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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 | 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 |
| 3 | Inflammatory bowel disease serology in Asia and the West显示文摘AIM:To study serological antibodies in Caucasians and Asians,in health and inflammatory bowel disease(IBD),in Australia and Hong Kong(HK).METHODS:Anti-glycan antibodies[anti-chitobioside(ACCA),anti-laminaribioside(ALCA)],and anti-mannobioside(AMCA),anti-Saccharomyces cervisiae(gASCA);and atypical perinuclear anti-neutrophil cytoplasmic antibody(pANCA)were tested in IBD patients,their unaffected relatives,and healthy controls in Australia and HK(China).Antibody status(positive or negative)and titre was compared between subjects of different geography,ethnicity and disease state.RESULTS:Ninety subjects were evaluated:21 Crohn’s disease(CD),32 ulcerative colitis(UC),29 healthy controls,and 8 IBD patient relatives.Forty eight subjects were Australian(29 Caucasian and 19 ethnic Han Chinese)and 42 were from HK(all Han Chinese).Caucasian CD patients had a significantly higher antibody prevalence of gASCA(67%vs 3%,P<0.001),ALCA(44%vs 6%,P=0.005),and AMCA(67%vs 15%,P=0.002),whereas HK CD patients had a higher prevalence of only AMCA(58%vs 25%,P=0.035),when compared with UC and healthy subjects in both countries.Caucasian CD had significantly higher gASCA prevalence(67%vs 0%,P<0.001)and titre(median59 vs 9,P=0.002)than HK CD patients.Prevalence and titres of ALCA,ACCA and AMCA did not differ between CD in the two countries.Presence of at least one antibody was higher in Caucasian than HK CD patients(100%vs 58%,P=0.045).pANCA did not differ between countries or ethnicity.CONCLUSION:Serologic CD responses differ between HK Asian and Australian Caucasian patients.Different genetic,environmental or disease pathogenic factors may account for these differences. | Lani Prideaux Michael A Kamm Peter De Cruz Daniel R van Langenberg Siew C Ng Iris Dotan | 2013 | World Journal of Gastroenterology2013，19，37： | 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 | Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models显示文摘AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD). | Nicha Wongjarupong Gabriela M Negron-Ocasio Roongruedee Chaiteerakij Benyam D Addissie Essa A Mohamed Kristin C Mara William S Harmsen J Paul Theobald Brian E Peters Joseph G Balsanek Melissa M Ward Nasra H Giama Sudhakar K Venkatesh Denise M Harnois Michael R Charlton Hiroyuki Yamada Alicia Algeciras-Schimnich Melissa R Snyder Terry M Therneau Lewis R Roberts | 2018 | World Journal of Gastroenterology2018，24，12： | 5 |
| 6 | Single-center study comparing computed tomography colonography with conventional colonoscopy显示文摘AIM:To compare the results from computed tomography (CT) colonography with conventional colonoscopy in symptomatic patients referred for colonoscopy. METHODS: The study included 227 adult outpatients, mean age 60 years, with appropriate indications for colonoscopy. CT colonography and colonoscopy were performed on the same day in a metropolitan teaching hospital. Colonoscopists were initially blinded to the results of CT colonography but there was segmental unblinding during the procedure. The primary outcome measures were the sensitivity and specificity of CT colonography for the identification of polyps seen at colonoscopy (i.e. analysis by polyp). Secondary outcome measures included an analysis by patient, extracolonic findings at CT colonography, adverse events with both procedures and patient acceptance and preference. RESULTS: Twenty-five patients (11%) were excluded from the analysis because of incomplete colonoscopy or poor bowel preparation that affected either CT colonography, colonoscopy or both procedures. Polyps and masses (usually cancers) were detected at colonoscopy and CT colonography in 35% and 42% of patients, respectively. Of nine patients with a finaldiagnosis of cancer, eight (89%) were identified by CT colonography as masses (5) or polyps (3). For polyps analyzed according to polyp, the overall sensitivity of CT colonography was 50% (95% CI, 39%-61%) but this increased to 71% (95% CI, 52%-85%) for polyps ≥ 6 mm in size. Similarly, specificity for all polyps was 48% (95% CI, 39%-58%) increasing to 67% (95% CI, 56%-76%) for polyps ≥ 6 mm. Adverse events were uncommon but included one colonic perforation at colonoscopy. Patient acceptance was high for both procedures but preference favoured CT colonography. CONCLUSION: Although CT colonography was more sensitive in this study than in some previous studies, the procedure is not yet sensitive enough for widespread application in symptomatic patients. | Ian C Roberts-Thomson Graeme R Tucker Peter J Hewett Peter Cheung Ruben A Sebben EE Win Khoo Julie D Marker Wayne K Clapton | 2008 | World Journal of Gastroenterology2008，14，3： | 4 |
