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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 | It is safe to use transdermal glyceryl trinitrate to lower blood pressure in patients with acute ischaemic stroke with carotid stenosis显示文摘Background There is concern that blood pressure(BP)lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the presence of carotid stenosis.We assessed the effect of glyceryl trinitrate(GTN)in patients with carotid stenosis using data from the Efficacy of Nitric Oxide in Stroke(ENOS)Trial.Methods ENOS randomised 4011 patients with acute stroke and raised systolic BP(140-220 mm Hg)to transdermal GTN or no GTN within 48 hours of onset.Those on prestroke antihypertensives were also randomised to stop or continue their medication for 7 days.The primary outcome was the modified Rankin Scale(mRS)at day 90.Ipsilateral carotid stenosis was split:<30%;30-<50%;50-<70%;≥70%.Data are ORs with 95%CIs adjusted for baseline prognostic factors.results 2023(60.5%)ischaemic stroke participants had carotid imaging.As compared with<30%,≥70%ipsilateral stenosis was associated with an unfavourable shift in mRS(worse outcome)at 90 days(OR 1.88,95%CI 1.44 to 2.44,p<0.001).Those with≥70%stenosis who received GTN versus no GTN had a favourable shift in mRS(OR 0.56,95%CI 0.34 to 0.93,p=0.024).In those with 50-<70%stenosis,continuing versus stopping prestroke antihypertensives was associated with worse disability,mood,quality of life and cognition at 90 days.Clinical outcomes did not differ across bilateral stenosis groups.Conclusions Following ischaemic stroke,severe ipsilateral carotid stenosis is associated with worse functional outcome at 90 days.GTN appears safe in ipsilateral or bilateral carotid stenosis,and might improve outcome in severe ipsilateral carotid stenosis. | Jason P Appleton Lisa J Woodhouse Andrew Belcher Daniel Bereczki Eivind Berge Valeria Caso Hui Meng Chang Hanne K Christensen Ronan Collins John Gommans Ann C Laska George Ntaios Serefnur Ozturk Gillian M Sare Szabolcs Szatmari Yongjun Wang Joanna M Wardlaw Nikola Sprigg Philip M Bath for the ENOS investigators | 2019 | Stroke & Vascular Neurology2019，4，1： | 6 |
| 4 | Molecular markers(PECAM-1,ICAM-3,HLA-DR)determine prognosis in primary non-Hodgkin's gastric lymphoma patients显示文摘瞄准:与主要 non-Hodgkin 的胃的淋巴瘤在病人调查 PECAM-1, ICAM-3 和 HLA 医生抗原的预示的意义。方法:我们免疫组织化学地在 36 个 B 房间麦芽类型主要胃的淋巴瘤病人学习了 PECAM-1, ICAM-3 和 HLA 医生抗原表示。十非恶意并且十个健康胃的织物标本被用作控制。Clinicopathological 和幸存数据与染色的结果被相关。结果:HLA 医生抗原表示在 33 个胃的淋巴瘤病人(91.7%) 和 6 个非恶意的病人(54.5%) 被检测。PECAM-1 染色了 10 个病人(27.8%) 的肿瘤房间, 9 个病人(25%) 的 endothelial 并且煽动性有良性的胃的疾病的 4 个病人(40%) 渗入。ICAM-3 表示在 17 个病人(47.2%) 的肿瘤房间上被观察,当 5 个非恶意的病人(50%) 被染色时积极也。任何一个都没为任何学习的基因健康控制被染色。在里面多,变量分析, HLA 医生抗原和 PECAM-1 被证明是与联系的统计上重要的独立预示的因素一赞成并且不利预后分别地(P=0.009 和 P=0.003 ) 。在 univariate 分析, PECAM-1 (+)/ICAM-3 (-) 和 HLA 医生(-)/ICAM-3 (-) 病人与确切相反的基因表示模式与那些相比展出了显著地减少的全面幸存(P=0.0041 和 P=0.0091,分别地) 。是 HLA 医生(+)/ICAM-3 (+)/PECAM-1 (-)(n=8 ) 的那些病人让显著地更高的幸存与这个组(n=24 )(P=0.0289 ) 的其余部分相比评价。结论:PECAM-1, ICAM-3 和 HLA 医生分别地是肿瘤扩大潜力和主人免疫者监视的代表性的标记。他们的联合使用可以帮助我们识别能得益于更好攻击的治疗学的协议的高风险的病人。 | Alexander Darom Ilias P Gomatos Emmanuel Leandros Emmu Chatzigianni Dimitris Panousopoulos Manousos M Konstadoulakis George Androulakis | 2006 | World Journal of Gastroenterology2006，12，12： | 4 |
| 5 | RANKL/RANK control Brca1 mutation-driven mammary tumors显示文摘 | Verena Sig Kwadwo Owusu-Boaitey Puma A Joshi Anoop Kavirayani Gerald Wimsberger Maria Novatchkova Ivona Kozieradzki Daniel Schramek Nnamdi Edokobi Jerome Hersl Aishia Sampson Ashley Odai-Afotey Conxi Lazaro Eva Gonzalez-Suarez Miguel A Pujaaa for CIMBA Holger Heyn Enrique Vidal Jennifer Cru. ickshank Hal Berman Renu Sarao Melita Tieevic Iris Uribesalgo Luigi Tortola Shuan Rao Yen Tan Georg Pfeiler Eva YHP Lee Zsuzsanna Bago-Horvath Lukas Kenner Helmuth Popper Christian Singer Rama Khokha LaundeRe P Jones Josef M Penninger | 2016 | Cell Research2016，26，7： | 3 |
