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Author Tilo Grosser

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Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs.

Katherine N Theken, Craig R Lee, Li Gong, Kelly E Caudle, Christine M Formea, Andrea Gaedigk, Teri E Klein, José A G Agúndez, Tilo Grosser,

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used analgesics due to their lack of addictive potential. However, NSAIDs have the potential to cause serious gastrointestinal, renal, and cardiovascular adverse events. CYP2C9 polymorphisms influence metabolism and clearance of several drugs in this class, thereby affecting drug exposure and potentially ... Read more >>

Clin. Pharmacol. Ther. (Clinical pharmacology and therapeutics)
[2020, :]

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Myeloid cell mPGES-1 mediates inflammatory pain hypersensitivity in mice

Lihong Chen, Guangrui Yang, David Cormode, Ashmita Saigal, Shravanthi Madhavan, Liudmila Mazaleuskaya, Gregory Grant, Garret FitzGerald, Tilo Grosser,

Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve inflammatory pain by predominant suppression of cyclooxygenase-2 derived prostaglandin (PG) E 2 . Innate immune cells contribute to inflammatory pain hypersensitivity and may be an attractive target for novel non-addictive approaches to pain management. We studied the contribution of PGE 2 produced by myeloid ... Read more >>

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Variability in the Analgesic Response to Ibuprofen Is Associated With Cyclooxygenase Activation in Inflammatory Pain.

Katherine N Theken, Elliot V Hersh, Nicholas F Lahens, Hyo Min Lee, Xuanwen Li, Eric J Granquist, Helen E Giannakopoulos, Lawrence M Levin, Stacey A Secreto, Gregory R Grant, John A Detre, Garret A FitzGerald, Tilo Grosser, John T Farrar,

The mechanisms underlying interindividual variability in analgesic efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) are not well understood. Therefore, we performed pain phenotyping, functional neuroimaging, pharmacokinetic/pharmacodynamic assessments, inflammation biomarkers, and gene expression profiling in healthy subjects who underwent surgical extraction of bony impacted third molars and were treated with ibuprofen (400 mg; ... Read more >>

Clin. Pharmacol. Ther. (Clinical pharmacology and therapeutics)
[2019, 106(3):632-641]

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Variability in the Analgesic Response to Ibuprofen Following Third-Molar Extraction is Associated with Differences in Activation of the Cyclooxygenase Pathway

Katherine Theken, Elliot Hersh, Nicholas Lahens, Hyo Min Lee, Eric Granquist, Helen Giannakopoulos, Lawrence Levin, Stacey Secreto-Dankanich, Gregory Grant, John Detre, Garret FitzGerald, Tilo Grosser, John Farrar,

Abstract The analgesic efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) has long been recognized to be limited by substantial interindividual variability in pain relief, but the underlying mechanisms are not well understood. We performed pain phenotyping, functional neuroimaging, pharmacokinetic/pharmacodynamic assessments, inflammation biomarkers, and gene expression profiling in healthy subjects who underwent ... Read more >>

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Lipocalin-Like Prostaglandin D Synthase but Not Hemopoietic Prostaglandin D Synthase Deletion Causes Hypertension and Accelerates Thrombogenesis in Mice.

Wen-Liang Song, Emanuela Ricciotti, Xue Liang, Tilo Grosser, Gregory R Grant, Garret A FitzGerald,

Prostaglandin (PG) D2 is formed by two distinct PGD synthases (PGDS): lipocalin-type PGDS (L-PGDS), which acts as a PGD2-producing enzyme and as extracellular lipophilic transporter, and hematopoietic PGDS (H-PGDS), a σ glutathione-S-transferase. PGD2 plays an important role in the maintenance of vascular function; however, the relative contribution of L-PGDS- and ... Read more >>

J. Pharmacol. Exp. Ther. (The Journal of pharmacology and experimental therapeutics)
[2018, 367(3):425-432]

Cited: 1 time

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Distinct vascular genomic response of proton and gamma radiation

Ricciotti Emanuela, Dimitra Sarantopoulou, Gregory Grant, Jenine Sanzari, Gabriel Krigsfeld, Amber Kiliti, Ann Kennedy, Tilo Grosser,

Abstract Purpose . The cardiovascular biology of proton radiotherapy is not well understood. We aimed to compare the genomic dose-response to proton and gamma radiation of the mouse aorta to assess whether their vascular effects may diverge. Materials and methods. We performed comparative RNA sequencing of the aorta following (4 ... Read more >>

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ISO-RELEVANCE FUNCTIONS - A SYSTEMATIC APPROACH TO RANKING GENOMIC FEATURES BY DIFFERENTIAL EFFECT SIZE

Soumyashant Nayak, Nicholas Lahens, Eun Ji Kim, Emanuela Ricciotti, George Paschos, Sarah Tishkoff, Dimitra Sarantopoulou, Shaon Sengupta, Barry Cooperman, Tilo Grosser, Gregory Grant,

Abstract It is common to measure large numbers of features to identify those differing between experimental conditions; for example using RNA-Seq to search for differentially expressed genes. Ranking by p-value allows for statistical control, but has well known issues: unreliability without many replicates; and significance of biologically irrelevant effect sizes. ... Read more >>

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Correction: Nonsteroidal anti-inflammatory drug choice and adverse outcomes in clopidogrel users: A retrospective cohort study.

