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Li H.,Chinese Institute of Basic Medical Sciences | Jiang Y.,Second Artillery General Hospital | Jiang X.,Chinese Institute of Basic Medical Sciences | Guo X.,Chinese Institute of Basic Medical Sciences | And 9 more authors.
Stem Cells | Year: 2014

Inefficient homing of systemically infused mesenchymal stem cells (MSCs) limits the efficacy of existing MSC-based clinical graft-versus-host disease (GvHD) therapies. Secondary lymphoid organs (SLOs) are the major niches for generating immune responses or tolerance. MSCs home to a wide range of organs, but rarely to SLOs after intravenous infusion. Thus, we hypothesized that targeted migration of MSCs into SLOs may significantly improve their immunomodulatory effect. Here, chemokine receptor 7 (CCR7) gene, encoding a receptor that specifically guides migration of immune cells into SLOs, was engineered into a murine MSC line C3H10T1/2 by retrovirus transfection system (MSCs/CCR7). We found that infusion of MSCs/CCR7 potently prolonged the survival of GvHD mouse model. The infused MSCs/CCR7 migrate to SLOs, relocate in proximity with T lymphocytes, therefore, potently inhibited their proliferation, activation, and cytotoxicity. Natural killer (NK) cells contribute to the early control of leukemia relapse. Although MSCs/CCR7 inhibited NK cell activity in vitro coculture, they did not impact on the proportion and cytotoxic capacities of NK cells in the peripheral blood of GvHD mice. In an EL4 leukemia cell loaded GvHD model, MSCs/CCR7 infusion preserved the graft-versus-leukemia (GvL) effect. In conclusion, this study demonstrates that CCR7 guides migration of MSCs to SLOs and thus highly intensify their in vivo immunomodulatory effect while preserving the GvL activity. This exciting therapeutic strategy may improve the clinical efficacy of MSC based therapy for immune diseases. Stem Cells 2014;32:1890-1903 © 2014 AlphaMed Press.

Yang B.,Chinese PLA General Hospital | Lu X.-C.,Chinese PLA General Hospital | Yu R.-L.,Chinese PLA General Hospital | Chi X.-H.,Second Artillery General Hospital | And 6 more authors.
Hematological Oncology | Year: 2012

The elderly population is susceptible to haematological malignancies, and these elderly patients are intolerant to cytotoxic drugs. Therefore, the exploration of a safe and reliable strategy exclusive of chemotherapy is critical in improving the prognosis of elderly patients with haematological malignancies. We evaluated the safety and the efficacy of autologous cytokine-induced killer (CIK) cells combined with recombinant human interleukin 2 (rhIL-2) in the treatment of haematological malignancies in elderly patients. Peripheral blood mononuclear cells were isolated from 20 elderly patients with haematological malignancies, then augmented by priming with interferon gamma, rhIL-2 and CD3 monoclonal antibody. The autologous CIK cells (2-3×109) were transfused back to patients, followed by a subcutaneous injection of IL-2 (1mU/day) for 10 consecutive days. The regimen was repeated every 4weeks. The host cellular immune function, tumour-related biological parameters, imaging characteristics, disease condition, quality of life and survival time were assessed. Fourteen patients received 8 cycles of transfusion and 6 received 4 cycles. No adverse effects were observed. The percentages of CD3+, CD3+CD8+ and CD3+CD56+ cells were significantly increased (p<0.05), and the levels of serum β2 microglobulin and lactate dehydrogenase (LDH) were markedly decreased (p<0.05) after autologous CIK cell transfusion. Cancer-related symptoms were profoundly alleviated, as demonstrated by the improved quality of life (p<0.01). Complete remission was observed in 11 patients, persistent partial remission in 7 patients and stable disease in 2 patients. At the end of follow-up, the mean survival time was 20months. Transfusion with autologous CIK cells plus rhIL-2 treatment is safe and effective for treating haematological malignancies in elderly patients. © 2011 John Wiley & Sons, Ltd.

Xie P.-W.,Beijing Institute of Radiation Medicine | Xie P.-W.,Central South University | Xie Y.,Second Artillery General Hospital | Zhang X.-J.,Beijing Institute of Radiation Medicine | And 4 more authors.
Nucleic Acid Therapeutics | Year: 2013

Dengue virus (DENV), a mosquito-borne flavivirus, causes serious diseases and threatens public health in tropical and subtropical areas worldwide. RNA interference (RNAi) is a prevailing strategy for antiviral therapy. In this paper, 6 single artificial microRNAs (amiRNAs) targeting the highly conserved regions of the DENV-2 genome were identified and inhibited virus replication efficiently. Then, effective tandem amiRNAs targeting 2 different DENV-2 genome regions were constructed and expressed simultaneously from a single microRNA-like polycistron to avoid virus variation or mutation escape. Finally, the most high-performance tandem amiRNA was embedded in a lenti-viral vector and inhibited DENV-2 virus replication stably and dose-dependently. Overall, these results indicated that RNAi based on multiple amiRNAs targeting viral conserved regions was an effective approach for improvements of nucleic acid inhibitors of DENV and provided a new therapeutic strategy for DENV infection in humans. © 2013, Mary Ann Liebert, Inc.