| 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 | Variations in Wool Growth with Nutrient Supply in Northern China显示文摘Field studies on essessment of nutritional status of the grazing sheep were carried out in each of the three major grassland regions, the eastern Inner Mongolia and beyond grassland, the Inner Mongolia - Ningxia - Gansu grassland and the Xinjiang grassland, in northern China. The results obtained showed that the wool production of fine wool sheep in these regions varied between regions and seasons, with similar seasonal patterns in all regions and that reducing the seasonal variations in nutrient supply would enhance wool production substantially. Nutritional limitations to wool growth of the grazing sheep in these regions were suggested, those were: the shortage of protein supply in winter and early spring; the poor quality of much of the pasture and the hay used as supplements, the low energy intake during winter which probably necessitated the use of body stores to maintain body temperature. | D X Lu,Iner(Mongolia Academy of Animal Sciences.Hohhot City.Inner Mongolia Autgolia Autonmous Region.PRC)Z C Feng,(Mongolia Academy of Animal Sciences.Hohhot City.Inner Mongolia Autgolia Autonmous Region.PRC)H R Wang,(Mongolia Academy of Animal Sciences.Hohhot City.Inner Mongolia Autgolia Autonmous Region.PRC)R Z Yang,(Xinjiang Institute of Animal Science.Xinjiang Academy of Animal Science.Yiu Hou Road.Urumqi.Xinjiang Uygur Autonomous Region PRC)C T Ma,(Chinese Academy of Agricultural Sciences.Lanzhou.Gansu.PRC)D B Purser,(CSIRO Division of Animal Production.Laboratory for Rural Research.Private Bag.P.O.Wembley.Western Australia 6014)J R Lindsay(CSIRO Division of Animal Production.Laboratory for Rural Research.Private Bag.P.O.Wembley.Western Australia 6014)D W Peter(CSIRO Division of Animal Production.Laboratory for Rural Research.Private Bag.P.O.Wembley.Western Australia 6014) | 1997 | 畜牧与饲料科学1997，22，S1： | 3 |
| 10 | Patients undergoing infrainguinal bypass to treat atherosclerotic vascular disease are underprescribed cardioprotective medications: effect on graft patency, limb salvage, and mortality显示文摘 | Peter K Henke Susan Blackburn Mary C Proctor Jeri Stevens Debabrata Mukherjee Sanjay Rajagopalin Gilbert R Upchurch James C Stanley Kim A Eagle | 2004 | Journal of Vascular Surgery2004，，： | 2 |
| 11 | Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study显示文摘 | Olivier Rixe Ronald M Bukowski M Dror Michaelson George Wilding Gary R Hudes Oliver Bolte Robert J Motzer Paul Bycott Katherine F Liau James Freddo Peter C Trask Sinil Kim Brian I Rini | 2007 | Lancet Oncology2007，，： | 2 |
| 12 | Ultraviolet light absorber mobility in crosslinked coatings : Experiments and modeling显示文摘 | PETERS C A ELLWOOD K R SRIVASTAVA Y | 2007 | Progress in Organic Coatings2007，，58： | 1 |
| 13 | Effects of age on the thickness of myelin sheaths in monkey primary visual cortex显示文摘 | Peters A Sethares C Killiany R J | 2001 | J Comp Neurol2001，435，2： | 1 |
| 14 | Effects of 17 alpha-ethynylestradiol on early - life development, sex differentiation and vitellogenin induction in mummichog ( Fundulus heteroclitus) 显示文摘 | PETERS R E M COURTENAY S C HEWITT L M et al | 2010 | Marine Environmental Research2010，69，3： | 1 |
| 15 | Stabilization and Preser- vation of Lactobacillus Acidophilus in Saccharide Matrices显示文摘 | PAUL B C MILLER D P PETER R C | 2000 | Cryobiology2000，41，1： | 1 |
| 16 | The epidemiology and cost of inpatient care for peripheral vascular disease, infec- tion, neuropathy, and ulceration in diabetes 显示文摘 | Currie C J Morgan C L L Peters J R | 1998 | Diabetes care1998，21，1： | 1 |
| 17 | A recombinant fowlpox virus that expresses the VP2 antigen of infectious bursal disease virus induces protection against mortality caused by the virus显示文摘 | BAYLISS C D PETERS R W COOK J K A | 1991 | Arch Virol1991，120，： | 1 |
| 18 | Neuroendocrine regulation of growth hormone secretion and growth in fish显示文摘 | PENG C PETER R E | 1997 | Zoologica Studies1997，36，2： | 1 |
| 19 | Valuation of an Amanzonian rainforest显示文摘 | Peters C A Gentry A H Mendelsohn R O | 1989 | Nature1989，339，： | 1 |
| 20 | Kernel-based object tracking 显示文摘 | DORIN C VISVANATHAN R PETER M | 2003 | IEEE Trans Pattern Anal Mach Intell2003，25，5： | 1 |
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