Topoisomerases induce transient protein linked DNA breaks which modulate the structure of DNA. Topoisomerase I (topo I) induces single strand DNA breaks that allow for conformational changes required during chromatic organization, mitosis, replication, and transcription. Topo I levels remain constant throughout the cell cycle. However, topoisomerase levels differ between normal and neoplastic tissues. In human lymphoma specimens, the concentrations of topo I have been found to be 5-15 fold higher than in normal tissues. This suggests that there may be a therapeutic window to exploit using Topo I inhibitors. The cytotoxicity of campothecins (and the analogue 9-AC) (Topo I inhibitors) is highly correlated with the ability to form DNA-protein adducts. Drug binding is reversible, and cytotoxicity cell cycle dependent. Drug resistance may be mediated through alterations in drug accumulation, altered cell cycle duration, or changes in the target enzyme. Pre-clinical data suggests that prolonged maintenance of drug levels above a threshold is beneficial, and that continuous infusion schedules may be preferable to bolus administration. Neoplasms such as mycosis fungoides with slow growth rates similarly may be best treated by continuous infusions of agents. Toxicity in phase I studies was primarily myelosuppression when a 72 hour infusion schedule was utilized. This could be ameliorated by growth factor support.
| Sherenian, Michael G; Singh, Anne M; Arguelles, Lester et al. (2018) Association of food allergy and decreased lung function in children and young adults with asthma. Ann Allergy Asthma Immunol 121:588-593.e1 |
| Baron, Kelly Glazer; Reid, Kathryn J; Malkani, Roneil G et al. (2017) Sleep Variability Among Older Adults With Insomnia: Associations With Sleep Quality and Cardiometabolic Disease Risk. Behav Sleep Med 15:144-157 |
| Makhija, Melanie M; Robison, Rachel G; Caruso, Deanna et al. (2016) Patterns of allergen sensitization and self-reported allergic disease in parents of food allergic children. Ann Allergy Asthma Immunol 117:382-386.e1 |
| Gupta, Ruchi S; Walkner, Madeline M; Greenhawt, Matthew et al. (2016) Food Allergy Sensitization and Presentation in Siblings of Food Allergic Children. J Allergy Clin Immunol Pract 4:956-62 |
| Raghanti, Mary Ann; Edler, Melissa K; Stephenson, Alexa R et al. (2016) Human-specific increase of dopaminergic innervation in a striatal region associated with speech and language: A comparative analysis of the primate basal ganglia. J Comp Neurol 524:2117-29 |
| Slama, Laurence; Jacobson, Lisa P; Li, Xiuhong et al. (2016) Longitudinal Changes Over 10 Years in Free Testosterone Among HIV-Infected and HIV-Uninfected Men. J Acquir Immune Defic Syndr 71:57-64 |
| Ye, Wen; Rosenthal, Philip; Magee, John C et al. (2015) Factors Determining ?-Bilirubin Levels in Infants With Biliary Atresia. J Pediatr Gastroenterol Nutr 60:659-63 |
| Arroyo-Ávila, Mariangelí; Santiago-Casas, Yesenia; McGwin Jr, Gerald et al. (2015) Clinical associations of anti-Smith antibodies in PROFILE: a multi-ethnic lupus cohort. Clin Rheumatol 34:1217-23 |
| Nodzenski, Michael; Muehlbauer, Michael J; Bain, James R et al. (2014) Metabomxtr: an R package for mixture-model analysis of non-targeted metabolomics data. Bioinformatics 30:3287-8 |
| Scholtens, Denise M; Muehlbauer, Michael J; Daya, Natalie R et al. (2014) Metabolomics reveals broad-scale metabolic perturbations in hyperglycemic mothers during pregnancy. Diabetes Care 37:158-66 |
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