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Jung Y.,ViroMed Co. | Ahn H.,ViroMed Co. | Kim D.-S.,ViroMed Co. | Hwang Y.R.,ViroMed Co. | And 5 more authors.
Biochemical and Biophysical Research Communications | Year: 2011

Recombinant human interleukin-11 (rhIL-11) has been shown to increase platelet counts in animals and humans and is the only drug approved for its use in chemotherapy-induced thrombocytopenia (CIT). However, due to its serious side effects, its clinical use has been limited. The current work presents significantly improved efficacy of rhIL-11 via knowledge based re-designing process. The interleukin-11 mutein (mIL-11) was found to endure chemical and proteolytic stresses, while retaining the biological activity of rhIL-11. The improved efficacy of mIL-11 was evident after subcutaneous administration of mIL-11 and rhIL-11 in the rodent and primate models. More than three-fold increase in maximum plasma concentration (Cmax) and area-under-the curve (AUC) was observed. Furthermore, three-fold higher increase in the platelet counts was obtained after seven consecutive daily subcutaneous mIL-11 injections than that with rhIL-11. The mIL-11 demonstrated not only improved stability but also enhanced efficacy over the currently used rhIL-11 regimen, thereby suggesting less toxicity. © 2011 Elsevier Inc.


Wu S.,Cancer Center | Zhang Y.,Dalian Medical University | Xu L.,Beijing Chest Hospital | Dai Y.,Soochow University of China | And 9 more authors.
Supportive Care in Cancer | Year: 2012

Purpose The aim of this study is to evaluate the efficacy and safety of genetically modified recombinant human IL-11 (mIL-11), using original IL-11 as an active control, in a multicenter randomized trial involving 88 cancer patients undergoing chemotherapy Methods Eighty-eight subjects who had platelets ≤75×109/L during the prior chemotherapy were randomized to the MR or RM group. Cohort MR consists of subcutaneous injection of mIL-11 (7.5 μg/kg/day) for 10 days, beginning 72 h after chemotherapy for a 21-day chemotherapy cycle (cycle-1) followed by that of recombinant human interleukin-11 (rhIL-11) (25 μg/kg/day) for another 10 days (cycle-2). Cohort RM represents the reverse sequence. Intent-to-treat populations of mIL-11 (n=73) or rhIL-11 (n=80) were analyzed to evaluate the safety. Results The incidence of drug-related adverse events of mIL-11 (32.9%) was lower than that of rhIL-11 (51.3%) (p=0.033). There were no unexpected ≥grade-3 adverse events, and no subject developed antibodies to the mIL-11 protein. Sixty-two subjects were analyzed for efficacy by measuring average platelet levels. Both mIL-11 and rhIL-11 increased nadir platelet levels (62.6± 34.9×109/L for mIL-11 vs. 60.2±31.7×10 9/L for rhIL-11) as compared with the untreated control group (41.2± 17.7×109/L) (p<0.0001). There was no statistical difference in average platelet levels and platelet recovery rate between mIL-11 and rhIL-11. Conclusions This study shows that mIL-11 is well tolerated and has thrombopoietic activity equivalent to one third of the clinical dose of rhIL-11, indicating the potential of mIL-11 for use in the treatment of CIT. © 2011 Springer-Verlag.


Gu Y.,Capital Medical University | Zhang J.,Capital Medical University | Guo L.,Capital Medical University | Cui S.,Capital Medical University | And 8 more authors.
Journal of Gene Medicine | Year: 2011

Background: The purpose of the present phase I clinical trial was to evaluate the safety, tolerability, and preliminary efficacy of naked DNA therapy expressing two isoforms of hepatocyte growth factor (pCK-HGF-X7) in critical limb ischemia (CLI) patients. Materials and methods: Twenty-one patients with CLI were consecutively assigned to receive increasing doses (cohort I: 4mg; cohort II: 8mg; cohort III: 12mg; and cohort IV: 16mg) of pCK-HGF-X7, which was administered into the ischemic calf and/or thigh muscle at days 1 and 15. A safety and tolerability evaluation and measurement of pain severity score using a visual analog scale (VAS), ulcer status, transcutaneous oxygen (TcPO 2) and ankle-brachial index (ABI) were performed throughout a 3-month follow-up period. Results: No serious adverse events were observed in any of the 21 patients for the 3-month follow-up period. A significant reduction in pain was observed in the treated patients, with the mean VAS decreasing from 5.95-1.64 (p<0.001). The mean ABI value increased from 0.49-0.63 (p=0.026) at 3-month follow-up. The mean TcPO 2 value on the dorsum of the foot, the anterior calf and posterior calf significantly increased from 28.25-39.28mmHg (p=0.012), from 22.00-30.63mmHg (p=0.046) and 32.05-47.19mmHg (p=0.001) at 3-month follow-up, respectively. Wound healing improvement was observed in the six of nine patients that had an ulcer at baseline. Conclusions: These results support the performance of a phase II randomized controlled trial with pCK-HGF-X7. © 2011 John Wiley & Sons, Ltd.


Li Y.,Nankai University | Bao X.,Nankai University | Chen X.,Nankai University | Jia X.-R.,Nankai University | And 2 more authors.
Chinese Journal of Tissue Engineering Research | Year: 2014

BACKGROUND: Results of recent studies demonstrated the modulation of thymosin β4 on hair cycle and regeneration, but the mechanism of action remains unclear. OBJECTIVE: To investigate the mechanism by which thymosin β4 increases hair regeneration through Wnt signal pathway. METHODS: After the mouse model of depilation was established using rosin/paraffin mixed agents, the experimental animals were randomly assorted to three different groups, including low-dose, high-dose and control groups, and a dose of 0.3 μg/50 μL, 3 μg/50 μL thymosin β4 and PBS was administered on the depilated backs every 12 hours, respectively. Then photography, hematoxylin-eosin staining, immunohistochemistry and in situ hybridization were applied to observe the growth of hair, and the expressions of β-catenin and LEF-1 mRNA in different groups at different time were quantitatively evaluated. RESULTS AND CONCLUSION: The hair growth of the low-dose group was faster than that of the other groups. Hematoxylin-eosin staining demonstrated inflammatory cells infiltration in the dermis after depilation, and the number of hair follicles that were in the phase of anagen was much more than the other groups as time went by. Immunohistochemistry of β-catenin showed the accumulation of intra-cellular β-catenin in the low-dose group at the bulge of follicles assessed by integrated absorbance analysis (P < 0.05), so did the in situ hybridization of LEF-1 mRNA. Low-dose thymosin β4 accelerates hair growth through Wnt signal pathway by elevating the level of β-catenin and LEF-1 mRNA.


Gao F.,CAS Technical Institute of Physics and Chemistry | Li L.,CAS Technical Institute of Physics and Chemistry | Fu C.,CAS Technical Institute of Physics and Chemistry | Nie L.,Beijing Northland Biotech Co. | And 2 more authors.
Advanced Materials | Year: 2013

Docyanine green (ICG) and LHRH-PE40 fusion protein are tethered onto drug carriers of silica nanorattles for imaging-guided tumor-specific drug delivery and bimodal therapy. The synergistic therapeutic effect of toxin PE40 and the chemotherapeutic drug docetaxel (Dtxl), specifically directed by LHRH to cancer, improves cancer treatment. Simultaneously, ICG enables real-time monitoring of the silica nanocomposites and therapeutic response. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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