Real-time molecular and cellular analysis: the new frontier of drug discovery

Taylor, D. Lansing; Woo, Elizabeth S.; Giuliano, Kenneth A.

doi:10.1016/s0958-1669(00)00180-4

Cited by 120 publications

(52 citation statements)

References 55 publications

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“…First, the cell has been regarded as an important object of study in toxicology, new drug development, and patient-drug interaction [1]. Second, the strategies in microscopic analysis of biological cells have been expanded by ongoing automation of sample preparation, ÿeld selection, focusing and imaging [2].…”

Section: Introductionmentioning

confidence: 99%

Human vs. machine: evaluation of fluorescence micrographs

Nattkemper

Twellmann

Ritter

et al. 2003

Computers in Biology and Medicine

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To enable high-throughput screening of molecular phenotypes, multi-parameter uorescence microscopy is applied. Object of our study is lymphocytes which invade human tissue. One important basis for our collaborative project is the development of methods for automatic and accurate evaluation of uorescence micrographs. As a part of this, we focus on the question of how to measure the accuracy of microscope image interpretation, by human experts or a computer system. Following standard practice we use methods motivated by receiver operator characteristics to discuss the accuracies of human experts and of neural network-based algorithms. For images of good quality the algorithms achieve the accuracy of the medium-skilled experts. In images with increased noise, the classiÿers are outperformed by some of the experts. Furthermore, the neural network-based cell detection is much faster than the human experts. ?

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Section: Introductionmentioning

confidence: 99%

Human vs. machine: evaluation of fluorescence micrographs

Nattkemper

Twellmann

Ritter

et al. 2003

Computers in Biology and Medicine

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“…screening of drug candidates (10), and in clinical applications (11), such as detecting rare cancer cells (12) or metaphase chromosome rearrangements (13). Also notable are systems for detecting dots visible by fluorescence in situ hybridization (14) and comet tails indicating DNA damage (15).…”

mentioning

confidence: 99%

Automated microscopy identifies estrogen receptor subdomains with large‐scale chromatin structure unfolding activity

2004

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Background:Recently, several transcription factors were found to possess large-scale chromatin unfolding activity; these include the VP16 acidic activation domain, BRCA1, E2F1, p53, and the glucocorticoid and estrogen steroid receptors. In these studies, proteins were fluorescently labeled and targeted to a multimerized array of DNA sequences in mammalian cultured cells, and changes in the appearance and/or size of the array were observed. This type of experiment is impeded by the low throughput of traditional microscopy. Methods: We report the application of automated microscopy to provide unattended, rapid, quantitative measurements of fluorescently labeled chromosome regions. Results: The automated image collection routine produced results comparable to results previously obtained by manual methods and was significantly faster. Using this

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“…[1][2][3] Although several promising studies have suggested using in situ cellular imaging as a tool, 4,5 investigating the interaction between target proteins and drugs using this tool remains difficult due to a lack of resolution and throughput. Hence, a new probe must be introduced for in situ cellular imaging to become a major process in new drug development.…”

Section: Introductionmentioning

confidence: 99%

In situ imaging of quantum dot-AZD4547 conjugates for tracking the dynamic behavior of fibroblast growth factor receptor 3

Hwang

Kim

Yoon

et al. 2017

IJN

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Fibroblast growth factor receptors (FGFRs) play an important role in determining cell proliferation, differentiation, migration, and survival. Although a variety of small-molecule FGFR inhibitors have been developed for cancer therapeutics, the interaction between FGFRs and FGFR inhibitors has not been well characterized. The FGFR–inhibitor interaction can be characterized using a new imaging probe that has strong, stable signal properties for in situ cellular imaging of the interaction without quenching. We developed a kinase–inhibitor-modified quantum dot (QD) probe to investigate the interaction between FGFR and potential inhibitors. Especially, turbo-green fluorescent protein-FGFR3s were overexpressed in HeLa cells to investigate the colocalization of FGFR3 and AZD4547 using the QD-AZD4547 probe. The result indicates that this probe is useful for investigating the binding behaviors of FGFR3 with the FGFR inhibitor. Thus, this new inhibitor-modified QD probe is a promising tool for understanding the interaction between FGFR and inhibitors and for creating future high-content, cell-based drug screening strategies.

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Real-time molecular and cellular analysis: the new frontier of drug discovery

Cited by 120 publications

References 55 publications

Human vs. machine: evaluation of fluorescence micrographs

Human vs. machine: evaluation of fluorescence micrographs

Automated microscopy identifies estrogen receptor subdomains with large‐scale chromatin structure unfolding activity

In situ imaging of quantum dot-AZD4547 conjugates for tracking the dynamic behavior of fibroblast growth factor receptor 3

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