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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 | Immune checkpoint inhibitor-related hepatotoxicity:A review显示文摘The application of immune checkpoint inhibitors(ICI)in advanced cancer has been a major development in the last decade.The indications for ICIs are constantly expanding into new territory across different cancers,disease stages and lines of therapy.With this increased use,adverse events including immune checkpoint inhibitor-related hepatotoxicity(ICH)have emerged as an important clinical problem.This along with the introduction of ICI as first-and second-line treatments for advanced hepatocellular carcinoma makes ICH very relevant to gastroenterologists and hepatologists.The incidence of ICH varies between 1%-20%depending on the number,type and dose of ICI received.Investigation and management generally involve excluding differential diagnoses and following a stepwise escalation of withholding or ceasing ICI,corticosteroid treatment and adding other immunosuppressive agents depending on the severity of toxicity.The majority of patients with ICH recover and some may even safely recommence ICI therapy.Guideline recommendations are largely based on evidence derived from retrospective case series which highlights a priority for future research. | Devika Remash David S Prince Catriona McKenzie Simone I Strasser Steven Kao Ken Liu | 2021 | World Journal of Gastroenterology2021，27，32： | 9 |
| 3 | BCL2 inhibits cell adhesion, spreading, and motility by enhancing actin polymerization显示文摘BCL2 最好作为多功能的 anti-apoptotic 蛋白质被知道。然而,很少在房间粘合剂和活动性事件对它的角色被知道。这里,我们证明 BCL2 可以在房间粘附的规定起一个作用,传播,并且活动性。BCL2 什么时候是在有教养的鼠科、人的房间线,传播的房间,粘附,和活动性的 overexpressed,被损害。与这些结果一致, Bcl2 的损失导致了在 Bcl2 空的老鼠观察的更高的活动性与野类型相比的胚胎的成纤维细胞(MEF ) 房间。房间粘附和活动性的 BCL2 规定的机制可以包含包含 BCL2,肌动朊,和 gelsolin 的建筑群的形成,它看起来机能上地减少 gelsolin 的切断的活动。我们观察到从 overexpressed BCL2 提高了的 MCF-7 和 NIH3T3 房间的 lysate 肌动朊聚合在在 vitro 试金没有房间。BCL2 和 F 肌动朊的共焦的 immunofluorescent 本地化在一致地传播期间证明 BCL2 的那增加的表情导致了增加的 F 肌动朊聚合。因此, BCL2 和 gelsolin 建筑群的形成(它可能包含另外的蛋白质) 看起来在房间粘附和移植的规定起一个关键作用。与癌症转移给房间活动性的确定的关联,这结果可以解释在一些肿瘤房间类型的 BCL2 的表示为什么为转移减少潜力并且与改进耐心的预后被联系。 | Hengning Ke Vandy I Parron Jeff Reece Jennifer Y Zhang Steven K Akiyama John E French | 2010 | Cell Research2010，20，4： | 3 |
| 4 | Community-level physiological profiles of bacteria and fungi: plate type and incubation temperature influences on contrasting soils显示文摘 | Aimée T Classen Sarah I Boyle Kristin E Haskins Steven T Overby Stephen C Hart | | FEMS Microbiology Ecology0，，： | 2 |
| 5 | Androgens and esophageal cancer: What do we know?显示文摘Significant disparities exist between genders for the development and progression of several gastrointestinal(GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatocellular cancers suggest a role for steroid sex hormones in regulation of GI carcinogenesis. Involvement of intrinsic gender-linked mechanisms is also possible for esophageal adenocarcinoma as its incidence is disproportionally high among men. However, the cause of the observed gender differences and the potential role of androgens in esophageal carcinogenesis remains unclear, even though the cancer-promoting role of androgen receptors(AR) shown in other cancers such as prostate and bladder suggests this aspect warrants exploration. Several studies have demonstrated expression of ARs in esophageal cancer. However, only one study has suggested a potential link between AR signaling and outcome- poorer prognosis. Two groups have analyzed data from cohorts with prostate cancer and one of