Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer

Autor: Satoshi Kishino, Nobuo Mochizuki, Satoshi Owada, Shogo Nomura, Rumi Fujioka, Hiroyasu Esumi, Katsuya Tsuchihara, Satoshi Yomoda, Masafumi Ikeda, Akihiro Sato
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Physiology
Cancer Treatment
Phases of clinical research
lcsh:Medicine
Kaplan-Meier Estimate
Drug research and development
Pharmacology
Kidney
Deoxycytidine
Biochemistry
Oxidative Phosphorylation
chemistry.chemical_compound
Clinical trials
0302 clinical medicine
Liver Function Tests
Blood plasma
Medicine
lcsh:Science
Energy-Producing Organelles
Multidisciplinary
medicine.diagnostic_test
Phase I clinical investigation
Organic Compounds
Monosaccharides
Mitochondria
Body Fluids
Chemistry
Blood
Liver
Oncology
Area Under Curve
030220 oncology & carcinogenesis
Physical Sciences
Biomarker (medicine)
Anatomy
Cellular Structures and Organelles
Carcinoma
Pancreatic Ductal

Research Article
medicine.drug
Carbohydrates
Gastroenterology and Hepatology
Bioenergetics
Lignans
Blood Plasma
Carcinoma
Adenosquamous

Pancreatic Cancer
03 medical and health sciences
Pharmacokinetics
Cell Line
Tumor

Gastrointestinal Tumors
Humans
Lactic Acid
Furans
Arctigenin
Medicine and health sciences
Plant Extracts
business.industry
Organic Chemistry
lcsh:R
Gluconeogenesis
Chemical Compounds
Cancers and Neoplasms
Biology and Life Sciences
Renal System
Cell Biology
Antineoplastic Agents
Phytogenic

Gemcitabine
Cori cycle
Arctium
Pancreatic Neoplasms
Research and analysis methods
Glucose
030104 developmental biology
chemistry
Drug Resistance
Neoplasm

Clinical medicine
lcsh:Q
Drug Screening Assays
Antitumor

business
Liver function tests
Biomarkers
Drugs
Chinese Herbal
Zdroj: PLoS ONE, Vol 13, Iss 6, p e0198219 (2018)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE