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Caroline Johnson   Dr.  Senior Scientist or Principal Investigator 
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Caroline Johnson published an article in January 2019.
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0 A
0 Biomarkers
0 Breast Cancer
0 Cancer
0 Climate Change
0 Mass Spectrometry
Top co-authors See all
Dean P. Jones

260 shared publications

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322

Richard Caprioli

252 shared publications

Mass Spectrometry Research Center; Vanderbilt University; Nashville Tennessee USA

Gary Siuzdak

244 shared publications

The Scripps Research Institute, Scripps Center for Metabolomics and Mass Spectrometry, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA;(B.W.);(A.P.),(L.T.H.),(G.S.)

John P. A. Ioannidis

106 shared publications

Stanford University, USA

Benedikt Warth

81 shared publications

The Scripps Research Institute, Scripps Center for Metabolomics and Mass Spectrometry, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA;(B.W.);(A.P.),(L.T.H.),(G.S.)

41
Publications
15
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687
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Publication Record
Distribution of Articles published per year 
(2008 - 2019)
Total number of journals
published in
 
27
 
Publications See all
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 PubMed View at PubMed 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 Defining Early-Onset Colon and Rectal Cancers Daniel Jacobs, Rebecca Zhu, Jiajun Luo, Gabriella Grisotti, ... Published: 06 November 2018
Frontiers in Oncology, doi: 10.3389/fonc.2018.00504
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Background: Colorectal cancer (CRC) incidence is rising in the young, yet the age of those affected is not clearly defined. In this study, we identify such cohorts and define clinicopathological features of early-onset colon and rectal cancers.
Article 0 Reads 4 Citations Spontaneous DNA damage to the nuclear genome promotes senescence, redox imbalance and aging Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja... Published: 01 July 2018
Redox Biology, doi: 10.1016/j.redox.2018.04.007
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach to determine if spontaneous nuclear DNA damage is sufficient to initiate senescence in mammals. Ercc1-/∆ mice with reduced expression of ERCC1-XPF endonuclease have impaired capacity to repair the nuclear genome. Ercc1-/∆ mice accumulated spontaneous, oxidative DNA damage more rapidly than wild-type (WT) mice. As a consequence, senescent cells accumulated more rapidly in Ercc1-/∆ mice compared to repair-competent animals. However, the levels of DNA damage and senescent cells in Ercc1-/∆ mice never exceeded that observed in old WT mice. Surprisingly, levels of reactive oxygen species (ROS) were increased in tissues of Ercc1-/∆ mice to an extent identical to naturally-aged WT mice. Increased enzymatic production of ROS and decreased antioxidants contributed to the elevation in oxidative stress in both Ercc1-/∆ and aged WT mice. Chronic treatment of Ercc1-/∆ mice with the mitochondrial-targeted radical scavenger XJB-5–131 attenuated oxidative DNA damage, senescence and age-related pathology. Our findings indicate that nuclear genotoxic stress arises, at least in part, due to mitochondrial-derived ROS, and this spontaneous DNA damage is sufficient to drive increased levels of ROS, cellular senescence, and the consequent age-related physiological decline.
PREPRINT-CONTENT 0 Reads 0 Citations Palbociclib and fulvestrant act in synergy to modulate central carbon metabolism in breast cancer cells Benedikt Warth, Amelia Palermo, Nicholas Rattray, Nathan Lee... Published: 16 June 2018
bioRxiv, doi: 10.1101/348722
DOI See at publisher website ABS Show/hide abstract
Palbociclib, is a selective inhibitor of cyclin-dependent kinases 4 and 6 and used as a first-line treatment for patients with estrogen receptor positive breast cancer. It has been shown that patients have improved progression-free survival when treated in combination with fulvestrant, an estrogen receptor antagonist. However, the mechanisms for this survival advantage are not known. We sought to analyze metabolic and transcriptomic changes in MCF-7 adenocarcinoma breast cancer cells following single and combined treatments to determine if selective metabolic pathways are targeted during combination therapy. Our results showed that 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 therapies synergism in the cell model. This study highlights the power of merging high-dimensional datasets to unravel mechanisms involved in cancer metabolism and therapy.
Article 1 Read 1 Citation Distinctive features of gastrointestinal stromal tumors arising from the colon and rectum Rebecca Zhu, Fangfang Liu, Gabriella Grisotti, Javier Perez-... Published: 01 April 2018
Journal of Gastrointestinal Oncology, doi: 10.21037/jgo.2017.11.12
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Colon and rectal gastrointestinal stromal tumors (GISTs) are rare and poorly characterized. Because the majority of treatment guidelines for GISTs are extrapolated from tumors of gastric and small bowel origin, our aim was to better characterize the unique clinicopathologic features and prognostic factors of colon and rectal GISTs to guide clinical care. The National Cancer Data Base (NCDB) was queried from 2006 to 2013 for cases of GISTs in the stomach, colon, and rectum. Patient demographics, clinical characteristics, and survival were compared. A total of 11,302 gastric GISTs were compared to 398 colon and 393 rectal GISTs. After propensity matching, compared to gastric GISTs, rectal GISTs had improved overall survival (HR =0.695, P=0.0264), while colon GISTs had worse overall survival (HR =1.6, P=0.0005). Surgical treatment for rectal GISTs was more likely to be local excision compared to colonic GISTs (51.1% vs. 8.4%, P<0.0001). Colon and gastric GISTs were less likely to receive systemic therapy compared to rectal GISTs (34.2% vs. 34.0% vs. 55.2%, P<0.0001). Adjuvant systemic therapy conveyed a survival advantage to rectal GISTs (HR =0.47, P=0.042) but not colon GISTs. There was a negative impact of adjuvant therapy on survival for colon GISTs <5 cm (HR =3.41, P=0.032). Patients with rectal GISTs live longer than those with colon and gastric GISTs, and adjuvant therapy prolongs their survival. Many patients with colon GISTs are treated with adjuvant therapy despite a detrimental effect on survival. Tumor biology of colon and rectal GISTs needs to be better studied to tailor treatment.
Article 0 Reads 3 Citations Metabolomics Reveals that Dietary Xenoestrogens Alter Cellular Metabolism Induced by Palbociclib/Letrozole Combination C... Benedikt Warth, Philipp Raffeiner, Ana Granados, Tao Huan, M... Published: 01 March 2018
Cell Chemical Biology, doi: 10.1016/j.chembiol.2017.12.010
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Recently, the palbociclib/letrozole combination therapy was granted accelerated US FDA approval for the treatment of estrogen receptor (ER)-positive breast cancer. Since the underlying metabolic effects of these drugs are yet unknown, we investigated their synergism at the metabolome level in MCF-7 cells. As xenoestrogens interact with the ER, we additionally aimed at deciphering the impact of the phytoestrogen genistein and the estrogenic mycotoxin zearalenone. A global metabolomics approach was applied to unravel metabolite and pathway modifications. The results clearly showed that the combined effects of palbociclib and letrozole on cellular metabolism were far more pronounced than that of each agent alone and potently influenced by xenoestrogens. This behavior was confirmed in proliferation experiments and functional assays. Specifically, amino acids and central carbon metabolites were attenuated, while higher abundances were observed for fatty acids and most nucleic acid-related metabolites. Interestingly, exposure to model xenoestrogens appeared to counteract these effects.
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