Increased tryptophan degradation in patients with bronchus carcinoma

2009 ◽  
Vol 19 (6) ◽  
pp. 803-808 ◽  
Author(s):  
A.B. ENGIN ◽  
Y. OZKAN ◽  
D. FUCHS ◽  
S. YARDIM-AKAYDIN
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Malinee Thanee ◽  
Sureerat Padthaisong ◽  
Manida Suksawat ◽  
Hasaya Dokduang ◽  
Jutarop Phetcharaburanin ◽  
...  

Abstract Background Sulfasalazine (SSZ) is widely known as an xCT inhibitor suppressing CD44v9-expressed cancer stem-like cells (CSCs) being related to redox regulation. Cholangiocarcinoma (CCA) has a high recurrence rate and no effective chemotherapy. A recent report revealed high levels of CD44v9-positive cells in CCA patients. Therefore, a combination of drugs could prove a suitable strategy for CCA treatment via individual metabolic profiling. Methods We examined the effect of xCT-targeted CD44v9-CSCs using sulfasalazine combined with cisplatin (CIS) or gemcitabine in CCA in vitro and in vivo models and did NMR-based metabolomics analysis of xenograft mice tumor tissues. Results Our findings suggest that combined SSZ and CIS leads to a higher inhibition of cell proliferation and induction of cell death than CIS alone in both in vitro and in vivo models. Xenograft mice showed that the CD44v9-CSC marker and CK-19-CCA proliferative marker were reduced in the combination treatment. Interestingly, different metabolic signatures and significant metabolites were observed in the drug-treated group compared with the control group that revealed the cancer suppression mechanisms. Conclusions SSZ could improve CCA therapy by sensitization to CIS through killing CD44v9-positive cells and modifying the metabolic pathways, in particular tryptophan degradation (i.e., kynurenine pathway, serotonin pathway) and nucleic acid metabolism.


Pteridines ◽  
2020 ◽  
Vol 31 (1) ◽  
pp. 91-99
Author(s):  
Deniz Öğütmen Koç ◽  
Yağmur Özhan ◽  
Ebru Türköz Acar ◽  
Nilgün Bireroğlu ◽  
Fatih Aslan ◽  
...  

AbstractChronic Hepatitis B virus (HBV) is still one of the major reasons for liver related mortality and morbidity all around the world. This study aimed to investigate the possible relationship between the immune system activation and presence, as well as progression, of hepatitis B infection by monitoring the tryptophan degradation and serum neopterin levels in patients with HBV. 110 patients with HBV and 23 healthy subjects were included in the study. The patients had significantly higher neopterin levels and increased kynurenine to tryptophan ratios, which were most probably due to enhanced indoleamine 2,3-dioxygenase (IDO) activity compared to healthy control. A strong positive correlation was found between neopterin levels and IDO activity in patient group. Neopterin levels and IDO activity were markedly increased in patients with histological activity index (HAI) ≥4 compared to HAI<4, and a significant correlation was found between neopterin and HAI. Moreover, there was a significant correlation between albumin levels and IDO activity in HBV patients. These findings suggest that tryptophan degradation results from IFN-γ-induced IDO activation, likewise depletion of albumin synthesis in HBV patients may result from diminished tryptophan availability. In conclusion, based on the study results, serum neopterin levels and IDO activity could provide additional immunological information for monitoring liver histological activity and can be used as prognostic markers in HBV disease.


Immunobiology ◽  
2009 ◽  
Vol 214 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Gozde Girgin ◽  
Terken Baydar ◽  
Maximilian Ledochowski ◽  
Harald Schennach ◽  
Duygu Nur Bolukbasi ◽  
...  

2014 ◽  
Vol 17 (3) ◽  
pp. 453-458 ◽  
Author(s):  
J. Małaczewska ◽  
A. K. Siwicki ◽  
R. Wójcik ◽  
W. a. Turski ◽  
E. Kaczorek

Abstract Kynurenic acid (KYNA), an endogenous neuroprotectant formed along the kynurenine pathway of tryptophan degradation, is a selective ligand of the GPR35 receptor, which can be found on the surface of various populations of human immune cells. In infections and inflammations, KYNA produces an anti-inflammatory effect through this receptor, by depressing the synthesis of reactive oxygen species and pro-inflammatory cytokines. However, it is still unrecognized whether receptors for kynurenic acid are also localized on immune cells of poikilothermic animals, or whether KYNA is able to affect these cells. The objective of this study has been to determine the effect of different concentrations of kynurenic acid (12.5 μM to 10 mM) on the viability and mitogenic response of lymphocytes and on the activity of phagocytic cells isolated from blood and the spleen of rainbow trout. The results imply low toxicity of kynurenic acid towards fish immune cells, and the proliferative effect observed at the two lowest concentrations of KYNA (12.5 μM and 25 μM) seems indicative of endogenous kynurenic acid being capable of activating fish lymphocytes. Non-toxic, micromole concentrations of KYNA, however, had no influence on the mitogenic response of lymphocytes nor on the activity of phagocytes in rainbow trout under in vitro conditions. There is some likelihood that such an effect could be observed at lower, nanomole concentrations of KYNA.


2005 ◽  
Vol 25 (3) ◽  
pp. 334-337 ◽  
Author(s):  
Katharina Schroecksnadel ◽  
Christiana Winkler ◽  
Christian Duftner ◽  
Barbara Wirleitner ◽  
Michael Schirmer ◽  
...  

2017 ◽  
Vol 106 (12) ◽  
pp. 3499-3506 ◽  
Author(s):  
Kyle L. Hogan ◽  
Danielle Leiske ◽  
Cleo M. Salisbury

2014 ◽  
Vol 2014 ◽  
pp. 1-22 ◽  
Author(s):  
Jazmin Reyes Ocampo ◽  
Rafael Lugo Huitrón ◽  
Dinora González-Esquivel ◽  
Perla Ugalde-Muñiz ◽  
Anabel Jiménez-Anguiano ◽  
...  

The kynurenine pathway (KP) is the main route of tryptophan degradation whose final product is NAD+. The metabolism of tryptophan can be altered in ageing and with neurodegenerative process, leading to decreased biosynthesis of nicotinamide. This fact is very relevant considering that tryptophan is the major source of body stores of the nicotinamide-containing NAD+coenzymes, which is involved in almost all the bioenergetic and biosynthetic metabolism. Recently, it has been proposed that endogenous tryptophan and its metabolites can interact and/or produce reactive oxygen species in tissues and cells. This subject is of great importance due to the fact that oxidative stress, alterations in KP metabolites, energetic deficit, cell death, and inflammatory events may converge each other to enter into a feedback cycle where each one depends on the other to exert synergistic actions among them. It is worth mentioning that all these factors have been described in aging and in neurodegenerative processes; however, has so far no one established any direct link between alterations in KP and these factors. In this review, we describe each kynurenine remarking their redox properties, their effects in experimental models, their alterations in the aging process.


Shock ◽  
2004 ◽  
Vol 21 (Supplement) ◽  
pp. 58
Author(s):  
B Wirleitner ◽  
B Frick ◽  
K Schroecksnadel ◽  
C Winkler ◽  
D Fuchs

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