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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 |
| 2 | Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion显示文摘Ischaemia-reperfusion injury(IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells(LSEC). Recent evidence suggests that LSEC coordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion(NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI. | Yuri L Boteon Richard Laing Hynek Mergental Gary M Reynolds Darius F Mirza Simon C Afford Ricky H Bhogal | 2017 | World Journal of Gastroenterology2017，23，48： | 4 |
| 3 | 光动力疗法治疗非小细胞肺癌显示文摘光动力疗法被越来越多地应用于治疗胸部恶性肿瘤。对于早期非小细胞肺癌(如支气管腔内肺癌)、X线检查阴性或同时性原发癌,光动疗法可作为主要治疗手段进行腔内根治性治疗。作为单一根治疗法,光动力疗法是治疗支气管镜可见≤1 cm且无软骨外浸润的肺部肿瘤的最有效方法。对于晚期非小细胞癌患者,光动力治疗可以作为综合根治疗法的一部分,用于减轻阻塞性支气管内病变,增加可手术性或缩小所需手术范围。本文对现有发表的应用光动力疗法治疗至少10例以上非小细胞肺癌病例的研究文献进行综述,提出了光动力疗法应用的治疗建议并进行了总结。 | Charles B Simone II Joseph S Friedberg Eli Glatstein James P Stevenson Daniel H Sterman Stephen M Hahn Keith A Cengel 袁光金 李金銮 朱宇熹 凌扬 | 2013 | 国际病理科学与临床杂志2013，33，3： | 3 |
| 4 | Longterm multiple color imaging of live cells using quantum dot bioconjugates 显示文摘 | Jaiswal J K Mattoussi H Mauro J M Simon S F | 2003 | Nature Biotechnolgy2003，21，： | 1 |
| 5 | Emotion processing in three systems:The medium and the message显示文摘 | SIMONS R DETENBER B H ROEDEMA T M | 1999 | Psychophysiology1999，36，5： | 1 |
| 6 | Porous Cobalt(II)-organic frameworks with corrugated walls:structurally robust gas-sorption materials显示文摘 | Simon M H Chang J S Sung H J | 2007 | An-gew Chem Int Ed2007，46，12： | 1 |
| 7 | Electrochemical moderately boron doped diamond annealing 显示文摘 | Simon N Girard H Manesse M | 2008 | Diamond & Related preconditioning of electrodes : effect of Materials2008，17，710： | 1 |
| 8 | Long-term multiple color imaging of live cells using quantum dot bioconjugates显示文摘 | JAISWAL J K MATTOUSSI H D SIMON S M | 2003 | Nature Biotechnol2003，21，1： | 1 |
| 9 | Kinetics of Fe(III)and Mn(IV)reduction by the Black Sea strain of Shewanella putrefaciens using in situ solid state voltammetric Au/Hg electrodes显示文摘 | DOLLHOPF M E NEALSON K H SIMON D M | 2000 | Marine Chemistry2000，70，1： | 1 |
| 10 | Expression of vascular endothelial growth factor anditsreceptors in human renal ontogenesis and in adult kidney显示文摘 | Simon M Grone H J Johren O | | 0，，02： | 1 |
| 11 | Bacterioplankton dynamics in the Gulf of Aqaba and the northern Red Sea in early spring显示文摘 | GROSSART H P SIMON M | 2002 | Marine Ecology Progress Series2002，239，1： | 1 |
| 12 | Attention to television:Alpha power and its relationship to image motion and emotion显示文摘 | SIMONS R DETENBER B H ROEDEMA T M | 2003 | Media Psychology2003，5，3： | 1 |
| 13 | Water absorption and states of water in smicrystalline poly (vinyl alcohol ) films 显示文摘 | Hodge R M Edward G H Simon G P | 1996 | Polymer1996，37，： | 1 |
| 14 | Chronic subduraI hemaLoma, in a, duita, nd elderly pa, tients显示文摘 | Iantosca M E Simon R H | 2000 | Neurosurgery clinics of north America2000，11，5： | 1 |
| 15 | Expression of vascular endothelial growth factor and its receptors in human renal antogenesis and in adult kidney 显示文摘 | Simon M Grone H J Johren O | 1995 | Am J Physiol1995，268，22： | 1 |
| 16 | Neutral atmospheric delay in interferometric synthetic aperture radar applications: Statistical description and mitigation显示文摘 | Emardson T R Simons M Webb H F | 2003 | Journal of Geophysical Research2003，108，5： | 1 |
| 17 | Population, time allocation and human capital:a general equilibrium analysis for Canada 显示文摘 | Maxime F Simon H Jean M | 2009 | Economic Modelling2009，26，： | 1 |
| 18 | Influence of tomato genotype on growth of inoculated and indigenous bacteria in the spermosphere显示文摘 | SIMON H M SMITH K P DODSWORTH J A | 2001 | Applied and Environmental Microbiology2001，67，2： | 1 |
| 19 | Phylogeny of Proteobacteria and Bacteroidetes from oxic habitats of a tidal flat ecosystem 显示文摘 | Stevens H Stubner M Simon M | 2005 | FEMS Mierobiol Eeol2005，54，3： | 1 |
| 20 | Routine morphine infusion in preterm newborns who received ventilatory support:a randomized controlled trial 显示文摘 | Simons SH van Dijk M van Lingen RA Roofthooft D Duivenvoorden H J Jongeneel N | 2003 | JAMA2003，290，18： | 1 |
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