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The association between pro-inflammatory cytokines, regional cerebral metabolism, and cognitive complaints following adjuvant chemotherapy for breast cancer
Authors:K. L. Pomykala  P. A. Ganz  J. E. Bower  L. Kwan  S. A. Castellon  S. Mallam  I. Cheng  R. Ahn  E. C. Breen  M. R. Irwin  D. H. S. Silverman
Affiliation:1. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, 200 Medical Plaza, Suite B114, Mail Code: 737024, Los Angeles, CA, 90095-7370, USA
2. Department of Health Policy & Management, UCLA Fielding School of Public Health, Los Angeles, CA, USA
3. Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
4. Division of Cancer Prevention and Control Research, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA
5. Department of Psychology, University of California, Los Angeles, CA, USA
6. Cousins Center of Psychoneuroimmunology, Semel Institute for Neuroscience, Los Angeles, CA, USA
7. VA Greater Los Angeles Health Care System, Los Angeles, CA, USA
8. Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Abstract:To examine relationships following adjuvant chemotherapy between circulating pro-inflammatory cytokines, regional cerebral metabolism, and cognitive complaints in early stage breast cancer patients. 33 breast cancer patients who had completed initial treatment (surgery, ± radiation, 23 chemotherapy, 10 no chemotherapy) obtained resting (18)F-FDG PET/CT brain imaging at baseline and 1 year later. Pro-inflammatory cytokine markers (IL-1ra, sTNF-RII, CRP, and IL-6) and cognitive complaints were also assessed at both time points. At baseline, consistent correlations were seen between the left medial frontal and right inferior lateral anterior temporal cortices and inflammatory markers within the chemotherapy group, and not in the no chemotherapy group. After 1 year, correlations persisted in the medial frontal cortex and the temporal cortex, the latter shifting superiorly. Both of these regional correlations demonstrated the highest levels of significance when looking across the 1 year time frame (IL-1ra: peak voxel p?p?p?=?0.001 after correction (medial prefrontal), p?p?=?0.001, p?=?0.029 corr. (anterior temporal), sTNF-RII: p?p?=?0.001, p?=?0.040 corr. (medial prefrontal)). Positive correlations were also seen within the chemotherapy group between baseline memory complaints and the medial frontal (p?p?p?p?p?p?=?0.002 corr.) cortices at baseline and 1 year later. Metabolism in the medial prefrontal cortex and anterior temporal cortex was found to correlate with both memory complaints and cytokine marker levels in chemotherapy patients.
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