Butyrylcholinesterase as a Blood Biomarker in Neuroblastoma

Abstract

Blood-based biomarkers are important in the detection of the disease and in the assessment of responses to therapy. In this study, butyrylcholinesterase was evaluated as a potential biomarker in newly diagnosed neuroblastoma (NB) patients at diagnosis and longitudinally during treatment. Plasma butyrylcholinesterase activities in age-matched and sex-matched children were used as controls. Pretreatment butyrylcholinesterase levels in NB subjects are on an average 2 times lower than butyrylcholinesterase levels in healthy subjects. Significantly, butyrylcholinesterase activities are ∼40% lower in MYCN-amplified as compared with nonamplified disease. As the course of chemotherapy progresses, butyrylcholinesterase activities recover and normalize to control values. The evident response to treatment indicates that plasma butyrylcholinesterase is a good biomarker of tumor response to therapy. Depressed butyrylcholinesterase levels in NB subjects are not caused by hepatic deficits suggesting a specific role for butyrylcholinesterase in NB. Further examination of the mechanism of altered butyrylcholinesterase production require an animal model that best approximates human condition. Studies in mice show that murine NB allografts significantly reduce butyrylcholinesterase activity in plasma. This finding correlates with changes observed in NB patients. In contrast, human NB xenografts produce the opposite effect, that is, butyrylcholinesterase plasma levels rise as the xenograft size increases. In the absence of any liver damage, dissimilarities between butyrylcholinesterase production in murine and human NB models suggest species-specific signaling pathways. This disparity also suggests that human NB xenograft mouse models do not approximate the human disease.

Radiolabeled (R)‐(–)‐5‐iodo‐3′‐O‐[2‐(ε‐guanidinohexanoyl)‐2‐phenylacetyl]‐2′‐deoxyuridine: A new theranostic for neuroblastoma

“…First, to avoid rapid degradation of GPAID by carboxylesterases present in mouse blood (Figure 1B), N1E cells were implanted IP, and IP injections were used as the route of GPAID administration. Second, we previously determined that a mouse NB allograft represents a more realistic model of NB 46 . Mice of both genders were treated with a single IP dose of 3.64 ± 0.10 MBq per mouse GPAID 1 week after the tumor implant.…”

Norepinephrine-Transporter-Targeted and DNA-Co-Targeted Theranostic Guanidines

“…We were faced with two major challenges related to this in vivo model. A mouse is an imperfect model for xenografts of human NB 91 and for the evaluation of drugs that are susceptible to circulating carboxylases. 39,92,93 Nonetheless, mice are always used as the initial in vivo animal model in the preclinical evaluation.…”

“…We were faced with two major challenges related to this in vivo model. A mouse is an imperfect model for xenografts of human NB and for the evaluation of drugs that are susceptible to circulating carboxylases. ,, Nonetheless, mice are always used as the initial in vivo animal model in the preclinical evaluation. To enhance the function of this model in our studies, we chose an intratumor route of the administration to avoid rapid catabolism of radioactive guanidines by circulating carboxylesterases.…”

Reduced Serum Cholinesterase Activity Distinguishes Hepatic Encephalopathy From 48 Types of Human Diseases

“…All 48 different types of diseases studied in the current study had the lower median serum CHE activities than that of healthy controls ( Table 1), implicating that decreased serum CHE might be a common feature of human diseases. Most of publications reported the dynamic changes of serum CHE activities in one speci c disease [32][33][34][35][36][37][38][39][40], we performed the systematical comparison of serum CHE activities (Table 1) and CHE as biomarkers (Fig. 1) in 48 different types of diseases for the rst time.…”