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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 | The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine显示文摘Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological roles.These roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ systems.Disruptions of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP proteins.Although it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs.The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of BMP9.Furthermore,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism.This review aims to summarize our current understanding of BMP9 across biology and the body. | Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu Rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid | 2019 | Genes & Diseases2019，6，3： | 15 |
| 3 | Expression and release of IL-29 by mast cells and modulation of mast cell behavior by IL-29显示文摘 | He, S Zhang, H Chen, H Yang, H Huang, T Chen, Y Lin, J Wang, F Chen, X Li, TL Yang, P | 2010 | 南京医科大学学报(自然科学版)2010，30，11： | 6 |
| 4 | Studies on solid-solid phase transition of polyols by infrared spectroscopy 显示文摘 | Feng H Y Liu X D He S M | 2000 | Thermochim Acta2000，348，： | 2 |
| 5 | Transeseterification kinetics of soybean oil for production of biodiesel in supereritical methanol显示文摘 | He H Y Sun S Y Wang T | 2007 | Journal of the American Oil Chemists''Society2007，84，4： | 1 |
| 6 | Reduction of lean NOX by ethanol over Ag/Al2O3 catalysts in the presence of H2O and SO2 显示文摘 | Saito M He H | 1998 | Catalysis Letters1998，50，12： | 1 |
| 7 | Investigation of composition and microstructure effect on fracture behaviour of tungsten heavy alloys显示文摘 | Islam S H Qu X He X | 2007 | Powder Metallurgy2007，50，1： | 1 |
| 8 | Thermal stability of recorded information at high densities显示文摘 | Charap S H Lu P L He Y J | 1997 | IEEE Trans Magn1997，33，1： | 1 |
| 9 | Induction of release and up - regulated gene expression of interleukin (IL) -8 in A549 cells by serine pro- teinases显示文摘 | Wang H Zheng Y He S | 2006 | BMC Cell Biol2006，15，7： | 1 |
| 10 | Apoptosis induction by the glucocorticoid hormone dexamethasone and the calcium-ATPase inhibitor thapsigargin involves Bcl-2 regulated,caspase activation显示文摘 | McColl K S He H Zhong H | 1998 | Molecular and Cellular Endocrinology1998，139，12： | 1 |
| 11 | Effects of epitopes com-bination and adjuvants on immune responses to anti-Alzhei-mer disease DNA vaccines in mice显示文摘 | HE Y SUN S H CHEN R W | 2005 | Alzheimer Dis AssocDisord2005，19，4： | 1 |
| 12 | Mechanical properties of single crystal tungsten microwhiskers characterized by nanoindentation 显示文摘 | HUANG H WU Y Q WANG S L HE Y H ZOU J HUANG B Y LIU C T | 2009 | Materials Science and Engeering A2009，53，12： | 1 |
| 13 | Endogenous amino acid loss at the terminal ileum of rats fed water-extractable or alkali-extractable soluble non-starch polysaccharides obtained from wheat bran when fed with and without xylanase显示文摘 | HE Y H LU W Q PIAO X S | 2006 | Journal of Animal and Veterinary Advances2006，5，8： | 1 |
| 14 | Sol-Gel Synthesis and char- acterization of ytterbium silicate powders显示文摘 | Wen H Dong S He P | 2007 | Journal of the American Ceramic Society2007，90，： | 1 |
| 15 | Single-crystal- line sodium-doped p-type ZnO and ZnMgO nanowires via eombination of thin-film and nano techniques 显示文摘 | HE H P LIN S S YUAN G D | 2011 | Jour- nal of Physical Chemistry: C2011，115，39： | 1 |
| 16 | Critical output - capacitor ESR for the stability of V2 controlled buck converter in CCM and DCM 显示文摘 | Zhou G H He S Z Zhang X | 2014 | Electronics Letters2014，50，12： | 1 |
| 17 | Microangiopathic haemolytic anaemia in metastasizing malignant tumours is not associated with a severe deficiency of the yon Willebrand factor- cleaving protease显示文摘 | Fontana S Gerritsen HE Kremer H J | 2001 | Br J Haematol2001，113，1： | 1 |
| 18 | The TIL commissioning and performance显示文摘 | X Zhang W Zheng X Wei F Jing Z Sui K Zheng Q Xu X Yuan X Jiang L Yang P Ma M Li J Wang D Hu S He F Li Z Peng B Feng H Zhou L Guo X Li X Zhang J Su Q Zhu H Yu R Zhao C Ma H He D Fan W Zhang | 2008 | Journal of Physics: Conference Series2008，，3： | 1 |
| 19 | Continuous Production of Biodiesel Fuel from Vegetable Oil Using Supercritical Methanol Process 显示文摘 | He H Y Wang T Zhu S L | 2006 | Fuel2006，7，35： | 1 |
| 20 | Continuous Production of Biodiesel Fuel from Vegetable Oil Using Supercritical Methanol Process 显示文摘 | He H Y Wang T Zhu S L | 2007 | Fuel2007，86，3： | 1 |
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