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| 1 | High 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 | 2009 | World Journal of Gastroenterology2009，15，17： | 40 |
| 2 | Multidisciplinary 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 | 2008 | World Journal of Gastroenterology2008，14，24： | 17 |
| 3 | 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 |
| 4 | Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial显示文摘 | Florian Lordick Yoon-Koo Kang Hyun-Cheol Chung Pamela Salman Sang Cheul Oh Gy?rgy Bodoky Galina Kurteva Constantin Volovat Vladimir M Moiseyenko Vera Gorbunova Joon Oh Park Akira Sawaki Ilhan Celik Heiko G?tte Helena Melezínková Markus Moehler | 2013 | Lancet Oncology2013，，6： | 14 |
| 5 | 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 |
| 6 | 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 |
| 7 | 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 |
| 8 | 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 |
| 9 | An open-label, multicentre biomarker-oriented AIO phase II trial of sunitinib for patients with chemo-refractory advanced gastric cancer显示文摘 | M. Moehler A. Mueller J.T. Hartmann M.P. Ebert S.E. Al-Batran P. Reimer M. Weihrauch F. Lordick T. Trarbach S. Biesterfeld M. Kabisch D. Wachtlin P.R. Galle | 2011 | European Journal of Cancer2011，，10： | 3 |
| 10 | Killing 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 | 2008 | World Journal of Gastroenterology2008，14，24： | 2 |
| 11 | LEOPARD-II:A randomized phase II study of radiochemotherapy RCT with 5FU and cisplatin plusminus cetuximab Cet in unresectable locally advanced esophageal cancer LAEC显示文摘 | Rades D Moehler MH Debus J | 2014 | J Clin Oncol2014，，： | 1 |
| 12 | Safety and efficacy of CPT-11/CF/5-Fu(IFL) versus FLF in previously untreaeed advanced or metastatic adoenocarcinoma of the stomach or gastroesophageal junction显示文摘 | Moehler MH Siebler J Hoehler T | 2003 | Proc AmSoc Clin Oncol2003，22，5： | 1 |
| 13 | New chemotherapeutic strategies in eolorectal caneer显示文摘 | Moehler M Teufel A Galle PR | 2005 | Recent Results Cancer Res2005，165，： | 1 |
| 14 | Involvement of alpha 1-2- fucosyltransferase I ( FUT1 ) and surface-expressed Lewis ( y ) (CD174) in first endothelial cell-cell contacts during angiogenesis 显示文摘 | Moehler TM Sauer S Witzel M | 2008 | J Cell Physiol2008，215，1： | 1 |
| 15 | Prospective,open,multi-centre phase Vll trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and oxaliplatin in patients with adenocarcinoma of the oesophagogastric junction显示文摘 | Moehler M Gockel I Roessler HP | 2013 | BMC Cancer2013，11，13： | 1 |
| 16 | An open-label, multicen-tre biomarker-oriented AIO phase II trial of sunitinib for patientswith chemo-refractory advanced gastric cancer 显示文摘 | Moehler M Mueller A Hartmann JT | 2011 | Eur J Cancer2011，47，10： | 1 |
| 17 | Salvage therapy for mul- tiple myeloma with thalidomide and CED chemotherapy 显示文摘 | Moehler TM Neben K Benner A | 2001 | Blood2001，98，13： | 1 |
| 18 | Novel ways to sensitise gastrointestinal cancer to apopsis显示文摘 | Schulze-Bergkamen H Weinmann A Moehler M | 2009 | Gut2009，58，： | 1 |
| 19 | Thalidomide in multiple myeloma显示文摘 | Moehler TM Hillengass J Glasmacher A | 2006 | Curr Pharm Biotechnol2006，7，6： | 1 |
| 20 | Cetuximab with irinotecan, folinic acid and 5-fluorouracil as first-line treatment in advanced gastroesophageal cancer:a prospective multi-center biomarker-oriented phase Ⅱ study显示文摘 | Moehler M Mueller A Trarbach T Lordick F Seufferlein T Kubicka S | 2011 | Ann Oncol2011，22，： | 1 |
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