20 results on '"Zi-Zhen Xu"'
Search Results
2. Dysregulated MDR1 by PRDM1/Blimp1 Is Involved in the Doxorubicin Resistance of Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma
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Ge Jiang, Shishuang Wu, Ran Li, Hongming Zhu, Junmin Li, Rufang Xiang, Zhen Jin, Xiaoyang Li, Yunxiang Zhang, Wen-Fang Wang, Kai Qing, Lining Wang, Zi-Zhen Xu, and Kai Xue
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ATP Binding Cassette Transporter, Subfamily B ,Drug resistance ,CHOP ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Drug Discovery ,PRDM1 ,Humans ,Pharmacology (medical) ,Pharmacology ,Reporter gene ,Chemistry ,Promoter ,General Medicine ,Prognosis ,Infectious Diseases ,Gene Expression Regulation ,Oncology ,Doxorubicin ,Drug Resistance, Neoplasm ,Cell culture ,Cancer research ,Lymphoma, Large B-Cell, Diffuse ,Positive Regulatory Domain I-Binding Factor 1 ,Neoplasm Recurrence, Local ,Germinal center B-cell like diffuse large B-cell lymphoma ,Rituximab ,Chromatin immunoprecipitation - Abstract
Introduction: The chemoresistance mechanism of diffuse large B-cell lymphoma (DLBCL) is still poorly understood, and patient prognosis remains unsatisfactory. This study aimed to investigate drug resistance mechanisms in non-germinal center B-cell-like (non-GCB) DLBCL. Methods: Doxorubicin (DOX)-resistant OCI-Ly3 cells were generated through long-term incubation of cells in a medium with gradually increasing DOX concentrations. The expression levels of genes related to drug metabolism were determined using a functional gene grouping polymerase chain reaction (PCR) array. Drug-resistant proteins were identified using bioinformatics, and molecular association networks were subsequently generated. The association and mechanism of key genes were determined using a dual-luciferase reporter assay System and chromatin immunoprecipitation (ChIP). The expression of drug-resistant genes and target genes was then measured using Western blotting and immunohistochemistry. The correlation between gene expressions was analyzed using Spearman’s rank correlation coefficient. Results: Using the PCR array, MDR1 was identified as the key gene that regulates DOX resistance in OCI-Ly3/DOX-A100, a non-GCB DLBCL cell line. The dual-luciferase reporter assay system demonstrated that MDR1 transcription could be inhibited by PRDM1. ChIP results showed that PRDM1 had the ability to bind to the promoter region (−1,132 to −996) of MDR1. In OCI-Ly3/DOX cells, NF-κB activity and PRDM1 expression decreased with an increase in drug-resistant index, whereas MDR1 expression increased with enhanced drug resistance. Immunohistochemical analysis revealed that relative MDR1 expression was higher than that of PRDM1 in human DLBCL tissue samples. A negative correlation was observed between MDR1 and PRDM1. Conclusion: In non-GCB DLBCL cells, NF-κB downregulates PRDM1 and thereby promotes MDR1 transcription by terminating PRDM1-induced transcriptional inhibition of MDR1. Such a mechanism may explain the reason for disease recurrence in non-GCB DLBCL after R-CHOP or combined CHOP with bortezomib treatment. Our findings may provide a potential therapeutic strategy for reducing drug resistance in patients with DLBCL.
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- 2021
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3. Enhanced Surface Mechanical Properties of Cr12MoV Using Ultrasonic Surface Rolling Process and Deep Cryogenic Treatment
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Ying Li Zhao, Rui Shan Xin, Feng Xue, Yun Fei Zhang, Shuai Ren, Jin Bao Chang, Ming Qiang Fan, and Zi Zhen Xu
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010302 applied physics ,Surface (mathematics) ,Materials science ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Atomic and Molecular Physics, and Optics ,Scientific method ,0103 physical sciences ,General Materials Science ,Ultrasonic sensor ,Cryogenic treatment ,Composite material ,0210 nano-technology - Abstract
Ultrasonic surface rolling process (USRP) combined with deep cryogenic treatment (USRP+DCT) was applied on quenched and tempered Cr12MoV. The results indicated that USRP and USRP+DCT could significantly improve the surface mechanical properties, leading to smaller surface roughness and smoother morphology with less cracks and defects. Test of microhardness showed that the hardness increase of USRP and USRP+DCT were 16.4% and 23.6%, respectively. In addition, the wear resistance was improved by USRP and USRP+DCT. Compared with USRP, USRP+DCT can further improve the surface mechanical properties of Cr12MoV.
