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1High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells显示文摘AIM: To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis. METHODS: The impact of miR-196a on the restriction targets HoxA7, HoxB8, HoxC8 and HoxD8 was analyzed by reverse transcription polymerase chain reaction (RT-PCR) after transient transfection of SW480 cancer cells. The miR-196a transcription profile in colorectal cancer samples, mucosa samples and diverse cancer cell lines was quantifi ed by RT-PCR. Transiently miR-196a-transfected colorectal cancer cells were used for diverse functional assays in vitro and for a xenograft lung metastasis model in vivo. RESULTS: HoxA7, HoxB8, HoxC8 and HoxD8 were restricted by miR-196a in a dose-dependent and gene-specific manner. High levels of miR-196a activated the AKT signaling pathway as indicated by increased phosphorylation of AKT. In addition, high levels of miR-196a promoted cancer cell detachment,migration, invasion and chemosensitivity towards platin derivatives but did not impact on proliferation or apoptosis. Furthermore, miR-196a increased the development of lung metastases in mice after tail vein injection. CONCLUSION: miR-196a exerts a pro-oncogenic influence in colorectal cancer.Carl Christoph Schimanski Kirsten Frerichs Fareed Rahman Martin Berger Hauke Lang Peter R Galle Markus Moehler Ines Gockel 2009World Journal of Gastroenterology2009,15,17:40
2Multidisciplinary management of gastric and gastroesophageal cancers显示文摘Carcinomas of the stomach and gastroesophageal junction are among the fi ve top leading cancer types worldwide. In spite of radical surgical R0 resections being the basis of cure of gastric cancer,surgery alone provides long-term survival in only 30% of patients with advanced International Union Against Cancer (UICC) stages in Western countries because of the high risk of recurrence and metachronous metastases. However,recent large phase-Ⅲ Studies improved the diagnostic and therapeutic options in gastric cancers,indicating a more multidisciplinary management of the disease. Multimodal strategies combining dif-ferent neoadjuvant and/or adjuvant protocols have clearly improved the gastric cancer prognosis when combined with surgery with curative intention. In particular,the perioperative (neoadjuvant,adjuvant) chemotherapy is now a well-established new standard of care for advanced tumors. Adjuvant therapy alone should be carefully discussed after surgical resection,mainly in individual patients with large lymph node positive tumors when neoadjuvant therapy could not be done. The palliative treatment options have also been remarkably improved with new chemotherapeutic agents and will further be enhanced with targeted therapies such as different monoclonal antibodies. This article reviews the most relevant literature on the multidisciplinary management of gastric and gastro-esophageal cancer,and discusses future strategies toimprove locoregional failures.Markus Moehler Orestis Lyros Ines Gockel Peter R Galle Hauke Lang 2008World Journal of Gastroenterology2008,14,24:17
3VEGF-D expression correlates with colorectal cancer aggressiveness and is downregulated by cetuximab显示文摘AIM:To gain mechanistic insights into the role played by epidermal growth factor receptor (EGFR) in the regulation of vascular endothelial growth factors (VEGFs) in colorectal cancer (CRC). METHODS:The impact of high-level expression of the growth factor receptors EGFR and VEGF receptor (VEGFR)3 and the VEGFR3 ligands VEGF-C and VEGF-D on disease progression and prognosis in human CRC was investigated in 108 patients using immunohistochemistry. Furthermore, the expression of the lymphangiogenic factors in response to the modulation of EGFR signalling by the EGFR-targeted monoclonal antibody cetuximab was investigated at the mRNA and protein level in human SW480 and SW620 CRC cell lines and a mouse xenograft model. RESULTS: