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1Modulation of liver tolerance by conventional and nonconventional antigen-presenting cells and regulatory immune cells显示文摘肝是有有免疫力的规定的优美机制的一个 tolerogenic 机关保证本地、全身的有免疫力的忍耐的保养到自我和外国抗原,但是那也能对病原体装有效有免疫力的回答。尽管有主要 histo 相容性建筑群失配,肝 allografts 的有免疫力的特权在猪首先被认出,并且称为 “肝忍耐 effect”。而且,肝移植自发地与仅仅低剂量的免疫力的抑制被接受,并且为一样的施主的非肝的共同移植的 allografts 导致忍耐。尽管这 immunotolerogenic 环境在机关移植的背景是有利的,它在象肝炎 B 一样的长期的传染的肝疾病是有害的,导致 tumorigenesis 完成的病原体坚持和弱反肿瘤或 C,疟疾,血吸虫病或。肝是 T 房间激活的一个主要地点,但是它得到 T 房间的差或不完全的激活,导致他们的未成功的激活,疲劳,他们的受动器功能的抑制和早死亡。这被病原体利用并且能损害病原体控制和清理或允许肿瘤生长。T 房间的肝的 priming 被传统的很多个本地人和 nonconventional 调停介绍抗原的房间(APC ) 由有免疫力的偏差支持忍耐, T 房间变应力缺乏或 apoptosis 感应,并且产生并且膨胀规章的 T 房间。这评论将集中于通讯在之间古典并且在在感应的忍耐和愿望的肝的 nonclassical APC 和淋巴细胞在这个过程讨论最近的卓见进天生的淋巴细胞的角色。Andrea Kristina Horst Katrin Neumann Linda Diehl Gisa Tiegs 2016Cellular & Molecular Immunology2016,13,3:26
2Calcium-dependent modulation and plasma membrane targeting of the AKT2 potassium channel by the CBL4/ ClPK6 calcium sensor/protein kinase complex显示文摘Katrin Held Franqois Pascaud Christian Eckert Pawel Gajdanowicz Kenji Hashimoto Claire Corratge-Faillie Jan Niklas Offenborn Benoit Lacombe Ingo Dreyer Jean-Baptiste Thibaud Jorg Kudla 2011Cell Research2011,21,7:23
3Detection of disseminated pancreatic cells by amplification of cytokeratin-19 with quantitative RT-PCR in blood,bone marrow and peritoneal lavage of pancreatic carcinoma patients显示文摘AIM: To evaluate the diagnostic potential of cytokeratin-19 (CK-19) mRNA for the detection of disseminated tumor cells in blood, bone marrow and peritoneal lavage in patients with ductal adenocarcinoma of the pancreas. METHODS: Sixty-eight patients with pancreatic cancer (n = 37), chronic pancreatitis (n = 16), and non-pan- creatic benign surgical diseases (n = 15, control group) were included in the study. Venous blood was taken preoperatively, intraoperatively and at postoperative d 1 and 10. Preoperative bone marrow aspirates and peritoneal lavage taken before mobilization of the tumor were analyzed. All samples were evaluated for disseminated tumor cells by CK-19-specific nested-PCR and quantitative fluorogenic RT-PCR. RESULTS: CK-19 mRNA expression was increased in 24 (64%) blood samples and 11 (30%) of the peritoneal lavage samples in the patients with pancreatic cancer. In 15 (40%) of the patients with pancreatic cancer, disseminated tumor cells were detected in venous blood and bone marrow and/or peritoneal lavage. In the peritoneal lavage, the detection rates were correlated with the tumor size and the tumor differentiation. CK-19 levels were increased in pT3/T4 and moderately/poorly differentiated tumors (G2/G3). Pancreatic cancer patients with at least one CK-19 mRNA-positive sample showed a trend towards shorter survival. Pancreatic cancerpatients showed significantly increased detection rates of disseminated tumor cells in blood and peritoneal lavage compared to the controls and the patients with chronic pancreatitis. CONCLUSION: Disseminated tumor cells can be detected in patients with pancreatic ductal adenocar- cinoma by CK-19 fluorogenic RT-PCR. In peritoneal lavage, detection rate is correlated with tumor stage and differentiation. In the clinical use, CK-19 is suitable for the distinction between malignant and benign pancreatic disease in combination with other tumor-specific markers.Katrin Hoffmann Christiane Kerner Wolfgang Wilfert Marc Mueller Joachim Thiery Johann Hauss Helmut Witzigmann 2007World Journal of Gastroenterology2007,13,2:20
4Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology显示文摘AIM: To evaluate ATP-binding cassette(ABC) transporters in colonic pathophysiology as they had recently been related to colorectal cancer(CRC) development. METHODS: Literature search was conducted on Pub Med using combinations of the following terms: ABC transporters, ATP binding cassette transporter proteins, inflammatory bowel disease, ulcerative, colitis, Crohns disease, colorectal cancer, colitis, intestinal inflammation, intestinal carcinogenesis, ABCB1/P-glycoprotein(P-gp/CD243/MDR1), ABCC2/multidrug resistance protein 2(MRP2) and ABCG2/breast cancer resistance protein(BCRP), Abcb1/Mdr1 a, abcc2/Mrp2, abcg2/Bcrp, knock-out mice, tight junction, membrane