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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 | Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model显示文摘AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase(ALT); aspartate aminotransferase and alkaline phosphatase(AP)] were found. In vitro, the administration of IL-1β resulted in a significant increase in HSC proliferation [0.94 ± 0.72 arbitrary units(A.U.) in untreated controls, 1.12 ± 0.80 A.U. at an IL-1β concentration of 0.1 ng/m L and 1.18 ± 0.73 A.U. at an IL-1β concentration of 1 ng/m L in samples from n = 6 donor animals; P < 0.001; analyses of variance(ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 μg/m L Anakinra(0.81 ± 0.60 A.U. in untreated controls, 0.92 ± 0.68 A.U. at an IL-1β concentration of 0.1 ng/m L, and 0.91 ± 0.69 A.U. at an IL-1β concentration of 1 ng/m L; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyprolinecontent, liver serum tests(ALT and AP) and profibrotic(collagen 1α1, collagen 1α2, transforming growth factor-β, and TIMP-1) and anti-fibrotic [matrix metalloproteinase 2(MMP2), MMP9 and MMP13 ] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1β and F4/80 m RNA expression levels were unaffected by Anakinra treatment.CONCLUSION: IL-1β expression is associated with the degree of liver fibrosis in Abcb4^(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4^(-/-) mice. | Florian P Reiter Ralf Wimmer Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk | 2016 | World Journal of Hepatology2016，8，8： | 3 |
| 3 | Studies and characterisations of various activated carbons used for carbon/carbon supercapacitors显示文摘 | J Gamby P.L Taberna P Simon J.F Fauvarque M Chesneau | 2001 | Journal of Power Sources2001，，1： | 3 |
| 4 | Risk-adjustment in hepatobiliarypancreatic surgery显示文摘AIM: The present study evaluates the performance of the POSSUM, the American Society of Anesthetists (ASA),APACHE and Childs classification in predicting mortality and morbidity in hepatopancreaticobiliary (HPB) surgery.We describe especially the limitations and advantages of risk in stratifying the patients.METHODS: We investigated 177 randomly chosen patients undergoing eledive complex HPB surgery in a single institution with a total of 71 pre-operative and intra-operative risk factors.Primary endpoint was in-hospital mortality and morbidity.Ordered logistic regression analysis was used to identify individual predictors of operative morbidity and mortality.RESULTS: The operative mortality in the series was 3.95% .This compared well with the p-POSSUM and APACHE predicted mortality of 4.31% and 4.29% respectively. Postoperative complications amounted to 45% with 24 (13.6%)patients having a major adverse event. On multivariate analysis the pre-operative POSSUM physiological score (OR = 1.18,P = 0.009) was superior in predicting complications compared to the ASA (P = 0.108), APACHE (P = 0.117)or Childs classification (P = 0.136). In addition, serum sodium, creatinine, international normalized ratio (INR),pulse rate, and intra-operative blood loss were independent risk factors. A combination of the POSSUM variables and INR offered the optimal combination of risk factors for risk prognostication in HPB surgery.CONCLUSION: Morbidity for elective HPB surgery can be accurately predicted and applied in everyday surgical practice as an adjunct in the process of informed consent and for effective allocation of resources for intensive and high-dependency care facilities. | Hemant M Kocher Paris P Tekkis Palepu Gopal Ameet G Patel Simon Cottam Irving S Benjamin | 2005 | World Journal of Gastroenterology2005，11，16： | 3 |
| 5 | 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 |
| 6 | Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial显示文摘 | Usha Chakravarthy Simon P Harding Chris A Rogers Susan M Downes Andrew J Lotery Lucy A Culliford Barnaby C Reeves | 2013 | The Lancet2013，，： | 2 |
| 7 | 3-Hydroxybenzo pyrene in the urine of smokers and non-smokers显示文摘 | Lafontaine M Champmartin C Simon P | 2006 | Toxicol Lett2006，162，23： | 1 |
| 8 | Diversity of G proteins in signal transduction显示文摘 | SIMON M I STRATHMANN P GAUTAN N | 1991 | Science1991，252，： | 1 |
| 9 | Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepatitisB using HBsAg and HBV DNA levels 显示文摘 | Rijckborst V Hansen BE Cakaloglu Y Ferenci P Tabak F Akdogan M Simon K Akarca US Flisiak R Verhey E Van Vuuren AJ Boucher CA ter Borg MJ Janssen HL | 2010 | Hepatology2010，52，2： | 1 |
| 10 | Locked nailing for the treat- ment of displaced articular fractures of the calcaneus:description of a new procedure with caJcanail显示文摘 | Goldzak M Mittlmeier T Simon P | 2012 | Eur J Orthop Surg Trauma- tol2012，22，： | 1 |
| 11 | Limitation of lowland riverine bacterioplankton by dissolved organic carbon and inorgan- ic nutrients显示文摘 | Douglas P Simon M Ryan M D | 2010 | Hydrobiologia2010，652，： | 1 |
| 12 | Estimation of the Effective Permeability in Magnetorheological Fluids 显示文摘 | Simon M Reitich F Jolly M P | 1999 | Journal of Intelligent Material Systems and Structures1999，10，11： | 1 |
| 13 | Goα12 and Goα3 subunits define a fourth class of G protein a subunits 显示文摘 | Strathmann M P Simon M I | 1991 | Proc Natl Acad Sci U S A1991，88，13： | 1 |
| 14 | Symmetry-based re- sistance as a novel means of lower limb rehabilitation 显示文摘 | Simon A M Brent G R Ferris D P | 2007 | Journal of Biomechanics2007，40，6： | 1 |
| 15 | Outcomed and clinicopa thologic variables associated with late recurrence after nephrectomy fkr localiged Renal cell carcinoma显示文摘 | SIMON P K CHRISTOPHER J M BRADLEY C L | 2011 | Urology2011，78，5： | 1 |
| 16 | Lithium insertion into host materials: the key to success for Li ion batteries显示文摘 | Broussely M Bieusan P Simon B | 1999 | Electrochimica Acta1999，45，7： | 1 |
| 17 | Alteration of the quality of milk by expression of sheep beta-lactoglobulin in transgenic mice显示文摘 | Simons J P McClenaghan M Clark A J | 1987 | Nature1987，328，： | 1 |
| 18 | Acute changes inblood-CSF barrier permselectivity to serum proteins afterintrathecal methotrexate and CNS irradiation显示文摘 | Livrea P Trojano M Simone IL | 1985 | J Neu-rol1985，231，6： | 1 |
| 19 | Mechanisms of ischemic brain damage 显示文摘 | Doyle K P Simon R P Stenzel-Poore M P | 2008 | Neurophannacology2008，55，3： | 1 |
| 20 | A Benthic community index for streams in the northern lakes and forests ecoregion 显示文摘 | Butcher J T Stewar P M Simon T P | 2003 | Ecological Indicators2003，3，3： | 1 |
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