| Title |
Investigation of the aryl hydrocarbon receptor and the intrinsic tumoral component of the kynurenine pathway of tryptophan metabolism in primary brain tumors
|
|---|---|
| Published in |
Journal of Neuro-Oncology, April 2018
|
| DOI | 10.1007/s11060-018-2869-6 |
| Pubmed ID | |
| Authors |
Anthony R. Guastella, Sharon K. Michelhaugh, Neil V. Klinger, Hassan A. Fadel, Sam Kiousis, Rouba Ali-Fehmi, William J. Kupsky, Csaba Juhász, Sandeep Mittal |
| Abstract |
There is mounting evidence supporting the role of tryptophan metabolism via the kynurenine pathway (KP) in the pathogenesis of primary brain tumors. Under normal physiological conditions, the KP is the major catabolic pathway for the essential amino acid tryptophan. However, in cancer cells, the KP becomes dysregulated, depletes local tryptophan, and contributes to an immunosuppressive tumor microenvironment. We examined the protein expression levels (in 73 gliomas and 48 meningiomas) of the KP rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) 1, IDO2, and tryptophan 2,3-dioxygenase (TDO2), as well as, the aryl hydrocarbon receptor (AhR), a carcinogenic transcription factor activated by KP metabolites. In addition, we utilized commercially available small-molecules to pharmacologically modulate IDO1, IDO2, TDO2, and AhR in patient-derived glioma and meningioma cell lines (n = 9 each). We observed a positive trend between the grade of the tumor and the average immunohistochemical staining score for IDO1, IDO2, and TDO2, with TDO2 displaying the strongest immunostaining. AhR immunostaining was present in all grades of gliomas and meningiomas, with the greatest staining intensity noted in glioblastomas. Immunocytochemical staining showed a positive trend between nuclear localization of AhR and histologic grade in both gliomas and meningiomas, suggesting increased AhR activation with higher tumor grade. Unlike enzyme inhibition, AhR antagonism markedly diminished patient-derived tumor cell viability, regardless of tumor type or grade, following in vitro drug treatments. Collectively, these results suggest that AhR may offer a novel and robust therapeutic target for a patient population with highly limited treatment options. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Portugal | 1 | 20% |
| Unknown | 4 | 80% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 36 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 17% |
| Researcher | 5 | 14% |
| Student > Master | 5 | 14% |
| Other | 3 | 8% |
| Professor | 3 | 8% |
| Other | 6 | 17% |
| Unknown | 8 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 28% |
| Biochemistry, Genetics and Molecular Biology | 6 | 17% |
| Agricultural and Biological Sciences | 3 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
| Immunology and Microbiology | 2 | 6% |
| Other | 6 | 17% |
| Unknown | 7 | 19% |
Attention Score in Context
This research output has an Altmetric Attention Score of 13. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 February 2023.
All research outputs
#2,811,440
of 25,374,917 outputs
Outputs from Journal of Neuro-Oncology
#185
of 3,255 outputs
Outputs of similar age
#56,860
of 340,599 outputs
Outputs of similar age from Journal of Neuro-Oncology
#7
of 93 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,255 research outputs from this source. They receive a mean Attention Score of 4.4. This one has done particularly well, scoring higher than 94% of its peers.
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We're also able to compare this research output to 93 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 93% of its contemporaries.