Elevated prefrontal myo-inositol and choline following breast cancer chemotherapy

Kesler, Shelli R.; Watson, Christa; Koovakkattu, Della; Lee, Clement; O’Hara, Ruth; Mahaffey, Misty L.; Wefel, Jeffrey S.

doi:10.1007/s11682-013-9228-1

Cited by 33 publications

(29 citation statements)

References 62 publications

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“…1C) mirror the pattern of their alterations in colorectal cancer, where glucose and myo-inositol are decreased while lactate and taurine are increased compared to normal tissues (34). Specifically to myo-inositol, it has been also reported that this metabolite was significantly increased in breast cancer survivors who underwent chemotherapy (44) and in healthy control subjects compared to men with prostate cancer (45). These findings suggest that the drop in myo-inositol levels is a common trend in malignancies.…”

Section: Discussionmentioning

confidence: 94%

Metabolic Reprogramming by Folate Restriction Leads to a Less Aggressive Cancer Phenotype

Ashkavand

O’Flanagan

Hennig

et al. 2017

Molecular Cancer Research

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Folate coenzymes are involved in biochemical reactions of one-carbon transfer, and deficiency of this vitamin impairs cellular proliferation, migration and survival in many cell types. Here the effect of folate restriction on mammary cancer was evaluated using three distinct breast cancer subtypes differing in their aggressiveness and metastatic potential: non-invasive basal-like (E-Wnt), invasive but minimally metastatic claudin-low (M-Wnt), and highly metastatic claudin-low (metM-Wntliver) cell lines, each derived from the same pool of MMTV-Wnt-1 transgenic mouse mammary tumors. NMR-based metabolomics was used to quantitate 41 major metabolites in cells grown in folate-free medium versus standard medium. Each cell line demonstrated metabolic reprogramming when grown in folate-free medium. In E-Wnt, M-Wnt and metM-Wntliver cells 12, 29, and 25 metabolites, respectively, were significantly different (p<0.05 and at least 1.5-fold change). The levels of eight metabolites (aspartate, ATP, creatine, creatine phosphate, formate, serine, taurine and β-alanine) were changed in each folate-restricted cell line. Increased glucose, decreased lactate, and inhibition of glycolysis, cellular proliferation, migration and invasion occurred in M-Wnt and metM-Wntliver cells (but not E-Wnt cells) grown in folate-free versus standard medium. These effects were accompanied by altered levels of several folate-metabolizing enzymes, indicating that the observed metabolic reprogramming may result from both decreased folate availability and altered folate metabolism. These findings reveal that folate restriction results in metabolic and bioenergetic changes and a less aggressive cancer cell phenotype. Implications Metabolic reprogramming driven by folate restriction represents a therapeutic target for reducing the burden of breast cancer.

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Section: Discussionmentioning

confidence: 94%

Metabolic Reprogramming by Folate Restriction Leads to a Less Aggressive Cancer Phenotype

Ashkavand

O’Flanagan

Hennig

et al. 2017

Molecular Cancer Research

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“…Findings from fMRI studies are supported by results from complementary techniques, including positron emission tomography, arterial spin labeling, and electroencephalography (EEG) . Magnetic resonance spectroscopy imaging has also provided further insight regarding certain pathophysiologic mechanisms, including inflammation and demyelination …”

Section: Chemotherapy Endocrine Therapy and Cognitionmentioning

confidence: 93%

Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer‐related cognitive impairment in adults

Wefel

Kesler

Noll

et al. 2014

CA A Cancer J Clinicians

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419

422

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Over the past few decades, a body of research has emerged confirming what many adult patients with noncentral nervous system cancer have long reported—that cancer and its treatment are frequently associated with cancer-related cognitive impairment (CRCI). The severity of CRCI varies, and symptoms can emerge early or late in the disease course. Nonetheless, CRCI is typically mild to moderate in nature and primarily involves the domains of memory, attention, executive functioning, and processing speed. Animal models and novel neuroimaging techniques have begun to unravel the pathophysiologic mechanisms underlying CRCI, including the role of inflammatory cascades, direct neurotoxic effects, damage to progenitor cells, white matter abnormalities, and reduced functional connectivity, among others. Given the paucity of research on CRCI with other cancer populations, this review synthesizes the current literature with a deliberate focus on CRCI within the context of breast cancer. A hypothetical case-study approach is used to illustrate how CRCI often presents clinically and how current science can inform practice. While the literature regarding intervention for CRCI is nascent, behavioral and pharmacologic approaches are discussed.

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“…BCC survivors show elevated neurochemical markers of microglial activity (i.e. myo-inositol) (Kesler, et al, 2013b) and increased peripheral pro-inflammatory cytokines levels (Ganz, et al, 2013;Kesler, et al, 2013a;Kesler, et al, 2013b;Pomykala, et al, 2013b;Vardy, et al,2007). Compared to healthy women, BCC survivors show increased pro-inflammatory cytokine levels with increased age (Kesler, et al, 2013a).…”

Section: Brain Aging Cancer and Chemotherapymentioning

confidence: 99%

Default mode network as a potential biomarker of chemotherapy-related brain injury

Kesler

2014

Neurobiology of Aging

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Chronic medical conditions and/or their treatments may interact with aging to alter or even accelerate brain senescence. Adult onset cancer, for example, is a disease associated with advanced aging and emerging evidence suggests a profile of subtle but diffuse brain injury following cancer chemotherapy. Breast cancer is currently the primary model for studying these “chemobrain” effects. Given the widespread changes to brain structure and function as well as the common impairment of integrated cognitive skills observed following breast cancer chemotherapy, it is likely that large-scale brain networks are involved. Default mode network (DMN) is a strong candidate considering its preferential vulnerability to aging and sensitivity to toxicity and disease states. Additionally, chemotherapy is associated with several physiologic effects including increased inflammation and oxidative stress that are believed to elevate toxicity in the DMN. Biomarkers of DMN connectivity could aid in the development of treatments for chemotherapy-related cognitive decline. For example, certain nutritional interventions could potentially reduce the metabolic changes (e.g. amyloid beta toxicity) associated with DMN disruption.

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Elevated prefrontal myo-inositol and choline following breast cancer chemotherapy

Cited by 33 publications

References 62 publications

Metabolic Reprogramming by Folate Restriction Leads to a Less Aggressive Cancer Phenotype

Metabolic Reprogramming by Folate Restriction Leads to a Less Aggressive Cancer Phenotype

Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer‐related cognitive impairment in adults

Default mode network as a potential biomarker of chemotherapy-related brain injury

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