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Facing challenges with hope:universal immune cells for hematologic malignancies 被引量:3
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作者 Yuqing Wang ruihao huang +3 位作者 Zheng Wang Jingkang Xiong Xiaoqi Wang Xi Zhang 《Cancer Biology & Medicine》 SCIE CAS CSCD 2023年第4期229-247,共19页
Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation(allo-HSCT)has been widely implemented to treat hematologic malignancies.However,graft-versus-host d... Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation(allo-HSCT)has been widely implemented to treat hematologic malignancies.However,graft-versus-host disease(GVHD)and complications of immunosuppressive drugs after allo-HSCT are the main causes of non-relapse mortality and a poor quality of life.In addition,GVHD and infusion-induced toxicity still occur with donor lymphocyte infusions(DLIs)and chimeric antigen receptor(CAR)T-cell therapy.Because of the special immune tolerance characteristics and anti-tumor ability of universal immune cells,universal immune cell therapy may strongly reduce GVHD,while simultaneously reducing tumor burden.Nevertheless,widespread application of universal immune cell therapy is mainly restricted by poor expansion and persistence efficacy.Many strategies have been applied to improve universal immune cell proliferation and persistence efficacy,including the use of universal cell lines,signaling regulation and CAR technology.In this review we have summarized current advances in universal immune cell therapy for hematologic malignancies with a discussion of future perspectives. 展开更多
关键词 Universal immune cells graft-versus-host disease immune tolerance chimeric antigen receptor
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Connexin 43-modified bone marrow stromal cells reverse the imatinib resistance of K562 cells via Ca^(2+)-dependent gap junction intercellular communication 被引量:1
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作者 Xiaoping Li Yunshuo Xiao +7 位作者 Xiaoqi Wang ruihao huang Rui Wang Yi Deng Jun Rao Qiangguo Gao Shijie Yang Xi Zhang 《Chinese Medical Journal》 SCIE CAS CSCD 2023年第2期194-206,共13页
Background: Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects mi... Background: Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects minimal residual disease (MRD), but the mechanism remains unknown. Methods: Immunohistochemistry assays were employed to compare the expression of Cx43 and hypoxia-inducible factor 1α (HIF-1α) in bone marrow (BM) biopsies of CML patients and healthy donors. A coculture system of K562 cells and several Cx43-modified bone marrow stromal cells (BMSCs) was established under IM treatment. Proliferation, cell cycle, apoptosis, and other indicators of K562 cells in different groups were detected to investigate the function and possible mechanism of Cx43. We assessed the Ca^(2+)-related pathway by Western blotting. Tumor-bearing models were also established to validate the causal role of Cx43 in reversing IM resistance. Results: Low levels of Cx43 in BMs were observed in CML patients, and Cx43 expression was negatively correlated with HIF-1α. We also observed that K562 cells cocultured with BMSCs transfected with adenovirus-short hairpin RNA of Cx43 (BMSCs-shCx43) had a lower apoptosis rate and that their cell cycle was blocked in G0/G1 phase, while the result was the opposite in the Cx43-overexpression setting. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca ^(2+ )is the key factor mediating the downstream apoptotic pathway. In animal experiments, mice bearing K562, and BMSCs-Cx43 had the smallest tumor volume and spleen, which was consistent with the in vitro experiments. Conclusions: Cx43 deficiency exists in CML patients, promoting the generation of MRD and inducing drug resistance. Enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy. 展开更多
关键词 Bone marrow microenvironment Connexin 43(Cx43) Gap junction intercellular communication HYPOXIA Imatinib resistance
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Corrigendum:Connexin 43-modified bone marrow stromal cells reverse the imatinib resistance of K562 cells via Ca^(2+)-dependent gap junction intercellular communication
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作者 Xiaoping Li Yunshuo Xiao +7 位作者 Xiaoqi Wang ruihao huang Rui Wang Yi Deng Jun Rao Qiangguo Gao Shijie Yang Xi Zhang 《Chinese Medical Journal》 SCIE CAS CSCD 2023年第10期1224-1224,共1页
