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896 results on '"Skala, Melissa C"'

263. Optically Based Rapid Screening Method for Proven Optimal Treatment Strategies before Treatment Begins

Author

VANDERBILT UNIV NASHVILLE TN, Skala, Melissa C, VANDERBILT UNIV NASHVILLE TN, and Skala, Melissa C

Abstract

This award seeks to develop high-throughput optical metabolic imaging (OMI) of primary breast tumor organoids (three-dimensional cultures of tumors) to rapidly test/screen breast cancer therapeutics as a strategy to streamline drug development and provide individualized treatment. The results outlined in this progress report indicate that OMI in primary breast tumor organoids can provide early, sensitive measures of treatment response. This system can therefore be used to streamline pre-clinical drug development, by reducing the number of animals, cost, and time required to screen new drugs and drug combinations. The feasibility of OMI measurements in organoids derived from primary human breast tumors has also been demonstrated, with the exciting possibility of providing individualized drug screens in patients before the patient is ever treated. This personalized drug planning approach could reduce toxicities of ineffective treatments, and enable improved outcomes through early, effective interventions. The single-cell analysis capabilities of this technique also have the potential to identify drug combinations that will eliminate treatment-resistant sub-populations of cells that are likely to cause metastases., The original document contains color images.

Published
2014

265. Autofluorescence flow sorting of breast cancer cell metabolism.

Author

Shah, Amy T., Cannon, Taylor M., Higginbotham, James N., Coffey, Robert J., and Skala, Melissa C.

Abstract

Clinical cancer treatment aims to target all cell subpopulations within a tumor. Autofluorescence microscopy of the metabolic cofactors NAD(P)H and FAD has shown sensitivity to anti-cancer treatment response. Alternatively, flow cytometry is attractive for high throughput analysis and flow sorting. This study measures cellular autofluorescence in three flow cytometry channels and applies cellular autofluorescence to sort a heterogeneous mixture of breast cancer cells into subpopulations enriched for each phenotype. Sorted cells were grown in culture and sorting was validated by morphology, autofluorescence microscopy, and receptor expression. Ultimately, this method could be applied to improve drug development and personalized treatment planning. [ABSTRACT FROM AUTHOR]

Published
2017
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274. The NADH Oxidase ENOX1, a Critical Mediator of Endothelial Cell Radiosensitization, Is Crucial for Vascular Development

Author

Venkateswaran, Amudhan, primary, Sekhar, Konjeti R., additional, Levic, Daniel S., additional, Melville, David B., additional, Clark, Travis A., additional, Rybski, Witold M., additional, Walsh, Alexandra J., additional, Skala, Melissa C., additional, Crooks, Peter A., additional, Knapik, Ela W., additional, and Freeman, Michael L., additional

Published
2014
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284. Validation and characterization of optical redox ratio measurements with a microplate reader in breast cancer cells

Author

Choi, Bernard, Kollias, Nikiforos, Zeng, Haishan, Kang, Hyun Wook, Wong, Brian J. F., Ilgner, Justus F., Nuttal, Alfred, Richter, Claus-Peter, Skala, Melissa C., Dewhirst, Mark W., Tearney, Guillermo J., Gregory, Kenton W., Marcu, Laura, Mandelis, Andreas, Morris, Michael D., Cannon, Taylor M., Shah, Amy T., and Skala, Melissa C.

Published
2015
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289. 150 Mutant KRAS-Dependent Changes in Exosomes and Recipient Cell Metabolism

Author

Beckler, Michelle Demory, primary, Higginbotham, James N., additional, Franklin, Jeff, additional, Halvey, Patrick J., additional, Ham, Amy-Joan L., additional, Liebler, Daniel C., additional, Li, Ming, additional, Buck, Jason R., additional, Manning, H. Charles, additional, Walsh, Alex J., additional, Skala, Melissa C., additional, and Coffey, Robert J., additional

Published
2013
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297. Optical Spectroscopy and Multiphoton Imaging for the Diagnosis and Characterization of Hyperplasias in the Mouse Mammary Gland

Author

DUKE UNIV DURHAM NC, Skala, Melissa C., DUKE UNIV DURHAM NC, and Skala, Melissa C.

Abstract

In these studies, the potential of optical techniques for early breast cancer detection were tested in animal models and cell culture. Optical spectroscopy, in vivo and in vitro microscopy studies indicate that optical methods show great promise for the early diagnosis of cancer, and may potentially provide biologically relevant information that could aid in treatment decisions. The features extracted from diffuse reflectance spectra measured in vivo from the hamster cheek pouch model of epithelial carcinogenesis, including the hemoglobin saturation, absorption and reduced scattering coefficient, were significantly lower in neoplastic tissues compared to normal tissues (p<0.05). Multiphoton lifetime microscopy experiments of the same animal model revealed that the lifetime of protein-bound NADH decreased with low grade and high grade precancers (consistent with the 2006 progress report) and the lifetime of protein-bound FAD increased with high grade precancer only (p<0.05) in vivo. No significant changes in the mean cellular redox ratio were found with precancer development (p>0.05) in vivo. However, there was an increase in the intracellular variability of the redox ratio with both high and low grade pre-cancers (p<0.05) in vivo. Genetic perturbations that depleted breast cancer cells (MCF7) of lactate dehydrogenase had no effect on the optical redox ratio, which was measured using confocal microscopy (p>0.05).

Published
2007

298. Optical Spectroscopy and Multiphoton Imaging for the Diagnosis and Characterization of Hyperplasias in the Mouse Mammary

Author

DUKE UNIV DURHAM NC, Skala, Melissa C., DUKE UNIV DURHAM NC, and Skala, Melissa C.

Abstract

The purpose of the first part of this project is to develop a method to diagnose mammary gland hyperplasias in an animal model in vivo using optical spectroscopy, so that the progression of benign lesions could be studied over time. The absorption and scattering parameters extracted from diffuse reflectance spectra measured in vivo were used to differentiate normal tissue (n=23) and benign lesions (n=16) in the mammary glands of ENU-treated FVBxB6 ApcMin/+ mice. Wilcoxon rank sum tests revealed a statistically significant increase (p<0.05) in total hemoglobin concentration for benign lesions compared to the normal mammary gland. Statistically significant differences (p<0.05) in the mean reduced scattering coefficient were also found between two sub-classes of benign lesions. The purpose of the second part of this project is to establish fluorescence lifetime imaging of NADH as an in vivo metabolic imaging technique, which could be used for pre-cancer diagnosis and for monitoring cancer therapies. Multiphoton microscopy of the fluorescence lifetime of normal (n=9) and pre-cancerous (n=12) epithelial tissues in vivo revealed a decrease in the lifetime of protein-bound NADH with pre-cancer development (p<0.05), and cell culture experiments on MCF10A human breast cells reveal that NADH fluorescence lifetimes are sensitive to changes in oxidative phosphorylation and glycolysis., The original document contains color images.

Published
2006

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