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- 2018
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4. The severe cytokine release syndrome in phase I trials of CD19-CAR-T cell therapy: a systematic review
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Rufang Xiang, Yuan-Fei Mao, Kai Qing, Lining Wang, Hongming Zhu, Xiaoyang Li, Yunxiang Zhang, Zhen Jin, Zi-Zhen Xu, and Junmin Li
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Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Lymphoma, B-Cell ,medicine.medical_treatment ,Antigens, CD19 ,Immunotherapy, Adoptive ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,otorhinolaryngologic diseases ,medicine ,Humans ,Adverse effect ,Receptors, Chimeric Antigen ,Hematology ,Clinical Trials, Phase I as Topic ,business.industry ,Incidence (epidemiology) ,General Medicine ,Immunotherapy ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Chimeric antigen receptor ,Lymphoma ,Clinical trial ,Cytokine release syndrome ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,business - Abstract
CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive results in treating acute lymphoblastic leukemia (B-ALL), chronic lymphoblastic leukemia (B-CLL), and B-cell non-Hodgkin lymphoma (B-NHL) over the past few years. Meanwhile, the cytokine release syndrome (CRS), which could be moderate or even life-threatening, has emerged as the most significant adverse effect in the clinical course of this novel targeting immunotherapy. In this systematic review, we analyzed the incidence of severe CRS in 19 clinical trials selected from studies published between 2010 and 2017. The pooled severe CRS proportion was 29.3% (95% confidence interval [CI] 12.3-49.1%) in B-ALL, 38.8% (95%CI 12.9-67.6%) in B-CLL, and 19.8% (95%CI 4.2-40.8%) in B-NHL. In the univariate meta regression analysis, the proliferation of CD19-CAR-T cell in vivo was correlated with the severe CRS. Specifically, total infusion cell dose contributed to the severe CRS occurring in B-ALL patients but not in B-CLL or B-NHL patients. Tumor burden was strongly associated with the severity of CRS in B-ALL. Besides, post-HSCT CD19 CAR-T cell infusion represented lower severe CRS incidence. Further investigations into the risk factors of CRS in B-CLL and B-NHL are needed.
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- 2018
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5. Fabrication of a Gradient Nano-/Micro-structured Surface Layer on an Al–Si Casting Alloy by Means of Ultrasonic–Electropulsing Coupling Rolling Process
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Haibo Wang, Zi-Zhen Xu, Song-Zhu Kure-Chu, Guolin Song, Toru Ogasawara, Xiaopei Li, Guoyi Tang, Hitoshi Yashiro, and Xiaohui Li
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010302 applied physics ,Materials science ,Fabrication ,Annealing (metallurgy) ,Alloy ,Metals and Alloys ,02 engineering and technology ,engineering.material ,021001 nanoscience & nanotechnology ,Microstructure ,01 natural sciences ,Industrial and Manufacturing Engineering ,Nanocrystalline material ,0103 physical sciences ,engineering ,Surface modification ,Ultrasonic sensor ,Surface layer ,Composite material ,0210 nano-technology - Abstract
By using a novel surface modification technique named ultrasonic–electropulsing coupling rolling (UECR) process on an Al–Si casting alloy rod, the surface of material was smoothened significantly. Meanwhile, a strengthened layer with a gradient change in hardness was obtained in the outer surface, corresponding to a homogeneous gradient nano-/micro-structure. The thickness of nanometer-thick laminated structures was at least 40 μm, which was much thicker than conventional ultrasonic rolling process. During UECR, the formation of the well-defined nanocrystalline structure was attributed to the high strain rate and simultaneous annealing process realized by ultrasonic impact and electropulsing treatment.
