Imaging Correlates of Differential Expression of Indoleamine 2,3-Dioxygenase in Human Brain Tumors

Batista, Carlos Eduardo Alves; Juhász, Csaba; Muzik, Otto; Kupsky, William J.; Barger, Geoffrey; Chugani, Harry T.; Mittal, Sandeep; Sood, Sandeep; Chakraborty, Pulak K.; Chugani, Diane C.

doi:10.1007/s11307-009-0225-0

Cited by 70 publications

(72 citation statements)

References 37 publications

(50 reference statements)

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“…15 Studies on brain tissue obtained at resective surgery from patients without autism but with tuberous sclerosis complex and intractable epilepsy or from patients with brain tumors who had undergone AMT PET scanning revealed that increased AMT uptake may represent tryptophan metabolism by the kynurenine pathway (which is related to brain inflammation) rather than the pathway for serotonin synthesis. 57,59 In the current study, semiquantitative analyses support our visual assessment that the asymmetries in basal ganglia and thalamus represent increased tryptophan metabolism, because the mean SUV from cases with no asymmetry had values that were closer to values of the lower side in cases who did show asymmetry. This observation is intriguing in light of accumulating evidence for a role of brain inflammation in ASD, as has been reported in both imaging and neuropathology studies.…”

Section: Discussionsupporting

confidence: 77%

Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial

Chugani

Wiznitzer³

et al. 2016

The Journal of Pediatrics

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Section: Discussionsupporting

confidence: 77%

Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial

Chugani

Wiznitzer³

et al. 2016

The Journal of Pediatrics

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“…IDO is expressed at high levels in some solid tumors, including colorectal cancer, where it is thought to play a role in immune evasion (9,(29)(30)(31)(32). Consistent with this, the competitive IDO inhibitor 1-mT is currently in clinical trials for the treatment of relapsed or refractory solid tumors (13,33).…”

Section: Discussionmentioning

confidence: 79%

IDO1 Plays an Immunosuppressive Role in 2,4,6-Trinitrobenzene Sulfate–Induced Colitis in Mice

Takamatsu

Hirata

Ohtaki

et al. 2013

The Journal of Immunology

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IDO, an enzyme that degrades the essential amino acid l-tryptophan to N-formylkynurenine, is known to exert immunomodulatory effects in a number of diseases and disorders. IDO expression is increased in tumors, where it is thought to be involved in tumor evasion by suppressing the immune response. A competitive inhibitor of IDO is currently being tested in clinical trials for relapsed or refractory solid tumors; however, there remains a concern that attenuation of the immunosuppressive function of IDO might exacerbate inflammatory responses. In this study, we investigated the role of IDO in 2,4,6-trinitrobenzene sulfate (TNBS)–induced colitis in mice by gene deletion and pharmacological inhibition. TNBS treatment induced significantly more severe colitis in Ido1 gene–deficient (Ido1−/−) mice than in Ido1 wild-type (Ido1+/+) mice, indicating a role for IDO1 in suppression of acute colitis. Consistent with this, the expression of Ido1 was increased in the colonic interstitial tissues of TNBS-treated Ido1+/+ mice. Furthermore, transplantation of Ido1+/+ bone marrow cells into Ido1−/− mice reduced the pathological damage associated with colitis, altered the expression of cytokines, including IFN-γ, TNF-α, and IL-10, and increased the number of CD4+ Foxp3+ regulatory T cells in the colon. Pharmacological inhibition of IDO enzymatic activity by oral administration of 1-methyltryptophan (1-methyl-l-tryptophan or 1-methyl-d-tryptophan) significantly increased the severity of TNBS-induced colitis in mice, demonstrating that both stereoisomers can promote colitis. Collectively, our data indicate that IDO1 plays an important immunoregulatory role in the colon.

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“…Preoperative AMT-PET studies were performed in 10 patients with meningioma (6 grade I, 2 grade II and 1 grade III) using a Siemens EXACT/ HR whole-body positron emission tomograph (Siemens Medical Systems) as described previously. 7,23 Briefly, after 6 h of fasting, AMT (37 MBq/kg) was administered intravenously. Twentyfive minutes after tracer injection, a dynamic emission scan of anti-mouse HRP (Southern Biotech).…”

Section: Methodsmentioning

confidence: 99%

“…6 We have previously demonstrated tryptophan metabolism in a variety of human brain tumors using α-[ 11 C]methyl-l-trypto phan (AMT) positron emission tomography (PET) imaging. [7][8][9][10] AMT is an amino acid radiotracer, which can measure expression and activity of indoleamine 2,3-dioxygenase (IDO), the first and rate-limiting step of the kynurenine pathway of tryptophan catabolism, can enable tumor cells to effectively evade the host's immune response. The potential role of this system was investigated in meningiomas.…”

Section: Introductionmentioning

confidence: 99%

In vivo metabolism of tryptophan in meningiomas is mediated by indoleamine 2,3-dioxygenase 1

Zitron¹,

Kamson²,

Kiousis³

et al. 2013

Cancer Biology & Therapy

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Imaging Correlates of Differential Expression of Indoleamine 2,3-Dioxygenase in Human Brain Tumors

Cited by 70 publications

References 37 publications

Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial

Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial

IDO1 Plays an Immunosuppressive Role in 2,4,6-Trinitrobenzene Sulfate–Induced Colitis in Mice

In vivo metabolism of tryptophan in meningiomas is mediated by indoleamine 2,3-dioxygenase 1

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