Browsing by Author "Wu, Jingjing"
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Item Open Access Efficacy and Safety of a Pegasparaginase-Based Chemotherapy Regimen vs an L-asparaginase-Based Chemotherapy Regimen for Newly Diagnosed Advanced Extranodal Natural Killer/T-Cell Lymphoma: A Randomized Clinical Trial.(JAMA oncology, 2022-06-16) Wang, Xinhua; Zhang, Lei; Liu, Xiangli; Li, Xin; Li, Ling; Fu, Xiaorui; Sun, Zhenchang; Wu, Jingjing; Zhang, Xudong; Yan, Jiaqin; Chang, Yu; Nan, Feifei; Zhou, Zhiyuan; Wu, Xiaolong; Tian, Li; Ma, Minrui; Li, Zhaoming; Yu, Hui; Zhu, Linan; Wang, Yingjun; Shi, Cunzhen; Feng, Xiaoyan; Li, Jiwei; Ding, Mengjie; Zhang, Jieming; Dong, Meng; Xue, Hongwei; Wang, Jinghua; Zou, Liqun; Su, Liping; Wu, Jianqiu; Liu, Lihong; Bao, Huizheng; Zhang, Liling; Guo, Yanzhen; Guo, Shuxia; Lu, Yi; Young, Ken H; Li, Wencai; Zhang, MingzhiImportance
The L-asparaginase-based SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen has shown higher response rates and survival benefit over an anthracycline-containing regimen. However, the safety profile was not satisfied. A well-tolerated regimen with promising efficacy is lacking.Objective
To compare the efficacy and safety of the DDGP (dexamethasone, cisplatin, gemcitabine, and pegaspargase) regimen with the SMILE regimen in newly diagnosed advanced-stage (III/IV) extranodal natural killer/T-cell lymphoma (ENKL).Design, setting, and participants
This was an open-label, multicenter, randomized clinical trial that took place across 12 participating hospitals in China from January 2011 to February 2019. Patients were eligible if they were 14 to 70 years old with newly diagnosed ENKL in stages III/IV and had an Eastern Cooperative Oncology Group performance status of 0 to 2. Eligible patients were evenly randomized to either the DDGP or SMILE group.Interventions
Patients in each group were treated with the assigned regimen every 21 days for 6 cycles.Main outcomes and measures
The primary end point was progression-free survival (PFS), and secondary end points included overall response rate and overall survival (OS). The adverse events between the DDGP and SMILE groups were compared.Results
Among the 87 randomized patients, 80 received treatment (40 in the DDGP group and 40 in the SMILE group); the median (IQR) age was 43 (12) years, and 51 (64%) were male. The baseline characteristics were similar between the groups. At a median follow-up of 41.5 months, the median PFS was not reached in the DDGP group vs 6.8 months in the SMILE group (HR, 0.42; 95% CI, 0.23-0.77; P = .004), and the median OS was not reached in the DDGP group vs 75.2 months in the SMILE group (HR, 0.41; 95% CI, 0.19-0.89, P = .02). The PFS rate at 3 years and OS rate at 5 years were higher in the DDGP group vs the SMILE group (3-year PFS, 56.6% vs 41.8%; 5-year OS, 74.3% vs 51.7%). The overall response rate was higher in the DDGP group than in the SMILE group (90.0% vs 60.0%; P = .002). Grade 3 and 4 hematologic toxic effects were more frequently reported in the SMILE group vs the DDGP group (leukopenia, 85.0% vs 62.5%; neutropenia, 85.0% vs 65.0%).Conclusions and relevance
In this randomized clinical trial, the DDGP regimen showed promising preliminary results for patients with newly diagnosed local advanced ENKL. A confirmation trial based on larger population is warranted.Trial registration
ClinicalTrials.gov Identifier: NCT01501149.Item Open Access Hospital distance, socioeconomic status, and timely treatment of ischemic stroke.(Neurology, 2019-08) Ader, Jeremy; Wu, Jingjing; Fonarow, Gregg C; Smith, Eric E; Shah, Shreyansh; Xian, Ying; Bhatt, Deepak L; Schwamm, Lee H; Reeves, Mathew J; Matsouaka, Roland A; Sheth, Kevin NOBJECTIVE:To determine whether lower socioeconomic status (SES) and longer home to hospital driving time are associated with reductions in tissue plasminogen activator (tPA) administration and timeliness of the treatment. METHODS:We conducted a retrospective observational study using data from the Get With The Guidelines-Stroke Registry (GWTG-Stroke) between January 2015 and March 2017. The study included 118,683 ischemic stroke patients age ≥18 who were transported by emergency medical services to one of 1,489 US hospitals. We defined