Human CRC specimens and cell lines displayed EGFR, VEGF-C and VEGF-D expression with varying intensities. VEGF-C expression was associated with histological grade. Strong expression of VEGF-D was significantly associated with lymph node metastases and linked to a trend for decreased survival in lymph node-positive patients. EGFR blockade with cetuximab resulted in a significant decrease of VEGF-D expression in vitro and in vivo. CONCLUSION:In conclusion, the expression of VEGF-D in colorectal tumours is significantly associated with lymphatic involvement in CRC patients and such expression might be blocked effectively by cetuximab.Markus Moehler Christian Frings Annett Mueller Ines Gockel Carl C Schimanski Stefan Biesterfeld Institute of Pathology Johannes Gutenberg University Mainz 55101 Germany Peter R Galle Martin H Holtmann 2008World Journal of Gastroenterology2008,14,26:15
4Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients显示文摘AIM:To investigate the efficacy and safety of capecitabine plus irinotecan±bevacizumab in advanced or metastatic colorectal cancer patients. METHODS:Forty six patients with previously untreated,locally-advanced or metastatic colorectal cancer(mCRC) were recruited between 2001-2006 in a prospective open-label phaseⅡtrial,in German community-based outpatient clinics.Patients received a standard capecitabine plus irinotecan(CAPIRI) or CAPIRI plus bevacizumab(CAPIRI-BEV) regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of>grade 2 toxicity.The treatment choice of bevacizumab was at the discretion of the physician.Theprimary endpoints were response and toxicity and secondary endpoints included progression-free survival and overall survival. RESULTS:In the CAPIRI group vs the CAPRI-Bev group there were more female than male patients(47% vs 24%) ,and more patients had colon as the primary tumor site(58.8%vs 48.2%) with fewer patients having sigmoid colon as primary tumor site(5.9%vs 20.7%) .Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev:82%vs 58.6%.Partial response rates were 29.4%and 34.5%,and tumor control rates were 70.6%and 75.9%,respectively.No complete responses were observed.The median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CAPIRI-Bev,respectively.The median overall survival for CAPIRI was 15 mo(458 d) and for CAPIRI-Bev 24 mo(733 d) .These differences were not statistically different.In the CAPIRI-Bev,group,two patients underwent a full secondary tumor resection after treatment,whereas in the CAPIRI group no cases underwent this procedure. CONCLUSION:Both regimens were well tolerated and offered effective tumor growth control in this outpatient setting.Severe gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal.Markus Moehler Martin F Sprinzl Murad Abdelfattah Carl C Schimanski Bernd Adami Werner Godderz Klaus Majer Dimitri Flieger Andreas Teufel Juergen Siebler Thomas Hoehler Peter R Galle Stephan Kanzler 2009World Journal of Gastroenterology2009,15,4:10
5LncRNA-encoded peptides: More than translational noise?显示文摘Nathalie Rion Markus A R #x000FC egg 2017Cell Research2017,27,5:8
6Chemokine receptor CXCR4-prognostic factor for gastrointestinal tumors显示文摘To review the implication of CXCR4 for gastrointestinal cancer, a 'Pubmed' analysis was performed in order to evaluate the relevance of CXCR4 and its ligands for gastrointestinal cancers. Search terms applied were 'cancer, malignoma, esophageal, gastric, colon, colorectal, hepatic, pancreatic, CXCR4, SDF-1α, and SDF-1b'. CXCR4 expression correlated with dissemination of diverse gastrointestinal malignomas. The CXCR4 ligand SDF-1α might act as 'chemorepellent' while SDF-1b might act as 'chemorepellent' for CTLs, inducing tumor rejection. The paracrine expression of SDF-1α was furthermore closely associated with neoangiogenesis. CXCR4 and its ligands influence the dissemination, immune rejection, and neoangiogenesis of human gastrointestinal cancers. Inhibition of CXCR4 might be an interesting therapeutic option.Carl C Schimanski Peter R Galle Markus Moehler 2008World Journal of Gastroenterology2008,14,30:7
