Browsing by Author "Xu, Bing"

Now showing 1 - 5 of 5
  • Thumbnail Image
    ItemOpen Access
    CS2164 and Venetoclax Show Synergistic Antitumoral Activities in High Grade B-Cell Lymphomas With MYC and BCL2 Rearrangements.
    (Frontiers in oncology, 2021-01) Yuan, Delin; Li, Genhong; Yu, Lian; Jiang, Yuelong; Shi, Yuanfei; Chen, Qiulin; Ma, Xiaomei; Pham, Lan V; Young, Ken H; Deng, Manman; Fang, Zhihong; Xu, Bing
    High-grade B-cell lymphoma with concurrent MYC and BCL2 rearrangements (HGBL-DHL) is a rare, aggressive mature B-cell malignancy with a high likelihood of treatment failure following front-line immunochemotherapies. Patients with HGBL-DHL who develop a relapsed or refractory disease have little effective therapeutic strategies and show very poor clinical outcomes, thus calling for development of novel therapies for this specific patient population. In this study, we investigated the preclinical anti-lymphoma efficacies and potential mechanism of action of a novel treatment approach, combining the BCL2 inhibitor venetoclax with CS2164, a new orally active multitarget inhibitor, in HGBL-DHL models. This combination therapy exhibited a robust synergistic cytotoxicity against HGBL-DHL cells, evidenced by cooperatively inducing loss of cell viability and promoting cell apoptosis. Moreover, coadministration of CS2164 and venetoclax resulted in significant superior suppression of HGBL-DHL cell growth and remarkably abrogated tumor burden in a HGBL-DHL-xenografted mouse model. The synergistic lethality of CS2164 and venetoclax in HGBL-DHL cells was associated with induction of DNA damage and impairment of DNA repair ability. Of importance, the combined treatment almost abolished the expression of both BCL2 and MYC, two hallmark proteins of HGBL-DHL, and substantially blunted the activity of PI3K/AKT/mTOR signaling cascade. In addition, MCL1 and BCL-XL, two well-characterized contributors for venetoclax resistance, were significantly lessened in the presence of CS2164 and venetoclax, thus leading to the accumulation of proapoptotic proteins BAX and PUMA and then initiating the intrinsic apoptosis pathway. Taken together, these findings suggest that the regimen of CS2164 and venetoclax is highly effective to eliminate HGBL-DHL cells in the preclinical setting, warranting further clinical investigations of this regimen for the treatment of unfavorable HGBL-DHL patients.
  • Thumbnail Image
    ItemOpen Access
    Functional elastic hydrogel as recyclable membrane for the adsorption and degradation of methylene blue.
    (PloS one, 2014-01) Bao, Song; Wu, Dongbei; Wang, Qigang; Su, Teng
    Developing the application of high-strength hydrogels has gained much attention in the fields of medical, pharmacy, and pollutant removal due to their versatility and stimulus-responsive properties. In this presentation, a high-strength freestanding elastic hydrogel membrane was constructed by clay nanosheets, N, N-dimethylacrylamide and 2-acrylamide-2-methylpropanesulfonic acid for adsorption of methylene blue and heavy metal ions. The maximum values of elongation and Young's modulus for 0.5% AMPSNa hydrogel were 1901% and 949.4 kPa, respectively, much higher than those of traditional hydrogels. The adsorptions were confirmed to follow pseudo-second kinetic equation and Langmuir isotherm model fits the data well. The maximum adsorption capacity of hydrogel towards methylene blue was 434.8 mg g(-1). The hydrogel also exhibited higher separation selectivity to Pb(2+) than Cu(2+). The methylene blue adsorbed onto the hydrogel membrane can be photocatalytically degraded by Fenton agent and the hydrogel membrane could be recycled at least five times without obvious loss in mechanical properties. In conclusion, this presentation demonstrates a convenient strategy to prepare tough and elastic clay nanocomposite hydrogel, which can not only be applied as recyclable membrane for the photocatalytic degradation of organic dye, but also for the recovery of valuables.
  • Thumbnail Image
    ItemOpen Access
    Implementation of regional Acute Stroke Care Map increases thrombolysis rates for acute ischaemic stroke in Chinese urban area in only 3 months.
    (Stroke and vascular neurology, 2020-09-24) Sui, Yi; Luo, Jianfeng; Dong, Chunyao; Zheng, Liqiang; Zhao, Weijin; Zhang, Yao; Xian, Ying; Zheng, Huaguang; Yan, Bernard; Parsons, Mark; Ren, Li; Xiao, Ying; Zhu, Haoyue; Ren, Lijie; Fang, Qi; Yang, Yi; Liu, Weidong; Xu, Bing
    BACKGROUND:The rate of intravenous thrombolysis for acute ischaemic stroke remains low in China. We investigated whether the implementation of a citywide Acute Stroke Care Map (ASCaM) is associated with an improvement of acute stroke care quality in a Chinese urban area. METHODS:The ASCaM comprises 10 improvement strategies and has been implemented through a network consisting of 20 tertiary hospitals. We identified 7827 patients with ischaemic stroke admitted from April to October 2017, and 506 patients underwent thrombolysis were finally included for analysis. RESULTS:Compared with 'pre-ASCaM period', we observed an increased rate of administration of tissue plasminogen activator within 4.5 hours (65.4% vs 54.5%; adjusted OR, 1.724; 95% CI 1.21 to 2.45; p=0.003) during 'ASCaM period'. In multivariate analysis models, 'ASCaM period' was associated with a significant reduction in onset-to-door time (114.1±55.7 vs 135.7±58.4 min, p=0.0002) and onset-to-needle time (ONT) (169.2±58.1 vs 195.6±59.3 min, p<0.0001). Yet no change was found in door-to-needle time. Clinical outcomes such as symptomatic intracranial haemorrhage, favourable functional outcome (modified Rankin Scale ≤2) and in-hospital mortality remained unchanged. CONCLUSION:The implementation of ASCaM was significantly associated with increased rates of intravenous thrombolysis and shorter ONT. The ASCaM may, in proof-of-principle, serve as a model to reduce treatment delay and increase thrombolysis rates in Chinese urban areas and possibly other highly populated Asian regions.