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- 2018
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6. Lithium-ion Migration in Layered Li1.06Ni0.5Co0.2Mn0.3O2 Cathode Materials Synthesized at Different Temperatures
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Zi-Zhen Xu
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Materials science ,chemistry ,law ,Ion migration ,Inorganic chemistry ,Electrochemistry ,chemistry.chemical_element ,Lithium ,Cathode ,law.invention - Published
- 2018
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7. HSP70-Hrd1 axis precludes the oncorepressor potential of N-terminal misfolded Blimp-1s in lymphoma cells
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Zi-Zhen Xu, Yi-Lei Zhao, Jian-Yong Li, Zhao Liu, Junmin Li, Zhi-Yin Liu, Ting Shi, Xiong-Ping Chen, Jian Lin, Guoyu Meng, Wen-Fang Wang, Li Yan, Jiang Zhu, Wu Zhang, Yi Xia, and Lanxuan Liu
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0301 basic medicine ,Protein Folding ,Ubiquitin-Protein Ligases ,Science ,Immunoblotting ,Mutant ,SUMO protein ,General Physics and Astronomy ,Mice, SCID ,Biology ,Plasma cell ,medicine.disease_cause ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Ubiquitin ,Mice, Inbred NOD ,RNA interference ,Cell Line, Tumor ,hemic and lymphatic diseases ,medicine ,Animals ,Humans ,HSP70 Heat-Shock Proteins ,lcsh:Science ,Genetics ,B-Lymphocytes ,Mutation ,Multidisciplinary ,HEK 293 cells ,Purine Nucleosides ,General Chemistry ,Xenograft Model Antitumor Assays ,Hsp70 ,Cell biology ,HEK293 Cells ,030104 developmental biology ,medicine.anatomical_structure ,Microscopy, Fluorescence ,biology.protein ,RNA Interference ,lcsh:Q ,Lymphoma, Large B-Cell, Diffuse ,Positive Regulatory Domain I-Binding Factor 1 ,HeLa Cells - Abstract
B lymphocyte-induced maturation protein-1 (Blimp-1) ensures B-cell differentiation into the plasma cell stage, and its instability constitutes a crucial oncogenic element in certain aggressive cases of activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). However, the underlying degradation mechanisms and their possible therapeutic relevance remain unexplored. Here, we show that N-terminal misfolding mutations in ABC-DLBCL render Blimp-1 protein susceptible to proteasome-mediated degradation but spare its transcription-regulating activity. Mechanistically, whereas wild-type Blimp-1 metabolism is triggered in the nucleus through PML-mediated sumoylation, the degradation of lymphoma-associated mutants is accelerated by subversion of this pathway to Hrd1-mediated cytoplasmic sequestration and ubiquitination. Screening experiments identifies the heat shock protein 70 (HSP70) that selects Blimp-1 mutants for Hrd1 association, and HSP70 inhibition restores their nuclear accumulation and oncorepressor activities without disrupting normal B-cell maturation. Therefore, HSP70-Hrd1 axis represents a potential therapeutic target for restoring the oncorepressor activity of unstable lymphoma-associated Blimp-1 mutants., The transcriptional repressor Blimp-1 has an important role in B-cell differentiation. Here the authors show that lymphoma-associated Blimp-1 mutants are selectively recognized by HSP70-Hrd1, which leads to their accelerated degradation and propose HSP70 inhibition as a therapeutic approach for certain lymphomas.
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- 2017
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8. Reactive oxygen species mediate oridonin-induced apoptosis through DNA damage response and activation of JNK pathway in diffuse large B cell lymphoma
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Wan-Bin Fu, Zi-Zhen Xu, Junmin Li, Pei Guo, Wen-Fang Wang, and Zhen Jin
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Male ,0301 basic medicine ,Cancer Research ,Cell Survival ,MAP Kinase Signaling System ,DNA damage ,viruses ,Antineoplastic Agents ,Apoptosis ,Biology ,Histones ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Cytotoxic T cell ,Cell Proliferation ,chemistry.chemical_classification ,Reactive oxygen species ,Kinase ,Intrinsic apoptosis ,Hematology ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Xenograft Model Antitumor Assays ,In vitro ,Mitochondria ,Disease Models, Animal ,030104 developmental biology ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Lymphoma, Large B-Cell, Diffuse ,Diterpenes, Kaurane ,Reactive Oxygen Species ,Diffuse large B-cell lymphoma ,DNA Damage - Abstract
This study investigated the cytotoxic effect of oridonin (ORI), a diterpenoid isolated from Rabdosia rubescens, in human diffuse large B cell lymphoma (DLBCL) in vitro and in vivo and the potential molecular mechanisms for ORI-induced cell apoptosis. ORI treatment caused reactive oxygen species (ROS)-mediated oxidative DNA damage response (DDR) and the c-Jun N-terminal kinase (JNK) pathway activation, leading to an induction of intrinsic apoptosis. ROS abolition blocked ORI-induced apoptosis and attenuated the expression of phospho-histone H2AX and phospho-JNK, indicating that ROS-mediated DNA damage and JNK pathway activation were involved in ORI-induced apoptosis. The systemic administration of ORI suppressed the growth of human DLBCL xenografts without showing significant toxicity. These findings suggest that ORI may have promising therapeutic application in DLBCL.
