Albumin Fusion at the N-Terminus or C-Terminus of HM-3 Leads to Improved Pharmacokinetics and Bioactivities.

HM-3, an integrin antagonist, exhibits anti-tumor biological responses and therefore has potential as a therapeutic polypeptide. However, the clinical applications of HM-3 are limited by its short half-life. In this study, we genetically fused human serum albumin (HSA) to the N or C-terminus of HM-3 to improve HM-3 pharmacokinetics. HM-3/HSA proteins were successfully expressed in Pichia pastoris and displayed improved pharmacokinetic properties and stability. Among them, the half-life of HM-3-HSA was longer than HSA-HM-3. In vitro, the IC50 values of HSA-HM-3 and HM-3-HSA were 0.38 ± 0.14 µM and 0.25 ± 0.08 µM in B16F10 cells, respectively. In vivo, the inhibition rates of B16F10 tumor growth were 36% (HSA-HM-3) and 56% (HM-3-HSA), respectively, indicating antitumor activity of HM-3-HSA was higher than HSA-HM-3. In conclusion, these results suggested that the HM-3/HSA fusion protein might be potential candidate HM-3 agent for treatment of melanoma and when HSA was fused at the C-terminus of HM-3, the fusion protein had a higher stability and activity.

Oxcarbazepine monotherapy in children with benign epilepsy with centrotemporal spikes improves quality of life.

BACKGROUND: Benign epilepsy with centrotemporal spikes (BECTS) is the most common type of childhood idiopathic focal epilepsy. BECTS is associated with pervasive cognitive deficits and behavior problems. While seizures can be easily controlled, it is crucial to select anti-epileptic drugs that do not impair cognition, do not cause psychosocial effects, and improve the quality of life. Previous studies showed effects of oxcarbazepine (OXC) monotherapy on the cognitive and psychosocial profiles of patients with BECTS. Here, we studied the effects of OXC monotherapy on the neuropsychologic profiles and quality of life in patients with BECTS in China. METHODS: Thirty-one patients aged 6 to 12 years newly diagnosed with BECTS were recruited. A psychometric assessment was performed before and during the follow-up of OXC monotherapy with Cognitive Computerized Task Battery, Depression Self-Rating Scale for children, Screen for Child Anxiety Related Emotional Disorders, and Quality of Life in Epilepsy-31 (QOLIE-31). The results of the assessments were compared to explore the effect of OXC monotherapy in patients with BECTS. RESULTS: Thirty children with BECTS completed the study. Five of ten cognitive test scores improved after treatment via OXC monotherapy, including visual tracing (F = 14.480, P < 0.001), paired associated learning (language) (F = 6.292, P < 0.001), paired associated learning (number) (F = 9.721, P < 0.05), word semantic (F = 6.003, P < 0.05), and simple subtraction (F = 6.229, P < 0.05). Of the neuropsychology data concerning the quality of life, statistically significant improvements were observed in emotion (F = 4.946, P < 0.05), QOLIE-social (F = 5.912, P < 0.05), and QOLIE-total (F = 14.161, P < 0.001). CONCLUSIONS: OXC is safe and does not impair neuropsychologic functions, with no obvious mood burden on children with BECTS. Most importantly, OXC has positive impacts on children's perception of quality of life, especially in terms of happiness and life satisfaction.