Young Hee Nam, Colleen M Brensinger, Warren B Bilker, Charles E Leonard, Scott E Kasner, Tilo Grosser, Xuanwen Li, Sean Hennessy,

[This corrects the article DOI: 10.1371/journal.pone.0193800.]. ... Read more >>

PLoS ONE (PloS one)
[2018, 13(7):e0200982]

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Weight-adjusted aspirin for cardiovascular prevention.

Katherine N Theken, Tilo Grosser,

Lancet (Lancet (London, England))
[2018, 392(10145):361-362]

Cited: 1 time

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COX-2 mediates pro-tumorigenic effects of PKCε in prostate cancer.

Rachana Garg, Jorge M Blando, Carlos J Perez, Priti Lal, Michael D Feldman, Emer M Smyth, Emanuela Ricciotti, Tilo Grosser, Fernando Benavides, Marcelo G Kazanietz,

The pro-oncogenic kinase PKCε is overexpressed in human prostate cancer and cooperates with loss of the tumor suppressor Pten for the development of prostatic adenocarcinoma. However, the effectors driving PKCε-mediated phenotypes remain poorly defined. Here, using cellular and mouse models, we showed that PKCε overexpression acts synergistically with Pten loss ... Read more >>

Oncogene (Oncogene)
[2018, 37(34):4735-4749]

Cited: 4 times

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Nonsteroidal anti-inflammatory drug choice and adverse outcomes in clopidogrel users: A retrospective cohort study.

Young Hee Nam, Colleen M Brensinger, Warren B Bilker, Charles E Leonard, Scott E Kasner, Tilo Grosser, Xuanwen Li, Sean Hennessy,

OBJECTIVE:To examine the comparative safety of individual NSAIDs when given concomitantly with clopidogrel. METHODS:We conducted a retrospective cohort study using Medicaid claims from five US states during 1999-2010, supplemented with Medicare claims for dual-enrollees. The exposure of interest was the first concomitant use of clopidogrel and one of the 10 ... Read more >>

PLoS ONE (PloS one)
[2018, 13(3):e0193800]

Cited: 3 times

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Urinary Prostaglandin Metabolites: An Incomplete Reckoning and a Flush to Judgment.

Tilo Grosser, Ali Naji, Garret A FitzGerald,

Circ. Res. (Circulation research)
[2018, 122(4):537-539]

Cited: 4 times

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Cyclooxygenase Inhibition: Pain, Inflammation, and the Cardiovascular System.

Tilo Grosser, Katherine N Theken, Garret A FitzGerald,

Inhibitors of the cyclooxygenases (COXs), the nonsteroidal antiinflammatory drugs (NSAIDs), relieve inflammatory pain, but are associated with gastrointestinal and cardiovascular complications. Given the widespread use of NSAIDs, there has been a longstanding interest in optimizing their risk-benefit ratio, for example by reducing their gastrointestinal risk. More recently, the focus has ... Read more >>

Clin. Pharmacol. Ther. (Clinical pharmacology and therapeutics)
[2017, 102(4):611-622]

Cited: 3 times

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The Cardiovascular Pharmacology of Nonsteroidal Anti-Inflammatory Drugs.

Tilo Grosser, Emanuela Ricciotti, Garret A FitzGerald,

The principal molecular mechanisms underlying the cardiovascular (CV) and renal adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs), such as myocardial infarction and hypertension, are understood in more detail than most side effects of drugs. Less is known, however, about differences in the CV safety profile between chemically distinct NSAIDs and ... Read more >>

Trends Pharmacol. Sci. (Trends in pharmacological sciences)
[2017, 38(8):733-748]

Cited: 11 times

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Reply: Collapse of the Aspirin Empire: Is it Diabetic Gastroparesis or Cardioprotective Paresis?

Deepak L Bhatt, Tilo Grosser, Jing-Fei Dong, Douglas Logan, Walter Jeske, Dominick J Angiolillo, Andrew L Frelinger, Juan Liang, Byron Cryer, Upendra Marathi,

J. Am. Coll. Cardiol. (Journal of the American College of Cardiology)
[2017, 69(23):2879]

Cited: 0 times

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Microfluidic whole blood testing of platelet response to pharmacological agents.

Ruizhi Li, Tilo Grosser, Scott L Diamond,

Platelets present a number of intracellular and transmembrane targets subject to pharmacological modulation, either for cardiovascular disease reduction or as an unintended drug response. Microfluidic devices allow human blood to clot on a defined surface under controlled hemodynamic and pharmacological conditions. The potencies of a number of antiplatelet and anticancer ... Read more >>

Platelets (Platelets)
[2017, 28(5):457-462]

Cited: 3 times

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Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis.