7工业4.0时代的人机关系:技术将如何改变工业劳动力结构显示文摘从现在到2025年,工业4.0将推动现有的工业劳动力结构发生巨大的转变。数字化工业技术将会削减一定数量的工作岗位,但同时也将带来更多的就业机会,此外,对劳动者的技能要求与过去相比将会有极大的差别。想要顺利过渡到工业4.0,企业需要对员工进行再培训,改进组织架构,并制定战略性的人才计划。Markus Lorenz Michael Rüβmann 2016中国工业评论2016,0,10:7
8In vivo subsurface morphological and functional cellular and subcellular imaging of the gastrointestinal tract with confocal mini-microscopy显示文摘瞄准:为在活体内评估一根最新发达的手持的共焦的探针在啮齿类动物的完全的胃肠道的显微镜的成像。方法:一根新奇僵硬共焦的探针(直径 7 公里) 为 fluorophore 刺激用 488 nm 单身者线激光在人为使用与类似于灵活 endomicroscopy 系统的光特征被设计。轻排放在 505 ~ 750 nm 被检测。看法的地多样地是 475 妈妈 475 妈妈。光片厚度是有 0.7 妈妈的侧面的分辨率的 7 妈妈。在不同深度(到 250 妈妈的表面) 的表面下的连续图象多样地在 1024 点在实时被产生由在轻轻的、稳定的接触把探查放到织物上的 1024 个象素(0.8 frames/s ) 。织物标本为组织病理学说的关联被取样。结果:食管,胃,小并且大肠和中央,肝,胰和胆囊是在在 n = 的高分辨率的视觉 ised 在活体内 48 个鼠标。有共焦的微型显微镜学探查的实时显微镜的成像是容易的完成。不同染色协议(荧光黄,吖啶黄,标记 FITC 的葡聚糖和 L。可食用嗯植物凝血素) 织物的每个加亮的特定的方面,和在活体内成像与常规组织学最优地相关。在活体内血流监视把功能的质量加到词法成像。结论:共焦的显微镜学是在甚至表面下的织物结构的高分辨率允许完全的官方补给的道的可视化的可行在活体内。在这研究评估的新共焦的探查设计与腹腔镜检查兼容并且显著地扩展可能的应用的地到 intra 腹的机关。它允许新在活体内染色和申请选择的立即的测试因此在病人从动物研究允许快速的转移到临床的使用。Martin Goetz Beena Memadathil Stefan Biesterfeld Constantin Schneider Sebastian Gregor Peter R Galle Markus F Neurath Ralf Kiesslich 2007World Journal of Gastroenterology2007,13,15:6
9Bcl-x_L and Myeloid cell leukaemia-1 contribute to apoptosis resistance of colorectal cancer cells显示文摘AIM: To explore the role of Bcl-xL and Myeloid cell leukaemia (Mcl)-1 for the apoptosis resistance of colorectal carcinoma (CRC) cells towards current treat-ment modalities. METHODS: Bcl-xL and Mcl-1 mRNA and protein ex-pression were analyzed in CRC cell lines as well as human CRC tissue by Western blot,quantitative PCRand immunohistochemistry. Bcl-xL and Mcl-1 protein expression was knocked down or increased in CRC cell lines by applying specific siRNAs or expression plas-mids,respectively. After modulation of protein expres-sion,CRC cells were treated with chemotherapeutic agents,an antagonistic epidermal growth factor recep-tor (EGFR1) antibody,an EGFR1 tyrosine kinase inhibi-tor,or with the death receptor ligand TRAIL. Apoptosis induction and cell viability were analyzed. RESULTS: Here we show that in human CRC tis-sue and various CRC cell lines both Bcl-xL and Mcl-1 are expressed. Bcl-xL expression was higher in CRC tissue than in surrounding non-malignant tissue,both on protein and mRNA level. Mcl-1 mRNA expression was significantly lower in ma-lignant tissues. However,protein expression was slightly higher. Viability rates of CRC cells were significantly decreased after knock down of Bcl-xL expression,and,to a lower extent,after knock down of Mcl-1 expression. Furthermore,cells with reduced Bcl-xL or Mcl-1 expression was more sensitive towards oxaliplatin-and irinotecan-induced apoptosis,and in the case of Bcl-xL also towards 5-FU-induced apoptosis. On the other hand,upregulation of Bcl-xL by transfec-tion of an expression plasmid decreased chemothera-peutic drug-induced apoptosis. EGF treatment clearly induced Bcl-xL and Mcl-1 expression in CRC cells. Apop-tosis induction upon EGFR1 blockage by cetuximab or PD168393 was increased by inhibiting Mcl-1 and Bcl-xL expression. More strikingly,CD95-and TRAIL-induced apoptosis was increased by Bcl-xL knock down. CONCLUSION: Our data suggest that Bcl-xL and,to a lower extent,Mcl-1,are important anti-apoptotic factors in CRC. Specific downregulation of Bcl-xL is a promising approach to sensitize CRC cells towards chemotherapy and targeted therapy.Henning Schulze-Bergkamen Roland Ehrenberg Lothar Hickmann Binje Vick Toni Urbanik Christoph C Schimanski Martin R Berger Arno Schad Achim Weber Steffen Heeger Peter R Galle Markus Moehler 2008World Journal of Gastroenterology2008,14,24:4
