Chinese PLA General Hospital

About: Chinese PLA General Hospital is a healthcare organization based out in Beijing, China. It is known for research contribution in the topics: Medicine & Population. The organization has 18037 authors who have published 12349 publications receiving 184803 citations. The organization is also known as: 301 Military Hospital.

Efficiency of CD19 chimeric antigen receptor-modified T cells for treatment of B cell malignancies in phase I clinical trials: a meta-analysis

Abstract: // Tengfei Zhang 1,2,* , Ling Cao 1,3,* , Jing Xie 4,* , Ni Shi 5 , Zhen Zhang 1,3 , Zhenzhen Luo 1,3 , Dongli Yue 1,3 , Zimeng Zhang 6 , Liping Wang 3 , Weidong Han 7 , Zhongwei Xu 8 , Hu Chen 9 and Yi Zhang 1,3,10,11 1 Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 2 Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States 3 Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 4 Center for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia 5 Comprehensive Cancer Center, the Ohio State University, Columbus, Ohio, United States 6 Department of Immunology, Harvard Medical School, Boston, Massachusetts United States 7 Molecular & Immunological/Bio-Therapeutic Department, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, China 8 Department of Gastroenterology, Pennsylvania Hospital, University of Pennsylvania, Philadelphia, Pennsylvania, United States 9 Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Science, Beijing, China 10 Engineering Key Laboratory for Cell Therapy of Henan Province, Zhengzhou, Henan, China 11 School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China * These authors have contributed equally to this work Correspondence to: Yi Zhang, email: // Keywords : CD19, chimeric antigen receptor, B cell malignancies, meta analysis, efficiency Received : July 06, 2015 Accepted : August 20, 2015 Published : September 10, 2015 Abstract Chimeric antigen receptor (CAR) modified T cells targeted CD19 showed promising clinical outcomes in treatment of B cell malignances such as chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL) and other indolent lymphomas. However, the clinical benefit varies tremendously among different trials. This meta-analysis investigated the efficacy (response rates and survival time) of CD19-CAR T cells in refractory B cell malignances in Phase I clinical trials. We searched publications between 1991 and 2014 from PubMed and Web of Science. Pooled response rates were calculated using random-effects models. Heterogeneity was investigated by subgroup analysis and meta-regression. Fourteen clinical trials including 119 patients were eligible for response rate evaluation, 62 patients in 12 clinical trials were eligible for progression-free survival analysis. The overall pooled response rate of CD19-CAR T cells was 73% (95% confidence interval [CI]: 46-94%). Significant heterogeneity across estimates of response rates was observed ( p < 0.001, I2=88.3%). ALL patients have higher response rate (93%, 95% CI: 65-100%) than CLL (62%, 95% CI: 27-93%) and lymphoma patients (36%, 95% CI: 1-83%). Meta-regression analysis identified lymphodepletion and no IL-2 administrated T cells as two key factors associated with better clinical response. Lymphodepletion and higher infused CAR T cell number were associated with better prognosis. In conclusion, this meta-analysis showed a high clinical response rate of CD19-CAR T cell-based immunotherapy in treatment of refractory B cell malignancies. Lymphodepletion and increasing number of infused CD19-CAR T cells have positive correlations with the clinical efficiency, on the contrary, IL-2 administration to T cells is not recommended.

Target selection for CAR-T therapy

Abstract: Chimeric antigen receptor-modified T (CAR-T) cells have achieved significant success in the treatment of several hematological malignancies. However, the translation of the existing achievements into the treatment of other tumors, especially solid tumors, is not smooth. In addition to the optimization of CAR structures, preparation, and clinical protocols, rational selecting and utilizing the targets was more pivotal. In this review, the criteria for target selection and some new strategies for targets utilization were summarized and discussed. This systematic review will help researchers better understand how the efficacy and safety of CAR-T treatment would be affected by targets and thus more rationally select targets and conduct clinical trials.

Tuning Alginate-Gelatin Bioink Properties by Varying Solvent and Their Impact on Stem Cell Behavior

Abstract: Bioink optimization is considered as one of main challenges in cell-laden 3D bioprinting. Alginate-Gelatin (Alg-Gel) hydrogel have been extensively used as bioink. However, its properties could be influenced by various parameters, and little is known about the evidence featuring the impact of solvent. Here we investigated four Alg-Gel bioink by varying solvent ionic strength (named B-1, B-2, B-3 and B-4). Mechanical properties and printability of bioink samples and their impacts on behaviors of encapsulated epidermal stem cells (ESCs) were tested. Bioink with increased ionic strength of solvent showed decreased stiffness and viscosity, and increased swelling and degradation by printability and mechanical property tests. Due to the increased swelling and degradation was associated with shape-maintenance of post-printing constructs, B-3 and B-4 were hardly observable after 14 days. Cellular behaviors were assessed through viability, proliferation, aggregation and differentiation tests. B-2 with optimal properties resulted in higher viability and proliferation of ESCs, and further facilitated cellular aggregation and lineage differentiation. We demonstrated that the solvent can be tuned by ionic strength to control the properties of Alg-Gel bioink and post-printing constructs, which represented a promising avenue for promotion of therapeutic stem cell behaviors in 3D bioprinting.

Clinical spectrum of SCN2A mutations.

Abstract: Mutations in SCN2A, the gene encoding α2 subunit of the neuronal sodium channel, are associated with a variety of epilepsies: benign familial neonatal-infantile seizures (BFNIS); genetic epilepsy with febrile seizures plus (GEFS+); Dravet syndrome (DS); and some intractable childhood epilepsies More than 10 new mutations have been identified in BFNIS, all of them are missense To date, only one nonsense mutation has been found in a patient with intractable childhood epilepsy and severe mental decline Recently, microduplication of chromosome 2q243 (containing eight genes including SCN2A, SCN3A, and the 3' end of SCN1A) was reported in a family with dominantly inherited neonatal seizures and intellectual disability Functional studies of SCN2A mutations show that they can cause divergent biophysical defects in Na(V)12 and impair cell surface expressions There is no consistent relationship between genotype and phenotype

A new tumor suppressor LncRNA ADAMTS9-AS2 is regulated by DNMT1 and inhibits migration of glioma cells

Abstract: Growing number of long noncoding RNAs (lncRNAs) are emerging as new modulators in cancer origination and progression. A lncRNA, ADAM metallopeptidase with thrombospondin type 1 motif, 9 (ADAMTS9) antisense RNA 2 (ADAMTS9-AS2), with unknown function, is the antisense transcript of tumor suppressor ADAMTS9. In the present study, we investigated the expression pattern and functional role of ADAMTS9-AS2 in glioma by using real-time PCR and gain-/loss-of-function studies. The results showed that the ADAMTS9-AS2 expression was significantly downregulated in tumor tissues compared with normal tissues and reversely associated with tumor grade and prognosis. Multivariate analysis of the prognosis factors showed that low ADAMTS9-AS2 expression was a significant independent predictor of poor survival in glioma. Overexpression of ADAMTS9-AS2 resulted in significant inhibition of cell migration in glioma, whereas knockdown of ADAMTS9-AS2 showed the opposite effect. We also found that ADAMTS9-AS2 expression was negatively correlated with DNA methyltransferase-1 (DNMT1). In addition, DNMT1 knockdown led to remarkable enhancement of ADAMTS9-AS2 expression. By 5-aza-dC treatment, the ADAMTS9-AS2 expression was also reactivated. The results suggested that ADAMTS9-AS2 is a novel tumor suppressor modulated by DNMT1 in glioma. LncRNA ADAMTS9-AS2 may serve as a potential biomarker and therapeutic target for glioma.