Tilo Grosser,

N. Engl. J. Med. (The New England journal of medicine)
[2017, 376(14):1389]

Cited: 1 time

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Time for nonaddictive relief of pain.

Tilo Grosser, Clifford J Woolf, Garret A FitzGerald,

Science (Science (New York, N.Y.))
[2017, 355(6329):1026-1027]

Cited: 16 times

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Enteric Coating and Aspirin Nonresponsiveness in Patients With Type 2 Diabetes Mellitus.

Deepak L Bhatt, Tilo Grosser, Jing-Fei Dong, Douglas Logan, Walter Jeske, Dominick J Angiolillo, Andrew L Frelinger, Lanyu Lei, Juan Liang, Jason E Moore, Byron Cryer, Upendra Marathi,

BACKGROUND:A limitation of aspirin is that some patients, particularly those with diabetes, may not have an optimal antiplatelet effect. OBJECTIVES:The goal of this study was to determine if oral bioavailability mediates nonresponsiveness. METHODS:The rate and extent of serum thromboxane generation and aspirin pharmacokinetics were measured in 40 patients with diabetes in ... Read more >>

J. Am. Coll. Cardiol. (Journal of the American College of Cardiology)
[2017, 69(6):603-612]

Cited: 28 times

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Timing of expression of the core clock gene Bmal1 influences its effects on aging and survival.

Guangrui Yang, Lihong Chen, Gregory R Grant, Georgios Paschos, Wen-Liang Song, Erik S Musiek, Vivian Lee, Sarah C McLoughlin, Tilo Grosser, George Cotsarelis, Garret A FitzGerald,

The absence of Bmal1, a core clock gene, results in a loss of circadian rhythms, an acceleration of aging, and a shortened life span in mice. To address the importance of circadian rhythms in the aging process, we generated conditional Bmal1 knockout mice that lacked the BMAL1 protein during adult ... Read more >>

Sci Transl Med (Science translational medicine)
[2016, 8(324):324ra16]

Cited: 56 times

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microRNA represses macromolecule.

Tilo Grosser,

In this issue of Blood, Xiang et al identify a novel mechanism, involving activation of the polyol pathway and repression of microRNA-24 (miR-24), through which hyperglycemia augments von Willebrand factor (VWF) expression and secretion. ... Read more >>

Blood (Blood)
[2015, 125(22):3365-3366]

Cited: 1 time

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Understanding multicellular function and disease with human tissue-specific networks.

Casey S Greene, Arjun Krishnan, Aaron K Wong, Emanuela Ricciotti, Rene A Zelaya, Daniel S Himmelstein, Ran Zhang, Boris M Hartmann, Elena Zaslavsky, Stuart C Sealfon, Daniel I Chasman, Garret A FitzGerald, Kara Dolinski, Tilo Grosser, Olga G Troyanskaya,

Tissue and cell-type identity lie at the core of human physiology and disease. Understanding the genetic underpinnings of complex tissues and individual cell lineages is crucial for developing improved diagnostics and therapeutics. We present genome-wide functional interaction networks for 144 human tissues and cell types developed using a data-driven Bayesian ... Read more >>

Nat. Genet. (Nature genetics)
[2015, 47(6):569-576]

Cited: 208 times

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Differential impairment of aspirin-dependent platelet cyclooxygenase acetylation by nonsteroidal antiinflammatory drugs.

Xuanwen Li, Susanne Fries, Ruizhi Li, John A Lawson, Kathleen J Propert, Scott L Diamond, Ian A Blair, Garret A FitzGerald, Tilo Grosser,

The cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs) may be influenced by interactions with antiplatelet doses of aspirin. We sought to quantitate precisely the propensity of commonly consumed NSAIDs—ibuprofen, naproxen, and celecoxib—to cause a drug-drug interaction with aspirin in vivo by measuring the target engagement of aspirin directly by MS. ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2014, 111(47):16830-16835]

Cited: 29 times

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Response to letters regarding article, "Drug resistance and pseudoresistance: an unintended consequence of enteric coating aspirin".

Tilo Grosser, Susanne Fries, John A Lawson, Shiv C Kapoor, Gregory R Grant, Garret A Fitzgerald,

Circulation (Circulation)
[2013, 128(12):e191]

Cited: 0 times

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Microfluidic assay of platelet deposition on collagen by perfusion of whole blood from healthy individuals taking aspirin.

Ruizhi Li, Susanne Fries, Xuanwen Li, Tilo Grosser, Scott L Diamond,

BACKGROUND:Microfluidic devices can create hemodynamic conditions for platelet assays. We validated an 8-channel device in a study of interdonor response to acetylsalicylic acid (ASA, aspirin) with whole blood from 28 healthy individuals. METHODS:Platelet deposition was assessed before treatment or 24 h after ingestion of 325 mg ASA. Whole blood (plus ... Read more >>

Clin. Chem. (Clinical chemistry)
[2013, 59(8):1195-1204]

Cited: 18 times

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