lipid function. RESULTS: Recently, human studies reported thatchanges in the levels of ABC transporters were early events in the adenoma-carcinoma sequence leading to CRC. A link between ABCB1, high fat diet and gut microbes in relation to colitis was suggested by the animal studies. The finding that colitis was preceded by altered gut bacterial composition suggests that deletion of Abcb1 leads to fundamental changes of hostmicrobiota interaction. Also, high fat diet increases the frequency and severity of colitis in specific pathogenfree Abcb1 KO mice. The Abcb1 KO mice might thus serve as a model in which diet/environmental factors and microbes may be controlled and investigated in relation to intestinal inflammation. Potential molecular mechanisms include defective transport of inflammatory mediators and/or phospholipid translocation from one side to the other of the cell membrane lipid bilayer by ABC transporters affecting inflammatory response and/or function of tight junctions, phagocytosis and vesicle trafficking. Also, diet and microbes give rise to molecules which are potential substrates for the ABC transporters and which may additionally affect ABC transporter function through nuclear receptors and transcriptional regulation. Another critical role of ABCB1 was suggested by the finding that ABCB1 expression identifies a subpopulation of pro-inflammatory Th17 cells which were resistant to treatment with glucocorticoids. The evidence for the involvement of ABCC2 and ABCG2 in colonic pathophysiology was weak. CONCLUSION: ABCB1, diet, and gut microbes mutually interact in colonic inflammation, a well-known risk factor for CRC. Further insight may be translated into preventive and treatment strategies.Vibeke Andersen Katrine Svenningsen Lina Almind Knudsen Axel Kornerup Hansen Uffe Holmskov Allan Stensballe Ulla Vogel 2015World Journal of Gastroenterology2015,21,41:10
5Incidence trends and survival prediction of hepatoblastoma in children:a population-based study显示文摘Background:Hepatoblastoma is a rare disease that nevertheless accounts for the majority of liver malignancies in children.Due to limited epidemiological data,therapy for hepatoblastoma tends to be individualized.This study aimed to evaluate incidence trends of hepatoblastoma and to develop a nomogram to predict the survival of children with newly diagnosed hepatoblastoma on a population-based level.Methods:Individuals up to 18 years of age with hepatoblastoma recorded in 18 registries of the Surveillance,Epi-demiology,and End Results(SEER)database between 2004 and 2015 were examined.Joinpoint regression analyses were applied to assess incidence trends in annual percentage change(APC).Multivariable Cox regression was used to identify factors associated with overall survival(OS).A nomogram was constructed to predict OS in individual cases based on independent predictors.Concordance index(C-index)and calibration curves were used to evaluate predic-tive performance.Results:Between 2004 and 2015,hepatoblastoma incidence increased significantly(APC,2.2%;95%confidence interval[CI]0.5%to 3.8%,P<0.05).In particular,this increase was observed among 2-to 4-year-old patients,males,and African-Americans.The 5-and 10-year OS rates were 81.5%and 81.0%,respectively.Age of 2 to 4 years,Afri-can-American ethnicity,and no surgery were independent predictors for short OS.Distant disease at presentation was found not to be an independent factor of survival.The nomogram had a C-index of 0.79(95%CI 0.74-0.84)with appropriate calibration curve fitting.Conclusions:We constructed a nomogram that integrates common factors associated with survival for hepatoblas-toma patients.It provides accurate prognostic prediction for children with hepatoblastoma.Jincheng Feng Georgios Polychronidis Ulrike Heger Giovanni Frongia Arianeb Mehrabi Katrin Hoffmann 2019Cancer Communications2019,39,1:10
