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Nicholas J.W. Rattray  - - - 
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Gary Siuzdak

175 shared publications

The Scripps Research Institute, Scripps Center for Metabolomics and Mass Spectrometry, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

Rima Kaddurah-Daouk

76 shared publications

Duke University

Benedikt Warth

61 shared publications

The Scripps Research Institute, Scripps Center for Metabolomics and Mass Spectrometry, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

Zhou Zhu

13 shared publications

Oncology Research, Pfizer Worldwide Research and Development, San Diego, CA 92121, USA

Caroline H. Johnson

8 shared publications

The Scripps Research Institute, Scripps Center for Metabolomics and Mass Spectrometry, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

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Article 0 Reads 0 Citations Palbociclib and Fulvestrant Act in Synergy to Modulate Central Carbon Metabolism in Breast Cancer Cells Benedikt Warth, Amelia Palermo, Nicholas J.W. Rattray, Natha... Published: 02 January 2019
Metabolites, doi: 10.3390/metabo9010007
DOI See at publisher website ABS Show/hide abstract
The aims of this study were to determine whether combination chemotherapeutics exhibit a synergistic effect on breast cancer cell metabolism. Palbociclib, is a selective inhibitor of cyclin-dependent kinases 4 and 6, and when patients are treated in combination with fulvestrant, an estrogen receptor antagonist, they have improved progression-free survival. The mechanisms for this survival advantage are not known. Therefore, we analyzed metabolic and transcriptomic changes in MCF-7 cells following single and combination chemotherapy to determine whether selective metabolic pathways are targeted during these different modes of treatment. Individually, the drugs caused metabolic disruption to the same metabolic pathways, however fulvestrant additionally attenuated the pentose phosphate pathway and the production of important coenzymes. A comprehensive effect was observed when the drugs were applied together, confirming the combinatory therapy’s synergism in the cell model. This study also highlights the power of merging high-dimensional datasets to unravel mechanisms involved in cancer metabolism and therapy.
Article 0 Reads 0 Citations Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids Caroline H. Johnson, Antonio F. Santidrian, Sarah E. Leboeuf... Published: 31 October 2017
Cancer & Metabolism, doi: 10.1186/s40170-017-0171-2
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Cancer cells that enter the metastatic cascade require traits that allow them to survive within the circulation and colonize distant organ sites. As disseminating cancer cells adapt to their changing microenvironments, they also modify their metabolism and metabolite production. A mouse xenograft model of spontaneous tumor metastasis was used to determine the metabolic rewiring that occurs between primary cancers and their metastases. An “autonomous” mass spectrometry-based untargeted metabolomic workflow with integrative metabolic pathway analysis revealed a number of differentially regulated metabolites in primary mammary fat pad (MFP) tumors compared to microdissected paired lung metastases. The study was further extended to analyze metabolites in paired normal tissues which determined the potential influence of metabolites from the microenvironment. Metabolomic analysis revealed that multiple metabolites were increased in metastases, including cholesterol sulfate and phospholipids (phosphatidylglycerols and phosphatidylethanolamine). Metabolite analysis of normal lung tissue in the mouse model also revealed increased levels of these metabolites compared to tissues from normal MFP and primary MFP tumors, indicating potential extracellular uptake by cancer cells in lung metastases. These results indicate a potential functional importance of cholesterol sulfate and phospholipids in propagating metastasis. In addition, metabolites involved in DNA/RNA synthesis and the TCA cycle were decreased in lung metastases compared to primary MFP tumors. Using an integrated metabolomic workflow, this study identified a link between cholesterol sulfate and phospholipids, metabolic characteristics of the metastatic niche, and the capacity of tumor cells to colonize distant sites.
Article 0 Reads 1 Citation Pharmacometabolomics and Precision Medicine Special Issue Editorial Nicholas J. W. Rattray, Rima Kaddurah Daouk Published: 20 March 2017
Metabolomics, doi: 10.1007/s11306-017-1191-1
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