Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D02011 (FAD)
 5,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Head and neck cancer patients suffer from toxicities, morbidities, and mortalities, and these ailments could be minimized through improved therapies. Drug discovery is a long, expensive, and complex process, so optimized assays can improve the success rate of drug candidates. This study applies optical imaging of cell metabolism to three-dimensional in vitro cultures of head and neck cancer grown from primary tumor tissue (organoids). This technique is advantageous because it measures cell metabolism using intrinsic fluorescence from NAD(P)H and FAD on a single cell level for a three-dimensional in vitro model. Head and neck cancer organoids are characterized alone and after treatment with standard therapies, including an antibody therapy, a chemotherapy, and combination therapy. Additionally, organoid cellular heterogeneity is analyzed quantitatively and qualitatively. Gold standard measures of treatment response, including cell proliferation, cell death, and in vivo tumor volume, validate therapeutic efficacy for each treatment group in a parallel study. Results indicate that optical metabolic imaging is sensitive to therapeutic response in organoids after 1 day of treatment (p<0.05) and resolves cell subpopulations with distinct metabolic phenotypes. Ultimately, this platform could provide a sensitive high-throughput assay to streamline the drug discovery process for head and neck cancer.
 ...
PMID:Metabolic Imaging of Head and Neck Cancer Organoids. 2809 87

Metabolic preferences of tumor cells vary within a single tumor, contributing to tumor heterogeneity, drug resistance, and patient relapse. However, the relationship between tumor treatment response and metabolically distinct tumor cell populations is not well-understood. Here, a quantitative approach was developed to characterize spatial patterns of metabolic heterogeneity in tumor cell populations within in vivo xenografts and 3D in vitro cultures (i.e., organoids) of head and neck cancer. Label-free images of cell metabolism were acquired using two-photon fluorescence lifetime microscopy of the metabolic co-enzymes NAD(P)H and FAD. Previous studies have shown that NAD(P)H mean fluorescence lifetimes can identify metabolically distinct cells with varying drug response. Thus, density-based clustering of the NAD(P)H mean fluorescence lifetime was used to identify metabolic sub-populations of cells, then assessed in control, cetuximab-, cisplatin-, and combination-treated xenografts 13 days post-treatment and organoids 24 h post-treatment. Proximity analysis of these metabolically distinct cells was designed to quantify differences in spatial patterns between treatment groups and between xenografts and organoids. Multivariate spatial autocorrelation and principal components analyses of all autofluorescence intensity and lifetime variables were developed to further improve separation between cell sub-populations. Spatial principal components analysis and Z-score calculations of autofluorescence and spatial distribution variables also visualized differences between models. This analysis captures spatial distributions of tumor cell sub-populations influenced by treatment conditions and model-specific environments. Overall, this novel spatial analysis could provide new insights into tumor growth, treatment resistance, and more effective drug treatments across a range of microscopic imaging modalities (e.g., immunofluorescence, imaging mass spectrometry).
 ...
PMID:Quantitative Spatial Analysis of Metabolic Heterogeneity Across in vivo and in vitro Tumor Models. 3173 71