6Potential role of chitinase 3-like-1 in inflammation-associated carcinogenic changes of epithelial cells显示文摘The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin,a polymer of N-acetylglucosamine.Chitin is the structural component of fungi,crustaceans,insects and parasitic nematodes,but is completely absent in mammals.Exposure to antigens containing chitin-or chitin-like structures sometimes induces strong T helper type-I responses in mammals,which may be associated with the induction of mammalian chitinases.Chitinase 3-like-1(CHI3L1) ,a member of the mammalian chitinase family,is induced specifically during the course of inflammation in such disorders as inflammatory bowel disease,hepatitis and asthma.In addition,CHI3L1 is expressed and secreted by several types of solid tumors including glioblastoma,colon cancer,breast cancer and malignant melanoma.Although the exact function of CHI3L1 in inflammation and cancer is still largely unknown,CHI3L1 plays a pivotal role in exacerbating the inflammatory processes and in promoting angiogenesis and remodeling of the extracellular matrix.CHI3L1 may be highly involved in the chronic engagement of inflammation which potentiates development of epithelial tumorigenesis presumably by activating the mitogen-activated protein kinase and the protein kinase B signaling pathways.Anti-CHI3L1 antibodies or pan-chitinase inhibitors may have the potential to suppress CHI3L1-mediated chronic inflammation and the subsequent carcinogenic change in epithelial cells.Katrin Eurich Mayuko Segawa Satoko Toei-Shimizu Emiko Mizoguchi 2009World Journal of Gastroenterology2009,15,42:9
7Subcellular Localization and In Vivo Interactions of the Arabidopsis thaliana Ethylene Receptor Family Members显示文摘气体的植物激素乙烯在更高的植物调整到环境条件的许多发展过程和回答。在 Arabidopsis thaliana,发信号的乙烯感觉和开始被与原核生物的二部件的传感器 histidine kinases 有关的五受体的一个家庭调停。在烟草(Nicotiana benthamiana ) 的标注荧光的受体的短暂表示表皮的叶房间证明所有乙烯受体被指向到 ER endomembrane 网络并且不本地化到 plasmalemma。在支持在 planta 覆盖研究,乙烯受体形式 homomeric 和 heteromeric,在在生活的 ER 的蛋白质建筑群种房间,由膜招募试金出现。在 vivo 相互作用模式可比较的 A 在酵母被发现基于配偶的 split-ubiquitin 系统。重叠但是乙烯受体基因的不同表示模式在不同植物纸巾建议乙烯受体建筑群的一篇微分作文。我们的调查结果可以在乙烯上有关键功能的含意荷尔蒙感觉,发信号的正式就职,信号变细和输出的调停受体的效率。Christopher Grefen Katrin Stadele Kamil Ruzicka Petr Obrdlik Klaus Hatter Jakub Horak 2008Molecular Plant2008,1,2:8
8大鼠肾移植1000例经验总结显示文摘目的:对大鼠肾移植进行经验总结以指导实验与临床研究。方法:作者在2004-01/2009-07海德堡大学移植中心期间,采用大鼠肾动、静脉与腹主动脉、腔静脉行端侧吻合。对于急性肾移植模型,输尿管直接植入膀胱内;对于慢性肾移植模型,输尿管采用端端吻合法。术中直接切除对侧肾脏,完成大鼠肾移植1000例,并对其进行总结。结果:只要供体肾脏冲洗良好,吻合时暖缺血时间小于30min,手术时间60min左右,吻合技术娴熟,移植成功率达98%以上。结论:该实验模型安全、方便、可行。肾移植成功的关键是手术技术。李占清 关晓海 王世军 陈晶 伊雪 邬鹏宇 肖志 Nickkholgh Arash Bruns Helge Hoffmann Katrin Schemmer Peter 2011中国组织工程研究与临床康复2011,15,5:7
9Palliative chemotherapy for gastroesophageal cancer in old and very old patients: A retrospective cohort study at the National Center for Tumor Diseases, Heidelberg显示文摘AIM:To investigate the outcome of palliative chemotherapy in old patients with gastroesophageal cancer at the National Center for Tumor Diseases,Heidelberg.METHODS:Using a prospectively generated database,we retrospectively analyzed 55 patients≥70years under palliative chemotherapy for advanced gastroesophageal cancer at the outpatient clinic of the National Center for Tumor Diseases Heidelberg,Germany between January 2006 and December2013.Further requirements for inclusion were(1)histologically proven diagnosis of gastroesophageal cancer;(2)advanced(metastatic or inoperable)disease;and(3)no history of radiation or radiochemotherapy.The clinical information included Eastern Cooperative Oncology Group performance status(ECOG PS),presence and site of metastases at diagnosis,date of previous surgery and perioperative chemotherapy,start and stop date of first-line treatment,toxicities and consecutive dosage reductions of first-line treatment,response to first-line therapy,date of progression,usage of second-line therapies and date and cause of death.Survival times[progression-free survival(PFS),overall survival(OS)and residual survival(RS)]were calculated.Toxicity and safety were examined.Prognostic factors including ECOG PS,age and previousperioperative treatment were analyzed.RESULTS:Median age of our cohort was 76 years.86%of patients received a combination of two cytotoxic drugs.76 percent of patients had an oxaliplatin-based first-line therapy with the oxaliplatin and 5-fluorouracil regimen being the predominantely chosen regimen(69%).Drug modifications due to toxicity were necessary in 56%of patients,and 11%of patients stopped treatment due to toxicities.Survival times of our cohort are in good accordance with the major phaseⅢtrials that