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- 2015
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9. Clinical significance of chemokine receptor CXCR4 and mammalian target of rapamycin (mTOR) expression in patients with diffuse large B-cell lymphoma
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Junmin Li, Jian-Kang Shen, Shu-Qing Zhao, and Zi-Zhen Xu
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Receptors, CXCR4 ,CXCR4 Inhibitor ,Combination therapy ,Gene Expression ,Biology ,CXCR4 ,03 medical and health sciences ,Chemokine receptor ,Antibodies, Monoclonal, Murine-Derived ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Molecular Targeted Therapy ,Cyclophosphamide ,PI3K/AKT/mTOR pathway ,Aged ,Retrospective Studies ,Aged, 80 and over ,Everolimus ,TOR Serine-Threonine Kinases ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,Immunohistochemistry ,Lymphoma ,Endocrinology ,Oncology ,Doxorubicin ,Vincristine ,030220 oncology & carcinogenesis ,Cancer research ,Prednisone ,Female ,Lymphoma, Large B-Cell, Diffuse ,Rituximab ,Diffuse large B-cell lymphoma ,030215 immunology ,medicine.drug - Abstract
To assess the relevance of C-X-C chemokine receptor type 4 (CXCR4) and mammalian target of rapamycin (mTOR) to large-B-cell lymphoma (DLBCL), levels of protein expression were measured in 56 DLBCL patients who had received rituximab-based therapy. Of these, 34 were positive for CXCR4 expression (60.7%) and 31 for mTOR (55.4%). CXCR4 expression was positively correlated with mTOR expression (r = 0.602; p = .000). CXCR4 expression was significantly associated with high lactate dehydrogenase (LDH) level (p = .009), high IPI score (p = .030) and non-GCB subtype (p = .006). Furthermore, the expression levels of CXCR4 and mTOR were negatively correlated with the chance of remission (p .05). Kaplan-Meier analysis indicated significantly shorter progression-free survival (PFS) and overall survival (OS) in patients positive for CXCR4 and mTOR expression. The combination therapy with CXCR4 inhibitor WZ811 and mTOR inhibitor everolimus showed syncergistic effect in DLBCL cell lines. These results suggest that the expression of CXCR4 and mTOR may be suitable as biomarkers of the prognosis of DLBCL and for development of new therapeutic strategies.
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- 2017
10. Combination of rituximab and mammalian target of rapamycin inhibitor everolimus (RAD001) in diffuse large B-cell lymphoma
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Ai-Hua Wang, Wan-Bin Fu, Li-Yun Chen, Zhi-Yin Liu, Zi-Zhen Xu, Pei Guo, Wen-Fang Wang, and Junmin Li
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Cancer Research ,Combination therapy ,Population ,Mice, Nude ,Antineoplastic Agents ,Apoptosis ,Pharmacology ,Antibodies, Monoclonal, Murine-Derived ,Mice ,immune system diseases ,Cell Line, Tumor ,hemic and lymphatic diseases ,medicine ,Animals ,Humans ,Everolimus ,education ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Sirolimus ,education.field_of_study ,business.industry ,TOR Serine-Threonine Kinases ,Cell Cycle ,Drug Synergism ,Hematology ,medicine.disease ,Xenograft Model Antitumor Assays ,Tumor Burden ,Lymphoma ,Disease Models, Animal ,Oncology ,Monoclonal ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,Signal Transduction ,medicine.drug - Abstract
We evaluated the efficacy of the anti-CD20 monoclonal antibody rituximab in combination with the mammalian target of rapamycin (mTOR) inhibitor everolimus for treating diffuse large B-cell lymphoma (DLBCL). The combination of rituximab and everolimus was more effective for inhibiting cell growth compared with single-agent therapy. An increase in G0/G1 cell cycle arrest and an increased population of cells in apoptosis were observed in the combination treatment group. The addition of rituximab reduced the overexpression of p-AKT caused by the negative feedback loop of everolimus and had an enhanced effect on inhibition of mTOR signaling, thus providing a rationale for this synergistic effect. Furthermore, combination treatment was also more effective than treatment with either agent alone for inhibiting the growth of DLBCL xenografts. Our study provides preclinical evidence and a theoretical basis for combination therapy with rituximab and everolimus in DLBCL.
