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| 1 | VEGF-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 | 2008 | World Journal of Gastroenterology2008,14,26: | 15 |
| 2 | Cyclooxygenase-2 and epithelial growth factor receptor up-regulation during progression of Barrett's esophagus to adenocarcinoma显示文摘瞄准:在整个 Barretts 食管的前进调查 cyclooxygenase-2 (COX-2 ) 和上皮的生长因素受体(EGFR ) 的表示() 。方法:COX-2 和 EGFR 蛋白质表情被使用免疫检测组织化学的方法。详细 cytomorphological 改变的 A 是坚定的。COX-2 和 EGFR 表示的区域被使用计算机成像系统确定。结果:COX-2 和 EGFR 的表情与前进一起增加了从到食管腺癌(EAC ) 。积极关联在 COX-2 表示和 EGFR 表示之间被发现。结论:COX-2 和 EGFR 可能在逐步的前进从是合作的到 EAC,从而导致致癌作用。 | Yan Li John M Wo Mukunda B Ray Whitney Jones Ruifeng R Su Susan Ellis Robert C G Martin | 2006 | World Journal of Gastroenterology2006,12,6: | 14 |
| 3 | Capecitabine 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 | 2009 | World Journal of Gastroenterology2009,15,4: | 10 |
| 4 | Bcl-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 | 2008 | World Journal of Gastroenterology2008,14,24: | 4 |
| 5 | Coexpression 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 | 2007 | World Journal of Gastroenterology2007,13,26: | 4 |
| 6 | A new Early Cretaceous dinosaur track assemblage and the first definite non-avian theropod swim trackway from China显示文摘The trackway of a swimming theropod (ichnogenus Characichnos) is reported from the Lower Cretaceous Feitianshan Formation of Sichuan, China. These swim tracks help confirm that non-avian theropods were capable of forging moderately deep bodies of water. The trackway occurs on the same surface as a typical walking trackway of a sauropod (ichnogenus Brontopodus). Both occurrences are the first reported from the Cretaceous of Sichuan, and the swim tracks are the first well-preserved example of a Characichnos trackway from China. Additionally, a theropod walking trackway and several ornithopod walking trackways (similar to the ichnogenus Caririchnium) occur in the same horizon. The ornithopod trackways show a parallel orientation, suggesting gregarious behavior of the trackmakers, which may have been iguanodontiforms and/or hadrosauriforms. The co-occurrence of theropod swim tracks and theropod walking tracks suggests a fluctuation of water depth within a distinct time span. | XING LiDa LOCKLEY Martin G ZHANG JianPing MILNER Andrew R C KLEIN Hendrik LI DaQing PERSONS IV W Scott EBI JieFang | 2013 | Chinese Science Bulletin2013,58,19: | 3 |
| 7 | Nanomaterial-based Li-ion battery electrodes显示文摘 | LIN C MARTIN C R SCROSATI B | 2001 | J Power Sources2001,9798,: | 2 |
| 8 | A high-rate,high-capacity nanostructured Sn-based anode prepared using sol-gel template synthesis 显示文摘 | LIN C MARTIN C R A | 2001 | J Electrochem Soc2001,148,2: | 2 |
| 9 | A high-rate,high-capacity,nanostructrued Sn-based anode prepared using sol-gel template synthesis显示文摘 | Li N C Martin C R | 2001 | J Electrochem Soc2001,148,2: | 2 |
| 10 | Effects of resistance training on the lipid profile in obese women显示文摘 | Costa R R Lima Alberton C Tagliari M Martins Kruel L F | 2011 | Journal of Sports Medicine and Physical Fitness2011,,1: | 2 |
| 11 | Wheat classification using image analysis and crush-force parameters 显示文摘 | ZayasI Martin C R Steele J L | 1996 | Trans of the ASAE1996,39,: | 1 |
| 12 | Base-pair neutral homozygotes can be discriminated by calibrated high-resolution melting of small amplicons显示文摘 | Gundry C N Dobrowolski S F Martin Y R | 2008 | Nucleic Acids Res2008,36,: | 1 |
| 13 | Nanomaterials: a membrane-basedsyntheticapproach显示文摘 | Martin C R | 1994 | Science1994,266,: | 1 |
| 14 | Hoek-Brown parameters for predicting the depth of brittle failure around tunnels显示文摘 | MARTIN C D KAISER P K MCCREATH D R | 1999 | Canadian Geotechnica1 Journal1999,36,1: | 1 |
| 15 | Long-term performance summary for the boot wetland treatment system 显示文摘 | Martin R J Keller H C Clarke A R | 2001 | Water Science and Technology2001,44,1112: | 1 |
| 16 | Recruitment of an inotropic reserve in moderately ischemic myocardium at the expense of metabolic recovery:a model of short term hibernation显示文摘 | Schulz R Guth BD Martin C | 1992 | Cir Res1992,70,: | 1 |
| 17 | A comparison of methods used to determine bi mass on naturalized swards显示文摘 | MARTIN R C ASTATKIE T COOPER J M | 2005 | Journal of Agronomy and Crop Science2005,191,2: | 1 |
| 18 | The effects of moisture on the flammability characteristics of textile materials显示文摘 | Miller B Martin J R Goswami B C | 1975 | Textile Research Journal1975,45,: | 1 |
| 19 | Inhibition of P-glycoprotein function by XR9576 in a solid tumour model can restore anticancer drug efficacy显示文摘 | Walker J Martin C Callaghan R | 2002 | Euro J Cancer2002,40,4: | 1 |
| 20 | Restrictions to the adaptation of influenza A virus H5 hemagglutinin to the human host显示文摘 | Harvey R Martin A C Zambon M | 2004 | J Virol2004,78,1: | 1 |