Department of Radiology

Laboratory of Molecular Imaging : Research Images about LND

Focus

This program focuses on developing metabolomic applications (MRS, MRI, LC-MS and optical methods) to diagnose cancer.

We have recently defined the detailed mechanism of action of lonidamine (LND). This antineoplastic agent selectively acidifies tumors and decreases their bioenergetic status. The mechanism includes:

  1. Inhibition of the mitochondrial pyruvate carrier (MPC)
  2. Inhibition of monocarboxylic acid transporters (MCT1 and MCT4)
  3. Inhibition of complex II at the ubiquitin dehydrogenase step, and inhibition of flux through the pentose shunt that decreases glutathione production and increases production of reactive oxygen species thereby enhancing tumor radiosensitivity

Faculty And Staff

Jerry D. Glickson, PhD

Jerry D. Glickson, PhD

Research Professor of Radiology
Professor of Biochemistry and Biophysics

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Seung Cheol Lee, PhD

Seung-Cheol Lee, PhD

Research Assistant Professor of Radiology

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Kavindra Nath, PhD

Kavindra Nath, PhD

Research Assistant Professor of Radiology

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Alexander Shestov, PhD

Research Investigator

David S. Nelson

Research Specialist

Recent Publications

1. Nath K, Nelson DS, Roman J, Putt ME, Lee SC, Leeper DB & Glickson JD. Effect of Lonidamine on Systemic Therapy of DB-1 Human Melanoma Xenografts with Temozolomide. Anticancer Res. 2017;37(7):3413-21.

2. Nancolas B, Guo L, Zhou R, Nath K, Nelson DS, Leeper DB, Blair IA, Glickson JD & Halestrap AP. The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters. Biochem J. 2016. PMCID: PMC4814305.

3. Nath K, Guo L, Nancolas B, Nelson DS, Shestov AA, Lee SC, Roman J, Zhou R, Leeper DB, Halestrap AP. Blair IA & Glickson JD. Mechanism of antineoplastic activity of lonidamine. Biochim Biophys Acta. 2016;1866(2):151-62. PMCID: PMC5138080.

4. Xu HN, Feng M, Nath K, Nelson D, Roman J, Zhao H, Lin Z, Glickson J & Li LZ. Optical Redox Imaging of Lonidamine Treatment Response of Melanoma Cells and Xenografts. Mol Imaging Biol. 2019;21(3):426-35. doi: 10.1007/s11307-018-1258-z.

5. Lee SC, Shestov AA, Guo L, Zhang Q, Roman JC, Liu X, Wang HY, Pickup S, Nath K, Lu P, Hofbauer S, Mesaros C, Wang YL, Nelson DS, Schuster SJ, Blair IA, Glickson JD & Wasik MA. Metabolic Detection of Bruton's Tyrosine Kinase Inhibition in Mantle Cell Lymphoma Cells. Mol Cancer Res. 2019;17(6):1365-77. doi: 10.158/541-7786.MCR-18-0256. Epub 2019 Mar 12.

 

Contact Us

Jerry D. Glickson, PhD
Research Professor of Radiology
Email: glickson@pennmedicine.upenn.edu
Phone: 215-898-1805
Fax: 215-573-2113

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