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- 2013
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11. Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma
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Zhao Liu, Wan-Bin Fu, Xiaoyang Li, Wen-Fang Wang, Kai Qing, Zi-Zhen Xu, Zhen Jin, and Junmin Li
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0301 basic medicine ,Cancer Research ,Apoptosis ,Mice ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,NF-kB ,Letter to the Editor ,B-Lymphocytes ,Chemistry ,TOR Serine-Threonine Kinases ,Imidazoles ,Drug Synergism ,lcsh:Diseases of the blood and blood-forming organs ,Hematology ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,NVP-BEZ235 ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Quinolines ,Heterografts ,Lymphoma, Large B-Cell, Diffuse ,Diterpenes, Kaurane ,Oridonin ,DNA damage ,Diffuse large B cell lymphoma ,lcsh:RC254-282 ,03 medical and health sciences ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Protein Kinase Inhibitors ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,B cell ,lcsh:RC633-647.5 ,Germinal center ,medicine.disease ,PI3K/mTOR ,030104 developmental biology ,Immunology ,Cancer research ,Diffuse large B-cell lymphoma - Abstract
We demonstrate the synergistic antitumor effect of oridonin and the PI3K/mTOR inhibitor NVP-BEZ235 on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma (non-GCB DLBCL) both in vitro and in vivo. The underlying mechanism may be multifunctional, involving apoptosis, AKT/mTOR and NF-kB inactivation, and ROS-mediated DNA damage response. Our findings pave the way for a new potential treatment option for non-GCB DLBCL with the combination of oridonin and NVP-BEZ235. Electronic supplementary material The online version of this article (doi:10.1186/s13045-016-0303-0) contains supplementary material, which is available to authorized users.
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- 2016
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12. Serum BAFF and APRIL levels in patients with autoimmune hemolytic anemia and their clinical significance
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Ye‑Fei Wang, Zi‑Zhen Xu, Bing‑Bing Zhao, Bei‑Wen Wei, and Hong Xiong
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Adult ,Male ,medicine.medical_specialty ,Tumor Necrosis Factor Ligand Superfamily Member 13 ,stomatognathic system ,hemic and lymphatic diseases ,Internal medicine ,B-Cell Activating Factor ,medicine ,Humans ,B-cell activating factor ,Glucocorticoids ,B cell ,Aged ,Autoimmune disease ,Hematology ,biology ,business.industry ,Middle Aged ,medicine.disease ,stomatognathic diseases ,medicine.anatomical_structure ,Immunology ,biology.protein ,Tumor necrosis factor alpha ,Female ,Anemia, Hemolytic, Autoimmune ,Antibody ,Autoimmune hemolytic anemia ,business ,Glucocorticoid ,medicine.drug - Abstract
B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) play crucial roles in B cell development, survival, and antibody production. Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease that occurs when antibodies target autologous red blood cells. Here, we analyzed the serum levels of BAFF and APRIL and their respective clinical associations in patients with AIHA. Serum BAFF and APRIL levels in patients with AIHA were significantly higher (P0.01) than in healthy individuals. Serum BAFF and APRIL levels were significantly augmented in patients with lower hemoglobin levels (hemoglobin was8 g/dL) and higher LDH activity (LDH480 IU/mL). Glucocorticoid treatment dramatically reduced serum levels of BAFF and APRIL. Thus, serum BAFF and APRIL levels may reflect the clinical activity of this disease. Our results indicate that analysis of serum concentrations of BAFF and APRIL potentially represents a useful tool for the assessment of AIHA disease activity and progression.
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- 2015
13. BAFF level increased in patients with autoimmune hemolytic anemia
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Yu-Bing, Zhao, Jun-Min, Li, Bei-Wen, Wei, and Zi-Zhen, Xu
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Original Article - Abstract
Introduction: BAFF (B-cell activating factor of the TNF family), an important regulator of B-cell, has been observed to be over-expressed in a variety of autoimmune diseases. Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease occurred when antibodies directed against autologous red blood cells. We assessed serum levels of BAFF in AIHA patients with different serological characteristics. Methods: Serum BAFF levels were measured in 44 AIHA patients with different direct antiglobulin test (DAT) results and 25 healthy controls. The correlation of BAFF expression with DAT results and serological characteristics was assessed. Results: Serum levels of BAFF in AIHA patients were significantly higher than in healthy subjects (AIHA: 1382.7 ± 1412.8 pg/ml, healthy control: 725.0 ± 415.7 pg/ml, P = 0.0057). Serum BAFF levels were significantly higher in patients with IgG(+)C3(+) or IgG(+) than healthy controls (DAT: negative) (P = 0.012, 0.004, respectively). No significant correlations were presented between serum BAFF levels and four serological parameters: hemoglobine, percentage of reticulocyte, total serum bilirubin, and lactate dehydrogenase. Conclusions: AIHA patients present higher serum BAFF levels than healthy controls, especially for those of IgG(+)C3(+) DAT result. This might lead to a new approach of AIHA treatment.
