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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 | Ellagic acid induces apoptosis through inhibition of nuclear factor κB in pancreatic cancer cells显示文摘AIM:To determine the effect of ellagic acid on apop-tosis and proliferation in pancreatic cancer cells and to determine the mechanism of the pro-survival effects of ellagic acid. METHODS:The effect of ellagic acid on apoptosis was assessed by measuring Phosphatidylserine externalization,caspase activity,mitochondrial membrane potential and DNA fragmentation;and proliferation by measuring DNA thymidine incorporation. Mitochondrial membrane potential was measured in permeabilized cells,and in isolated mitochondria. Nuclear factor kB(NF-kB) activity was measured by electromobility shift assay(EMSA) . RESULTS:We show that ellagic acid,a polyphenolic compound in fruits and berries,at concentrations 10 to 50 mmol/L stimulates apoptosis in human pancreatic adenocarcinoma cells. Further,ellagic acid decreases proliferation by up to 20-fold at 50 mmol/L. Ellagic acid stimulates the mitochondrial pathway of apoptosis associated with mitochondrial depolarization,cytochrome C release,and the downstream caspaseactivation. Ellagic acid does not directly affect mitochondria. Ellagic acid dose-dependently decreased NF-kB binding activity. Furthermore,inhibition of NF-kB activity using IkB wild type plasmid prevented the effect of ellagic acid on apoptosis. CONCLUSION:Our data indicate that ellagic acid stimulates apoptosis through inhibition of the prosu-rvival transcription factor NF-kB. | Mouad Edderkaoui Irina Odinokova Izumi Ohno Ilya Gukovsky Vay Liang W Go Stephen J Pandol Anna S Gukovskaya | 2008 | World Journal of Gastroenterology2008，14，23： | 30 |
| 3 | Antidiabetic thiazolidinediones induce ductal differentiation but not apoptosis in pancreatic cancer cells显示文摘AIM: Thiazolidinediones (TZD) are a new class of oral antidiabetic drugs that have been shown to inhibit growth of same epithelial cancer cells. Although TZD were found to be ligands for peroxisome proliferator-activated receptor γ (PPARγ), the mechanism by which TZD exert their anticancer effect is presently unclear. In this study,we analyzed the mechanism by which TZD inhibit growth of human pancreatic carcinoma cell lines in order to evaluate the potential therapeutic use of these drugs in pancreatic adenocarcinoma.METHODS: The effects of TZD in pancreatic cancer cells were assessed in anchorage-independent growth assay.Expression of PPARγ was measured by reverse-transcription polymerase chain reaction and confirmed by Western blot analysis. PPARγ activity was evaluated by transient reporter gene assay. Flow cytometry and DNA fragmentationassay were used to determine the effect of TZD on cell cycle progression and apoptosis respectively. The effect of TZD on ductal differentiation markers was performed by Western blot.RESULTS: Exposure to TZD inhibited colony formation in a PPARγ-dependent manner. Growth inhibition was linked to G1 phase cell cycle arrest through induction of the ductal differentiation program without any increase of the apoptotic rate.CONCLUSION: TZD treatment in pancreatic cancer cells has potent inhibitory effects on growth by a PPAR-dependent induction of pacreatic ductal differentiation. | Elisabetta Ceni Tommaso Mello Mirko Tarocchi David W Crabb Anna Caldini Pietro Invernizzi Calogero Surrenti Stefano Milani Andrea Galli | 2005 | World Journal of Gastroenterology2005，11，8： | 15 |
