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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 | Promoting metastasis: neutrophils and T cells join forces显示文摘 | Zvi G Fridlender Steven M Albelda Zvi Granot | 2015 | Cell Research2015，25，7： | 7 |
| 3 | Renal cell carcinoma: Evolving and emerging subtypes显示文摘Our knowledge of renal cell carcinoma(RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC. | Suzanne M Crumley Mukul Divatia Luan Truong Steven Shen Alberto G Ayala Jae Y Ro | 2013 | World Journal of Clinical Cases2013，1，9： | 7 |
| 4 | Ovarian autoimmune disease: clinical concepts and anima models显示文摘卵巢不是一个 immunologically 给予优惠的机关,但是在为卵巢特定的抗原的 tolerogenic 机制的一个故障在生育力上有灾难性的后果在里面女人,和这在自体免疫的疾病的鼠科的模型被复制。孤立的卵巢的自体免疫的疾病在女人是稀罕的,由于疾病和无能到的严厉可能播送越过代授与卵巢的疾病的基因信息。尽管如此,自体免疫的卵巢炎经常与另外的自体免疫的疾病联合被观察,特别地自体免疫的肾的疾病,并且在社会和单个健康上拿使用费。在老鼠的研究揭示了保护卵巢免受自体免疫的攻击的伤害的至少二机制。这些机制为自体免疫的管理者(亚耳河) 由导出胸腺的规章的 T 房间,以及一个角色包括 autoreactive T 房间的控制,在髓的 thymic 导致限制织物的抗原的表示的一个 transcriptional 管理者上皮的房间在 T 房间的开发期间。尽管后者机制不完全地被定义,也的失败导致自体免疫调停指向和卵巢的滤泡的弄空,这很好被建立。在这评论,我们将探讨自体免疫调停的临床的特征和后果在女人的卵巢的不孕,以及由动物揭示了的疾病的可能的机制当模特儿。 | Bryce D Warren William K Kinsey Lynda K McGinnis Lane K Christenson Susmita Jasti Anne M Stevens Brian K Petroff Margaret G Petroff | 2014 | Cellular & Molecular Immunology2014，11，6： | 3 |
| 5 | Clinical classification of symptomatic heterotopic pancreas of the stomach and duodenum:A case series and systematic literature review显示文摘BACKGROUND Heterotopic pancreas(HP)is an aberrant anatomic malformation that occurs most commonly in the upper gastrointestinal tract.While the majority of heterotopic pancreatic lesions are asymptomatic,many manifest severe clinical symptoms which require surgical or endoscopic intervention.Understanding of the clinical manifestations and symptoms of HP is limited due to the lack of large volume studies in the literature.The purpose of this study is to review symptomatic cases at a single center and compare these to a systematic review of the literature in order to characterize common clinical manifestations and treatment of this disease.AIM To classify the common clinical manifestations of heterotopic pancreas.METHODS A retrospective review was conducted of pathologic samples containing heterotopic pancreas from 2000-2018.Review was limited to HP of the upper gastrointestinal tract due to the frequency of presentation in this location.Symptomatic patients were identified from review of the medical records and clinical symptoms were tabulated.These were compared to a systematic review of the literature utilizing Pub Med and Embase searches for papers pertaining to heterotopic pancreas.Publications describing symptomatic presentation of HP were selected for review.Information including demographics,symptoms,presentation and treatment were compiled and analyzed.RESULTS Twenty-nine patient were identified with HP at a single center,with six of these identified has having clinical symptoms.Clinical manifestations included,gastrointestinal bleeding,gastric ulceration with/without perforation,pancreatitis,and gastric outlet obstruction.Systemic review of the literature yielded 232 publications detailing symptomatic cases with only 20 studies describing ten or more patients.Single and multi-patient studies were combined to form a cohort of 934 symptomatic patients.The majority of patients presented with abdominal pain(67%)combined with one of the following clinical categories:(1)Dyspepsia,(n=445,48%);(2)Pancreatitis(n=260,28%);(3)Gastrointestinal bleeding(n=80,9%);and(4)Gastric outlet obstruction(n=80,9%).The majority of cases(n=832,90%)underwent surgical or endoscopic resection with 85%reporting resolution or improvement in their symptoms.CONCLUSION Heterotopic pancreas can cause significant clinical symptoms in the upper gastrointestinal tract.Better understanding and classification of this disease may result in more accurate identification and treatment of this malformation. | Michael T Le Compte Brandon Mason Keenan J Robbins Motoyo Yano Deyali Chatterjee Ryan C Fields Steven M Strasberg William G Hawkins | 2022 | World Journal of Gastroenterology2022，28，14： | 3 |
| 6 | Cholangiocarcinoma, gone without the Wnt?显示文摘Cholangiocarcinoma(CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells. A recent study by Boulter et al implicates the Wnt signaling cascade in cholangiocarcinogenesis. Wnt ligands Wnt7 B and Wnt10 A were found to be highly overexpressed in human CCA tissue. Wnt7 B protein was present throughout the tumor stroma, and often co-localized with a subset of CD68+ macrophages. To address in a direct manner whether Wnt signaling is engaged in development of CCA, Boulter et al explored the Wnt signaling pathway in an experimental model that recapitulates the multi-stage progression of human CCA.Wnt ligands found to be elevated in human CCA were also upregulated during the course of CCA development following thioacetamide treatment. Wnt10 a increased during the(pre-cancerous) regenerative phase, while Wnt7 b induction paralleled tumor growth. Along with upregulation of target genes, the findings demonstrate that the canonical Wnt pathway is progressively activated during cholangio-carcinogenesis. Macrophage depletion,eliminating a major source of Wnt7 b, prevented activation of the canonical Wnt cascade, and resulted in reduced number and volume of tumors in this model. Moreover,specific inhibitors of the canonical Wnt pathway(ICG-001 and C-59) caused reduction of tumor area and number,in xenograft and thioacetamide models of CCA. The aggregated findings show that experimental, and presumably human CCA, is a Wnt-driven tumor. Modulation of Wnt signaling, alone or in combination with surgicalor chemotherapy approaches, holds promise in the management of this fatal malignancy. | Anne T R Noll Thorsten Cramer Steven W M Olde Damink Frank G Schaap | 2016 | World Journal of Hepatology2016，8，26： | 3 |
