An important component of this methodology is to assess the role of the tumor microenvironment on tumor growth and survival. To tackle this problem, we have adapted the original approach of Warburg (Warburg, 1923), by combining thin tissue slices with Stable Isotope Resolved Metabolomics (SIRM) to determine detailed metabolic activity of human tissues. SIRM enables the tracing of metabolic transformations of source molecules such as glucose or glutamine over defined time periods, and is a requirement for detailed pathway tracing and flux analysis. In our approach, we maintain freshly resected tissue slices (both cancerous and non- cancerous from the same organ of the same subject) in cell culture media, and treat with appropriate stable isotope-enriched nutrients, e.g. 13C6-glucose or 13C5, 15N2 -glutamine. These slices are viable for at least 24 h, and make it possible to eliminate systemic influence on the target tissue metabolism while maintaining the original 3D cellular architecture. It is therefore an excellent pre-clinical platform for assessing the effect of therapeutic agents on target tissue metabolism and their therapeutic efficacy on individual patients (Xie et al., 2014; Sellers et al., 2015).

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Published in Bio-Protocol, v. 6, no. 3, article e1730, p. 1-12.

© 2016 Bio-protocol LLC

The copyright holders have granted the permission for posting the article here.

Funding Information

This work was supported in part by the following grants: NIH P01 CA163223-01A1, NIH 5R01ES022191-04, NIH 3R01ES022191-04S1, NIH 1U24DK097215-01A1, and the Kentucky Challenge for Excellence.