10Femtojoule electro-optic modulation using a silicon– organic hybrid device显示文摘Energy-efficient electro-optic modulators are at the heart of short-reach optical interconnects,and silicon photonics is considered the leading technology for realizing such devices.However,the performance of all-silicon devices is limited by intrinsic material properties.In particular,the absence of linear electro-optic effects in silicon renders the integration of energy-efficient photonic–electronic interfaces challenging.Silicon–organic hybrid(SOH)integration can overcome these limitations by combining nanophotonic silicon waveguides with organic cladding materials,thereby offering the prospect of designing optical properties by molecular engineering.In this paper,we demonstrate an SOH Mach–Zehnder modulator with unprecedented efficiency:the 1-mm-long device consumes only 0.7 fJ bit^(-1) to generate a 12.5 Gbit s^(-1) data stream with a bit-error ratio below the threshold for hard-decision forward-error correction.This power consumption represents the lowest value demonstrated for a non-resonant Mach–Zehnder modulator in any material system.It is enabled by a novel class of organic electro-optic materials that are designed for high chromophore density and enhanced molecular orientation.The device features an electro-optic coefficient of r33<180 pm V^(-1) and can be operated at data rates of up to 40 Gbit s^(-1).Sebastian Koeber Robert Palmer Matthias Lauermann Wolfgang Heni Delwin L Elder Dietmar Korn Markus Woessner Luca Alloatti Swen Koenig Philipp C Schindler Hui Yu Wim Bogaerts Larry R Dalton Wolfgang Freude Juerg Leuthold Christian Koos 2015Light(Science & Applications)2015,4,1:4
11Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma-a rationale for a molecular targeting strategy?显示文摘AIM: To define the (co-)expression pattern of target receptor-tyrosine-kinases (RTK) in human gastric adenocarcinoma. METHODS: The (co-)expression pattern of VEGFR1-3,PDGFRα/b and EGFR1 was analyzed by RT-PCR in 51 human gastric adenocarcinomas. In addition,IHC staining was applied for confirmation of expression and analysis of RTK localisation. RESULTS: The majority of samples revealed a VEGFR1 (98%),VEGFR2 (80%),VEGFR3 (67%),PDGFRα (82%) and PDGFRβ(82%) expression,whereas only 62% exhibited an EGFR1 expression. 78% of cancers expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRα revealed a predominantly cytoplasmatic staining in tumor cells,accompanied by an additional nuclear staining for VEGFR3 ,EGFR1 was almost exclusively detected on the membrane of tumor cells. PDGFRβ was restricted to stromal pericytes,which also depicted a PDGFRα expression.receptor-tyrosine-kinases coexpression in gastric adenocarcinoma and might therefore encourage an application of multiple-target RTK-inhibitors within a combination therapy.Daniel Drescher Markus Moehler Ines Gockel Kirsten Frerichs Annett Müller Friedrich Dünschede Thomas Borschitz Stefan Biesterfeld Martin Holtmann Thomas Wehler Andreas Teufel Kerstin Herzer Thomas Fischer Martin R Berger Theodor Junginger Peter R Galle Carl C Schimanski 2007World Journal of Gastroenterology2007,13,26:4
12Systematic analysis of the safety and benefits of transvaginal hybrid-NOTES cholecystectomy显示文摘AIM: To evaluate transvaginal hybrid-NOTES cholecystectomy(TVC) during its clinical establishment and compare it with the traditional laparoscopic technique(LC).METHODS: The specific problems and benefits of TVC were reviewed using a registry analysis,a comparative cohort study and a randomized clinical trial. At first,feasibility,safety and specific complications of the TVC were analyzed based on the first 488 data sets of the German NOTES Registry(GNR). Hereafter,we compared the early postoperative results of our first 50 TVC-patients with those of 50 female LCpatients matched by age,BMI and ASA classification. The same cohort was contacted an average of two years later to evaluate long-term results concerning pain and satisfaction with the aesthetic results and the overall postoperative results as well as sexual intercourse