these found a decreased incidence of esophageal squamous and adenocarcinoma after androgen deprivation therapy. However, very limited information is available about the effects of androgen and AR-initiated signaling on esophageal cancer cell growth in vitro and in vivo. Possible mechanisms for androgens/AR involvement in the regulation of esophageal cancer growth are considered, and the potential use of AR as a prognostic factor and clinical target is highlighted, although insufficient evidence is available to support clinical trials of novel therapies. As esophageal adenocarcinoma is a gender linked cancer with a large male predominance further studies are warranted to clarify the role of androgens and ARs in shaping intracellular signaling and genomic responses in esophageal cancer. | Olga A Sukocheva Bin Li Steven L Due Damian J Hussey David I Watson | 2015 | World Journal of Gastroenterology2015，21，20： | 2 |
| 6 | Pancreatic cancer显示文摘 | Theresa Pluth Yeo Ralph H Hruban Steven D Leach Robb E Wilentz Taylor A Sohn Scott E Kern Christine A Iacobuzio-Donahue Anirban Maitra Michael Goggins Marcia I Canto Ross A Abrams Daniel Laheru Elizabeth M Jaffee Manuel Hidalgo Charles J Yeo | 2002 | Current Problems in Cancer2002，，4： | 2 |
| 7 | Thyroid carcinoma显示文摘 | Steven I Sherma | 2003 | The Lancet2003，，9356： | 2 |
| 8 | Differential expression of brain proteins in glycogen synthase kinase-3 transgenic mice:a proteomics point of view 显示文摘 | Stevens I Spittaels K | 2002 | Proteomics2002，2，1： | 1 |
| 9 | Transvaginal laparoscopically assisted endoscopic choIecystectomy:a hybrid approach to natural orilice surgery显示文摘 | Bessler M Stevens PD M i lone L | 2007 | Gastrointest Endosc2007，66，6： | 1 |
| 10 | Effect of climate conditions and plant developmental stage on the stability of antibodies expressed in transgenic tobacco 显示文摘 | Stevens LH Stoopen GM Elbers I J | 2000 | Plant Physiol2000，124，1： | 1 |
| 11 | Chitosan as antimicrobial agent: applications and mode of action 显示文摘 | Rabea E I Badawy M E T Stevens C V | 2003 | Biomacromolecules2003，4，： | 1 |
| 12 | Renal cell carcinoma显示文摘 | Brian I Rini Steven C Campbell Bernard Escudier | 2009 | The Lancet2009，，9669： | 1 |
| 13 | Intreduction to Building Projection-based Tiled Display Systems显示文摘 | M Hereld I R Judson R L Stevens | 2000 | IEEE Computer Graphics and Applications2000，20，4： | 1 |
| 14 | Chitosan as antimicrobial agent:applications and mode of action 显示文摘 | Rabea E I Badawy M E T Stevens C V | 2003 | Biomacromolecules2003，24，： | 1 |
| 15 | Does a latitudinal gradient in seedling survival favour larger seeds in the tropics显示文摘 | Moles A T Warton D I Stevens R D | 2004 | Ecology Letters2004，7，： | 1 |
| 16 | An effectiveness model of liquid-desiccant system heat/mass exchangers显示文摘 | Stevens D I | 1989 | Solar energy1989，42，6： | 1 |
| 17 | The planktonic index of biotic integrity (P-IBI): an approach for assessing lake ecosystem health 显示文摘 | Douglas D Steven I Mohiuddin M | 2009 | Ecological Indicators2009，9，6： | 1 |
| 18 | Chitosan as antimicrobial agent: Applications and mode of action 显示文摘 | Rabea E I Badawy M E T Stevens C V | 2003 | Biomacromolecules2003，4，： | 1 |
| 19 | Inheritance of the waist-to-hip ratio in the national heart, lung, and blood institute family heart study 显示文摘 | FEITOSA M F BORECKI I STEVEN C | 2000 | Obesity Research2000，8，： | 1 |
| 20 | An effectiveness mo-del of liquid-desiccant system heat / mass exchangers 显示文摘 | Stevens D I Braun J E Klein S A | 1989 | Solar Energy1989，42，6： | 1 |
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