Mu and Kappa opioid receptor immunolabeling indicates the prognosis of oropharyngeal squamous cell carcinoma: A cross-sectional observational study.

BACKGROUND: Opioids are the most effective drugs currently available for cancer pain management. The administration of morphine, in addition to its analgesic effect, can alter tumor development. OBJECTIVE: To characterize the immunoexpression of opioid receptors µ and κ in oropharyngeal squamous cell carcinoma, and correlate it with prognostic factors, proliferation markers, and cell death. MATERIALS AND METHODS: A retrospective, cross-sectional observational study was carried out with 50 patients diagnosed at Haroldo Juaçaba Hospital. Sociodemographic, clinicopathological, and overall survival data were collected, and excisional biopsies were taken for immunohistochemistry using tissue microarrays for opioid receptors µ and κ, Ki-67, and caspase-3. Immunolabeling was evaluated and correlated with other variables using Mann-Whitney, Kruskal-Wallis, Spearman correlation, log-rank (Mantel-Cox), and Cox regression tests. RESULTS: Immunoexpression of opioid receptors µ and κ, Ki-67, and caspase-3 was significantly higher in p16+ and p16- primary tumors and lymph node metastases than in surgical resection margins. The overall survival of patients with p16- tumors was 57.53 ± 8.43 months and that of patients with p16+ tumors was slightly higher at 75.92 ± 11.14 months. Multivariate analysis showed that the expression of opioid receptors µ and κ in the nucleus was directly associated with a lower and higher risk of death, respectively. CONCLUSION: We found increased expression of opioid receptors µ and κ in tumor tissues. The nuclear expression of opioid receptors µ and κ influences overall survival and may be a prognostic factor of oropharyngeal squamous cell carcinoma.

Neonatal handling increases neurogenesis, BDNF and GR in the hippocampus favoring memory acquisition in rats.

Early life is a critical period for the development of the central nervous system (CNS) when the brain undergoes functional organization, neuronal proliferation and migration. This study aimed to evaluate influences and possible interactions of the neonatal handling (NH) on morphologic, biochemical and molecular markers in the hippocampus, as well as on Mu opioid receptors (MOR) immunoreactivity when adolescent rats were exposed to morphine. On postnatal day (PND) 1, male pups were assigned to two experimental groups: unhandled (UH) or neonatal handling (NH), whose procedure was applied from PND2 to PND9. On PND 50, animals were submitted to memory behavioral test, anesthesia and euthanasia for blood collection and hippocampus removal. Animals exposed to NH showed: i) increased levels of proBDNF and brain-derived neurotrophic factor (BDNF); ii) increased memory performance; iii) decreased lipid peroxidation (LP) in plasma and hippocampus; iv) increased antioxidant defenses; v) increased glucocorticoids receptor (GR) levels. Interestingly, our data showed a positive correlation between BDNF and working memory after NH procedure (r2 = 0.73; P = 0.006). Animals submitted to NH showed an increased per se of MOR immunoreactivity regardless of morphine exposure, while this increasing was also observed in the UH group after morphine exposure, even in a small extent. NH beneficial influence during early stage of life can be reflected during the development of the puppies, enhancing memory performance, preventing oxidative events and improving molecular targets in hippocampus. Further experimental studies in addition to clinical ones are needed to validate NH protocol as a therapeutic tool.