by means of two domains of the German version of the Female Sexual Function Index(FSFI-d). Consequently,we performed a randomized clinical trial comparing 20 TVC-patients with 20 needlescopic/3-trocar cholecystectomies(NC) also concerning the early postoperative results as well as pain,satisfaction and quality of life by means of the Eypasch Gastrointestinal Quality of Life Index(GIQLI) in the later course. Finally,we discussed the results in accordance with other published studies.RESULTS: The complication(3.5%) and conversion rates(4.1%) for TVC were low in the GNR and comparable to those of the LC. Access related intraoperative complications included injuries to the bladder(n = 4; 0.8%) and bowel(n = 3; 0.6%). The study cohort revealed less postoperative pain after TVC comparing to the LC-patients on the day of surgery(NRS,1.5/10 vs 3.1/10,P = 0.003),in the morning(NRS,1.9/10 vs 2.8/10,P = 0.047) and in the evening(NRS,1.1/10 vs 1.8/10,P = 0.025) of postoperative day(POD) one. The randomized clinical trial consistently found less cumulative pain until POD 2(NRS,8/40 vs 14/40,P = 0.043),as well as until POD 10(NRS,22/190 vs 41/190,P = 0.010). Furthermore,the TVC-patients had a better quality of life on POD 10 than did the LC-patients(GIQLI,124/144 vs 107/144,P = 0.028). The complication rates were comparable and no specific problems were detected in the long-term follow-up for sexual intercourse for either group. The TVC-patients were more satisfied with the aesthetic result in the long-term course in the matched cohort analysis(1.00 vs 1.88,P < 0.001) as well as in the randomized clinical trial(1.00 vs 1.70,P < 0.001) when compared with the LC-patients.CONCLUSION: TVC is a feasible procedure with a high safety profile and has advantages in regard to postoperative pain and aesthetic results when compared with LC or NC.Dirk R Bulian Jurgen Knuth Kai S Lehmann Axel Sauerwald Markus M Heiss 2015World Journal of Gastroenterology2015,21,38:3
13Quantification of human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) mRNA in testicular tissue of infertile patients显示文摘Aim: To evaluate the quantitative detection of human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) mRNA as diagnostic parameters in the workup of testicular tissue specimens from patients presenting with non-obstructive azoospemia. Methods: hTR and hTERT mRNA expression were quantified in 38 cryopreserved testicular tissue specimens by fluorescence real-time reverse transcription- polymerase chain reaction (RT-PCR)in a LightCycler(r). This was paralleled by conventional histological workup in all tissue specimens and additional semithin sectioning preparation in cases with maturation arrest ( n = 12) and Sertoli-cell-only syndrome ( n = 12). Results: The average normalized hTERT expression (NhTERT) Was 131.9 ± 48.0 copies (mean ± SD) in tissue specimens with full spermatogenesis, NhTERT = 51.2 ± 17.2 copies in those with maturation arrest and NhTERT = 2.7 ± 2.4 copies in those with Sertoli-cell-only syndrome (SCOS). The discriminant analysis showed that detection of NhTERT (NhTR) had a predictive value of 86.8 % (55.3 % ) for correct classification in one of the three histological subgroups.Conclusion: Our results demonstrate that quantitative detection of hTERT mRNA expression in testicular tissue enables a molecular-diagnostic classification of gametogenesis. Quantitative detection of hTERT in testicular biopsies is thus well suited for supplementing the histopathological evaluation.Mark Schrader Markus Müller Rüdiger Heicappell Bernd Straub Kurt Miller 2001Asian Journal of Andrology2001,3,4:3
14Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis显示文摘Phil A Hart Terumi Kamisawa William R Brugge Jae Bock Chung Emma L Culver László Czakó Luca Frulloni Vay Liang W Go Thomas M Gress Myung-Hwan Kim Shigeyuki Kawa Kyu Taek Lee Markus M Lerch Wei-Chih Liao Matthias L?hr Kazuichi Okazaki Ji Kon Ryu Nicolas Sc 2013Gut2013,,12:2
