Ju‐Hee Oh

BACKGROUND: Antibody drug conjugates (ADCs) targeting the epidermal growth factor receptor (EGFR), such as depatuxizumab mafodotin (Depatux-M), is a promising therapeutic strategy for glioblastoma (GBM) but recent clinical trials did not demonstrate a survival benefit. Understanding the mechanisms of failure for this promising strategy is critically important. METHODS: PDX models were employed to study efficacy of systemic vs intracranial delivery of Depatux-M. Immunofluorescence and MALDI-MSI w

Despite the importance of the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-RANK signaling mechanisms on osteoclast differentiation, little has been studied on how RANK expression is regulated or what regulates its expression during osteoclastogenesis. We show here that insulin signaling increases RANK expression, thus enhancing osteoclast differentiation by RANKL. Insulin stimulation induced RANK gene expression in time-and dose-dependent manners and insulin receptor shRNA com

Quercetin is a biologically active flavonoid that has been used as a popular health supplement. It is reported that quercetin may cause flavonoid-drug interaction mediated by P-glycoprotein, the most predominant efflux transporter. In this study, we comprehensively evaluated the potential of the pharmacokinetic interaction of quercetin mediated by multidrug resistance-associated protein 2 (MRP2), another major efflux transporter. MRP2-transfected MDCKII cells and LS174T cells were used to evalua

INTRODUCTION: Natural products have been used traditionally for the treatment and prevention of diseases for thousands of years and are nowadays consumed as dietary supplements and herbal medicine. To ensure the safe and effective use of these herbal products, information about bioavailability of active compounds in plasma or target tissues should be provided via validated analytical methods combined with appropriate sampling methods. OBJECTIVE: To provide comprehensive and abridged information

Obatoclax, a pan-Bcl2 inhibitor, shows antitumor activities in various solid malignancies. Bcl2-deficient mice have shown the importance of Bcl2 in osteoclasts, as the bone mass of the mice was increased by the induced apoptosis of osteoclasts. Despite the importance of Bcl2, the effects of obatoclax on the proliferation and differentiation of osteoclast precursors have not been studied extensively. Here, we describe the anti-proliferative effects of obatoclax on osteoclast precursors and its ne

Patients with type 2 diabetes mellitus have a high risk of cardiovascular disease mainly caused by dyslipidemia. Metformin and atorvastatin are preferentially used to treat type 2 diabetes mellitus and dyslipidemia, respectively. The aim of this study was to develop a once-a-day fixed-dose combination tablet containing metformin and atorvastatin. For this purpose, we designed gastroretentive bilayer tablets consisting of 500 mg metformin in a sustained release layer and 10 mg atorvastatin in an

BACKGROUND/AIMS: We aimed to define an optimal target population and drug-specific biomarkers that may predict dipeptidyl peptidase (DPP)-4 inhibitor responses in non-alcoholic fatty liver disease (NAFLD). METHODS: An exploration study (study I) was performed using three different NAFLD models (basket study design; high-fat diet [HFD], methionine choline-deficient diet [MCD], and high-cholesterol Western diet [WD] models). RNA transcriptome analysis was performed on pre-studied liver tissues to

Breast cancer resistance protein (BCRP) mediates pharmacokinetic drug interactions. This study evaluated the potential of quercetin to inhibit and induce BCRP in vitro and in vivo. The inhibition of BCRP was investigated for quercetin and its metabolites using BCRP/mBcrp1-overexpressing MDCKII cells by flow cytometry. The induction of BCRP was investigated in LS174T cells using quantitative PCR. The expression of rat BCRP in rat small intestine, liver, and kidney was also measured after multiple

BACKGROUND AND AIM: Necroptosis is an emerging cell death pathway that allows cells to undergo "cellular suicide" in a caspase-independent manner. We investigated the fate of hepatic stellate cells (HSCs) under necroptotic stimuli. METHODS AND RESULTS: The RNA level of mixed lineage kinase domain-like protein (MLKL) is higher in patients with non-alcoholic fatty liver disease than in healthy controls. Hepatic fibrosis was significantly lower in MLKL-KO bile duct ligation (KO-BDL) mice than in wi

The aim of this study was to investigate the effect of anesthesia on the pharmacokinetics of bromosulfophthalein (BSP) with focus on biliary clearance. The plasma concentration profile and biliary clearance of intravenously administered BSP was compared in conscious freely moving bile duct catheterized rats and rats anesthetized with ketamine or Zoletil. The plasma concentration of BSP in conscious rats was similar to that of anesthetized rats, irrespective of the anesthetic used. There was no s

The combination of severe plastic deformation, deformational heat, and frictional heat generated during the high-pressure torsion process has a great effect on microstructural evolutions, including grain refinement, dynamic recrystallization and recovery. In particular, the low melting temperature metallic alloys (e.g., aluminum and magnesium) also induce nano-precipitations in the matrix during high-pressure torsion, which results in both unique microstructure and mechanical properties of the n

BACKGROUND: Disruption of the blood-brain barrier (BBB) in high-grade brain tumors is characterized by contrast accumulation on diagnostic imaging. This window of opportunity study correlates contrast imaging features with the tumor distribution of BBB-permeable (levetiracetam) and -impermeable (cefazolin) drugs. METHODS: Patients with a clinical diagnosis of a high-grade brain tumor underwent MRI for surgical planning. Cefazolin and levetiracetam were administered prior to skin incision, and se