Tryptophan Catabolism and Response to Therapy in Locally Advanced Rectal Cancer (LARC) Patients
FRONTIERS IN ONCOLOGY
Authors: Crotti, Sara; Fraccaro, Alessandra; Bedin, Chiara; Bertazzo, Antonella; Di Marco, Valerio; Pucciarelli, Salvatore; Agostini, Marco
Abstract
In locally advanced rectal cancer patients (LARC), preoperative chemoradiation improves local control and sphincter preservation. The response rate to treatment varies substantially between 20 and 30%, and it is an important prognostic factor. Indeed, nonresponsive patients are subjected to higher rates of local and distant metastases, and worse survival compared to patients with complete response. In the search of predictive biomarkers for response prediction to therapy in LARC patients, we found increased plasma tryptophan levels in nonresponsive patients. On the basis of plasma levels of 5-hydroxy-tryptophan and kynurenine, the activities of tryptophan 5-hydroxylase 1 (TPH1) and indoleamine-2,3-dioxygenases 1 (IDO1)/tryptophan-2,3-dioxygenase (TDO2) have been obtained and data have been correlated with gene expression profiles. We demonstrated that TDO2 overexpression in nonresponsive patients correlates with kynurenine plasma levels. Finally, through the gene expression and targeted metabolomic analysis in paired healthy mucosa-rectal cancer tumor samples, we evaluated the impact of tryptophan catabolism at tissue level in responsive and nonresponsive patients.
Synergistic Anxiolytic Effect of Curcumin and Zinc on Acute and Chronic Models of Anxiety in Mice
JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH
Authors: Anandan, Isswariya; Selvaraj, Nitya; Meenakshi, R.; Rajamohammad, Meher Ali; Anandabaskar, Nishanthi; Jayabalan, Nalini Devi
Abstract
Introduction: Anxiety disorders being ranked at sixth position in the global burden of diseases is affecting over 250 million people. Curcumin, an active phytochemical flavonoid, has shown to induce the monoamine neurotransmitter serotonin, a prominent neurotransmitter in modulating the brain state in anxiety. Also, evidences reveal that zinc plays a key role in human neurodevelopment and supplementation of zinc enhanced the efficacy of antidepressant drugs through synergistic action. Aim: To evaluate the synergistic antianxiety effect of curcumin and zinc on acute and chronic models of anxiety in male swiss albino mice. Materials and Methods: A total of 36 male Swiss Albino mice, weighing 20-30 g, were randomly grouped to six groups, such that each group consisted of six mice. Group 1 served as control. Group 2 received standard drug diazepam 3 mg/kg Intra Peritoneal (IP). Group 3 and 4 received curcumin at doses of 5 and 10 mg/kg, respectively. Group 5 and 6 received curcumin at doses 5 and 10 mg/kg per oral (p.o) along with zinc chloride 10 mg/kg IP, respectively. The anxiolytic effect was studied in two validated models of anxiety such as Elevated Plus Maze (EPM) test and light/dark box test. Each animal was tested initially in the EPM followed by light/dark box test after administration of drug/vehicle one hour prior to the experiment in acute study. Following a washout period of one week, the animals were utilised for the study of chronic anxiolytic effect wherein the drugs were administered once daily for 14 days. Results: Curcumin at doses of 5 mg/kg and 10 mg/kg with zinc chloride 10 mg/ kg showed a significant increase in the number of entries and time spent in open arm in EPM both on acute and chronic administration (p<0.001). In the light/dark box test, curcumin at doses of 5 mg/kg and 10 mg/kg when given along with zinc chloride 10 mg/kg significantly increased the number of entries and time spent in the light compartment both in acute and chronic models (p<0.001). Conclusion: The anxiolytic effect of synergistic action of curcumin and zinc was efficacious in both acute and chronic models of anxiety in mice.