included mostly younger patients:PFS and OS were 5.8 and 9.5 mo,respectively.Survival differed significantly between patient groups with low(≤1)and high(≥2)ECOG PS(12.7 mo vs 3.8 mo,P<0.001).Very old patients(≥75 years)did not show a worse outcome in terms of survival.Patients receiving secondline treatment(51%)had a significantly longer RS than patients with best supportive care(6.8 vs 1.4 mo,P=0.001).Initial ECOG PS was a strong prognostic factor for PFS,OS and RS.CONCLUSION:Old patients with non-curable gastroesophageal cancer should be offered chemotherapy,and ECOG PS is a tool for balancing benefit and harm upfront.Second-line treatment is reasonable.Anne Katrin Berger Stefanie Zschaebitz Christine Komander Dirk Jger Georg Martin Haag 2015World Journal of Gastroenterology2015,21,16:6
10Characterization of HULC, a Novel Gene With Striking Up-Regulation in Hepatocellular Carcinoma, as Noncoding RNA显示文摘Katrin Panzitt Marisa M.O. Tschernatsch Christian Guelly Tarek Moustafa Martin Stradner Heimo M. Strohmaier Charles R. Buck Helmut Denk Renée Schroeder Michael Trauner Kurt Zatloukal 2007Gastroenterology2007,,1:4
11Exploratory study on microRNA profiles from plasma-derived extracellular vesicles in Alzheimer’s disease and dementia with Lewy bodies显示文摘Background:Because of the increasing life expectancy in our society,aging-related neurodegenerative disorders are one of the main issues in global health.Most of these diseases are characterized by the deposition of misfolded proteins and a progressive cognitive decline.Among these diseases,Alzheimer’s disease(AD)and dementia with Lewy bodies(DLB)are the most common types of degenerative dementia.Although both show specific features,an important neuropathological and clinical overlap between them hampers their correct diagnosis.In this work,we identified molecular biomarkers aiming to improve the misdiagnosis between both diseases.Methods:Plasma extracellular vesicles(EVs)-from DLB,AD and healthy controls-were isolated using size-exclusion chromatography(SEC)and characterized by flow cytometry,Nanoparticle Tracking Analysis(NTA)and cryo-electron microscopy.Next Generation Sequencing(NGS)and related bibliographic search was performed and a selected group of EV-associated microRNAs(miRNAs)was analysed by qPCR.Results:Results uncovered two miRNAs(hsa-miR-451a and hsa-miR-21-5p)significantly down-regulated in AD samples respect to DLB patients,and a set of four miRNAs(hsa-miR-23a-3p,hsa-miR-126-3p,hsa-let-7i-5p,and hsamiR-151a-3p)significantly decreased in AD respect to controls.The two miRNAs showing decreased expression in AD in comparison to DLB provided area under the curve(AUC)values of 0.9 in ROC curve analysis,thus suggesting their possible use as biomarkers to discriminate between both diseases.Target gene analysis of these miRNAs using prediction online tools showed accumulation of phosphorylation enzymes,presence of proteasome-related proteins and genes involved in cell death among others.Conclusion:Our data suggest that plasma-EV associated miRNAs may reflect a differential profile for a given dementia-related disorder which,once validated in larger cohorts of patients,could help to improve the differential diagnosis of DLB versus AD.Ana Gámez-Valero Jaume Campdelacreu Dolores Vilas Lourdes Ispierto Ramón Reñé RamiroÁlvarez MPilar Armengol Francesc E.Borràs Katrin Beyer 2019Translational Neurodegeneration2019,8,1:4
12Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis显示文摘Katrin M Sjoquist Bryan H Burmeister B Mark Smithers John R Zalcberg R John Simes Andrew Barbour Val Gebski 2011Lancet Oncology2011,,7:4
13Product Variability of the ‘Cineole Cassette' Monoterpene Synthases of Related Nicotiana Species显示文摘Anke Fahnrich Katrin Krause Birgit Piechulla 2011Molecular Plant2011,4,6:4