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- 2015
14. Activation of the PI3K/AKT/mTOR pathway in diffuse large B cell lymphoma: clinical significance and inhibitory effect of rituximab
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Zhi-Yin Liu, Ai-Hua Wang, Wen-Fang Wang, Junmin Li, Li-Yun Chen, Zi-Zhen Xu, and Zu-Guang Xia
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Adult ,Male ,Vincristine ,Blotting, Western ,CHOP ,Antibodies, Monoclonal, Murine-Derived ,Young Adult ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Humans ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Aged ,Sirolimus ,business.industry ,TOR Serine-Threonine Kinases ,RPTOR ,Drug Synergism ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Lymphoma ,Immunology ,Cancer research ,Rituximab ,Female ,Lymphoma, Large B-Cell, Diffuse ,Phosphatidylinositol 3-Kinase ,business ,Diffuse large B-cell lymphoma ,Proto-Oncogene Proteins c-akt ,medicine.drug ,Signal Transduction - Abstract
Diffuse large B cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma and accounts for approximately 30 % of newly diagnosed lymphoid neoplasms in Western countries, and 40–50 % in China. A better understanding of the biology of DLBCL is needed for the development of potential therapeutic agents that target specific intracellular pathways. In this study, expression of the important components of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway and their clinical significance were investigated in 73 DLBCL cases. The effect of rituximab alone or combined with the PI3K/AKT/mTOR pathway inhibitor rapamycin was further evaluated in the DLBCL cell lines. A total of 73 patients were identified, including 45 men and 28 women aged 18 to 78 years (median age 50 years). Of these patients, p-AKT was positive in 40 cases (54.8 %), p-p70S6K in 34 cases (46.6 %), and p-4E-BP1 in 33 cases (45.2 %). Activation of the PI3K/AKT/mTOR pathway was related to poor disease outcome in DLBCL patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) but not in those treated with rituximab-CHOP. Rituximab combined with rapamycin synergically downregulated the PI3K/AKT/mTOR signaling pathway. Western blot analysis revealed a baseline activation status of the PI3K/AKT/mTOR pathway in DLBCL cell lines, with high levels of p-AKT, p-mTOR, in addition to downstream molecules p-p70S6K and p-4E-BP1. The results indicate that the PI3K/AKT/mTOR pathway is a potentially important signaling route and an unfavorable prognostic factor for DLBCL. Patients with PI3K/AKT/mTOR activation experience a more rapidly deteriorating clinical course with poor treatment response and decreased survival time. Addition of rituximab could downregulate PI3K/AKT/mTOR activation, reversing its negative effect on chemotherapy-treated patients. In addition, our results indicate that the combination of rituximab and inhibition of the activated PI3K/AKT/mTOR pathway could be a promising target for DLBCL therapeutic intervention in the future.
- Published
- 2013
15. The prognostic value of immunohistochemical subtyping in Chinese patients with de novo diffuse large B-cell lymphoma undergoing CHOP or R-CHOP treatment
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Zi-Zhen Xu, Zhi-Xiang Shen, Zu-Guang Xia, Yu Zheng, Fei Ding, Jun-Pei Hu, Yu Chen, Qiu-Sheng Chen, Wei-Li Zhao, Qi Zhu, Shu-Qing Zhao, and Junmin Li
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Pathology ,Adolescent ,medicine.medical_treatment ,Antineoplastic Agents ,Kaplan-Meier Estimate ,CHOP ,Antibodies, Monoclonal, Murine-Derived ,Young Adult ,International Prognostic Index ,Asian People ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,Medicine ,Humans ,Cyclophosphamide ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Chemotherapy ,Hematology ,business.industry ,Antibodies, Monoclonal ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Immunohistochemistry ,Subtyping ,Lymphoma ,Treatment Outcome ,Doxorubicin ,Vincristine ,Prednisone ,Rituximab ,Female ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,medicine.drug - Abstract
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with recognised variability in molecular aetiology and clinical outcome. Though the use of agents such as rituximab significantly improves outcome, intrinsic genetic and morphological factors greatly affect the response to treatment. The objective of this study was to evaluate the prognostic value of immunohistochemical subtyping and the International Prognostic Index (IPI) for predicting treatment outcome in Chinese DLBCL patients. We followed 108 cases of DLBCL and performed prognostic analyses based on molecular subtyping of the disease through immunostaining of tissue samples. The use of rituximab conferred a clinical benefit to DLBCL patients regardless of disease subtype. Importantly, this treatment regimen also improved outcomes in patients with the non-germinal centre B-cell-like (GCB) DLBCL subtype, frequently associated with poorer prognosis. Our results suggest that IPI was the best tool for the prediction of treatment outcome in our patient cohort, regardless of treatment regimen. Furthermore, the use of rituximab alongside classical chemotherapy regimens can improve the outcomes for DLBCL patients who exhibit both GCB and non-GCB subtypes of the disease.