Li X.,Capital Medical University | Sun W.-J.,Second Artillery General Hospital
OncoTargets and Therapy | Year: 2015

This study aimed to investigate the activity of arsenic trioxide (As2O3) combined with ascorbic acid, ifosfamide, and prednisone chemotherapy in patients with repeatedly relapsed and refractory multiple myeloma (MM). Here, we retrospectively analyzed medical data of 30 MM patients showing progressive disease after receiving at least two previous lines of treatment including an immunomodulatory agent (thalidomide or lenalidomide) and a proteasome inhibitor. There were 19 men and eleven women, aged 54–73 (median 65) years, in this study. The distribution of different isotypes included immunoglobulin G(IgG) (12 patients), IgA (six patients), IgD (three), and light chain (nine patients). All the patients were Durie–Salmon stage III and had relapsed at least three times; the median cycles of prior therapies was 15 (range 10–18). The patients were treated with As2O3, ascorbic acid, and CP (ifosfamide 1 g on day 1, day 3, day 5, and day 7; prednisone 30 mg taken orally for 2 weeks). As2O3 was administered as an intravenous infusion at a dose of 10 mg/d and ascorbic acid at a dose of 2 g/d for 14 days of each 4-week cycle. The results showed that after 2 cycles of therapy, there were five patients that attained partial response, 15 had minimal response, five had no change, and five had progressive disease. The overall response rate was 66.7% (20/30 cases), 50% (10/20 cases), and 40% (2/5 cases), respectively, after 2, 4, and 6 cycles of the therapy. But there were no patients that attained complete remission. The median time of overall survival and progression-free survival were 48 (29–120) and 6 (2–8) months, respectively. The most common treatment-related adverse events included neutropenia, fatigue, anemia, thrombocytopenia, and infection that could be tolerated. The results showed that As2O3 combined with ascorbic acid, ifosfamide, and prednisone chemotherapy may be a choice treatment for repeatedly relapsed and refractory MM patients. © 2015 Li and Sun.

Zhao Y.,Second Artillery General Hospital | Ding J.-H.,Second Artillery General Hospital | Yin S.-H.,Second Artillery General Hospital | Hou X.-L.,Chinese PLA General Hospital | Zhao K.,Second Artillery General Hospital
Colorectal Disease | Year: 2014

Aim: Moderate to severe pain after stapled haemorrhoidopexy (SH) is not uncommon. This study was designed to identify the predictors of postoperative pain after SH in a single centre. Method: Seventy-six patients with Grade II to IV haemorrhoids who underwent SH were selected from a prospectively compiled database. Preoperative data, including patient characteristics, manometry results and surgical data, were documented. Pain was evaluated during the first 24 h after the operation. Its intensity was classified into three grades according to the visual analogue scale (VAS) score: mild (VAS ≤ 3), moderate (VAS >3 to <5) and severe (VAS ≥ 5). Analgesics were not routinely given but were administered if the patient had moderate or severe pain. Both univariate and multivariate analyses were used to determine the predictors of postoperative pain. Results: Moderate and severe pain was noted in 43 (58.9%) patients. No patient was readmitted due to persistent anal pain during the month following discharge. Postoperative pain was significantly associated with gender (P = 0.017), age (P = 0.014), first initial sensory volume (P = 0.023) and constipation (P = 0.005) in univariate analysis. Multivariate analysis identified male gender as an independent predictor of postoperative moderate to severe pain (P = 0.037, OR = 3.1, 95% CI 1.07-9.09). The initial sensory volume and preoperative coexisting constipation were negative predictors of postoperative moderate to severe pain after SH (P = 0.037, OR = 0.320, 95% CI 0.110-0.934, and P = 0.036, OR = 0.255, 95% CI 0.071-0.913, respectively). Conclusion: Male gender and the initial sensory volume are predictors of postoperative pain after SH. Anal manometry is recommended before the SH procedure. An active analgesia protocol should be considered for male patients with a low initial sensory volume after SH. © 2013 The Association of Coloproctology of Great Britain and Ireland.

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