A biological basis for depression in pancreatic cancer

Botwinick, Isadora; Pursell, Lisa; Yu, Gary; Cooper, Thomas R.; Mann, J. John; Chabot, John A.

doi:10.1111/hpb.12201

Cited by 43 publications

(29 citation statements)

References 16 publications

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“…Increased levels of AHR activity in tumors, characterized by increased CYP1B1 mRNA expression, have been shown to positively correlate with poor survival in glioma patients (Opitz et al, 2011). In addition, studies examining metabolite concentrations in pancreatic adenocarcinomas identified a positive correlation between KA levels and tumor size (Botwinick et al, 2014). Such evidence supports the notion that AHR stimulation may increase tumor aggressiveness through metabolites of the kynurenine pathway.…”

Section: Host Metabolism Of Tryptophanmentioning

confidence: 74%

Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation

Hubbard¹,

Murray²,

Perdew³

2015

Drug Metab Dispos

488

432

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The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor recognized for its role in xenobiotic metabolism. The physiologic function of AHR has expanded to include roles in immune regulation, organogenesis, mucosal barrier function, and the cell cycle. These functions are likely dependent upon ligandmediated activation of the receptor. High-affinity ligands of AHR have been classically defined as xenobiotics, such as polychlorinated biphenyls and dioxins. Identification of endogenous AHR ligands is key to understanding the physiologic functions of this enigmatic receptor. Metabolic pathways targeting the amino acid tryptophan and indole can lead to a myriad of metabolites, some of which are AHR ligands. Many of these ligands exhibit species selective preferential binding to AHR. The discovery of specific tryptophan metabolites as AHR ligands may provide insight concerning where AHR is activated in an organism, such as at the site of inflammation and within the intestinal tract.

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Section: Host Metabolism Of Tryptophanmentioning

confidence: 74%

Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation

Hubbard¹,

Murray²,

Perdew³

2015

Drug Metab Dispos

488

432

View full text Add to dashboard Cite

show abstract

“…Indeed, other products of the IDO degradation pathway, such as kynurenic and xanthurenic acid, are more potent AHR ligands than kynurenine 36 . In fact, kynurenic acid levels have been observed to positively correlate with the size of pancreatic adenocarcinomas 37 . Utilizing a glioma line with AHR expression ablated in a xenograph model, results suggested that many of the effects of kynurenine on tumor cell growth appear to be mediated by the AHR.…”

Section: Presence Of Endogenous Ahr Ligands That May Influence Tumorimentioning

confidence: 99%

Aryl hydrocarbon receptor ligands in cancer: friend and foe

2014

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“…Reduced serum tryptophan is associated with more severe somatic symptoms (RSC) but not anxiety or depression scales in a sample of colorectal cancer patients (Huang et al, 2002). In pancreatic cancer patients, a lower kynurenic acid:tryptophan ratio in serum is associated with worse symptoms of anxiety and depression (Botwinick et al, 2014). Regarding cognitive function, only one study has examined inflammatory correlates of impairment in cancer patients prior to treatment and found that levels of IL-6 were found to be associated with poorer executive functioning and levels of IL-8 were inversely associated with measures of memory (Meyers, et al, 2005).…”

Section: Cancer Patients Prior To Treatmentmentioning

confidence: 99%

Pre-treatment effects of peripheral tumors on brain and behavior: Neuroinflammatory mechanisms in humans and rodents

Schrepf¹,

Lutgendorf²,

Pyter³

2015

Brain, Behavior, and Immunity

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Cancer patients suffer high levels of affective and cognitive disturbances, which have been attributed to diagnosis-related distress, impairment of quality of life, and side effects of primary treatment. An inflammatory microenvironment is also a feature of the vast majority of solid tumors. However, the ability of tumor-associated biological processes to affect the central nervous system (CNS) has only recently been explored in the context of symptoms of depression and cognitive disturbances. In this review, we summarize the burgeoning evidence from rodent cancer models that solid tumors alter neurobiological pathways and subsequent behavioral processes with relevance to affective and cognitive disturbances reported in human cancer populations. We consider, in parallel, the evidence from human clinical cancer research demonstrating that affective and cognitive disturbances are common in some malignancies prior to diagnosis and treatment. We further consider the underlying neurobiological pathways, including altered neuroinflammation, tryptophan metabolism, prostaglandin synthesis and associated neuroanatomical changes, that are most strongly implicated in the rodent literature and supported by analogous evidence from human cancer populations. We focus on the implications of these findings for behavioral researchers and clinicians, with particular emphasis on methodological issues and areas of future research.

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A biological basis for depression in pancreatic cancer

Cited by 43 publications

References 16 publications

Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation

Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation

Aryl hydrocarbon receptor ligands in cancer: friend and foe

Pre-treatment effects of peripheral tumors on brain and behavior: Neuroinflammatory mechanisms in humans and rodents

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