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Changes in Oxidant Defense, Apoptosis, and Cognitive Abilities During Treatment for Childhood Leukemia.

Publication ,  Journal Article
Moore, IMK; Koerner, KM; Gundy, PM; Montgomery, DW; Insel, KC; Harris, LL; Taylor, OA; Hockenberry, MJ
Published in: Biological research for nursing
July 2018

Aggressive central nervous system (CNS)-directed treatment for acute lymphoblastic leukemia (ALL), the most prevalent cancer among children and adolescents, prevents metastasis of leukemia cells into the brain. Up to 60% of survivors experience cognitive problems, but knowledge about risk factors for and mechanisms of neurologic injury is lacking. Objectives of the present study were to (1) quantify changes in oxidant defense and apoptosis over the course of ALL therapy and (2) elucidate risk factors for long-term cognitive problems. The sample included 71 children with ALL. Cerebrospinal fluid (CSF) samples were collected at diagnosis and during intrathecal chemotherapy administration. Oxidant defense was measured by reduced glutathione (GSH), oxidized glutathione (GSSG), and the ratio of GSH:GSSG. Apoptosis was measured by activity of several cysteine-dependent aspartate-specific protease (abbreviated as caspase) enzymes that initiate (caspases 8 and 9) or execute (caspases 3/7) apoptosis. Cognitive abilities were assessed by standardized measures of short-term memory, visual-motor integration, and attention 3 years after ALL diagnosis. GSH and GSSG concentration increased significantly during ALL therapy, and a low GSH:GSSG ratio was indicative of an oxidized extracellular environment. Caspase enzyme activity increased significantly, and caspases 3/7 activity was significantly and negatively associated with performance on measures of cognitive abilities. Younger age at time of ALL diagnosis was associated with some measures of attention. Efflux of glutathione into CSF maintains oxidant defense by scavenging free radicals and other reactive oxygen species and is an early event in apoptosis. These mechanisms may be involved in neurologic injury associated with CNS-directed treatment and subsequent cognitive problems.

Duke Scholars

Published In

Biological research for nursing

DOI

EISSN

1552-4175

ISSN

1099-8004

Publication Date

July 2018

Volume

20

Issue

4

Start / End Page

393 / 402

Related Subject Headings

  • Reactive Oxygen Species
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Oxidation-Reduction
  • Nursing
  • Male
  • Humans
  • Glutathione
  • Cognition
  • Child, Preschool
  • Child
 

Citation

APA
Chicago
ICMJE
MLA
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Moore, I. M. K., Koerner, K. M., Gundy, P. M., Montgomery, D. W., Insel, K. C., Harris, L. L., … Hockenberry, M. J. (2018). Changes in Oxidant Defense, Apoptosis, and Cognitive Abilities During Treatment for Childhood Leukemia. Biological Research for Nursing, 20(4), 393–402. https://doi.org/10.1177/1099800418763124
Moore, Ida M Ki, Kari M. Koerner, Patricia M. Gundy, David W. Montgomery, Kathleen C. Insel, Lynnette L. Harris, Olga A. Taylor, and Marilyn J. Hockenberry. “Changes in Oxidant Defense, Apoptosis, and Cognitive Abilities During Treatment for Childhood Leukemia.Biological Research for Nursing 20, no. 4 (July 2018): 393–402. https://doi.org/10.1177/1099800418763124.
Moore IMK, Koerner KM, Gundy PM, Montgomery DW, Insel KC, Harris LL, et al. Changes in Oxidant Defense, Apoptosis, and Cognitive Abilities During Treatment for Childhood Leukemia. Biological research for nursing. 2018 Jul;20(4):393–402.
Moore, Ida M. Ki, et al. “Changes in Oxidant Defense, Apoptosis, and Cognitive Abilities During Treatment for Childhood Leukemia.Biological Research for Nursing, vol. 20, no. 4, July 2018, pp. 393–402. Epmc, doi:10.1177/1099800418763124.
Moore IMK, Koerner KM, Gundy PM, Montgomery DW, Insel KC, Harris LL, Taylor OA, Hockenberry MJ. Changes in Oxidant Defense, Apoptosis, and Cognitive Abilities During Treatment for Childhood Leukemia. Biological research for nursing. 2018 Jul;20(4):393–402.
Journal cover image

Published In

Biological research for nursing

DOI

EISSN

1552-4175

ISSN

1099-8004

Publication Date

July 2018

Volume

20

Issue

4

Start / End Page

393 / 402

Related Subject Headings

  • Reactive Oxygen Species
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Oxidation-Reduction
  • Nursing
  • Male
  • Humans
  • Glutathione
  • Cognition
  • Child, Preschool
  • Child