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1帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh 2021中华肿瘤防治杂志2021,28,24:49
2CaMKII in cerebral ischemia显示文摘神经原上的 Ischemic 侮辱触发引起 Ca 导致 neuronal 房间死亡(excitotoxicity ) 的 2+ 超载的过多的、病理学的 glutamate 版本。Ca 2+/calmodulin (凸轮) 依赖者蛋白质 kinase II (CaMKII ) 是位于 neuronal 粘性下面并且学习的生理的有刺激性的 glutamate 信号的一个主要调停人。Glutamate 刺激在 T286 触发 CaMKII 的 autophosphorylation,使 kinase 成为 “ 的一个过程; autonomous”(从 Ca 2+ 刺激的部分活跃的独立人士) 并且那为 synaptic 的形式被要求粘性。最近的研究为侮辱以后的 neuroprotection 作为潜在的药目标也建议了自治 CaMKII 活动,在在 neuronal 文化的 glutamate 侮辱以后并且在在 vivo 的焦点的服的局部缺血以后。然而, CaMKII 和凸轮 kinase 家庭的另外的成员在 neuronal 死亡和幸存的规定被含有。这里,我们在 excitotoxicity 和服的局部缺血讨论过去的调查结果和凸轮 kinase 功能的可能的机制,与 CaMKII 和它的规定的一个焦点。Steven J COULTRAP Rebekah S VEST Nicole M ASHPOLE Andy HUDMON K Ulrich BAYEF 2011Acta Pharmacologica Sinica2011,32,7:6
3Mycophenolate mofetil for maintenance of remission in steroid-dependent autoimmune pancreatitis显示文摘Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis.For steroid-dependent disease,azathioprine has been used for maintenance of remission.Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis;however,there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis.A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil,which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production.Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events.The patient was managed without a biliary stent.However,there was a return of symptoms,jaundice,increase in transaminases,and hyperbilirubinemia when the prednisone dose reached 11 mg per day.In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis,the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events,but it did not enable discontinuation of the steroids.Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.Jamie B Sodikoff Steven A Keilin Sheila J Bharmal Melinda M Lewis Gottumukkala S Raju Field F Willingham 2012World Journal of Gastroenterology2012,18,18:6
4The use of ultrasonic cleaning for ultrafiltration membranes in the dairy industry显示文摘S Muthukumaran K Yang A Seuren S Kentish M Ashokkumar G.W Stevens F Grieser 2004Separation and Purification Technology2004,,1:2
5Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma显示文摘This report describes a patient that developed recurrent metastatic hepatocellular carcinoma(HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed.Michael L Caparelli Nathan J Roberts Timothy S Braverman Robert M Stevens Edward R Broun Shyam Allamaneni 2016World Journal of Hepatology2016,8,23:2
6Complete genomes of two clinical Staphylococcus aureus strains:evidence for the rapid evolution of virulence and drug resistance显示文摘Holden MT Feil EJ Lindsay JA Peacock SJ Day NP Enright MC Foster TJ Moore CE Hurst L Atkin R Barron A Bason N Bentley SD Chillingworth C Chillingworth T Churcher C Clark L Corton C Cronin A Doggett J Dowd L Feltwell T Hance Z Harris B Hauser H Holroyd S Jagels K James KD Lennard N Line A Mayes R Moule S Mungall K Ormond D Quail MA Rabbinowitsch E Rutherford K Sanders M Sharp S Simmonds M Stevens K Whitehead S Barrell BG Spratt BG Parkhill J 2004Proc Natl Acad Sci USA2004,101,26:1
7Stigma: the feelings and experiences of 46 people with mental illness 显示文摘Dinos S Stevens S Serfaty M 2004British Journal of Psychiatry2004,184,6:1
8Polyethylene wear debris and long-term clinical failure of the Charite disc prosthesis: A study of 4 patients 显示文摘Andre V O Steven M Filip S 2007Spine2007,32,2:1
9The potential of brain natriunetic peptide as a biomarker for New York Heart Association class during the outpatient treatment of heart failure 显示文摘Lee S C Stevens T L Sandberg S M 2002J Card Fail2002,8,3:1
10The potential of brain natriuretic peptide as a biomarker for New York Heart Association class during the out patient treatment of heart failure显示文摘Lee SC Stevens T L Sandberg S M 2002J Card Fail2002,8,3:1
11Pattern of liver enzyme elevations in acute ST - elevation myocardial in- farction显示文摘LOFTHUS D M STEVENS S R ARMSTRONG P W 2012Coron Artery Dis2012,23,1:1
12Immune and pathologic responses in mice infected with Brucella abortus 19, RB51, or 2308 显示文摘Stevens M G Olsen S C Pugh G W 1994Infec Immunity1994,62,:1
13The proto- toxin lynxl acts on nicotinic acetylcholine receptors to balance neuronal activity and survival in vivo显示文摘Miwa J M Stevens T R King S L 2006Neu- ron2006,51,5:1
14Process requirements for achieving full-flow disinfection of recirculating water using ozonation and UV irradiation 显示文摘STEVEN T S MARK J S SCOTT M T 2009Aquacuhural Engineering2009,40,1:1
15Comparison of immune responses and resistance to Brucellosis in mice vaccinated with Brucella abortus 19 or RB51 显示文摘Stevens M G Olsen S C Pugh G W 1995Infect Immun1995,63,:1
16Comparison of the gravimetric,phenol red, and 14C-PEG-3350 methods to determine water absorption in the rat single-pass intestinal perfusion model显示文摘Steven C S Rinaldi M T Vukovinsky K E 2001AAPS Pharm Sci2001,3,3:1
17Channel of distribution profits when channel members form conjectures显示文摘Jeuland A P Steven M S 1988Marketing Science1988,7,2:1
18Negative pressure wound therapy:a vacuum of evidence?显示文摘Steven G Marc M Stefan S 2008Arch Surg2008,143,2:1
19Adaptive Tracking of Multiple Hot-spot IR Images显示文摘Peter S M Steven K R 1983IEEE Trans1983,28,10:1
20Partial mediation of glucocorticoid antiproliferative effects by lipocortins 显示文摘ALMAWI W Y SAOUDA M S STEVENS A C 1996J Lmmunol1996,157,12:1
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