- Published
- 2009
16. Nonequilibrium Segregation and Fracture Mechanism of High-Manganese Cryogenic Steels
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Zi-Zhen Xu, K. S. Xue, Jia Li, J. Q. Shen, B. Wang, W. Wang, and D. Y. Sun
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Austenite ,Toughness ,Materials science ,Alloy steel ,Metallurgy ,technology, industry, and agriculture ,Charpy impact test ,chemistry.chemical_element ,Fractography ,Manganese ,engineering.material ,Intergranular fracture ,chemistry ,engineering ,Grain boundary - Abstract
Nonequilibrium segregation of manganese at grain boundaries of high-manganese austenitic steels, which was reported previously, was verified by AES and TEM—EDS analysis in this study. The deformation behavior of high-manganese steels with different manganese content was characterized, and the low-temperature toughness for various heat-treatment conditions was determined. On the basis of these data, the fracture mechanisms are discussed. The “hard-shell” model of low-temperature fracture of high-manganese steels, which was proposed by Xue in the earlier paper, was validated by the ultra-microhardness test.
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- 1998
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17. Summary of 615 patients of chronic myeloid leukemia in Shanghai from 2001 to 2006
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Li Wang, Ai-Hua Wang, Yu Chen, Li Zhou, Li Zhang, Yu Yao, Zhi-Xiang Shen, Jiong Hu, Zi-Zhen Xu, Junmin Li, and Yan-Yan Wang
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Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,China ,Adolescent ,Alpha interferon ,lcsh:RC254-282 ,Disease-Free Survival ,Piperazines ,Internal medicine ,hemic and lymphatic diseases ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,neoplasms ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Incidence (epidemiology) ,Research ,Incidence ,Myeloid leukemia ,Imatinib ,Retrospective cohort study ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Treatment efficacy ,Transplantation ,Pyrimidines ,Treatment Outcome ,Immunology ,Benzamides ,Imatinib Mesylate ,Female ,business ,Chronic myelogenous leukemia ,medicine.drug - Abstract
Background To retrospectively review the incidence, treatment efficacy, we followed up newly diagnosed chronic myelogenous leukemia (CML) patients residing in Shanghai during 2001-2006. Methods All eligible cases were reviewed with the data of efficacy responses as well as overall survival (OS) and progression-free survival (PFS) time. Results A total of 615 cases entered the study. CML mainly afflicted those aged 40-60 years old and was slightly more frequent in males than females. More than 85% of the patients were in chronic phase (CP) when diagnosed. All patients were divided into four groups based on the main regimens - hydroxyurea, interferon alpha (IFN-α), imatinib, and hemopoietic stem cell transplantation (HSCT). With the median follow-up of 18 months, imatinib treatment induced 92.2% complete hematologic responses, and 64.3% complete cytogenetic responses among CML-CP patients. Overall the therapeutic efficacy in the imatinib group was higher than that in the hydroxyurea or IFN-α group. Meanwhile, in the imatinib group, all response rates of patients in CP were significantly greater than that in accelerated or blastic crisis phase. The patients treated with imatinib also showed the most promising results regarding OS and PFS. Patients receiving HSCT decreased markedly in number with the introduction of imatinib. Conclusions The number of new patients arising in Shanghai increased from 2001 to 2006. There were still patients receiving hydroxyurea and IFN-α. As the first-line regime for CML, imatinib was less administered in Shanghai before, but has received considerable development and great responses since 2003.
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- 2010
18. Activation of PI3K/Akt/mTOR Pathway in Diffuse Large B-Cell Lymphomas: Clinical Significance and Inhibitory Effect by Rituximab
- Author
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Jiong Hu, Jun-Min Li, Ai-hua Wang, and Zi-zhen Xu
- Subjects
Phosphoinositide 3-kinase ,biology ,business.industry ,Immunology ,RPTOR ,Cell Biology ,Hematology ,CHOP ,Pharmacology ,medicine.disease ,Biochemistry ,medicine.anatomical_structure ,immune system diseases ,hemic and lymphatic diseases ,biology.protein ,Cancer research ,Medicine ,Rituximab ,business ,Protein kinase B ,Diffuse large B-cell lymphoma ,PI3K/AKT/mTOR pathway ,B cell ,medicine.drug - Abstract
Abstract 1934 Poster Board I-957 A better understanding of the biology of diffuse large B cell lymphoma(DLBCL) is needed in the developement of potential therapeutic agents that target specific intracellular pathway. In this study, expression of the important members of PI3K/Akt/mTOR signaling pathway and their clinical significance were investigated in 73 cases of DLBCL. Immunohistochemical analyses showed that activation of Akt and its downstream targets such as p-p70S6K, p-4E-BP1, YB-1 and Mcl-1 were present in DLBCL cases. Activation of PI3K/Akt/mTOR pathway was related to poor disease outcome in DLBCL patients treated by CHOP but not in those treated by R-CHOP. Rituximab combined with chemotherapy could down-regulate PI3K/Akt/mTOR activation and reverse its negative effect on chemotherapy-treated patients. The effect of Rituximab alone or combined with the mTOR inhibitor Rapamycin was further evaluated in DLBCL cell line SUDHL-4. Rituximab combined with Rapamycin possessed synergic effect in down-regulating PI3K/Akt/mTOR signaling pathway, inhibited proliferation and caused G1 arrest in DLBCL cell line. The results showed that PI3K/Akt/mTOR signaling pathway activation presented in DLBCL may be considered as a prognostic biomarker and a promising target for therapeutic intervention. Disclosures: No relevant conflicts of interest to declare.
