ArticleMolecular imaging and biology2019
Quantitative Imaging of Morphometric and Metabolic Signatures Reveals Heterogeneity in Drug Response of Three-Dimensional Mammary Tumor Spheroids.
Article in Molecular imaging and biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Breast Cancer Multicellular Spheroid Models-A Tool for Studying Cancer Biology; a Possible Platform for Drug Screening and Personalized Medicine.International journal of molecular sciences · 2026Review
- Phasor S-FLIM: a new paradigm for fast and robust spectral fluorescence lifetime imaging.Nature methods · 2021Article
- Cartilage and bone tissue engineering using adipose stromal/stem cells spheroids as building blocks.World journal of stem cells · 2020Review
- Cytotoxic and Antiproliferative Effects of Preussin, a Hydroxypyrrolidine Derivative from the Marine Sponge-Associated FungusMarine drugs · 2019Article
- Commemorating Britton Chance.Molecular imaging and biology · 2019Article
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1 author at 1 institution in 1 country.
Funding
Abstract
purposeIn order to monitor the drug responses of three-dimensional mammary tumor spheroids and to elucidate the role of inter- and intra-spheroid heterogeneity in determining drug sensitivity in the spheroids, an integrated image analysis framework was developed for morphometric and metabolic characterization of the three-dimensional tumor spheroids. PROCEDURE: Three-dimensional spheroid cultures of primary mammary tumor epithelial cells isolated from freshly excised tumors from a transgenic mouse model of adenocarcinoma (MMTV-PyMT) were imaged by using vital dyes and mitochondrial membrane potential markers. Custom-developed java and python program codes facilitated image processing, numerical computation, and graphical analysis of large datasets generated from the experiments. A panel of cancer drugs (rapamycin, BEZ235, MK2206, and flavopiridol) was tested to determine the degree of drug sensitivity as well as heterogeneity in drug response.
resultsA new quantitative metric (growth/toxicity) was developed based on morphometric parameters that were found to track the growth and apoptotic cell populations. Further, this study identified two parameters, namely, skew and kurtosis-which report the spatial heterogeneity in mitochondrial metabolism within the spheroids. The results of this study show that three-dimensional tumor spheroids selectively respond to cancer drugs depending on the specific metabolic pathways (AKT inhibition pathway in the present study), and there exists significant heterogeneity in the untreated tumor spheroids. Drug sensitivity of the spheroids was found to be associated with significant alterations in mitochondrial heterogeneity within the spheroids.
conclusionsIn conclusion, the quantitative imaging of morphometric and metabolic analysis in large image datasets can serve as an excellent tool box for characterizing tumor heterogeneity in three-dimensional tumor spheroids and potentially, in intact tumors as well.
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