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| 1 | 帕博利珠单抗治疗伴脑转移NSCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析显示文摘背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NSCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNS)中的疗效。中期结果已发表,现报道对NSCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NSCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)<2分。患者每2周接受一次帕博利珠单抗(10 mg/kg)治疗。队列1为程序性死亡配体1(programmed cell death ligand 1,PD-L1)≥1%的患者,队列2为PD-L1<1%或未评估的患者。主要终点是脑转移患者缓解比例。所有经治患者均纳入疗效与安全性终点的分析。该研究已结束入组,并于Clinicaltrials.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NSCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NSCLC合并CNS转移。 | Sarah B GOLDBERG Kurt A SCHALPER Scott N GETTINGER Amit MAHAJAN Roy S HERBST Anne C CHANG Rogerio LILENBAUM Frederick H WILSON Sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRSH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对) | 2021 | 中国肺癌杂志2021，24，9： | 34 |
| 2 | Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales显示文摘 | C.P Wilkinson Frederick L Ferris Ronald E Klein Paul P Lee Carl David Agardh Matthew Davis Diana Dills Anselm Kampik R Pararajasegaram Juan T Verdaguer | 2003 | Ophthalmology2003，，9： | 4 |
| 3 | Rheumatoid arthritis显示文摘 | David L Scott Frederick Wolfe Tom WJ Huizinga | 2010 | The Lancet2010，，9746： | 3 |
| 4 | Serelaxin increases the antifibrotic action of rosiglitazone in a model of hepatic fibrosis显示文摘AIM To determine the effect of combined serelaxin and rosiglitazone treatment on established hepatic fibrosis.METHODS Hepatic fibrosis was induced in mice by carbon tetrachloride administration for 6 wk, or vehicle alone(nonfibrotic mice). For the final 2 wk, mice were treated with rosiglitazone, serelaxin, or both rosiglitazone and serelaxin. Serum liver enzymes and relaxin levels were determined by standard methods. The degree of liver collagen content was determined by histology and immunohistochemistry. Expression of type?Ⅰ?collagen was determined by quantitative PCR. Activation of hepatic stellate cells was assessed by alpha-smoothmuscle actin(SMA) levels. Liver peroxisome proliferator activated receptor-gamma coactivator 1 alpha(PGC1α) was determined by Western blotting.RESULTS Treatment of mice with CCl4 resulted in hepatic fibrosis as evidenced by increased liver enzyme levels(ALT and AST), and increased liver collagen and SMA. Monotherapy with either serelaxin or rosiglitazone for 2 wk was generally without effect. In contrast, the combination of serelaxin and rosiglitazone resulted in significantly improved ALT levels(P < 0.05). Total liver collagen content as determined by Sirius red staining revealed that only combination treatment was effective in reducing total liver collagen(P < 0.05). These results were supported by immunohistochemistry for type?Ⅰ?collagen, in which only combination treatment reduced fibrillar collagen levels(P < 0.05). The level of hepatic stellate cell activation was modestly, but significantly, reduced by serelaxin treatment alone, but combination treatment resulted in significantly lower SMA levels. Finally, while hepatic fibrosis reduced liver PGC1α levels, the combination of serelaxin and rosiglitazone resulted in restoration of PGC1α protein levels.CONCLUSION The combination of serelaxin and rosiglitazone treatment for 2 wk was effective in significantly reducing established hepatic fibrosis, providing a potential new treatment strategy. | Robert G Bennett Ronda L Simpson Frederick G Hamel | 2017 | World Journal of Gastroenterology2017，23，22： | 2 |
| 5 | The prevalence and etiology of elevated aminotransferase levels in the United States显示文摘 | Jeanne M Clark Frederick L Brancati Anna Mae Diehl | 2003 | The American Journal of Gastroenterology2003，，5： | 2 |
| 6 | The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system显示文摘 | Sandrine Funes Joseph A Hedrick Galya Vassileva Lisa Markowitz Susan Abbondanzo Andrei Golovko Shijun Yang Frederick J Monsma Eric L Gustafson | 2003 | Biochemical and Biophysical Research Communications2003，，： | 2 |
| 7 | Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales显示文摘 | C.P Wilkinson Frederick L Ferris Ronald E Klein Paul P Lee Carl David Agardh Matthew Davis Diana Dills Anselm Kampik R Pararajasegaram Juan T Verdaguer | 2003 | Ophthalmology2003，，9： | 2 |
| 8 | Soil moisture: A central and unifying theme in physical geography显示文摘 | Legates David R Mahmood Rezaul Levia Delphis F DeLiberty Tracy L Quiring Steven M Houser Chris Nelson Frederick E | 2011 | Progress in Physical Geography2011，，1： | 2 |
| 9 | Interleukin- 6 in theinjured patient 显示文摘 | Emest E Frederick A | 1996 | AnnSurg1996，224，： | 1 |
| 10 | Structura1 comparison of anticancer drug- DNA complexes:adriamycin and daunomycin显示文摘 | Wi11iams L D Ughetto G | 1990 | Biochemistry1990，29，10： | 1 |
| 11 | RNA interference gene therapy in dominant retinitis pigmentosa and cone-rod dystrophy mouse models caused by GCAP1 mutations显示文摘 | Jiang L Frederick JM Baehr W | 2014 | Front Mol Neurosci2014，7，： | 1 |
| 12 | Matrix met- alloproteinase-10 is a critical effector of protein kinase Ciota- Par6alpha-mediated lung cancer显示文摘 | Frederick LA Matthews JA Jamieson L | 2008 | Oncogene2008，27，35： | 1 |
| 13 | Pregnancy-associated plasma protein-A(PAPP-A)and cardiovascularrisk显示文摘 | Consuegra-Sanchez L Fredericks S Kaski JC | 2009 | Atherosclerosis2009，203，2： | 1 |
| 14 | Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas显示文摘 | Frederick L Wang XY Eley G | | 0，，05： | 1 |
| 15 | Free radicals显示文摘 | Frederick V L | 1993 | Clinical Chemistry1993，65，12： | 1 |
| 16 | What is IgG4? A review of the biology of a unique immunoglobulin subtype显示文摘 | Ajay Nirula Scott M Glaser Susan L Kalled Frederick R Taylora | 2011 | Current Opinion in Rheumatology2011，，1： | 1 |
| 17 | Safety and effectiveness of insulin pump the rapy in children and adolescents with type 1 diabetes显示文摘 | Leslie P Plontnick Loretta M Clark Frederick L | 2003 | Diabetes Care2003，26，： | 1 |
| 18 | The information content of the auditor's going concern evaluation 显示文摘 | Jones Frederick L | 1996 | Journal of Accounting and Public Policy1996，1，： | 1 |
| 19 | Microvascu- lar anastomotic coupler assessment in head and neck recon- struction 显示文摘 | Frederick J W Sweeny L Carroll W R | 2013 | Otolaryngol Head Neck Surg2013，149，： | 1 |
| 20 | A computerized method of visual acuity testing显示文摘 | Roy W Beck Pamela S Moke Andrew H Turpin Frederick L Ferris John Paul SanGiovanni Chris A Johnson Eileen E Birch Danielle L Chandler Terry A Cox R.Clifford Blair Raymond T Kraker | 2003 | American Journal of Ophthalmology2003，，2： | 1 |
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