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- 2009
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19. The prognostic value of immunohistochemical subtyping in Chinese patients with de novo diffuse large B-cell lymphoma undergoing CHOP or R-CHOP treatment.
- Author
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Zu-Guang Xia, Zi-Zhen Xu, Wei-Li Zhao, Shu-Qing Zhao, Fei Ding, Yu Chen, Qiu-Sheng Chen, Yu Zheng, Qi Zhu, Jun-Pei Hu, Zhi-Xiang Shen, and Jun-Min Li
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- *
PROGNOSIS , *IMMUNOHISTOCHEMISTRY , *B cell differentiation , *LYMPHOMAS , *ETIOLOGY of diseases , *RITUXIMAB , *MORPHOLOGY - Abstract
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with recognised variability in molecular aetiology and clinical outcome. Though the use of agents such as rituximab significantly improves outcome, intrinsic genetic and morphological factors greatly affect the response to treatment. The objective of this study was to evaluate the prognostic value of immunohistochemical subtyping and the International Prognostic Index (IPI) for predicting treatment outcome in Chinese DLBCL patients. We followed 108 cases of DLBCL and performed prognostic analyses based on molecular subtyping of the disease through immunostaining of tissue samples. The use of rituximab conferred a clinical benefit to DLBCL patients regardless of disease subtype. Importantly, this treatment regimen also improved outcomes in patients with the non-germinal centre B-cell-like (GCB) DLBCL subtype, frequently associated with poorer prognosis. Our results suggest that IPI was the best tool for the prediction of treatment outcome in our patient cohort, regardless of treatment regimen. Furthermore, the use of rituximab alongside classical chemotherapy regimens can improve the outcomes for DLBCL patients who exhibit both GCB and non-GCB subtypes of the disease. [ABSTRACT FROM AUTHOR]
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- 2010
- Full Text
- View/download PDF
20. Summary of 615 patients of chronic myeloidleukemia in Shanghai from 2001 to 2006.
- Author
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Ai-Hua Wang, Yan-Yan Wang, Yu Yao, Zi-Zhen Xu, Li Zhou, Li Wang, Li Zhang, Yu Chen, Zhi-Xiang Shen, Jiong Hu, and Jun-Min Li
- Subjects
CHRONIC myeloid leukemia ,TREATMENT effectiveness ,DISEASE progression ,HEMATOPOIETIC system ,STEM cell transplantation ,HYDROXYUREA ,IMATINIB - Abstract
Background: To retrospectively review the incidence, treatment efficacy, we followed up newly diagnosed chronic myelogenous leukemia (CML) patients residing in Shanghai during 2001-2006. Methods: All eligible cases were reviewed with the data of efficacy responses as well as overall survival (OS) and progression-free survival (PFS) time. Results: A total of 615 cases entered the study. CML mainly afflicted those aged 40-60 years old and was slightly more frequent in males than females. More than 85% of the patients were in chronic phase (CP) when diagnosed. All patients were divided into four groups based on the main regimens - hydroxyurea, interferon alpha (IFN-a), imatinib, and hemopoietic stem cell transplantation (HSCT). With the median follow-up of 18 months, imatinib treatment induced 92.2% complete hematologic responses, and 64.3% complete cytogenetic responses among CML-CP patients. Overall the therapeutic efficacy in the imatinib group was higher than that in the hydroxyurea or IFN-α group. Meanwhile, in the imatinib group, all response rates of patients in CP were significantly greater than that in accelerated or blastic crisis phase. The patients treated with imatinib also showed the most promising results regarding OS and PFS. Patients receiving HSCT decreased markedly in number with the introduction of imatinib. Conclusions: The number of new patients arising in Shanghai increased from 2001 to 2006. There were still patients receiving hydroxyurea and IFN-α. As the first-line regime for CML, imatinib was less administered in Shanghai before, but has received considerable development and great responses since 2003. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
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