Following the original article’s publication,[1]the authors declared that the affiliation of the first author Xiaoping Li was submitted incorrectly,while correct author affiliations should be as follows.The authors a... Following the original article’s publication,[1]the authors declared that the affiliation of the first author Xiaoping Li was submitted incorrectly,while correct author affiliations should be as follows.The authors apologize for any inconvenience caused. 展开更多
关键词 submitted communication COR
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Ginsenoside Rg1 improves anti-tumor efficacy of adoptive cell therapy by enhancing T cell effector functions
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作者 Yue Liu Lingna An +3 位作者 Chengfei Yang Xiaoqi Wang ruihao huang Xi Zhang 《Blood Science》 2023年第3期170-179,共10页
Adoptive cell therapy(ACT)has emerged with remarkable efficacies for tumor immunotherapy.Chimeric antigen receptor(CAR)T cell therapy,as one of most promising ACTs,has achieved prominent effects in treating malignant ... Adoptive cell therapy(ACT)has emerged with remarkable efficacies for tumor immunotherapy.Chimeric antigen receptor(CAR)T cell therapy,as one of most promising ACTs,has achieved prominent effects in treating malignant hematological tumors.However,the insufficient killing activity and limited persistence of T cells in the immunosuppressive tumor microenvironment limit the further application of ACTs for cancer patients.Many studies have focused on improving cytotoxicity and persistence of T cells to achieve improved therapeutic effects.In this study,we explored the potential function in ACT of ginsenoside Rg1,the main pharmacologically active component of ginseng.We introduced Rg1 during the in vitro activation and expansion phase of T cells,and found that Rg1 treatment upregulated two T cell activation markers,CD69 and CD25,while promoting T cell differentiation towards a mature state.Transcriptome sequencing revealed that Rg1 influenced T cell metabolic reprogramming by strengthening mitochondrial biosynthesis.When co-cultured with tumor cells,Rg1-treated T cells showed stronger cytotoxicity than untreated cells.Moreover,adding Rg1 to the culture endowed CAR-T cells with enhanced anti-tumor efficacy.This study suggests that ginsenoside Rg1 provides a potential approach for improving the anti-tumor efficacy of ACT by enhancing T cell effector functions. 展开更多
关键词 Anti-tumor efficacy Adoptive cell therapy CAR-T Ginsenoside Rg1 Metabolic regulation
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Current status and prospects of hematopoietic stem cell transplantation in China 被引量:18
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作者 Xiaoqi Wang ruihao huang +1 位作者 Xiaohui Zhang Xi Zhang 《Chinese Medical Journal》 SCIE CAS CSCD 2022年第12期1394-1403,共10页
Hematopoietic stem cell transplantation(HSCT)is a highly effective and unique medical procedure for the treatment of most hematological malignancies.The first allogeneic transplantation was performed by E.Donnall Thom... Hematopoietic stem cell transplantation(HSCT)is a highly effective and unique medical procedure for the treatment of most hematological malignancies.The first allogeneic transplantation was performed by E.Donnall Thomas in 1957.Since then,the field has evolved and expanded worldwide.The first successful allogenic HSCT(allo-HSCT)in China was conducted in 1981.Although the development of allo-HSCT in China lagged,China has since made considerable contributions to the process of HSCT worldwide,with more than 10,000 HSCTs performed annually.In particular,haploid HSCT(haplo-HSCT)technology represented in the Beijing Protocol has demonstrated similar efficacy to human leukocyte antigen-matched HSCT and has gradually become the pre-dominant choice for allo-HSCT in China.Currently,the number of haplo-HSCT procedures exceeds 5000 per year,and the Beijing Protocol has been greatly improved by implementing updated individualized strategies for controlling complications,relapse,and infection management.In addition,innovative haplo-HSCT technologies developed by different medical transplantation centers,such as Soochow,Zhejiang,Fujian,Chongqing,and Anhui,have emerged,providing inspiration for the refinement of global practice.This review will focus on the current activity in this field and highlight important trends that are vital in China’s allo-HSCT process,examining the current viewpoint and future directions. 展开更多
关键词 Hematopoietic stem cell transplantation HAPLOIDENTICAL China
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