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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 | miR-200 family expression is downregulated upon neoplastic progression of Barrett's esophagus显示文摘AIM: To investigate miR-200 family expression in Barrett's epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma. METHODS: Real-time reverse transcriptase-polymerase chain reaction was used to measure miR-200, ZEB1 and ZEB2 expression. Ingenuity Pathway Analysis of miR-200 targets was used to predict biological outcomes. RESULTS: Barrett's epithelium expressed lower levels of miR-141 and miR-200c than did gastric and duodenal epithelia (P < 0.001). In silico analysis indicated roles for the miR-200 family in molecular pathways that distinguish Barrett's epithelium from gastric and duodenalepithelia, and which control apoptosis and proliferation. All miR-200 members were downregulated in adenocarcinoma (P < 0.02), and miR-200c expression was also downregulated in non-invasive epithelium adjacent to adenocarcinoma (P < 0.02). The expression of all miR-200 members was lower in Barrett's epithelium derived high-grade dysplastic cell lines than in a cell line derived from benign Barrett's epithelium. We observed signif icant inverse correlations between miR-200 family expression and ZEB1 and ZEB2 expression in Barrett's epithelium and esophageal adenocarcinoma (P < 0.05). CONCLUSION: miR-200 expression might contribute to the anti-apoptotic and proliferative phenotype of Barrett's epithelium and regulate key neoplastic processes in this epithelium. | Cameron M Smith David I Watson Mary P Leong George C Mayne Michael Z Michael Bas PL Wijnhoven Damian J Hussey | 2011 | World Journal of Gastroenterology2011，17，8： | 13 |
| 3 | Prevalence of occult hepatitis B virus infection in haemodialysis patients from central Greece显示文摘AIM:To assess the hepatitis B virus(HBV)-DNA and the prevalence of occult HBV infection in end-stage renal failure(ESRF)patients from Central Greece. METHODS:Sera from 366 ESRF patients attending five out of six dialysis units from Central Greece were investigated for HBV-DNA by real-time polymerase chain reaction.Only serum samples with repeatedly detectable HBV-DNA were considered positive.IgG antibodies to hepatitis C virus(anti-HCV)were tested by a third generation enzyme linked immunosorbent assay(ELISA),while IgG antibodies to hepatitis E virus (anti-HEV)were tested by two commercially available ELISAs.RESULTS:HBV-DNA was detected in 15/366 patient (4.1%)and HBsAg in 20/366(5.5%).The prevalenc of occult HBV infection was 0.9%(3/346 HBsAg negative patients).Occult HBV was not associate with a specific marker of HBV infection or anti-HCV o anti-HEV reactivity.There was no significant differenc in HBV-DNA titres,demographic and biochemica features,between patients with occult HBV infectio and those with HBsAg-positive chronic HBV infection. CONCLUSION:In central Greece,4%of ESRF patient had detectable HBV-DNA,though in this setting,th prevalence of occult HBV seems to be very low(0.9%). | Paraskevi Mina Sarah P Georgiadou Christos Rizos George N Dalekos Eirini I Rigopoulou | 2010 | World Journal of Gastroenterology2010，16，2： | 8 |
| 4 | Use of enzymatic methods for rapid enumeration of coliforms in freshwaters 显示文摘 | George I Petit M Servais P | 2000 | Appl Environ Microbiol2000，88，： | 2 |
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| 6 | Pitfalls in the computed tomographic evaluation of the lumbar spine in disc disease显示文摘 | Braun I F Lin J P George A E | 1984 | Neuroradiology1984，26，1： | 1 |
| 7 | Labeling products of complete graphs with a condition at distance two显示文摘 | Georges J P Mauro D W Stein M I | 2001 | SIAM Jour- nal on Discrete Mathematics2001，14，1： | 1 |
| 8 | A Problem Generator-solver Heuristic for Vehicle Routing with Soft Time Windows 显示文摘 | GEORGE I MANOLIS K GREGORY P | 2003 | Omega2003，31，： | 1 |
| 9 | Microstructure,mechanical properties and wear of Ni-Al-Fe alloys显示文摘 | Munroe P R George M Baker I | 2002 | Mater Sci Eng A2002，325，12： | 1 |
| 10 | Redction and coordination of arsenic in Indian Mustard显示文摘 | Picketing I J Prince P C George M J | 2000 | Plant physiology2000，122，4： | 1 |
| 11 | Antigenic and genetic char- acteristics of swine - origin 2009 A( H1N1 ) influenza viruses cir- culating in humans 显示文摘 | Garten R J Davis C T Russell C A Shu B Lindstrom S Balish A Sessions W M Xu X Skepner E Deyde V Okomo - Adhi- ambo M Gubareva L Barnes J Smith C B Emery S L Hillman M J Rivailler P Smagala J de Graaf M Burke D F Fouchier R A Pappas E Alpuche - Aranda C M Lopez - Gatell H Ohvera H Lopez I Myers C A Faix D Blair P J Yu C Keene K M Dotson P D Jr Boxrud D Sambol A R Abid S H St George K Bannerman T Moore A L Stringer D J Blevins P Demmler - Harrison G J Ginsberg M Kriner P Waterman S Smole S Guevara H F Belongia E A Clark P A Beatrice S T Donis R Katz J Finelli L Bridges C B Shaw M Jernigan D B Uyeki T M Smith D J Klimov A I Cox N J | 2009 | Science2009，325，5937： | 1 |
| 12 | Microstructure, mechanical properties and wear of Ni-Al-Fe alloys 显示文摘 | Munroe P R George M Baker I | 2002 | Mater Sci Eng A (S0921- 5093 )2002，325，1： | 1 |
| 13 | Understanding emotional prosody activates right hemisphere regions显示文摘 | Parekh P I Rosinsky N | 1996 | Arch Neurol1996，53，： | 1 |
| 14 | Are Antidepressant Drugs That Combine Serotonergic and Noradrenergic Mechanisms of Action More Effective Than the Selective Serotonin Reuptake Inhibitors in Treating Major Depressive Disorder? A Meta-analysis of Studies of Newer Agents显示文摘 | George I P Michael ET Maurizio F | 2007 | Biol psychiatry2007，62，11： | 1 |
| 15 | Phase transitions and hygroscopic growth of aerosol particles containing humic acid and mixtures of humic acid and ammonium sulphate显示文摘 | BADGER C L GEORGE I GRIFFITHS P T | 2006 | Atmos Chem Phys2006，6，： | 1 |
| 16 | Labeling products of complete graphs with a condition at distance two显示文摘 | GEORGES J P MAURO D W STEIN M I | 2000 | SIAM J Discrete Math2000，14，1： | 1 |
| 17 | Involvement of estrogen receptors α and β in the regulation of cervical permeability显示文摘 | George I Gorodeski Dipika P A L | 2000 | Am J Physiol Cell Physio12000，278，： | 1 |
| 18 | Microstructure,mechanical properties and wear of NiAlFe alloys显示文摘 | MUNROE P R GEORGE M BAKER I KENNEDY F E | 2002 | Mater Sci Eng A2002，325，： | 1 |
| 19 | New and Selective Ryanodine Receptor Activators for Insect Control显示文摘 | GEORGE P CORDOVA I D JAMES D B | 2009 | Bioorgl Med Chem2009，7，12： | 1 |
| 20 | Labelling products of complete graphs with a condition at distance two显示文摘 | Georges J P Mauro D W Stein M I | 2001 | SIAM J Discrete Math2001，14，1： | 1 |
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