14Current techniques for AB0-incompatible living donor liver transplantation显示文摘For a long time, it was considered medical malpractice to neglect the blood group system during transplantation. Because there are far more patients waiting for organs than organs available, a variety of attempts have been made to transplant AB0-incompatible(AB0i) grafts. Improvements in AB0 i graft survival rates have been achieved with immunosuppression regimens and plasma treatment procedures. Nevertheless, some grafts are rejected early after AB0 i living donor liver transplantation(LDLT) due to antibody mediated rejection or later biliary complications that affect the quality of life. Therefore, the AB0 i LDLT is an option only for emergency situations, and it requires careful planning. This review compares the treatment possibilities and their effect on the patients' graft outcome from 2010 to the present. We compared 11 transplant center regimens and their outcomes. The best improvement, next to plasma treatment procedures, has been reached with the prophylactic use of rituximab more than one week before AB0 i LDLT. Unfortunately, no standardized treatment protocols are available. Each center treats its patients with its own scheme. Nevertheless, the transplant results are homogeneous. Due to refined treatment strategies, AB0 i LDLT is a feasible option today and almost free of severe complications.Silke Rummler Astrid Bauschke Erik B?rthel Heike Jütte Katrin Maier Patrice Ziehm Christina Malessa Utz Settmacher 2016World Journal of Transplantation2016,6,3:4
15Perioperative chemotherapy for advanced gastric cancer - results from a tertiary-care hospital in Germany显示文摘BACKGROUND Neoadjuvant/perioperative chemotherapy is the recommended treatment for advanced stages of gastric cancer(>T2,N+)before tumour resection in many European guidelines.However,there is no consensus as to whether perioperative chemotherapy is as effective in distal as in proximal tumours,in addition to a relevant uncertainty concerning appropriate treatment modalities for elderly patients.AIM To investigate the role of perioperative chemotherapy in advanced gastric cancer in patients from a German tertiary clinic with respect to efficacy,localisation,and age.METHODS We performed a retrospective analysis of 158 patients from our clinic with adenocarcinoma of the stomach or the gastroesophageal junction who underwent resection between 2008 and 2016.The data were evaluated particularly in relation to patient age,tumour site,and perioperative therapy.RESULTS Administration of perioperative chemotherapy did not lead to a significant survival advantage in our study population.The 5-year survival rates were 40%for patients who received perioperative chemotherapy and 29%for the group without perioperative chemotherapy(P=0.125).Our patients were on average distinctly older than patients in most of the published randomised controlled trials.Patients elder than 75 years received perioperative chemotherapy far less frequently.Patients with a proximal tumour received perioperative chemotherapy much more often.CONCLUSION This analysis reconfirms our previous data concerning the effectiveness of perioperative chemotherapy for advanced gastric cancer.There is reasonable doubt that the quality of the existing randomized controlled trials is sufficient to generally justify perioperative chemotherapy in patients with advanced gastric cancer independent of tumour localization or age.Katrin Bauer Giulia Manzini Doris Henne-Bruns Peter Buechler 2020World Journal of Gastrointestinal Oncology2020,12,5:4
16Rodent epididymal cDNAs identified by sequence homology to human and canine counterparts显示文摘Aim: Identification of the rodent counterparts of human and canine epididymal cDNAs HE3, HE4 and CeS/Ly6G5C by sequence homology and analysis of their expression patterns and regulation level in the rat. Methods:'Electronic screening' of Expressed Sequence Tag (EST) and genomic databases, followed by RT-PCR and Northern blot analysis. Results: Rodent ESTs and genomic sequences homologous to HE3, HE4 and CeS/Ly6G5C were identified in the public databases and the 'full-length' rat cDNAs cloned. To emphasise their homology to the human and canine genes, they were named Me3/Re3, Me4/Re4 and Re8 for mouse and rat counterparts, respectively, mRNA expression patterns were analysed in rats, including rat HE1 and HE5/CD52 counterparts as controls. Re3 and Re8 mRNAs were only found in the rat epididymis, while Re4 showed a broader tissue distribution. Within the epididymis,Re3 and Re4 mRNAs were detected in all regions; ReS, on the other hand, was restricted to the caput. During postnatal development, Re3 and control