| 4 | Insulin resistance,adipokine profile and hepatic expression of SOCS-3 gene in chronic hepatitis C显示文摘AIM:to analyze adipokine concentrations,insulin resistance and hepatic expression of suppressor of cytokine signaling 3(SOCS-3)in patients with chronic hepatitis C genotype 1 with normal body weight,glucose and lipid profile.METHODS:The study group consisted of 31 patients with chronic hepatitis C and 9 healthy subjects.Total levels of adiponectin,leptin,resistin,visfatin,omentin,osteopontin and insulin were measured using an ELISA kit.The hepatic expression of SOCS-3 was determined by the use of the reverse transcription polymerase chain reaction method.RESULTS:Homeostasis model assessment for insulin resistance(HOMA-IR)values were significantly higher in hepatitis C virus(HCV)infected patients without metabolic disorders compared to healthy controls(2.24 vs 0.59,P=0.0003).Hepatic steatosis was observed in 32.2%of patients with HCV infection and was found in patients with increased HOMA-IR index(2.81 vs1.99,P=0.05)and reduced adiponectin level(5.96vs 8.37,P=0.04).Inflammatory activity(G≥2)was related to increased osteopontin concentration(34.04vs 23.35,P=0.03).Advanced liver fibrosis(S≥2)was associated with increased levels of omentin and osteopontin(436.94 vs 360.09,P=0.03 and 32.84 vs20.29,P=0.03)and reduced resistin concentration(1.40 vs 1.74,P=0.047).No correlations were reported between adipokine profile,HOMA-IR values and hepatic expression of the SOCS-3 gene.CONCLUSION:We speculated that no relationship between adipokines and HOMA-IR values may indicate that HCV can induce insulin resistance itself.Some adipokines appear to be biochemical markers of steatosis,inflammation and fibrosis in patients with chronic HCV infection. | Kamila Wójcik Elzbieta Jabonowska Aleksandra Omulecka Anna Piekarska | 2014 | World Journal of Gastroenterology2014，20，30： | 8 |
| 5 | Ghrelin and gastrin in advanced gastric cancer before and after gastrectomy显示文摘AIM: To investigate plasma ghrelin, gastrin and growth hormone secretagogue receptor (GHS-R) expression in advanced gastric cancer (GC) before and after resection. METHODS: Seventy subjects in whom endoscopy of the upper gastrointestinal tract was performed in the Department of General Surgery at Cracow University during the past decade: (1) 25 patients with GC associated with Helicobacter pylori (H. pylori) infection; (2) 10 patients with GC 4-5 years after (total or subtotal) gastrectomy; (3) 25 healthy H. pylori-negative controls, matched by age and BMI to the above two groups; and (4) 10 GC patients 4-5 years after total gastrectomy. Ghrelin and gastrin plasma concentrations were measured by specific radioimmunoassay under fasting conditions and postprandially at 60 and 90 min after ingestion of a mixed meal. GHS-R expression was examined in biopsy samples from intact healthy mucosa and GC tissue using semi-quantitative reverse transcription-polymerase chain reaction. RESULTS: In healthy controls, fasting plasma ghrelin levels were significantly elevated and declined markedly at 60 and 90 min after a mixed meal. The concomitant enhanced ghrelin, GHS-R and gastrin expression in GC tissue over that recorded in intact mucosa, and the marked rise in plasma gastrin in these subjects under fasting conditions indicate the role of these hormonal factors in GC formation. Fasting plasma levels and postprandial response of ghrelin and gastrin appear to be inversely correlated in healthy subjects. Feeding in the controls resulted in a significant fall in plasma ghrelin with a subsequent rise in plasma gastrin, but in H. pylori-positive GC patients submitted to total or distal gastrectomy, feeding failed to affect significantly the fall in plasma ghrelin that was recorded in these patients before surgery. Fasting ghrelin concentrations were significantly lower in patients 4-5 years after total gastrectomy compared to those in healthy controls and to these in GC patients before surgery. CONCLUSION: Elevated plasma gastrin and suppression of fasting ghrelin in patients with GC suggest the existence of a close relationship between these two hormones in gastric carcinogenesis. | Anna Zub-Pokrowiecka Kazimierz Rembiasz Peter C Konturek Andrzej Budzyński Stanisaw J Konturek Marek Winiarski Wadysaw Bielański | 2011 | World Journal of Gastroenterology2011，17，4： | 7 |
