehensive Cancer Center
2025
Nebraska Medical Center
2023
University of Nebraska Medical Center
2020-2023
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 Bone metastatic prostate cancer (BM-PCa) significantly reduces overall patient survival and is currently incurable. Current standard immunotherapy showed promising results for PCa patients with metastatic, but less advanced, disease (i.e., fewer than 20 bone lesions) suggesting that growth in contributes to response immunotherapy. We found that: (1) stimulates recruitment of neutrophils, the most abundant immune cell bone, (2) neutrophils heavily infiltrate regions tumor BM-PCa...
Bone metastatic disease of prostate cancer (PCa) is incurable and progression in bone largely dictated by tumor-stromal interactions the microenvironment. We showed previously that neutrophils initially inhibit PCa growth yet becomes resistant to neutrophil response. Further, isolated from tumor-bone lost their ability suppress tumor through unknown mechanisms. With this study, our goal was define impact on function throughout determine potential as predictive biomarkers disease. Using...
<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 Introduction: Despite the advent of targeted therapies, prognosis lung non-small cell cancer (NSCLC) remains poor. Thus, identifying metabolic programs in aggressive disease may allow for development novel treatment strategies. Prior work early-stage NSCLC has demonstrated that lactate import via monocarboxylate transporter 1 (MCT1) is associated with higher recurrence and mortality. However, potential targeting MCT1 efficacy resistance unknown. Methods: cells were cultured standard...
Abstract Despite advances in therapy and early screening, non-small cell lung cancer (NSCLC) remains responsible for the most cancer-related deaths worldwide. There is an urgent need to elucidate drivers of NSCLC progression develop better treatment options, but these efforts are often limited by a lack clinically relevant model systems. To address this need, we developed series patient-derived xenografts (PDX) from clinical study tumor metabolism. We confirmed that models retain genetic,...