15Infectious, atopic and inflammatory diseases, childhood adversities and familial aggregation are independently associated with the risk for mental disorders: Results from a large Swiss epidemiological study显示文摘AIM To examine the associations between mental disorders and infectious, atopic, inflammatory diseases while adjusting for other risk factors.METHODS We used data from PsyC oL aus, a large Swiss Population Cohort Study(n = 3720; age range 35-66). Lifetime diagnoses of mental disorders were grouped into the following categories: Neurodevelopmental, anxiety(early and late onset), mood and substance disorders. They were regressed on infectious, atopic and other inflammatory diseases adjusting for sex, educational level, familial aggregation, childhood adversities and traumatic experiences in childhood. A multivariate logistic regression was applied to each group of disorders. In a complementary analysis interactions with sex were introduced via nested effects. RESULTS Associations with infectious, atopic and other chronic inflammatory diseases were observable together with consistent effects of childhood adversities and familial aggregation, and less consistent effects of trauma in each group of mental disorders. Streptococcal infections were associated with neurodevelopmental disorders(men), and measles/mumps/rubella-infections with early and late anxiety disorders(women). Gastric inflammatory diseases took effect in mood disorders(both sexes) and in early disorders(men). Similarly, irritable bowel syndrome was prominent in a sex-specific way in mood disorders in women, and, moreover, was associated with early and late anxiety disorders. Atopic diseases were associated with late anxiety disorders. Acne(associations with mood disorders in men) and psoriasis(associations with early anxiety disorders in men and mood disorders in women) contributed sex-specific results. Urinary tract infections were associated with mood disorders and, in addition, in a sex-specific way with late anxiety disorders(men), and neurodevelopmental and early anxiety disorders(women).CONCLUSION Infectious, atopic and inflammatory diseases areimportant risk factors for all groups of mental disorders. The sexual dimorphism of the associations is pronounced.Vladeta Ajdacic-Gross Aleksandra Aleksandrowicz Stephanie Rodgers Margot Mutsch Anja Tesic Mario Müller Wolfram Kawohl Wulf R?ssler Erich Seifritz Enrique Castelao Marie-Pierre F Strippoli Caroline Vandeleur Roland von K?nel Rosa Paolicelli Markus A Landolt Cornelia Witthauer Roselind Lieb Martin Preisig 2016World Journal of Psychiatry2016,6,4:2
16Killing of p53-deficient hepatoma cells by parvovirus H-1 and chemotherapeutics requires promyelocytic leukemia protein显示文摘AIM: To evaluate the synergistic targeting and killing of human hepatocellular carcinoma (HCC) cells lacking p53 by the oncolytic autonomous parvovirus (PV) H-1 and chemotherapeutic agents and its dependence on functional promyelocytic leukemia protein (PML). METHODS: The role of p53 and PML in regulating cy-totoxicity and gene transfer mediated by wild-type (wt) PV H-1 were explored in two pairs of isogenic human hepatoma cell lines with different p53 status. Further-more,H-1 PV infection was combined with cytostatic drug treatment. RESULTS: While the HCC cells with different p53 status studied were all susceptible to H-1 PV-induced apoptosis,the cytotoxicity of H-1 PV was morepronounced in p53-negative than in p53-positive cells. Apoptosis rates in p53-negative cell lines treated by genotoxic drugs were further enhanced by a treatment with H-1 PV. In flow cytometric analyses,H-1 PV infection resulted in a reduction of the mitochondrial transmembrane potential. In addition,H-1 PV cells showed a significant increase in PML expression. Knocking down PML expression resulted in a striking reduction of the level of H-1 PV infected tumor cell death. CONCLUSION: H-1 PV is a suitable agent to circumvent the resistance of p53-negative HCC cells to genotoxic agents,and it enhances the apoptotic process which is dependent on functional PML. Thus,H-1 PV and its oncolytic vector derivatives may be considered as therapeutic options for HCC,particularly for p53-negative tumors.Maike Sieben Kerstin Herzer Maja Zeidler Vera Heinrichs Barbara Leuchs Martin Schuler Jan J Cornelis Peter R Galle Jean Rommelaere Markus Moehler 2008World Journal of Gastroenterology2008,14,24:2
