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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 | Hepatic expression and cellular distribution of the glucose transporter family显示文摘Glucose and other carbohydrates are transported into cells using members of a family of integral membrane glucose transporter (GLUT) molecules. To date 14 members of this family, also called the solute carrier 2A proteins have been identified which are divided on the basis of transport characteristics and sequence similarities into several families (Classes 1 to 3). The expression of these different receptor subtypes varies between different species, tissues and cellular subtypes and each has differential sensitivities to stimuli such as insulin. The liver is a contributor to metabolic carbohydrate homeostasis and is a major site for synthesis, storage and redistribution of carbohydrates. Situations in which the balance of glucose homeostasis is upset such as diabetes or the metabolic syndrome can lead metabolic disturbances that drive chronic organ damage and failure, confirming the importance of understanding the molecular regulation of hepatic glucose homeostasis. There is a considerable literature describing the expression and function of receptors that regulate glucose uptake and release by hepatocytes, the most import cells in glucose regulation and glycogen storage. However there is less appreciation of the roles of GLUTs expressed by non parenchymal cell types within the liver, all of which require carbohydrate to function. A better understanding of the detailed cellular distribution of GLUTs in human liver tissue may shed light on mechanisms underlying disease pathogenesis. This review summarises the available literature on hepatocellular expression of GLUTs in health and disease and highlights areas where further investigation is required. | Sumera Karim David H Adams Patricia F Lalor | 2012 | World Journal of Gastroenterology2012，18，46： | 5 |
| 3 | Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer cells reveals novel therapeutic targeting strategies显示文摘在地岬基因的 Oncogenic 变化在人的癌症是很普通的,导致有描绘得好的选择优点,而且不太听说得好的危险的房间。我们执行了一幅大规模 loss-of-function 屏幕识别被转变 KRAS 的结肠癌房间,然而并非由缺乏这 oncogene 的衍生物要求的基因。最高得分的基因然后在 KRAS 变异、野类型的癌症房间的一块更大的面板被测试。表示 oncogenic KRAS 的癌症房间被发现高度依赖于抄写因素 GATA2 和 DNA 复制开始管理者 CDC6。与已知的目标用许多药扩大这分析,我们发现有变异的 KRAS 的癌症房间与 topoisomerase 抑制显示出选择嗜好到 proteasome 功能,以及合成致命性。联合指向引起的这些功能改善了相对野类型的房间 KRAS 变异的房间杀死。这些观察建议新奇目标和在地岬变异的癌症为最佳的效果联合存在治疗的新方法,它传统地被看作对治疗高度倔强。 | Michael Steckel Miriam Molina-Arcas Britta Weigelt Michaela Marani Patricia H Warne Hanna Kuznetsov Gavin Kelly Becky Saunders Michael Howell Julian Downward David C Hancock | 2012 | Cell Research2012，22，8： | 5 |
| 4 | Safety and Efficacy of Antigen-Specific Regulatory T-Cell Therapy for Patients With Refractory Crohn’s Disease显示文摘 | Pierre Desreumaux Arnaud Foussat Matthieu Allez Laurent Beaugerie Xavier Hébuterne Yoram Bouhnik Maria Nachury Valérie Brun Hervé Bastian Nathalie Belmonte Michel Ticchioni Agnès Duchange Patricia Morel–Mandrino Virginie Neveu Nathalie Clerget–Chossat Mig | 2012 | Gastroenterology2012，，5： | 4 |
| 5 | Concentration and chemical composition of PM 2.5 in Shanghai for a 1-year period显示文摘 | Boming Ye Xueli Ji Haizhen Yang Xiaohong Yao Chak K Chan Steven H Cadle Tai Chan Patricia A Mulawa | 2002 | Atmospheric Environment2002，，4： | 2 |
| 6 | LIGHT, a New Member of the TNF Superfamily, and Lymphotoxin α Are Ligands for Herpesvirus Entry Mediator显示文摘 | Davide N Mauri Reinhard Ebner Rebecca I Montgomery Kristine D Kochel Timothy C Cheung Guo-Liang Yu Steve Ruben Marianne Murphy Roselyn J Eisenberg Gary H Cohen Patricia G Spear Carl F Ware | 1998 | Immunity1998，，： | 1 |
| 7 | Variations in microbial community composition through two soil depth profiles显示文摘 | NOAH F JOSHUA P S PATRICIA A H | 2003 | Soil Biol Biochem2003，35，1： | 1 |
| 8 | Casts of Aporrectodea caliginosa (Savigny) and Lumbricus rubellus (Hoffmeister) differ in microbial activity,nutrient availability and aggregate stability显示文摘 | Richard J H Patricia M F Jacqueline E P | 2003 | Pedobiologia2003，47，： | 1 |
| 9 | Large-scale HCV RNA screening in first time blood donors: the first step towards genomic screening of blood donations显示文摘 | Juraj P Patricia H John B | 1999 | Vox Sang1999，76，3： | 1 |
| 10 | Variations in microbial communitycomposition through two soil depth profiles显示文摘 | NOAH F JOSHUA P S PATRICIA A H | 2003 | Soil Biology and Biochemistry2003，35，1： | 1 |
| 11 | Improved technique for pancreatic MRI:value of oblique fat suppression imaging with oral barium administration显示文摘 | Thomas H Patricia J Mergo CS | 1998 | JCAT1998，22，8： | 1 |
| 12 | Training pharmacy workers in recognition,management,and prevention of STDs:district-randomized controlled trial显示文摘 | PATRICIA G JAMES H CESAR C | 2003 | Bull WHO2003，81，11： | 1 |
| 13 | Pituitary Adenylate Cyclase Activating Polypeptide (PACAP)Reduces Food Intake in Mice 显示文摘 | Morley J E Michael H Patricia M | 1992 | Peptides1992，13，： | 1 |
| 14 | An overview of the functionality of expolysaccharides produced by lactic acid bacteria显示文摘 | PATRICIA R M JEROEN H PIETERNELA Z | 2002 | International Dairy Journal2002，12，： | 1 |
| 15 | Nitrate in drinking water and the incidence of gastric,esophageal,and brain cancerin Yorkshire,England显示文摘 | Jennifer H B Roger C P Patricia A M | 1998 | Cancer Causes and Control1998，，9： | 1 |
| 16 | Tumor angiogensis and tissue factor expression during hepatocellular carcinoma progression in a transgenic mouse mode显示文摘 | Evelyhe D Patricia H Ande V | 2003 | J Hepatol2003，38，6： | 1 |
| 17 | In vitro proliferation,expansion,and differentiation of a CD34^+ cell-enriched Hematopoietic cell population from human umbilical cord blood in response to recombinant cytokines显示文摘 | Patricia FG Margarita RT Mayani H | 2002 | Archi Med Rese2002，33，： | 1 |
| 18 | Changes in glutathione S-transferase activity in DDT resistant natural Mexican populations of Anopheles albimanus under different insecticide resistance management strategies显示文摘 | Patricia R P Américo D R Janet H | 2006 | Pesticide Biochemistry and Physiology2006，86，2： | 1 |
| 19 | Management's view stock splits 显示文摘 | Baker H K Patricia L G | 1980 | Financial Management1980，9，2： | 1 |
| 20 | Variations in microbialcommunity composition through two soil depth profiles显示文摘 | Noah F Joshua P S Patricia A H | 2003 | Soil Biology and Biochemistry2003，35，16： | 1 |
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