PMID- 29556248
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 9
DP  - 2018
TI  - Growth of Triple Negative and Progesterone Positive Breast Cancer Causes 
      Oxidative Stress and Down-Regulates Neuroprotective Transcription Factor NPAS4 
      and NPAS4-Regulated Genes in Hippocampal Tissues of TumorGraft Mice-an Aging 
      Connection.
PG  - 58
LID - 10.3389/fgene.2018.00058 [doi]
LID - 58
AB  - While the refinement of existing and the development of new chemotherapeutic 
      regimens has significantly improved cancer treatment outcomes and patient 
      survival, chemotherapy still causes many persistent side effects. Central nervous 
      system (CNS) toxicity is of particular concern, as cancer patients experience 
      significant deficits in memory, learning, cognition, and decision-making. These 
      chemotherapy-induced cognitive changes are termed chemo brain, and manifest in 
      more than half of cancer survivors. Moreover, recent studies have emerged 
      suggesting that neurocognitive deficits manifest prior to cancer diagnosis and 
      treatment, and thus may be associated with tumor presence, a phenomenon recently 
      termed "tumor brain." To dissect the molecular mechanisms of tumor brain, we used 
      TumorGraft(TM) models, wherein part of a patient's tumor is grafted into 
      immune-deficient mice. Here, we analyzed molecular changes in the hippocampal 
      tissues of mice carrying triple negative (TNBC) or progesterone receptor positive 
      (PR+BC) xenografts. TNBC growth led to increased oxidative damage, as detected by 
      elevated levels of 4-hydroxy-2-nonenal, a product of lipid peroxidation. 
      Furthermore, the growth of TNBC and PR+BC tumors altered global gene expression 
      in the murine hippocampus and affected multiple pathways implicated in PI3K-Akt 
      and MAPK signaling, as well as other pathways crucial for the proper functioning 
      of hippocampal neurons. TNBC and PR+BC tumor growth also led to a significant 
      decrease in the levels of neuronal transcription factor NPAS4, a regulator that 
      governs the expression of brain-derived neurotrophic factor (BDNF), and several 
      other key brain neurotrophic factors and pro-survival molecules. The decreased 
      expression of ERK1/2, NPAS4, and BDNF are also seen in neurodegenerative 
      conditions and aging, and may constitute an important tumor brain mechanism.
FAU - Kovalchuk, Anna
AU  - Kovalchuk A
AD  - Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada.
AD  - Leaders in Medicine Program, Cumming School of Medicine, University of Calgary, 
      Calgary, AB, Canada.
FAU - Ilnytskyy, Yaroslav
AU  - Ilnytskyy Y
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, 
      Canada.
FAU - Rodriguez-Juarez, Rocio
AU  - Rodriguez-Juarez R
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, 
      Canada.
FAU - Katz, Amanda
AU  - Katz A
AD  - Department of Oncology, Champions Oncology, Baltimore, MD, United States.
FAU - Sidransky, David
AU  - Sidransky D
AD  - Department of Oncology, Champions Oncology, Baltimore, MD, United States.
AD  - Department of Otolaryngology and Oncology, Johns Hopkins University, Baltimore, 
      MD, United States.
FAU - Kolb, Bryan
AU  - Kolb B
AD  - Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada.
FAU - Kovalchuk, Olga
AU  - Kovalchuk O
AD  - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, 
      Canada.
LA  - eng
PT  - Journal Article
DEP - 20180305
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC5845109
OTO - NOTNLM
OT  - animal models
OT  - brain ageing
OT  - gene expression
OT  - non-CNS cancer
OT  - tumor brain
EDAT- 2018/03/21 06:00
MHDA- 2018/03/21 06:01
PMCR- 2018/03/05
CRDT- 2018/03/21 06:00
PHST- 2017/11/24 00:00 [received]
PHST- 2018/02/08 00:00 [accepted]
PHST- 2018/03/21 06:00 [entrez]
PHST- 2018/03/21 06:00 [pubmed]
PHST- 2018/03/21 06:01 [medline]
PHST- 2018/03/05 00:00 [pmc-release]
AID - 10.3389/fgene.2018.00058 [doi]
PST - epublish
SO  - Front Genet. 2018 Mar 5;9:58. doi: 10.3389/fgene.2018.00058. eCollection 2018.