ABSTRACT
Patients undergoing mFOLFOX6 treatment were classified into a hyperammonemia group (NH3 group) or a non-hyperammonemia group (Non-NH3 group) in order to investigate risk factors related to the onset of hyperammonemia. The NH3 group demonstrated significantly lower lymphocyte counts, hemoglobin and albumin levels, and estimated glomerular filtration rates compared to the Non-NH3 group, suggesting that the NH3 group was experiencing renal dysfunction and loss of skeletal muscle mass due to malnutrition. Amino acid fractionation in the NH3 group revealed high urea levels, and delayed urea excretion was identified. Fluorocitric acid, a fluorouracil metabolite, inhibits aconitase in the tricarboxylic acid cycle. In addition, decreased renal urea transporter function due to renal impairment leads to delayed urea excretion. These factors may induce secondary decreases in urea cycle function, leading to hyperammonemia.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/drug therapy , Hyperammonemia/chemically induced , Aged , Amino Acids/blood , Female , Fluorouracil/adverse effects , Humans , Leucovorin/adverse effects , Male , Organoplatinum Compounds/adverse effects , Risk FactorsABSTRACT
Retinoids including natural vitamin A, its derivatives and synthetic compounds work as transcription factors through the retinoic acid receptors (RAR, RXR). All-trans retinoic acid (ATRA), a family of retinoids, is an internal ligand of RAR and well known as a useful differentiation inducer to treat acute promyelocytic leukemia (APL). ATRA therapy is now established as an initial treatment for APL. Recently, to improve therapeutic potency and reduce adverse effects of ATRA, a novel synthetic selective agonist for RARalpha and beta, Am80, was developed and applied to APL treatment. In this study, we tested whether Am80 was capable of inducing neuronal differentiation in a human neuroblastoma cell line, NH-12 and compared the differentiation effects between Am80 and ATRA. Morphological studies demonstrated that Am80 induced more potent neurite outgrowth and also proved lesser cell toxicity than ATRA. Am80 up-regulated the expression of tropomyosin-related kinase B as well as ATRA. Moreover, Am80 increased the expression of the neuronal marker, growth-associated protein 43. These findings suggest that Am80 induces neuronal differentiation to a greater extent than ATRA and thus may help establishing therapeutic strategies against neuronal degenerative disorders such as Parkinson's disease.
