Genome-wide analyses of platinum-induced ototoxicity in childhood cancer patients: Results of GO-CAT and United Kingdom MAGIC consortia.

Hearing loss (ototoxicity) is a major adverse effect of cisplatin and carboplatin chemotherapy. The aim of this study is to identify novel genetic variants that play a role in platinum-induced ototoxicity. Therefore, a genome-wide association study was performed in the Genetics of Childhood Cancer Treatment (GO-CAT) cohort (n = 261) and the United Kingdom Molecular Genetics of Adverse Drug Reactions in Children Study (United Kingdom MAGIC) cohort (n = 248).

Pharmacogenetics of chemotherapy treatment response and -toxicities in patients with osteosarcoma: a systematic review.

Background: Osteosarcoma is the most common bone tumor in children and adolescents. Despite multiagent chemotherapy, only 71% of patients survives and these survivors often experience long-term toxicities. The main objective of this systematic review is to provide an overview of the discovery of novel associations of germline polymorphisms with treatment response and/or chemotherapy-induced toxicities in osteosarcoma.

coding for LAT2 is associated with early disease progression in osteosarcoma and transports doxorubicin.

Despite (neo) adjuvant chemotherapy with cisplatin, doxorubicin and methotrexate, some patients with primary osteosarcoma progress during first-line systemic treatment and have a poor prognosis. In this study, we investigated whether patients with early disease progression (EDP), are characterized by a distinctive pharmacogenetic profile. Germline DNA from 287 Dutch high-grade osteosarcoma patients was genotyped using the DMET Plus array (containing 1,936 genetic markers in 231 drug metabolism and transporter genes).

Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods.

The widespread and increasing use of engineered nanomaterials (ENM) increases the risk of human exposure, generating concern that ENM may provoke adverse health effects. In this respect, their physicochemical characteristics are critical. The immune system may respond to ENM through inflammatory reactions.

Analysis of Drug Metabolizing Gene Panel in Osteosarcoma Patients Identifies Association Between Variants in and and Methotrexate Levels and Toxicities.

High-dose methotrexate is a cornerstone agent in the chemotherapeutic treatment of patients with osteosarcoma. However, patients often develop methotrexate-induced toxicities. We aim to identify determinants of methotrexate-induced toxicities in osteosarcoma patients by investigating the relation between drug plasma levels, methotrexate-induced toxicities, and germline variants in genes related to drug absorption, distribution, metabolism, and elimination.

Proguanil and cycloguanil are organic cation transporter and multidrug and toxin extrusion substrates.

Background: Malaria, HIV/AIDS, and tuberculosis endemic areas show considerable geographical overlap, leading to incidence of co-infections. This requires treatment with multiple drugs, potentially causing adverse drug-drug interactions (DDIs). As anti-malarials are generally positively charged at physiological pH, they are likely to interact with human organic cation transporters 1 and 2 (OCT1 and OCT2).