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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 | New genes emerging for colorectal cancer predisposition显示文摘Colorectal cancer(CRC)is one of the most frequent neoplasms and an important cause of mortality in the developed world.This cancer is caused by both genetic and environmental factors although 35%of the variation in CRC susceptibility involves inherited genetic differences.Mendelian syndromes account for about5%of the total burden of CRC,with Lynch syndrome and familial adenomatous polyposis the most common forms.Excluding hereditary forms,there is an important fraction of CRC cases that present familial aggregation for the disease with an unknown germline genetic cause.CRC can be also considered as a complex disease taking into account the common diseasecommom variant hypothesis with a polygenic model of inheritance where the genetic components of common complex diseases correspond mostly to variants of low/moderate effect.So far,30 common,low-penetrance susceptibility variants have been identified for CRC.Recently,new sequencing technologies including exomeand whole-genome sequencing have permitted to add a new approach to facilitate the identification of new genes responsible for human disease predisposition.By using whole-genome sequencing,germline mutations in the POLE and POLD1 genes have been found to be responsible for a new form of CRC genetic predisposition called polymerase proofreading-associated polyposis. | Clara Esteban-Jurado Pilar Garre Maria Vila Juan José Lozano Anna Pristoupilova Sergi Beltrán Anna Abulí Jenifer Muoz Francesc Balaguer Teresa Ocaa Antoni Castells Josep M Piqué Angel Carracedo Clara Ruiz-Ponte Xavier Bessa Montserrat Andreu Luis Bujanda Trinidad Caldés Sergi Castellví-Bel | 2014 | World Journal of Gastroenterology2014，20，8： | 3 |
| 3 | Liver fat deposition and mitochondrial dysfunction in morbid obesity:An approach combining metabolomics with liver imaging and histology显示文摘AIM: To explore the usefulness of magnetic resonance imaging(MRI) and spectroscopy(MRS) for assessment of non-alcoholic fat liver disease(NAFLD) as compared with liver histological and metabolomics findings. METHODS: Patients undergoing bariatric surgery following procedures involved in laparoscopic sleeve gastrectomy were recruited as a model of obesityinduced NAFLD in an observational, prospective, singlesite, cross-sectional study with a pre-set duration of 1 year. Relevant data were obtained prospectively and surrogates for inflammation, oxidative stress and lipid and glucose metabolism were obtained through standard laboratory measurements. To provide reliable data from MRI and MRS, novel procedures were designed to limit sampling variability and other sources of error using a 1.5T Signa HDx scanner and protocols acquired from the 3D or 2D Fat SAT FIESTA prescription manager. We used our previously described 1H NMRbased metabolomics assays. Data were obtained immediately before surgery and after a 12-mo period including histology of the liver and measurement of metabolites. Values from 1H NMR spectra obtained after surgery were omitted due to technical limitations.RESULTS: MRI data showed excellent correlation with the concentration of liver triglycerides, other hepatic lipid components and the histological assessment, w h i c h e xc l u d e d t h e p r e s e n c e o f n o n-a l c o h o l i c steatohepatitis(NASH). MRI was sufficient to follow up NAFLD in obese patients undergoing bariatric surgery and data suggest usefulness in other clinical situations. The information provided by MRS replicated that obtained by MRI using the-CH3 peak(0.9 ppm), the-CH2- peak(1.3 ppm, mostly triglyceride) and the-CH=CH- peak(2.2 ppm). No patient depicted NASH. After surgery all patients significantly decreased their body weight and steatosis was virtually absent even in patients with previous severe disease. Improvement was also observed in the serum concentrations of selected variables. The most relevant findings using metabolomics indicate increased levels of triglyceride and monounsaturated fatty acids in severe steatosis but those results were accompanied by a significant depletion of diglycerides, polyunsaturated fatty acids, glucose-6-phosphate and the ATP/AMP ratio. Combined data indicated the coordinated action on mitochondrial fat oxidation and glucose transport activity and may support the consideration of NAFLD as a likely mitochondrial disease. This concept may helpto explain the dissociation between excess lipid storage in adipose tissue and NAFLD and may direct the search for plasma biomarkers and novel therapeutic strategies. A limitation of our study is that data were obtained in a relatively low number of patients.CONCLUSION: MRI is sufficient to stage NAFLD in obese patients and to assess the improvement after bariatric surgery. Other data were superfluous for this purpose. | Nahum Calvo Raúl Beltrán-Debón Esther Rodríguez-Gallego Anna Hernández-Aguilera Maria Guirro Roger Mariné-Casadó Lidón Millá Josep M Alegret Fàtima Sabench Daniel del Castillo María Vinaixa Miguelàngel Rodríguez Xavier Correig Roberto García-álvarez Javier A Menendez Jordi Camps Jorge Joven | 2015 | World Journal of Gastroenterology2015，21，24： | 2 |