  • Thumbnail Image
    ItemOpen Access
    PD-1/PD-L1 expression and interaction by automated quantitative immunofluorescent analysis show adverse prognostic impact in patients with diffuse large B-cell lymphoma having T-cell infiltration: a study from the International DLBCL Consortium Program.
    (Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2019-06) Li, Ling; Sun, Ruifang; Miao, Yi; Tran, Thai; Adams, Lisa; Roscoe, Nathan; Xu, Bing; Manyam, Ganiraju C; Tan, Xiaohong; Zhang, Hongwei; Xiao, Min; Tzankov, Alexandar; Visco, Carlo; Dybkaer, Karen; Bhagat, Govind; Tam, Wayne; Hsi, Eric D; van Krieken, J Han; You, Hua; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés JM; Møller, Michael B; Piris, Miguel A; Zhang, Mingzhi; Winter, Jane N; Medeiros, L Jeffrey; Rassidakis, George Z; Vaupel, Christine A; Li, Yong; Dakappagari, Naveen; Xu-Monette, Zijun Y; Young, Ken H
    Programmed cell death protein 1/programmed cell death protein ligand1 (PD-1/PD-L1) interaction is an important immune checkpoint targeted by anti-PD-1/PD-L1 immunotherapies. However, the observed prognostic significance of PD-1/PD-L1 expression in diffuse large B-cell lymphoma treated with the standard of care has been inconsistent and even contradictory. To clarify the prognostic role of PD-1/PD-L1 expression and interaction in diffuse large B-cell lymphoma, in this study we used 3-marker fluorescent multiplex immunohistochemistry and Automated Quantitative Analysis Technology to assess the CD3+, PD-L1+, and PD-1+CD3+ expression in diagnostic samples and PD-1/PD-L1 interaction as indicated by presence of PD-1+CD3+ cells in the vicinity of PD-L1+ cells, analyzed their prognostic effects in 414 patients with de novo diffuse large B-cell lymphoma, and examined whether PD-1/PD-L1 interaction is required for the prognostic role of PD-1+/PD-L1+ expression. We found that low T-cell tissue cellularity, tissue PD-L1+ expression (irrespective of cell types), PD-1+CD3+ expression, and PD-1/PD-L1 interaction showed hierarchical adverse prognostic effects in the study cohort. PD-1/PD-L1 interaction showed higher sensitivity and specificity than PD-1+ and PD-L1+ expression in predicting inferior prognosis in patients with high CD3+ tissue cellularity ("hot"/inflammatory tumors). However, both PD-1+ and PD-L1+ expression showed adverse prognostic effects independent of PD-1/PD-L1 interaction, and PD-1/PD-L1 interaction showed favorable prognostic effect in PD-L1+ patients without high CD3+ tissue cellularity. Macrophage function and tumor-cell MYC expression may contribute to the PD-1-independent adverse prognostic effect of PD-L1+ expression. In summary, low T-cell tissue cellularity has unfavorable prognostic impact in diffuse large B-cell lymphoma, and tissue PD-L1+ expression and T-cell-derived PD-1+ expression have significant adverse impact only in patients with high T-cell infiltration. PD-1/PD-L1 interaction in tissue is essential but not always responsible for the inhibitory effect of PD-L1+/PD-1+ expression. These results suggest the benefit of PD-1/PD-L1 blockade therapies only in patients with sufficient T-cell infiltration, and the potential of immunofluorescent assays and Automated Quantitative Analysis in the clinical assessment of PD-1/PD-L1 expression and interaction.
  • Thumbnail Image
    ItemOpen Access
    The Tsinghua-Lancet Commission on Healthy Cities in China: unlocking the power of cities for a healthy China.
    (Lancet (London, England), 2018-04-17) Yang, Jun; Siri, José G; Remais, Justin V; Cheng, Qu; Zhang, Han; Chan, Karen KY; Sun, Zhe; Zhao, Yuanyuan; Cong, Na; Li, Xueyan; Zhang, Wei; Bai, Yuqi; Bi, Jun; Cai, Wenjia; Chan, Emily YY; Chen, Wanqing; Fan, Weicheng; Fu, Hua; He, Jianqing; Huang, Hong; Ji, John S; Jia, Peng; Jiang, Xiaopeng; Kwan, Mei-Po; Li, Tianhong; Li, Xiguang; Liang, Song; Liang, Xiaofeng; Liang, Lu; Liu, Qiyong; Lu, Yongmei; Luo, Yong; Ma, Xiulian; Schwartländer, Bernhard; Shen, Zhiyong; Shi, Peijun; Su, Jing; Wu, Tinghai; Yang, Changhong; Yin, Yongyuan; Zhang, Qiang; Zhang, Yinping; Zhang, Yong; Xu, Bing; Gong, Peng