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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 | Procalcitonin,and cytokines document a dynamic inflammatory state in non-infected cirrhotic patients with ascites显示文摘AIM:To quantitate the simultaneous serum and ascitic fluid levels of procalcitonin and inflammatory markers in cirrhotics with and without ascites.METHODS:A total of 88 consecutive severe cirrhotic patients seen in a large city hospital liver clinic were studied and divided into two groups,those with and without ascites.Group 1 consisted of 41 cirrhotic patients with massive ascites,as demonstrated by necessity for therapeutic large-volume paracentesis.Group 2consisted of 47 cirrhotic patients without any clinically documented ascites to include either a recent abdominal computed tomography scan or ultrasound study.Serum and ascitic fluid levels of an array of inflammatory markers,including procalcitonin,were measured and compared to each other and a normal plasma panel(NPP).RESULTS:The values for inflammatory markers assayed in the serum of Groups 1 and 2,and ascitic fluid of the Group 1.The plasma levels of the inflammatory cytokines interleukin(IL)-2,IL-4,IL-6,IL-8,interferon gamma(IFNγ)and epidermal growth factor(EGF)were all significantly greater in the serum of Group 1as compared to that of the serum obtained from the Group 2 subjects(all P<0.05).There were significantly greater serum levels of IL-6,IL-8,IL-10,monocyte chemoattractant protein-1,tumor necrosis factor-α,vascular endothelial growth factor and EGF when comparing Group 2 to the NPP.There was no significant difference for IL-1A,IL-1B,IL-2,IL-4 and IFNγlevels between these two groups.Serum procalcitonin levels were increased in cirrhotics with ascites compared to cirrhotics without ascites,but serum levels were similar to ascites levels within the ascites group.Furthermore,many of these cytokines,but not procalcitonin,demonstrate an ascites-to-serum gradient.Serum procalcitonin does not demonstrate any significant difference segregated by liver etiology in the ascites group;but ascitic fluid procalcitonin is elevated significantly in car-diac cirrhosis/miscellaneous subgroup compared to the hepatitis C virus and alcoholic cirrhosis subgroups.CONCLUSION:Procalcitonin in the ascitic fluid,but not in the serum,differentiates between cirrhotic subgroup reflecting the dynamic interplay of ascites,bacterial translocation and the peri-peritoneal cytokine. | Bashar M Attar Christopher M Moore Magdalena George Nicolae Ion-Nedelcu Rafael Turbay Annamma Zachariah Guiliano Ramadori Jawed Fareed David H Van Thiel | 2014 | World Journal of Gastroenterology2014，20，9： | 4 |
| 3 | Disease dependent qualitative and quantitative differences in the inflammatory response to ascites occurring in cirrhotics显示文摘AIM:To assess differing patterns and levels of ascitic fluid cyctokine and growth factors exist between those with a high risk and low risk of spontaneous bacterial peritonitis(SBP). METHODS: A total of 57 consecutive patients with ascites requiring a large volume paracentesis were studied. Their age, gender, specific underlying disease conditions were recorded after a review of their clinical records. Each underwent a routine assessment prior to their paracentesis consisting of a complete blood count, complete metabolic profile and prothrombin time/international normalized ratio(INR) determination. The ascitic fluid was cultured and a complete cellcount and albumin determination was obtained on the fluid. In addition, blood and ascitic fluid was assessed for the levels of interleukin interleukin(IL)-1A, IL-1B, IL-2, IL-4, IL-8, IL-10, monocyte chemotactic protein(MCP)-1, tumor necrosis factor(TNF)-α, interferon(IFN)-γ, vascular endothelial growth factor(VEGF) and epidermal growth