| 4 | Susceptibility Genetic Variants Associated With Colorectal Cancer Risk Correlate With Cancer Phenotype显示文摘 | Anna Abulí Xavier Bessa Juan Ramón González Clara Ruiz–Ponte Alejandro Cáceres Jenifer Mu?oz Victoria Gonzalo Francesc Balaguer Ceres Fernández–Rozadilla Dolors González Luisa de Castro Juan Clofent Luís Bujanda Joaquín Cubiella Josep M a Re?é Juan Diego | 2010 | Gastroenterology2010，，3： | 2 |
| 5 | Induction of macrophage nitric oxide production by gram-negative flagellin involves signaling via heteromeric Toll-like receptor 5/Toll-like receptor 4 complexes显示文摘 | MIZEL S B ANNA N H MARLENA A M | 2003 | The Journal of Immunology2003，170，： | 1 |
| 6 | Plasma Fatty Acid-Binding Protein 4 Increases with Renal Dysfunction in Type 2 Diabetic Patients without Microalbuminuria显示文摘 | Cabré Anna Lázaro Iolanda Girona Josefa Manzanares Josep M Marimón Francesc Plana Núria Heras Mercedes Masana Lluís | 2008 | Clinical Chemistry2008，，1： | 1 |
| 7 | Structure and correlations of the flux line lattice in crystalline Nb through the peak effect显示文摘 | Gammel P L Yaron U Ramirez A P Bishop D J Chang A M Ruel R Pfeiffer L N Bucher E D'Anna G Huse D A Mortensen K Eskildsen M R Kes P H | | 0，，： | 1 |
| 8 | Effects of mood stabilizers on DNA damage in an animal model of mania 显示文摘 | Andreazza A C Kauer-Sant'Anna M Frey B N | 2008 | J Psychiatry Neurosci2008，33，6： | 1 |
| 9 | Platelet factor 4 limits Th17 differentiation and cardiac allograft rejection显示文摘 | Shi Guanfang Field David J Ko Kyung-ae Ture Sara Srivastava Kalyan Levy Scott Kowalska M Anna Poncz Mortimer Fowell Deborah J Morrell Craig N | 2014 | Journal of Clinical Investigation2014，，： | 1 |
| 10 | Biological Signatures of Asymptomatic Extra- and Intracranial Atherosclerosis: The Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) Study显示文摘 | Elena López-Cancio Amparo Galán Laura Dorado Marta Jiménez María Hernández Mónica Millán Silvia Reverté Anna Su?ol Jaume Barallat Anna Massuet Maria Teresa Alzamora Antonio Dávalos Juan Francisco Arenillas | 2012 | Stroke2012，，10： | 1 |
| 11 | Unintentional changes of defence traits in GM trees can influence plant-herbivore interactions显示文摘 | Joakim Hj(a)ltén Anna Lindau Anders Wennstr(o)m | 2007 | Basic and Applied Ecology2007，8，5： | 1 |
| 12 | PIAS proteins as roprossors of Oct4 function显示文摘 | Elena T Anna M Vladimir N | 2007 | J Mol Biol2007，374，： | 1 |
| 13 | A nongradient based algorithm for the determination of surface tension from a pendant drop:Application to low Bond number drop shapes显示文摘 | ALVAREZ N J WALKER L M ANNA S L | | 0，，2： | 1 |
| 14 | Twist and snail expression in pharyngeal squamous cell carcinoma stroma is related to cancer progression显示文摘 | Anna J M Mervi N M Ylermi S | 2011 | BMC Cancer2011，11，： | 1 |
| 15 | Constitutive expression of transgenes encoding derivatives of the synthetic antimicrobial peptide BP100: impact on rice host plant fitness显示文摘 | Anna N Mafia M Nuri C | 2012 | BMC Plant Biology2012，12，： | 1 |
| 16 | The effect of exercise and nettle supplementation on oxidative stress markers in the rat brain显示文摘 | Anna Toldy Krisztián Stadler Mária Sasvári Judit Jakus Kyung J. Jung Hae Y. Chung István Berkes Csaba Nyakas Zsolt Radák | 2005 | Brain Research Bulletin2005，，6： | 1 |
| 17 | A comparison of the non - essential elements cadmium, mercury and lead found in fish and sediment from Alaska and California 显示文摘 | JAMES P M DON W E ANNA N K | 2005 | Sci Total Environ2005，339，： | 1 |
| 18 | Global supply chain network dynamics with multicriteria decision-making under risk and uncertainty显示文摘 | Anna N Dmytro M | 2005 | Transportation Research Part E : Logistics and Transportation Review2005，41，6： | 1 |
| 19 | On the application of a membrane air-liquid contactor for air dehumidification显示文摘 | Carlo I Enrico N Anna M | 1997 | Energy and Buildings1997，25，3： | 1 |
| 20 | Comparison of antioxidant activities of onion and garlic extracts by inhibi-tion of lipid peroxidation and radical scavenging activity显示文摘 | Anna M N Riitta P P Marjukka A | 2003 | Food Chemistry2003，81，： | 1 |
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