NDLI: Monitoring metabolic responses to chemotherapy in single cells and tumors using nanostructure-initiator mass spectrometry (NIMS) imaging

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Acidosis induces reprogramming of cellular metabolism to mitigate oxidative stress

PGC-1α supports glutamine metabolism in breast cancer

Deficiency of metabolic regulator FGFR4 delays breast cancer progression through systemic and microenvironmental metabolic alterations

The metabolic demands of cancer cells are coupled to their size and protein synthesis rates

Quinoline 3-sulfonamides inhibit lactate dehydrogenase A and reverse aerobic glycolysis in cancer cells

LKB1 is a central regulator of tumor initiation and pro-growth metabolism in ErbB2-mediated breast cancer

Ets-1 global gene expression profile reveals associations with metabolism and oxidative stress in ovarian and breast cancers

Linking vitamin B1 with cancer cell metabolism

Cerebellar granule neuron progenitors are the source of Hk2 in the postnatal cerebellum

The role of Bergmann glial cells in cerebellar development

Expression and phosphorylation of the AS160_v2 splice variant supports GLUT4 activation and the Warburg effect in multiple myeloma

Reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells

Respiratory complex I is essential to induce a Warburg profile in mitochondria-defective tumor cells

Calorie restriction and cancer prevention: a mechanistic perspective

Balancing glycolytic flux: the role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatases in cancer metabolism

Metabolic changes in cancer cells upon suppression of MYC

p53 promotes the expression of gluconeogenesis-related genes and enhances hepatic glucose production

Activated lymphocytes as a metabolic model for carcinogenesis

Hexokinase-2-mediated aerobic glycolysis is integral to cerebellar neurogenesis and pathogenesis of medulloblastoma

Monitoring metabolic responses to chemotherapy in single cells and tumors using nanostructure-initiator mass spectrometry (NIMS) imaging

Sterol regulatory element binding protein-dependent regulation of lipid synthesis supports cell survival and tumor growth

The long and winding road to the mitochondrial pyruvate carrier

Why Cancer & Metabolism? Why now?

Monitoring metabolic responses to chemotherapy in single cells and tumors using nanostructure-initiator mass spectrometry (NIMS) imaging

Content Provider	Springer Nature : BioMed Central
Author	O’Brien, Peter J Lee, Michelle Spilker, Mary E Zhang, Cathy C Yan, Zhengming Nichols, Timothy C Li, Wenlin Johnson, Caroline H Patti, Gary J Siuzdak, Gary
Abstract	Background Tissue imaging of treatment-induced metabolic changes is useful for optimizing cancer therapies, but commonly used methods require trade-offs between assay sensitivity and spatial resolution. Nanostructure-Initiator Mass Spectrometry imaging (NIMS) permits quantitative co-localization of drugs and treatment response biomarkers in cells and tissues with relatively high resolution. The present feasibility studies use NIMS to monitor phosphorylation of 3′-deoxy-3′-fluorothymidine (FLT) to FLT-MP in lymphoma cells and solid tumors as an indicator of drug exposure and pharmacodynamic responses. Methods NIMS analytical sensitivity and spatial resolution were examined in cultured Burkitt’s lymphoma cells treated briefly with Rapamycin or FLT. Sample aliquots were dispersed on NIMS surfaces for single cell imaging and metabolic profiling, or extracted in parallel for LC-MS/MS analysis. Docetaxel-induced changes in FLT metabolism were also monitored in tissues and tissue extracts from mice bearing drug-sensitive tumor xenografts. To correct for variations in FLT disposition, the ratio of FLT-MP to FLT was used as a measure of TK1 thymidine kinase activity in NIMS images. TK1 and tumor-specific luciferase were measured in adjacent tissue sections using immuno-fluorescence microscopy. Results NIMS and LC-MS/MS yielded consistent results. FLT, FLT-MP, and Rapamycin were readily detected at the single cell level using NIMS. Rapid changes in endogenous metabolism were detected in drug-treated cells, and rapid accumulation of FLT-MP was seen in most, but not all imaged cells. FLT-MP accumulation in xenograft tumors was shown to be sensitive to Docetaxel treatment, and TK1 immunoreactivity co-localized with tumor-specific antigens in xenograft tumors, supporting a role for xenograft-derived TK1 activity in tumor FLT metabolism. Conclusions NIMS is suitable for monitoring drug exposure and metabolite biotransformation with essentially single cell resolution, and provides new spatial and functional dimensions to studies of cancer metabolism without the need for radiotracers or tissue extraction. These findings should prove useful for in vitro and pre-clinical studies of cancer metabolism, and aid the optimization of metabolism-based cancer therapies and diagnostics.
Related Links	https://cancerandmetabolism.biomedcentral.com/counter/pdf/10.1186/2049-3002-1-4.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
ISSN	20493002
DOI	10.1186/2049-3002-1-4
Journal	Cancer & Metabolism
Issue Number	1
Volume Number	1
Language	English
Publisher	BioMed Central
Publisher Date	2013-01-23
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Metabolomics Metabolic Diseases Imaging Radiology Cell Biology Mass spectrometry imaging Pharmacodynamic response Biomarker Thymidine kinase activity TK1 3′-Deoxy-3′-Fluorothymidine Tumor proliferation Nanostructure-initiator mass spectrometry
Content Type	Text
Resource Type	Article
Subject	Cancer Research
Journal Impact Factor	6/2023
5-Year Journal Impact Factor	5.4/2023

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Monitoring metabolic responses to chemotherapy in single cells and tumors using nanostructure-initiator mass spectrometry (NIMS) imaging

Monitoring tumor cell proliferation by targeting dna synthetic processes with.

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Liquid chromatography-tandem mass spectrometry method for quantification of thymidine kinase activity in human serum by monitoring the conversion of 3'-deoxy-3'-fluorothymidine to 3'-deoxy-3'-fluorothymidine monophosphate.

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Validity of Simplified 3′-Deoxy-3′-[18F]Fluorothymidine Uptake Measures for Monitoring Response to Chemotherapy in Locally Advanced Breast Cancer

Monitoring metabolic responses to chemotherapy in single cells and tumors using nanostructure-initiator mass spectrometry (NIMS) imaging

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