Systems Biology and Birth Defects Prevention: Blockade of the Glucocorticoid Receptor Prevents Arsenic-Induced Birth Defects

Background: The biological mechanisms by which environmental metals are associated with birth defects are largely unknown. Systems biology–based approaches may help to identify key pathways that mediate metal-induced birth defects as well as potential targets for prevention

Predictive Models of Skeletal Developmental Defects from ToxCast High-Throughput Screening Data

Presented at The Teratology Society-54thAnnual Meetin

Transarterial embolization for hepatocellular adenomas: Case report and literature review

Hepatocellular adenoma (HCAs) is a rare benign tumor in the liver. Bleeding and malignant transformation are the two severe outcomes of HCAs. Transarterial embolization (TAE) is used to treat HCAs; however, its role in an elective setting is uncertain. Here, we report a case with HCA treated by TAE in an elective setting, followed by resection after 2 months, because of stable disease. Further, we performed a comprehensive review of PubMed database for studies published between January 2000 and June 2018 involving TAE to treat HCA. The review included 22 studies involving 1504 patients with HCA, of whom 89.4% were female. Only 171/1504 (11.4%) patients received TAE, among whom resection was avoided in 80 (46.8%) patients, of whom 31 (38.7%) were bleeding before TAE and 49 (61.3%) were not. Based on data of 115 tumors reviewed, the rate of complete and partial response were 9.6% and 74.8%, respectively, with an overall (complete + partial) response of 84.3%. No mortality or adverse side effects were noted. Therefore, both in elective setting and in the setting of bleeding, TAE can be considered safe in the management of HCAs and may be regarded as reasonable alternative management to hepatic resection

Systems Biology and Birth Defects Prevention: Blockade of the Glucocorticoid Receptor Prevents Arsenic-Induced Birth Defects

Background: The biological mechanisms by which environmental metals are associated with birth defects are largely unknown. Systems biology–based approaches may help to identify key pathways that mediate metal-induced birth defects as well as potential targets for prevention. Objectives: First, we applied a novel computational approach to identify a prioritized biological pathway that associates metals with birth defects. Second, in a laboratory setting, we sought to determine whether inhibition of the identified pathway prevents developmental defects. Methods: Seven environmental metals were selected for inclusion in the computational analysis: arsenic, cadmium, chromium, lead, mercury, nickel, and selenium. We used an in silico strategy to predict genes and pathways associated with both metal exposure and developmental defects. The most significant pathway was identified and tested using an in ovo whole chick embryo culture assay. We further evaluated the role of the pathway as a mediator of metal-induced toxicity using the in vitro midbrain micromass culture assay. Results: The glucocorticoid receptor pathway was computationally predicted to be a key mediator of multiple metal-induced birth defects. In the chick embryo model, structural malformations induced by inorganic arsenic (iAs) were prevented when signaling of the glucocorticoid receptor pathway was inhibited. Further, glucocorticoid receptor inhibition demonstrated partial to complete protection from both iAs- and cadmium-induced neurodevelopmental toxicity in vitro. Conclusions: Our findings highlight a novel approach to computationally identify a targeted biological pathway for examining birth defects prevention