mRNAs were found from the earliest stages investigated, while Re8 mRNA was observed only from day 24 postnatum, corresponding to the onset of spermatogenesis in the prepubertal testis.Castration and testosterone supplementation of adult male rats suggested that none of the cloned mRNAs was directly androgen-regulated. Efferent duct ligation, however, showed that Re8 mRNA levels depended on testicular factors other than androgens. Conclusion: The novel rodent cDNAs can now be used to monitor epididymal gene expression more closely and to set up various regulatory and functional studies.Katrin Kppler-Hanno Christiane Kirchhoff 2003Asian Journal of Andrology2003,5,4:4
17Hexachlorobutadiene(HCBD)contamination in the Arctic environment:A review显示文摘Hexachlorobutadiene(HCBD)is a halogenated hydrocarbon that is primarily produced as an unintentional byproduct in the manufacture of chlorinated solvents.Similarities between HCBD and other persistent organic pollutants(POPs)led to its listing in 2015 for global regulation under the Stockholm Convention on POPs.HCBD's toxicity and propensity for long-range transport means there is special concern for its potential impacts on Arctic ecosystems.The present review comprehensively summarizes all available information of the occurrence of HCBD in the Arctic environment,including its atmospheric,terrestrial,freshwater and marine ecosystems and biota.Overall,reports of HCBD in Arctic environmental media are scarce.HCBD has been measured in Arctic air collected from monitoring stations in Finland and Canada,yet there is a dearth of data for other abiotic matrices(i.e.soils,sediments,glacier ice,freshwaters and seawater).Low HCBD concentrations have been measured in Arctic terrestrial and marine biota,which is consistent with laboratory studies that indicate that HCBD has the potential to bioaccumulate,but not to biomagnify.Available data for Arctic biota suggest that terrestrial birds and mammals and seabirds,have comparatively higher HCBD concentrations than fish and marine mammals,warranting additional research.Although spatial and temporal trends in HCBD concentrations in the Arctic are currently limited,future monitoring of HCBD in the Arctic will be important for assessing the impact of global regulations newly-imposed by the Stockholm Convention on POPs.Jennifer E.Balmer Hayley Hung Katrin Vorkamp Robert J.Letcher Derek C.G.Muir 2019Emerging Contaminants2019,5,1:3
18Gastrointestinal perforation in metastatic colorectal cancer patients with peritoneal metastases receiving bevacizumab显示文摘AIM:To investigate the safety and efficacy of adding bevacizumab to first-line chemotherapy in metastatic colorectal cancer patients with peritoneal disease.METHODS:We compared rates of gastrointestinal perforation in patients with metastatic colorectal cancer and peritoneal disease receiving first-line chemotherapy with and without bevacizumab in three distinct cohorts:(1) the AGITG MAX trial(Phase Ⅲ randomised clinical trial comparing capecitabine vs capecitabine and bevacizumab vs capecitabine,bevacizumab and mitomycin C);(2) the prospective Treatment of Recurrent and Advanced Colorectal Cancer(TRACC) registry(any first-line regimen ± bevacizumab);and(3) two cancer centres in New South Wales,Australia [Macarthur Cancer Therapy Centre and Liverpool Cancer Therapy Centre(NSWCC) from January 2005 to Decenber 2012,(any first-line regimen ± bevacizumab).For the AGITG MAX trial capecitabine was compared to the other two arms(capecitabine/bevacizumab and capecitabine/bevacizumab/mitomycin C).In the AGITG MAX trial and the TRACC registry rates of gastrointestinal perforation were also collected in patients who did not have peritoneal metastases.Secondary endpoints included progression-free survival,chemotherapy duration,and overall survival.Time-toevent outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test.RESULTS:Eighty-four MAX,179 TRACC and 69 NSWCC patients had peritoneal disease.There were no gastrointestinal perforations recorded in either the MAX subgroup or the NSWCC cohorts.Of the patients without peritoneal disease in the MAX trial,4/300(1.3%) in the bevacizumab arms had gastrointestinal perforations compared to 1/123(0.8%) in the capecitabine alone