factor(EGF) utilizing the Randox Biochip platforms(Boston, MA). A serum-ascites gradient, for each cytokine and growth factor was calculated. The results are reported as mean ± SEM between disease groups with statistical analysis consisting of the student t-test(two tailed) with a P value of 0.05 defining significance. RESULTS: No clinically important demographic or biochemical differences between the 4 groups studied were evident. In contrast, marked difference in the cytokine and growth factors levels and pattern were evident between the 4 disease groups. Individuals with alcoholic cirrhosis had the highest levels of IL-1A, IL-1B, IL-4, IFNγ. Those with malignant disease had the highest levels of IL-2. Those with hepatitis C virus(HCV) associated cirrhosis had the highest value for IL-6, IL-8, IL-10, MCP-1 and VEGF. Those with cardiac disease had the highest level of TNF-α and EGF. The calculated serum- ascites gradients for the cardiac and malignant disease groups had a greater frequency of negative values signifying greater levels of IL-8, IL-10 and MCP-1 in ascites than did those with alcohol or HCV disease. CONCLUSION: These data document important differences in the cytokine and growth factor levels in plasma, ascitic fluid and the calculated plasma- ascites fluid gradients in cirrhotics requiring a large volume paracentesis. These differences may be important in determining the risk for bacterial peritonitis. | Bashar M Attar Magdalena George Nicolae Ion-Nedelcu Guilliano Ramadori David H Van Thiel | 2014 | World Journal of Hepatology2014，6，2： | 3 |
| 4 | Inhibition of hepatitis C virus replication by single-stranded RNA structural mimics显示文摘AIM: To examine the effect of hepatitis C virus (HCV) structural mimics of regulatory regions of the genome on HCV replication.METHODS: HCV RNA structural mimics were constructed and tested in a HCV genotype 1b aBB7 replicon,and a Japanese fulminant hepatitis-1 (JFH-1) HCV genotype 2a infection model.All sequences were computer-predicted to adopt stem-loop structures identical to the corresponding elements in full-length viral RNA.Huh7.5 cells bearing the BB7 replicon or infected with JFH-1 virus were transfected with expression vectors generating HCV mimics and controls.Cellular HCV RNA and protein levels were quantified by real-time polymerase chain reaction and Western blotting,respectively.To evaluate possible antisense effects,complementary RNAs spanning a mimic were prepared.RESULTS: In the BB7 genotype 1b replicon system,mimics of the polymerase (NS-5B),X and BA regions inhibited replication by more than 90%,50%,and 60%,respectively.In the JFH-1 genotype 2 infection system,mimics that were only 74% and 46% identical in sequence relative to the corresponding region in JFH-1 inhibited HCV replication by 91.5% and 91.2%,respectively,as effectively as a mimic with complete identity to HCV genotype 2a.The inhibitory effects were confirmed by NS3 protein levels.Antisense RNA molecules spanning the 74% identical mimic had no significant effects.CONCLUSION: HCV RNA structural mimics can inhibit HCV RNA replication in replicon and infectious HCV systems and do so independent of close sequence identity with the target. | Robert Smolic Martina Smolic John H Andorfer Catherine H Wu Robert M Smith George Y Wu | 2010 | World Journal of Gastroenterology2010，16，17： | 2 |
| 5 | 利用天然气的碳同位素比值建立热成因气模型显示文摘利用同位素模型预测甲烷、乙烷和丙烷的δ^(13)C值(干酪根/油生成气态物的程度指标),并用于指示Ⅱ型干酪根的生气特征。通过把气体的多组份动力学模型与同位素模型相结合,可得到气体组份转化率与生成温度之间的相关性。δ^(13)C_1,δ^(13)C_2和δ^(13)C_3之间的关系式利用天然气的热解模型进行限制。通过西得克萨斯Delaware和Val Verde盆地海相腐泥型页岩(Ⅱ型干酪根)生成的气体数据对同位素模型进行验证与校对。这些气体相对不受运移和生物气的混合影响,所以,气体碳同位素比值的变化能初步反映成熟度的演化程度。因此,这些数据对解释气体生成温度和来源于Ⅱ型干酪根的气体δ^(13)C值是有实际价值的。 | Melodye A R George E C Chung H M 刘全有 | 2002 | 天然气地球科学2002，13，5： | 2 |
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