[Clinical Practice of 177Lu-DOTATATE in the Treatment of Neuroendocrine Tumors].

Most of the neuroendocrine tumors(NETs) overexpress the somatostatin receptor(SSTR),which provides a reliable target for SSTR-targeted peptide receptor radionuclide therapy(PRRT).Compared with drug therapy,PRRT has high objective response rate and significantly prolongs patients' survival.Moreover,the patients have good tolerance to this therapy.Considering that PRRT is in clinical trial phase in China,this article elaborates on the selection and preparation of patients,pre-treatment medications,administration methods,treatment cycles,side effects,follow-up plan,and the combination of PRRT with other drugs based on the published international guidelines in this field and our experience from clinical practice.Hoping that relevant professionals can well understand the principle of PRRT and apply it in clinical practice,we write this article to provide a basis for serving real-world patients and carrying out clinical trials.

Nrf2 degradation by the ubiquitin proteasome pathway is inhibited by KIAA0132, the human homolog to INrf2.

INrf2 tethering of the transcription factor Nrf2 in the cytosol prevents Nrf2 activation of antioxidant response element (ARE) mediated gene expression. This investigation was undertaken to determine if tethering affected Nrf2 degradation. Data is presented showing that Nrf2 is degraded by the ubiquitin-proteasome pathway. Nrf2 co-immunoprecipitated with a HA tagged ubiquitin polymer and accumulated in cells expressing inactive ubiquitin activating enzyme El. Inhibition of proteasome activity resulted in accumulation of Nrf2. The rate of Nrf2 degradation, measured under conditions where the majority of Nrf2 was not tethered, exhibited a T(1/2) of approximately 3 h. Over-expression of human INrf2, KIAA0132, blocked Nrf2 conjugation to the ubiquitin polymer and blocked Nrf2 degradation. These results suggest that association of Nrf2 with INrf2 inhibits ubiquitin-proteasome degradation of Nrf2. Maintaining the majority of Nrf2 in a tethered form, resistant to ubiquitin-proteasome dependent degradation, allows a pool of Nrf2 to be available for rapid Nrf2/ARE-dependent gene transcription following stress mediated release from INrf2. Further, the observation that free Nrf2 is degraded by the ubiquitin proteasome pathway provides a potential mechanism by which ARE-dependent gene transcription is attenuated after induction.