| 7 | Hepatocellular carcinoma after Iocoregional therapy:Magnetic resonance imaging findings in falsely negative exams显示文摘AIM:To elucidate causes for false negative magnetic resonance imaging(MRI)exams by identifying imaging characteristics that predict viable hepatocellular carcinoma(HCC)in lesions previously treated with locoregional therapy when obvious findings of recurrence are absent.METHODS:This retrospective institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study included patients who underwent liver transplantation at our center between 1/1/2000 and 12/31/2012 after being treated for HCC with locoregional therapy.All selected patients had a contrast-enhanced MRI after locoregional therapy within 90 d of transplant that was prospectively interpreted as without evidence of residual or recurrenttumor.Retrospectively,2 radiologists,blinded to clinica and pathological data,independently reviewed the pre transplant MRIs for 7 imaging features.Liver explan histopathology provided the reference standard,with clinically significant tumor defined as viable tumor≥1.0cm in maximum dimension.Fisher’s exact test was firs performed to identify significant imaging features.RESULTS:Inclusion criteria selected for 42 patients with 65 treated lesions.Fourteen of 42 patients(33%and 16 of 65 treated lesions(25%)had clinically significant viable tumor on explant histology.None o the 7 imaging findings examined could reliably and reproducibly determine which treated lesion had viable tumor when the exam had been prospectively read as without evidence of viable HCC.CONCLUSION:After locoregional therapy some treated lesions that do not demonstrate any MRI evidence o HCC will contain viable tumor.As such even patients with a negative MRI following treatment should receive regular short-term imaging surveillance because some have occult viable tumor.The possibility of occult tumo should be a consideration when contemplating any action which might delay liver transplant. | David Becker-Weidman Jesse M Civan Sandeep P Deshmukh Christopher G Roth Steven K Herrine Laurence Parker Donald G Mitchell | 2016 | World Journal of Hepatology2016，8，16： | 2 |
| 8 | Severe Hand, Foot, and Mouth Disease Associated with Coxsackievirus A6 - Alabama, Connecticut, California, and Nevada, November 201 1 - February 2012显示文摘 | McIntyre Mary G Stevens Kelly M Davidson Sherri Pippin Tina Magill Dagny Kulhanjian Julie A Kelly Daniel Greenhow Tara L Salas Maria L Yagi Shigeo Padilla Tasha Berumen Ricardo Glaser Carol Landry Marie Louise Lott Jason Chen Lei Paulson | 2012 | EN2012，，12： | 2 |
| 9 | Optimization of soil-adjusted vegetation indices显示文摘 | Rondeaux G Steven M Baret F | 1996 | Remote Sensing of Environment1996，55，2： | 1 |
| 10 | Acapripoxvirus detection PCR and antibody ELISA based on the major antigen P32, the homolog of the vaccinia virus H3L gene显示文摘 | Hdine H G Stevens M P FoordAJ | 1999 | Immunol Methods1999，227，12： | 1 |
| 11 | Evolutionary topology optimization for temperature reduction of heat conducting fields显示文摘 | Li Q Steven G P Xie Y M | 2004 | International Journal of Heat and Mass Transfer2004，47，23： | 1 |
| 12 | Kinetics and mechanisms of the low-temperature degradation of cellulose显示文摘 | Emsley A M Stevens G C | 1994 | Cellulose1994，1，1： | 1 |
| 13 | A capripoxvirus detection PCR and antibody ELISA based on the maior antigen P32, the homolog of the vaccinia virus H3L gene 显示文摘 | Heine H G Stevens M P Foord A J | 1999 | J Immune Meth1999，277，： | 1 |
| 14 | Evolutionary structural optimization(ESO)using a bi-directional algorithm显示文摘 | Steven G P Xie Y M | 1998 | Engi-neering Computation1998，15，8： | 1 |
| 15 | A simple evolutionary procedure for structural optimization显示文摘 | XIE Y M STEVEN G P | 1993 | Computers & Structures1993，49，5： | 1 |
| 16 | Surface modification of polymer surfaces: atmospheric plasma versus vacuum plasma treatments 显示文摘 | Shenton M J Stevens G C | 2001 | Journal of Physics D: Applied Physics2001，34，4： | 1 |
| 17 | A simple checkerboard suppression algorithm for evolutionary structural optimization 显示文摘 | Li O Steven G P Xie Y M | 2001 | Structural and Multidisciplinary Optimization2001，22，3： | 1 |
| 18 | A simple evolutionary procedure for structural optimization显示文摘 | Xie Y M Steven G P | 1993 | Computers and Structures1993，49，5： | 1 |
| 19 | A simple evolutionary procedure for structures optimization显示文摘 | XIE Y M STEVEN G P | 1993 | Comput Struet1993，49，： | 1 |
| 20 | A simple evolutionary procedure for structural optimization 显示文摘 | Xie Y M Steven G P | 1993 | Computers and Structures1993，49，5： | 1 |
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