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Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle.
This article was published in the following journal.
Name: PloS one
Uracil-tegafur (UFT) is an oral anticancer drug containing uracil and 5‑fluorouracil prodrug tegafur and is widely used for adjuvant chemotherapy of colorectal cancer. Although clinical data show ci...
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The purpose of this research study is to determine if consuming arctigenin, a natural compound from a Chinese herb called Arctium lappa (commonly called greater burdock), is safe, and to m...
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The oxygen consumption level above which aerobic energy production is supplemented by anaerobic mechanisms during exercise, resulting in a sustained increase in lactate concentration and metabolic acidosis. The anaerobic threshold is affected by factors that modify oxygen delivery to the tissues; it is low in patients with heart disease. Methods of measurement include direct measure of lactate concentration, direct measurement of bicarbonate concentration, and gas exchange measurements.
A cytochrome form of lactate dehydrogenase found in the MITOCHONDRIA. It catalyzes the oxidation of L-lactate to PYRUVATE with transfer of electrons to CYTOCHROME C. The enzyme utilizes FMN and PROTOHEME IX as cofactors.
A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.
Increase in blood LACTATE concentration often associated with SEPTIC SHOCK; LUNG INJURY; SEPSIS; and DRUG TOXICITY. When hyperlactatemia is associated with low body pH (acidosis) it is LACTIC ACIDOSIS.
The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs).
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In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...