Parathyroidectomy decreases serum intact parathyroid hormone and calcium levels and prolongs overall survival in elderly hemodialysis patients with severe secondary hyperparathyroidism.

BACKGROUND: The objective of this study was to assess the effect of parathyroidectomy (PTX) treatment on prolonging overall survival (OS) as well as decreasing levels of intact parathyroid hormone (iPTH), calcium (Ca), and phosphorus (P) in elderly hemodialysis patients with severe secondary hyperparathyroidism (SHPT). METHODS: A total of 304 elderly hemodialysis patients with severe SHPT were consecutively enrolled in this cohort study. According to whether PTX operations were applied, patients were classified into PTX group (N = 112) and Control group (N = 192) and were followed up for 3 years. Mortality rate and OS were evaluated, and iPTH, Ca, and P levels were recorded. RESULTS: Compared to control group, increased iPTH (P < 0.001), higher Ca (P = 0.003), elevated AST (P = 0.022), and lower Hb (P = 0.049) concentrations were observed in the PTX group at baseline. The 1-year mortality (P < 0.001), 2-year mortality (P < 0.001), and 3-year mortality (P < 0.001) was reduced in PTX group compared to Control group, and PTX was correlated with prolonged OS (P < 0.001). Multivariate Cox's regression analysis further revealed that PTX treatment (P < 0.001, HR = 0.177) was an independent factor for better OS. Moreover, patients in PTX group had decreased iPTH (P < 0.05) and Ca (P < 0.05) levels compared to Control group at M1-M36, while no difference was found in serum P level between the two groups at M1-M36. CONCLUSION: Parathyroidectomy decreases iPTH and Ca levels, and it associates with favorable survival in elderly hemodialysis patients with severe SHPT.

PKC?-dependent activation of the ubiquitin proteasome system is responsible for high glucose-induced human breast cancer MCF-7 cell proliferation, migration and invasion.

Type 2 diabetes mellitus (T2DM) has contributed to advanced breast cancer development over the past decades. However, the mechanism underlying this contribution is poorly understood. In this study, we determined that high glucose enhanced proteasome activity was accompanied by enhanced proliferation, migration and invasion, as well as suppressed apoptosis, in human breast cancer MCF-7 cells. Proteasome inhibitor bortezomib (BZM) pretreatment mitigated high glucose-induced MCF-7 cell growth and invasion. Furthermore, high glucose increased protein kinase C delta (PKC?)-phosphorylation. Administration of the specific PKC? inhibitor rottlerin attenuated high glucose-stimulated cancer cell growth and invasion. In addition, PKC? inhibition by both rottlerin and PKC? shRNA significantly suppressed high glucose-induced proteasome activity. Our results suggest that PKC?-dependent ubiquitin proteasome system activation plays an important role in high glucose- induced breast cancer cell growth and metastasis.