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| 1 | BCLC策略:预后预测和治疗推荐2022版更新显示文摘2018版BCLC预后和治疗推荐策略发布后,肝细胞癌(简称HCC)的研究又取得了重大进展。本次更新基于肝癌各领域的研究进展结果。重点关注影响策略的重要研究进展。虽然近年的研究结果成绩斐然,但将其引入为临床医生和研究者提供行动依据的循证模型指南来说证据效力依然不够确切。本文对该问题进行分析,阐述了为HCC患者制定个体化治疗临床决策所需的批判性思维和专业知识。 | Reig M Forner A Rimola J Ferrer-Fabrega J Burrel M Garcia-Criado A Kelley RK Galle PR Mazzaferro V Salem R Sangro B Singal AG Vogel A Fuster J Ayuso C Bruix J 刘永凡(摘译) 崔笑(摘译) 耿小平(审校) | 2022 | 肝胆外科杂志2022，30，5： | 80 |
| 2 | 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 |
| 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 | Chemokine 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 | 2008 | World Journal of Gastroenterology2008，14，30： | 7 |
| 5 | 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 |
| 6 | 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 |
| 7 | hnpaet of oxidized low density lipoprotein on vascular cells显示文摘 | Galle J Hansen-Hagge T Wanner C | 2006 | Atherosclerosis2006，185，2： | 1 |
| 8 | CrN-Ag self-lubricating hard coatings显示文摘 | Mulligan C P Gall D | 2005 | Surface & Coatings Technology2005，200，： | 1 |
| 9 | Combined hemodynamic overloard of the left and right ventricles as a possible cause of interventricular septum preponderance in high blood press-ure显示文摘 | Fiorentini C Gall C Tamborini G | 1988 | Am Heart J1988，116，： | 1 |
| 10 | The role of ABO blood groups in the incidence of deep vein thrombosis 显示文摘 | Wautrecht J C Galle C Motte S | 1998 | Thromb Haemost1998，79，3： | 1 |
| 11 | Growth and physical properties of epitaxial metastable cubic TAN(001) 显示文摘 | Shin C S Gall D Desjardins P | 1999 | Appl Phys Lett1999，75，24： | 1 |
| 12 | Effect of Drying on Cement-based Materials Pore Structure as Ddentified by Mercury Intrusion Porosimetry-A Comparative Study Between Oven-, vacuum-, and Freeze-Drying显示文摘 | Galle C | 2001 | Cement and Concrete Research2001，31，10： | 1 |
| 13 | Development and worldwide distribution of the Anglo Nubian goat显示文摘 | Stemmer A Marianna S S Gall C | 2009 | Tropical and Subtropical Agroecosystems2009，11，1： | 1 |
| 14 | Vitamin D levels and mor- tality in type 2 diabetes 显示文摘 | Joergensen C Gall MA Schmedes A | 2010 | Diabetes Care2010，33，10： | 1 |
| 15 | Mice, melatonin and the circadian system 显示文摘 | KORF H W VON GALL C | 2006 | Mol Cell Endocrinol2006，252，12： | 1 |
| 16 | Melatonin: a clock-output, a clock-input 显示文摘 | Stehle JH Von Gall C Korf HW | 2003 | J Neuroendocrino12003，15，4： | 1 |
| 17 | The auxili-like phosphoprotein Swa2p is required for clathrin function in yeast显示文摘 | GALL W E HIGGINBOTHAM M A CHEN C Y | 2000 | Curr Biol2000，10，： | 1 |
| 18 | Applications of spray drying in microencapsulation of food ingredients : An over- view 显示文摘 | Adem G Galle R Odile C | 2007 | Food Research International2007，40，9： | 1 |
| 19 | An Investigation of Relationships between Communication Style and Leader Member Exchange 显示文摘 | Yrle A C Hartman S Galle W P | 2002 | Journal of Communication Management2002，6，1： | 1 |
| 20 | Atherogenic lipoproteins, oxidative stress, and cell death显示文摘 | Galle J Heermeier K Wanner C | 1999 | Kidney Int Suppl1999，71，： | 1 |
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