each patient's SES based on zip code median household income. We calculated the driving time between each patient's home zip code and the hospital where he or she was treated using the Google Maps Directions Application Programing Interface. The primary outcomes were tPA administration and onset-to-arrival time (OTA). Outcomes were analyzed using hierarchical multivariable logistic regression models. RESULTS:SES was not associated with OTA (p = 0.31) or tPA administration (p = 0.47), but was associated with the secondary outcomes of onset-to-treatment time (OTT) (p = 0.0160) and in-hospital mortality (p = 0.0037), with higher SES associated with shorter OTT and lower in-hospital mortality. Driving time was associated with tPA administration (p < 0.001) and OTA (p < 0.0001), with lower odds of tPA (0.83, 0.79-0.88) and longer OTA (1.30, 1.24-1.35) in patients with the longest vs shortest driving time quartiles. Lower SES quintiles were associated with slightly longer driving time quartiles (p = 0.0029), but there was no interaction between the SES and driving time for either OTA (p = 0.1145) or tPA (p = 0.6103). CONCLUSIONS:Longer driving times were associated with lower odds of tPA administration and longer OTA; however, SES did not modify these associations.Item Open Access Innate αβ T Cells Mediate Antitumor Immunity by Orchestrating Immunogenic Macrophage Programming(Cancer Discovery, 2019-09-01) Hundeyin, Mautin; Kurz, Emma; Mishra, Ankita; Rossi, Juan Andres Kochen; Liudahl, Shannon M; Leis, Kenna R; Mehrotra, Harshita; Kim, Mirhee; Torres, Luisana E; Ogunsakin, Adesola; Link, Jason; Sears, Rosalie C; Sivagnanam, Shamilene; Goecks, Jeremy; Islam, KM Sadeq; Dolgalev, Igor; Savadkar, Shivraj; Wang, Wei; Aykut, Berk; Leinwand, Joshua; Diskin, Brian; Adam, Salma; Israr, Muhammad; Gelas, Maeliss; Lish, Justin; Chin, Kathryn; Farooq, Mohammad Saad; Wadowski, Benjamin; Wu, Jingjing; Shah, Suhagi; Adeegbe, Dennis O; Pushalkar, Smruti; Vasudevaraja, Varshini; Saxena, Deepak; Wong, Kwok-Kin; Coussens, Lisa M; Miller, GeorgeAbstract Unconventional T-lymphocyte populations are emerging as important regulators of tumor immunity. Despite this, the role of TCRαβ+CD4−CD8−NK1.1− innate αβ T cells (iαβT) in pancreatic ductal adenocarcinoma (PDA) has not been explored. We found that iαβTs represent ∼10% of T lymphocytes infiltrating PDA in mice and humans. Intratumoral iαβTs express a distinct T-cell receptor repertoire and profoundly immunogenic phenotype compared with their peripheral counterparts and conventional lymphocytes. iαβTs comprised ∼75% of the total intratumoral IL17+ cells. Moreover, iαβT-cell adoptive transfer is protective in both murine models of PDA and human organotypic systems. We show that iαβT cells induce a CCR5-dependent immunogenic macrophage reprogramming, thereby enabling marked CD4+ and CD8+ T-cell expansion/activation and tumor protection. Collectively, iαβTs govern fundamental intratumoral cross-talk between innate and adaptive immune populations and are attractive therapeutic targets. Significance: We found that iαβTs are a profoundly activated T-cell subset in PDA that slow tumor growth in murine and human models of disease. iαβTs induce a CCR5-dependent immunogenic tumor-associated macrophage program, T-cell activation and expansion, and should be considered as novel targets for immunotherapy. See related commentary by Banerjee et al., p. 1164. This article is highlighted in the In This Issue feature, p. 1143Item Open Access Real world effectiveness of warfarin among ischemic stroke patients with atrial fibrillation: observational analysis from Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study.