arm.In the TRACC registry 3/126(2.4%) patients who had received bevacizumab had a gastrointestinal perforation compared to 1/53(1.9%) in the chemotherapy alone arm.In a further analysis of patients without peritoneal metastases in the TRACC registry,the rate of gastrointestinal perforations was 9/369(2.4%) in the chemotherapy/bevacizumab group and 5/177(2.8%) in the chemotherapy alone group.The addition of bevacizumab to chemotherapy was associated with improved progression-free survival in all three cohorts:MAX 6.9 m vs 4.9 m,HR = 0.64(95%CI:0.42-1.02);P = 0.063;TRACC 9.1 m vs 5.5 m,HR = 0.61(95%CI:0.37-0.86);P = 0.009;NSWCC 8.7 m vs 6.8 m,HR = 0.75(95%CI:0.43-1.32);P = 0.32.Chemotherapy duration was similar across the groups.CONCLUSION:Patients with peritoneal disease do not appear to have an increased risk of gastrointestinal perforations when receiving first-line therapy with bevacizumab compared to systemic therapy alone.Aflah Roohullah Hui-Li Wong Katrin M Sjoquist Peter Gibbs Kathryn Field Ben Tran Jeremy Shapiro Joe Mckendrick Desmond Yip Louise Nott Val Gebski Weng Ng Wei Chua Timothy Price Niall Tebbutt Lorraine Chantrill 2015World Journal of Gastroenterology2015,21,17:3
19Growing Operational Use of FY-3 Data in the ECMWF System显示文摘This paper reviews the data quality and impact of observations from the FY-3 satellite series used operationally in the ECMWF system. This includes data from the passive microwave radiometers MWHS-1, MWHS-2 and MWRI, as well as observations from the radio occultation receiver GNOS. Evaluations against background equivalents show that the quality of the observations is broadly comparable to that of similar instruments on other polar-orbiting satellites, even though biases for the passive microwave observations can be somewhat larger and more complex for some channels. An observing system experiment shows that the FY-3 instruments jointly contribute significantly to the forecast skill in the ECMWF system. Positive impact of up to 2% is seen for most variables out to the day-2 forecasts over hemispheric scales, with significant benefits for total column water vapor or for temperature and wind in the stratosphere out to day 4.Niels BORMANN David DUNCAN Stephen ENGLISH Sean HEALY Katrin LONITZ Keyi CHEN Heather LAWRENCE Qifeng LU 2021Advances in Atmospheric Sciences2021,38,8:3
20Role of soluble factors and three-dimensional culture in in vitro differentiation of intestinal macrophages显示文摘AIM: To examine the factor(s) involved in differentiation of intestinal macrophages (IMACs) using a recently established in vitro model. METHODS: To test whether soluble or membrane bound factors induce IMAC-differentiation, freshly elutriated monocytes (MO) were incubated with conditioned media or cell membranes of intestinal epithelial cells (IEC) or cultured with IEC in transwell systems. To determine the importance of an active migration of MO, three- dimensional aggregates from a 1:1-mixture of MO and IEC were examined by immunohistochemistry and flow cytometry. Apoptosis was examined by caspase-3 Western blots. Extracellular matrix production in differentiation models was compared by immunohistochemistry. RESULTS: IMAC differentiation was observed in a complex three-dimensional co-culture model (multicellular spheroid, MCS) with IEC after migration of MO into the spheroids. By co-culture of MO with conditioned media or membrane preparations of IEC no IMAC differentiation was induced. Co-culture of MO with IEC in transwell- cultures, with the two cell populations separated by a membrane also did not result in intestinal-like differentiation of MO. In contrast to IEC-spheroids with immigrating MO in mixed MCS of IEC and MO only a small subpopulation of MO was able to survive the seven day culture period. CONCLUSION: Intestinal-like differentiation of MO in vitro is only induced in the complex three-dimensional MCS model after immigration of MO indicating a roleof cell-matrix and/or cell-cell interactions during the differentiation of IMACs.Tanja Spoettl Martin Hausmann Katrin Menzel Heidi Piberger Hans Herfarth Juergen Schoelmerich Frauke Bataille Gerhard Rogler 2007World Journal of Gastroenterology2007,13,7:3
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