Tissue 2-Hydroxyglutarate and Preoperative Seizures in Patients With Diffuse Gliomas.

Background And Objectives: Mutant isocitrate dehydrogenase () 1/2 gene products gain a new ability to produce D-2-hydroxyglutarate (D2HG). mutations are thought to be associated with seizures owing to the structural similarity between D2HG and glutamate. However, the effects of D2HG on seizures in clinical settings are not fully understood.

Applications of MALDI mass spectrometry imaging for pharmacokinetic studies during drug development.

The concentration and distribution of a drug or its metabolites in tissues are key factors for understanding drug efficacy or toxicity. Conventional pharmacokinetic studies show that the plasma concentration of a drug is often unrelated to the intra-tissue concentration. Moreover, it is difficult to predict the distribution of a drug in tissues, particularly those with complex structures, even though the overall tissue concentration is measured by using homogenizing procedures.

Distribution of erlotinib in rash and normal skin in cancer patients receiving erlotinib visualized by matrix assisted laser desorption/ionization mass spectrometry imaging.

Background: The development of skin rashes is the most common adverse event observed in cancer patients treated with epidermal growth factor receptor-tyrosine kinase inhibitors such as erlotinib. However, the pharmacological evidence has not been fully revealed.

Results: Erlotinib distribution in the rashes was more heterogeneous than that in the normal skin, and the rashes contained statistically higher concentrations of erlotinib than adjacent normal skin in the superficial skin layer (229 ± 192 vs.

MALDI mass spectrometry imaging of erlotinib administered in combination with bevacizumab in xenograft mice bearing B901L, EGFR-mutated NSCLC cells.

Combination therapy of erlotinib plus bevacizumab improves progression-free survival of patients with epidermal growth factor receptor-mutated (EGFR-mutated) advanced non-small-cell lung cancer (NSCLC) compared with erlotinib alone. Although improved delivery and distribution of erlotinib to tumours as a result of the normalization of microvessels by bevacizumab is thought to be one of the underlying mechanisms, there is insufficient supporting evidence. B901L cells derived from EGFR-mutated NSCLC were subcutaneously implanted into mice, and mice were treated with bevacizumab or human IgG followed by treatment with erlotinib.

Heterogeneous distribution of alectinib in neuroblastoma xenografts revealed by matrix-assisted laser desorption ionization mass spectrometry imaging: a pilot study.

Background And Purpose: The penetration of the anaplastic lymphoma kinase (ALK) inhibitor alectinib in neuroblastomas and the relationship between alectinib and ALK expression are unknown. The aim of this study was to perform a quantitative investigation of the inter- and intra-tumoural distribution of alectinib in different neuroblastoma xenograft models using matrix-assisted laser desorption ionization MS imaging (MALDI-MSI).

Experimental Approach: The distribution of alectinib in NB1 (ALK amplification) and SK-N-FI (ALK wild-type) xenograft tissues was analysed using MALDI-MSI.

Evaluation of the heterogeneous tissue distribution of erlotinib in lung cancer using matrix-assisted laser desorption ionization mass spectrometry imaging.

Although drug distribution in tumor tissues has a significant impact on efficacy, conventional pharmacokinetic analysis has some limitations with regard to its ability to provide a comprehensive assessment of drug tissue distribution. Erlotinib is a tyrosine kinase inhibitor that acts on the epidermal growth factor receptor; however, it is unclear how this drug is histologically distributed in lung cancer. We used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze erlotinib distribution in the tumor and normal lung tissues of a mouse xenograft model and patient with non-small cell lung cancer.

High-performance liquid chromatography-tandem mass spectrometry for simultaneous determination of raltegravir, dolutegravir and elvitegravir concentrations in human plasma and cerebrospinal fluid samples.

A simple sample treatment procedure and sensitive liquid chromatography-tandem mass spectrometry method were developed for the simultaneous quantification of the concentrations of human immunodeficiency virus-1 integrase strand transfer inhibitors - raltegravir, dolutegravir and elvitegravir - in human plasma and cerebrospinal fluid (CSF). Plasma and CSF samples (20 μL each) were deproteinized with acetonitrile. Raltegravir-d was used as the internal standard.

Pharmacokinetic profiles of significant adverse events with crizotinib in Japanese patients with ABCB1 polymorphism.

Crizotinib is a standard treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC). We undertook this study to investigate the pharmacokinetics of crizotinib and clinical and pharmacogenomic factors that may increase the risk of adverse events (AEs). We defined clinically significant AEs as grade 4 hematological toxicity, grade ≥3 non-hematological toxicity, and any grade of interstitial lung disease.

Visualizing spatial distribution of alectinib in murine brain using quantitative mass spectrometry imaging.

In the development of anticancer drugs, drug concentration measurements in the target tissue have been thought to be crucial for predicting drug efficacy and safety. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is commonly used for determination of average drug concentrations; however, complete loss of spatial information in the target tissue occurs. Mass spectrometry imaging (MSI) has been recently applied as an innovative tool for detection of molecular distribution of pharmacological agents in heterogeneous targets.

A novel method for evaluating antibody-dependent cell-mediated cytotoxicity by flowcytometry using cryopreserved human peripheral blood mononuclear cells.

Analyzing the cytotoxic functions of effector cells, such as NK cells against target cancer cells, is thought to be necessary for predicting the clinical efficacy of antibody-dependent cellular cytotoxicity (ADCC) -dependent antibody therapy. The (51)Cr release assay has long been the most widely used method for quantification of ADCC activity. However, the reproducibilities of these release assays are not adequate, and they do not allow evaluation of the lysis susceptibilities of distinct cell types within the target cell population.

Innate immunity in an in vitro murine blastocyst model using embryonic and trophoblast stem cells.

The immune system has two broad components-innate and adaptive immunity. Adaptive immunity becomes established only after the onset of hematopoiesis, whereas the innate immune system may be actively protecting organisms from microbial invasion much earlier in development. Here, we address the question of whether the innate immune system functions in the early-stage embryo, i.