ABSTRACT
Background: Quercetin is a flavonoid, with antioxidant and autophagy-modulating activities. Cisplatin is one of the platinum-based anticancer drugs. Early development of peripheral neuropathy as an adverse effect of cisplatin interferes with the continuation of therapy. Oxidative stress and autophagy impairment may play a role. Aim: This study aimed to explore the possible protective effects of quercetin against cisplatin-induced peripheral neuropathy. Methods: Twenty-four male Wistar rats were divided into three groups: Group 1 (control group) and Group 2 (cisplatin group) where peripheral neuropathy was induced using single ip injection of cisplatin. Group 3 (cisplatin + quercetin group) received single ip injection of cisplatin and was then treated with quercetin for 14 days. At the end of the experiment, nociception was evaluated by tail immersion test, and then, blood was collected for analysis of nerve growth factor. Sciatic nerve was used to assess histopathological changes and light chain 3-II by immunohistochemical staining. Reduced glutathione, malondialdehyde, mTOR, and caspase-3 were estimated in sciatic nerve tissue homogenate. Results: This research work revealed that quercetin significantly improved cisplatin-induced nociceptive impairment, attenuated cisplatin-induced oxidative stress, autophagy, and apoptosis to protect against neuronal death. Conclusion: From the current study, quercetin can act as a promising protective agent against cisplatin-induced peripheral neuropathy.
ABSTRACT
BACKGROUND: Despite the undeniable benefit of tamoxifen therapy for ER-positive breast cancer patients, approximately one-third of those patients either do not respond to tamoxifen or develop resistance. Thus, it is a crucial step to identify novel, reliable, and easily detectable biomarkers indicating resistance to this drug. OBJECTIVE: The aim of this work is to explore SOX2 and AGR2 biomarker expression in the tumor tissue of ER-positive breast cancer patients in combination with the evaluation of serum AGR2 level of these patients in order to validate these biomarkers as early predictors of tamoxifen resistance. METHODS: This study was conducted on 224 ER-positive breast cancer patients. All patients were primarily subjected to serum AGR2 levelling by ELISA and their breast cancer tissue immunostained for SOX2 and AGR2. After 5 years of follow-up, the patients were divided into 3 groups: group 1 was tamoxifen sensitive and groups 2 and 3 were tamoxifen resistant. Time to failure of tamoxifen treatment was considered the time from the beginning of tamoxifen therapy to the time of discovery of breast cancer recurrence or metastases (in months). RESULTS: SOX2 and AGR2 biomarkers expression and serum AGR2 level were significantly higher in groups 2 and 3 in comparison to group 1, while the relationship between Her2 neu expression and Ki67 index in the 3 different groups was statistically nonsignificant. Lower SOX2 and AGR2 expression and low AGR2 serum levels in the studied patients of groups 2 and 3 were significantly associated with longer time-to-failure of tamoxifen treatment. According to the ROC curve, the combined use of studied markers validity was with a sensitivity of 100%, specificity of 96%, PPV 96%, and NPV 100% (p < 0.001; AUC: 0.984). CONCLUSIONS: Integrated use of SOX2 and AGR2 biomarkers with serum AGR2 assay holds a promising hope for their future use as predictive markers for early detection of tamoxifen resistance in ER-positive breast cancer patients.