| 6 | Tumor necrosis factor-α-induced protein 1 and immunity to hepatitis B virus显示文摘AIM: To compare the gene expression profile in a pair of HBV-infected twins.METHODS: The gene expression profile was compared in a pair of HBV-infected twins.RESULTS: The twins displayed different disease outcomes. One acquired natural immunity against HBV,whereas the other became a chronic HBV carrier. Eightyeight and forty-six genes were found to be up- or downregulated in their PBMCs, respectively. Tumor necrosis factor-alpha-induced protein 1 (TNF-αIP1) that expressed at a higher level in the HBV-immune twins was identified and four pairs of siblings with HBV immunity by RTPCR. However, upon HBV core antigen stimulation,TNF-αIP1 was downregulated in PBMCs from subjects with immunity, whereas it was slightly upregulated in HBV carriers. Bioinformatics analysis revealed a K+channel tetramerization domain in TNF-αIP1 that shares a significant homology with some human, mouse, and C elegan proteins.CONCLUSION: TNF-αIP1 may play a role in the innate immunity against HBV. | Marie C Lin Nikki P Lee Ning Zheng Pai-Hao Yang Oscar G Wong Hsiang-Fu Kung Chee-Kin Hui John M Luk George Ka-Kit Lau | 2005 | World Journal of Gastroenterology2005，11，48： | 3 |
| 7 | Ordered Intermetallics显示文摘 | E P George M Yamaguchi K S Kumar C T Liu | 1994 | Annual Review of Materials Science1994，，： | 2 |
| 8 | Lung injury and acute respiratory distress syndrome after cardiopulmonary bypass显示文摘 | George Asimakopoulos Peter L.C Smith Chandana P Ratnatunga Kenneth M Taylor | 1999 | The Annals of Thoracic Surgery1999，，3： | 2 |
| 9 | 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 |
| 10 | A new steel slag for cement manufacture: Mineralogy and hydraulicity显示文摘 | Conjeaud M George C M Sorrentino F P | 1981 | Cement and Concrete Research1981，11，： | 1 |
| 11 | An integrated anal ytical approach for determining the origin of solid bitumens in the McArthur Basin,Northern Australia显示文摘 | George S C Llorca S M Hamilton P J | 1994 | Org Geochem1994，21，： | 1 |
| 12 | Colorectal carcinoma associated with serrated adenoma-prevalence, histological feathers and prognosis显示文摘 | Makinen M J George SM Jemvall P | 2001 | J Pathol2001，193，3： | 1 |
| 13 | The ecology of medical care revisited显示文摘 | Larry A Green George E Fryer Jr Barbara P Yawn David lanier Susan M Dovey | 2001 | The New England Journal of Medicine2001，334，26： | 1 |
| 14 | 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 |
| 15 | CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients显示文摘 | Savoldo Barbara Ramos Carlos Almeida Liu Enli Mims Martha P Keating Michael J Carrum George Kamble Rammurti T Bollard Catherine M Gee Adrian P Mei Zhuyong Liu Hao Grilley Bambi Rooney Cliona M Heslop Helen E Brenner Malcolm K Dotti Gianpie | 2011 | Journal of Clinical Investigation2011，，5： | 1 |
| 16 | The Innas hydraulic transformer: the key to the hydrostatic common pressure rail显示文摘 | Vael Georges E M Achten P A J Fu Zhao | 2000 | SAE2000，，01： | 1 |
| 17 | Measurement and modelling of the high power performance of carbon based supereapacitors 显示文摘 | Peter J M George L P Sarki M K | 2000 | J Power Sources2000，91，1： | 1 |
| 18 | Narrow molecular weight resins by a free-radical polymerization process显示文摘 | GEORGES M K VEREGIN R P N KAZMAIER P M | 1993 | Macromolecules1993，26，11： | 1 |
| 19 | Narrow molecular weight resins by a free-radical polymerization process显示文摘 | Georges M K Veregin R P N Kazmaizer P M ct al | 1993 | Macromolecules1993，26，： | 1 |
| 20 | The correlation of the indentation size effect measured with indenters of various shapes显示文摘 | Swadener J G George E P Pharr G M | 2002 | J Mech Phys Solids2002，50，4： | 1 |
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