(BMJ (Clinical research ed.), 2015-07-31) Xian, Ying; Wu, Jingjing; O'Brien, Emily C; Fonarow, Gregg C; Olson, DaiWai M; Schwamm, Lee H; Bhatt, Deepak L; Smith, Eric E; Suter, Robert E; Hannah, Deidre; Lindholm, Brianna; Maisch, Lesley; Greiner, Melissa A; Lytle, Barbara L; Pencina, Michael J; Peterson, Eric D; Hernandez, Adrian FTo examine the association between warfarin treatment and longitudinal outcomes after ischemic stroke in patients with atrial fibrillation in community practice.Observational study.Hospitals (n = 1487) participating in the Get With The Guidelines (GWTG)-Stroke program in the United States, from 2009 to 2011.12,552 warfarin naive atrial fibrillation patients admitted to hospital for ischemic stroke and treated with warfarin compared with no oral anticoagulant at discharge, linked to Medicare claims for longitudinal outcomes.Major adverse cardiovascular events (MACE) and home time, a patient centered outcomes measure defined as the total number of days free from institutional care after discharge. A propensity score inverse probability weighting method was used to account for all differences in observed characteristics between treatment groups.Among 12,552 survivors of stroke, 11,039 (88%) were treated with warfarin at discharge. Warfarin treated patients were slightly younger and less likely to have a history of previous stroke or coronary artery disease but had similar severity of stroke as measured by the National Institutes of Health Stroke Scale. Relative to those not treated, patients treated with warfarin had more days at home (as opposed to institutional care) during the two years after discharge (adjusted home time difference 47.6 days, 99% confidence interval 26.9 to 68.2). Patients discharged on warfarin treatment also had a reduced risk of MACE (adjusted hazard ratio 0.87, 99% confidence interval 0.78 to 0.98), all cause mortality (0.72, 0.63 to 0.84), and recurrent ischemic stroke (0.63, 0.48 to 0.83). These differences were consistent among clinically relevant subgroups by age, sex, stroke severity, and history of previous coronary artery disease and stroke.Among ischemic stroke patients with atrial fibrillation, warfarin treatment was associated with improved long term clinical outcomes and more days at home. Clinical trial registration Clinical trials NCT02146274.Item Open Access RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer(Cancer Cell, 2018-11) Wang, Wei; Marinis, Jill M; Beal, Allison M; Savadkar, Shivraj; Wu, Yue; Khan, Mohammed; Taunk, Pardeep S; Wu, Nan; Su, Wenyu; Wu, Jingjing; Ahsan, Aarif; Kurz, Emma; Chen, Ting; Yaboh, Inedouye; Li, Fei; Gutierrez, Johana; Diskin, Brian; Hundeyin, Mautin; Reilly, Michael; Lich, John D; Harris, Philip A; Mahajan, Mukesh K; Thorpe, James H; Nassau, Pamela; Mosley, Julie E; Leinwand, Joshua; Kochen Rossi, Juan A; Mishra, Ankita; Aykut, Berk; Glacken, Michael; Ochi, Atsuo; Verma, Narendra; Kim, Jacqueline I; Vasudevaraja, Varshini; Adeegbe, Dennis; Almonte, Christina; Bagdatlioglu, Ece; Cohen, Deirdre J; Wong, Kwok-Kin; Bertin, John; Miller, GeorgeItem Open Access γδ T Cells Promote Steatohepatitis by Orchestrating Innate and Adaptive Immune Programming(Hepatology, 2020-02) Torres‐Hernandez, Alejandro; Wang, Wei; Nikiforov, Yuri; Tejada, Karla; Torres, Luisana; Kalabin, Aleksandr; Adam, Salma; Wu, Jingjing; Lu, Lu; Chen, Ruonan; Lemmer, Aaron; Camargo, Jimmy; Hundeyin, Mautin; Diskin, Brian; Aykut, Berk; Kurz, Emma; Kochen Rossi, Juan A; Khan, Mohammed; Liria, Miguel; Sanchez, Gustavo; Wu, Nan; Su, Wenyu; Adams, Steven; Haq, Muhammad Israr Ul; Farooq, Mohammad Saad; Vasudevaraja, Varshini; Leinwand, Joshua; Miller, GeorgeBackground and Aims The recruitment and activation of inflammatory cells in the liver delineates the transition from hepatic steatosis to steatohepatitis (SH). Approach and Results We found that in SH, γδT cells are recruited to the liver by C‐C chemokine receptor (CCR) 2, CCR5, and nucleotide‐binding oligomerization domain‐containing protein 2 signaling and are skewed toward an interleukin (IL)‐17A+ phenotype in an inducible costimulator (ICOS)/ICOS ligand–dependent manner. γδT cells exhibit a distinct Vγ4+, PD1+, Ly6C+CD44+ phenotype in SH. Moreover, γδT cells up‐regulate both CD1d, which is necessary for lipid‐based antigens presentation, and the free fatty acid receptor, CD36. γδT cells are stimulated to express IL‐17A by palmitic acid and CD1d ligation. Deletion, depletion, and targeted interruption of γδT cell recruitment protects against diet‐induced SH and accelerates disease resolution. Conclusions We demonstrate that hepatic γδT cells exacerbate SH, independent of IL‐17 expression, by mitigating conventional CD4+ T‐cell expansion and modulating their inflammatory program by CD1d‐dependent vascular endothelial growth factor expression.