| 6 | Gene and cell therapy based treatment strategies for inflammatory bowel diseases显示文摘Inflammatory bowel diseases(IBD)are a group of chronic inflammatory disorders most commonly affecting young adults.Currently available therapies can result in induction and maintenance of remission,but are not curative and have sometimes important side effects.Advances in basic research in IBD have provided new therapeutic opportunities to target the inflammatory process involved.Gene and cell therapy approaches are suitable to prevent inflammation in the gastrointestinal tract and show therefore potential in the treatment of IBD.In this review,we present the current progress in the field of both gene and cell therapy and future prospects in the context of IBD.Regarding gene therapy,we focus on viral vectors and their applications in preclinical models.The focus for cell therapy is on regulatory T lymphocytes and mesenchymal stromal cells,their potential for the treatment of IBD and the progress made in both preclinical models and clinical trials. | Sander van der Marel Anna Majowicz Sander van Deventer Harald Petry Daniel W Hommes Valerie Ferreira | 2011 | World Journal of Gastrointestinal Pathophysiology2011，2，6： | 3 |
| 7 | Sulfation of extracellular polysaccharides of red microalgae: reparation, characterization and properties显示文摘 | Shimona G Anna M Jacob W | 2002 | Biochemical and Biophysical Methods2002，50，： | 1 |
| 8 | The catecholamine biosynthesis route in potato is affected by stress显示文摘 | Anna W V Katarzyna L K Aleksandra S | 2004 | Plant Physiology and Biochemistry2004，42，： | 1 |
| 9 | Simultaneous determination of N-oxides and free bases of pyrrolizidine alkaloids by cation-exchange solid-phase and ion-pair high-performance liquid chromatography显示文摘 | TOMASZ M KAZIMIERZ G ANNA W | 2002 | J Chromatography A2002，949，12： | 1 |
| 10 | Divergent effects of exercise on metabolic and mitogenic signaling pathways in human skeletal muscle显示文摘 | Ulrika W Xin Jian J Anna K | 1998 | FASEB1998，12，： | 1 |
| 11 | Genetic and physiological variation in pigment composition of Emiliania Huxleyi (Prymnesiophyceae) and the potential use of its pigment ratios as a quantitative physiological marker显示文摘 | Stolte W Kraay G W Anna A M | 2000 | J Phycol2000，36，： | 1 |
| 12 | Development of complete hydrolysis of pectins from apple pomace显示文摘 | AGNIESZKA W MAGDALENA M ANNA S J | 2015 | Food Chemistry2015，172，： | 1 |
| 13 | Cognitive existential couple therapy for newly diagnosed prostate cancer patients and their partners : A descriptive pilot study显示文摘 | Anna L Collin's Anthony W Love Sidney Bloeh | 2013 | Psycho - Oncology2013，22，2： | 1 |
| 14 | Cerebral white matter changes are associated with abnormalities on neurological examination in non-disabled elderly: the LADIS study显示文摘 | Anna P Alida G van der Flier W | 2013 | J Neurol2013，260，4： | 1 |
| 15 | Increase of regulatory T cells in the peripheral blood of cancer patients 显示文摘 | Anna M W Dominik W Michael S | 2003 | Clin Cancer Res2003，9，2： | 1 |
| 16 | Noninvasive diagnosis and monitor-ing of nonalcoholic steatohepatitis显示文摘 | Anna W Arthur JM Ariel E | | 0，，： | 1 |
| 17 | US prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: Results from a national survey显示文摘 | David R Strutton Jonathan W Kowalski PharmD Dee Anna Glaser Paul E Stang | 2004 | Journal of the American Academy of Dermatology2004，，2： | 1 |
| 18 | Pectic acids in the production of wood-containing paper显示文摘 | Kenneth E S Anna C S Jeffrey W T | 1998 | TAPPI J1998，81，7： | 1 |
| 19 | Low pH,caprylate incubation as a second viral inactivation step in the manufacture of albumin:Parametric and validation studies显示文摘 | Anna J Eric U David J John W | | 0，，03： | 1 |
| 20 | Recognition of Uranium Oxides in Soil Particulate Matter by Means of /L-Raman Spectrometry显示文摘 | Stefaniak E A Anita A Anna W | 2008 | Journal of Nuclear Materials2008，381，15： | 1 |
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