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Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9.
TLDR
Assessment of selectivity of potential clinical candidates may be important to an optimal safety profile for this new class of antihyperglycemic agents, according to the results of toxicity and tolerability studies. Expand
Cloning, Expression, and Up-regulation of Inducible Rat Prostaglandin E Synthase during Lipopolysaccharide-induced Pyresis and Adjuvant-induced Arthritis*
TLDR
The results demonstrate that PGE synthase is up-regulated in vivo after LPS or adjuvant administration and suggest that this is a key enzyme involved in the formation of PGE2in COX-2-mediated inflammatory and pyretic responses. Expand
Deletion of phosphodiesterase 4D in mice shortens alpha(2)-adrenoceptor-mediated anesthesia, a behavioral correlate of emesis.
TLDR
Findings strongly support the hypothesis that inhibition of PDE4D is pivotal to the anesthesia-reversing effect of PMNPQ and is likely responsible for emesis induced by PDE 4 inhibitors. Expand
Genomic characterization of a large panel of patient-derived hepatocellular carcinoma xenograft tumor models for preclinical development
TLDR
PDX models resemble histopathological and genomic characteristics of clinical HCC tumors, as well as recapitulate the differential responses of HCC patients to the standard-of-care treatment, which becomes a clinically relevant platform for drug screening, biomarker discovery and translational research in preclinical setting. Expand
Microsomal Prostaglandin E Synthase-1 Is a Major Terminal Synthase That Is Selectively Up-Regulated During Cyclooxygenase-2-Dependent Prostaglandin E2 Production in the Rat Adjuvant-Induced Arthritis
TLDR
Results show that mPGES-1 is up-regulated throughout the development of AIA and suggest that it plays a major role in the elevated production of PGE2 in this model. Expand
HIP1–ALK, A Novel ALK Fusion Variant that Responds to Crizotinib
TLDR
Discovery of HIP1 as a fusion partner of ALK in NSCLC is a novel finding, and in vivo efficacy studies demonstrated that the HIP1–ALK-containing PDX model was sensitive to treatment with crizotinib. Expand
Development of a liver-targeted stearoyl-CoA desaturase (SCD) inhibitor (MK-8245) to establish a therapeutic window for the treatment of diabetes and dyslipidemia.
TLDR
The discovery of MK-8245 is found, a potent, liver-targeted SCD inhibitor with preclinical antidiabetic and antidyslipidemic efficacy with a significantly improved therapeutic window. Expand
Long-term outcome of 231 patients with essential thrombocythemia: prognostic factors for thrombosis, bleeding, myelofibrosis, and leukemia.
TLDR
Chinese patients have a low risk of bleeding, and prior myelofibrosis is a major risk factor for evolution to acute myeloid leukemia, and leukemic transformation with hydroxyurea therapy alone is rare and warrants further prospective studies. Expand
Synthesis and SAR of pyrimidine-based, non-nucleotide P2Y14 receptor antagonists.
TLDR
Compound 18q was identified as a 10 nM P2Y(14) antagonist with good oral bioavailability and provided sufficient exposure in mice to be used as a tool for future in vivo studies. Expand
Activating JAK1 mutation may predict the sensitivity of JAK-STAT inhibition in hepatocellular carcinoma
TLDR
The results suggested that JAK1S703I is an activating mutation for JAK-STAT signaling pathway in vitro and in vivo, and Jak-STAT pathway might represent a new therapeutic approach for HCC treatment. Expand
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