17Genetic association of autoimmune hepatitis and human leucocyte antigen in German patients显示文摘AIM: To report on our large German collective and updated data of 142 patients with autoimmune hepatitis (AIH) type 1. METHODS: Key investigations performed were liver biopsy, serum autoantibodies as well as serum markers such as IgG and elevated transaminases. Antinuclear antigen (ANA) and smooth muscle antigen (SMA) autoantibodies characterized type 1 AIH. Type 3 (AIH) was solely characterized by the occurrence of soluble liver antigen/liver-pancreas antigen (SLA/LP) autoantibodies either with or without ANA or SMA autoantibodies. RESULTS: Most prevalent HLAs were A2 (68 patients, 48%), B8 (63 patients, 44%), C7 (90 patients, 63%), DR3 (49 patients, 38%), DR4 (49 patients, 38%) and DQ2 (42 patients, 30%). Compared to the Italian and North American patients, we found fewer patients with a DQ2 subtype. Furthermore, the B8-DR3-DQ2 human leucocyte antigen (HLA) was also less prominent compared to the North American patients. However, prevalences of B8, DR3, DR4, DR7, DR11 and DR13 were comparable to the Italian and North American patients. Furthermore, we report on an additional subgroup of patients with SLA/LP positive AIH. Generally, in this subgroup of patients the same HLA subtypes were favoured as the AIH type 1. CONCLUSION: Although HLA subtypes were comparable between these three collectives, the German patients were distinct from the Italian and North American patients with respect to DQ2 and from the North American patients with respect to B8-DR3-DQ2HLA. A clinical correlation, e.g. difference in severity or treatability of AIH type 1, has yet to be determined.Andreas Teufel Markus Wrns Arndt Weinmann Catherine Centner Anja Piendl Ansgar W Lohse Peter R Galle Stephan Kanzler 2006World Journal of Gastroenterology2006,12,34:2
18Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing显示文摘The impact of the microenvironment on innate lymphoid cell(ILC)-mediated immunity in humans remains largely unknown.Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127+ILCs across four human tissues.Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs,and signatures of tissue-residency,activation and modified metabolism in colon and lung ILCs.Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets.In the lung we identified both CRTH2+and CRTH2−ILC2 with lung-specific signatures,which could be recapitulated by alarmin-exposure of circulating ILC2.Finally,we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells,revealing a subset of potentially immature ILCs with TCR-δ rearrangement.Our study provides a useful resource for in-depth understanding of ILC-mediated immunity in humans,with implications for disease.Luca Mazzurana Paulo Czarnewski Viktor Jonsson Leif Wigge Markus Ringnér Teresa CWilliams Avinash Ravindran Åsa KBjörklund Jesper Säfholm Gunnar Nilsson Sven-Erik Dahlén Ann-Charlotte Orre Mamdoh Al-Ameri Charlotte Höög Charlotte Hedin Sylwester Szczegielniak Sven Almer Jenny Mjösberg 2021Cell Research2021,31,5:2
19Culture and the self: implications for cognition显示文摘Markus H R Kitayama S 1991Emotion and Motivation Psychological Review1991,98,2:1
20Comparison of left ventricular lead placement via the coronary venous approach versus lateral thoracotomy in patients receiving cardiac resynchronization therapy 显示文摘Koos R Sinha AM Markus K 2004Am J Cardiol2004,94,:1
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