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| 1 | Tyrosine kinase of insulin-like growth factor receptor as target for novel treatment and prevention strategies of colorectal cancer显示文摘AIM: To investigate the antineoplastic potency of the novel insulin-like growth factor 1 receptor (IGF-1R) tyro- sine kinase inhibitor (TKI) NVP-AEW541 in cell lines and primary cell cultures of human colorectal cancer (CRC). METHODS: Cells of primary colorectal carcinomas were from 8 patients. Immunostaining and crystal violet stain- ing were used for analysis of growth factor receptor pro- tein expression and detection of cell number changes, respectively. Cytotoxicity was determined by measuring the release of the cytoplasmic enzyme lactate dehydro- genase (LDH). The proportion of apoptotic cells was determined by quantifying the percentage of sub-G1 (hypodiploid) cells. Cell cycle status reflected by the DNA content of the nuclei was detected by flow cytometry. RESULTS: NVP-AEW541 dose-dependently inhibited the proliferation of colorectal carcinoma cell lines and primary cell cultures by inducing apoptosis and cell cycle arrest. Apoptosis was characterized by caspase-3 activa- tion and nuclear degradation. Cell cycle was arrested at the G1/S checkpoint. The NVP-AEW541-mediated cell cycle-related signaling involved the inactivation of Akt and extracellular signal-regulated kinase (ERK) 1/2, the upregulation of the cyclin-dependent kinase inhibitors p21Waf1/CIP1 and p27Kip1, and the downregulation of the cell cycle promoter cyclin D1. Moreover, BAX was upregu- lated during NVP-AEW541-induced apoptosis, whereas Bcl-2 was downregulated. Measurement of LDH release showed that the antineoplastic effect of NVP-AEW541 was not due to general cytotoxicity of the compound. However, augmented antineoplastic effects were ob-served in combination treatments of NVP-AEW541 with either 5-FU, or the EGFR-antibody cetuximab, or the HMG-CoA-reductase inhibitor fluvastatin. CONCLUSION: IGF-1R-TK inhibition is a promising novel approach for either mono- or combination treatment strategies of colorectal carcinoma and even for CRC che- moprevention. | Michael Hpfner Andreas P Sutter Alexander Huether Viola Baradari Hans Scherübl | 2006 | World Journal of Gastroenterology2006，12，35： | 10 |
| 2 | Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells显示文摘AIM: To investigate the antiproliferative effect of the histone deacetylase (HDAC) inhibitor MS-275 on cholangiocarcinoma cells alone and in combination with conventional cytostatic drugs (gemcitabine or doxorubicin) or the novel anticancer agents sorafenib or bortezomib. METHODS: Two human bile duct adenocarcinoma cell lines (EGI-1 and TFK-1) were studied. Crystal violet staining was used for detection of cell number changes. Cytotoxicity was determined by measuring the release of the cytoplasmic enzyme lactate dehydrogenase (LDH). Apoptosis was determined by measuring the enzyme activity of caspase-3. Cell cycle status reflected by the DNA content was detected by flow cytometry.RESULTS: MS-275 treatment potently inhibited the proliferation of EGI-1 and TFK-1 cholangiocarcinoma cells by inducing apoptosis and cell cycle arrest. MS-275-induced apoptosis was characterized by activation of caspase-3, up-regulation of Bax and down-regulation of Bcl-2. Cell cycle was predominantly arrested at the G1/S checkpoint, which was associated with induction of the cyclin-dependent kinase inhibitor p21Waf/CIP1. Furthermore, additive anti-neoplastic effects were observed when MS-275 treatment was combined with gemcitabine or doxorubicin, while combination with the multi-kinase inhibitor sorafenib or the proteasome inhibitor bortezomib resulted in overadditive anti-neoplastic effects.CONCLUSION: The growth of human cholangiocarcinoma cells can be potently inhibited by MS-275 alone or in combination with conventional cytostatic drugs or new, targeted anticancer agents. | Viola Baradari Michael Hpfner Alexander Huether Detlef Schuppan Hans Scherübl | 2007 | World Journal of Gastroenterology2007，13，33： | 10 |
| 3 | Near-infrared fluorescence sentinel lymph node detection in gastric cancer: A pilot study显示文摘AIM: To investigate feasibility and accuracy of nearinfrared fluorescence imaging using indocyanine green: nanocolloid for sentinel lymph node(SLN) detection in gastric cancer.METHODS: A prospective, single-institution, phaseI feasibility trial was conducted. Patients suffering from gastric cancer and planned for gastrectomy were included. During surgery, a subserosal injection of 1.6 m L ICG:Nanocoll was administered around the tumor. NIR fluorescence imaging of the abdominal cavity was performed using the Mini-FLARE? NIR fluorescence imaging system. Lymphatic pathways and SLNs were visualized. Of every detected SLN, the corresponding lymph node station, signal-to-background ratio and histopathological diagnosis was determined. Patients underwent standard-of-care gastrectomy. Detected SLNs outside the standard dissection planes were also resected and evaluated.RESULTS: Twenty-six patients were enrolled. Four patients were excluded because distant metastases were found during surgery or due to technical failure of the injection. In 21 of the remaining 22 patients, at least 1 SLN was detected by NIR Fluorescence imaging(mean 3.1 SLNs; range 1-6). In 8 of the 21 patients, tumor-positive LNs were found. Overall accuracy of the technique was 90%(70%-99%; 95%CI), which decreased by higher p T-stage(100%, 100%, 100%, 90%, 0% for respectively Tx, T1, T2, T3, T4 tumors). All NIR-negative SLNs were completely effaced by tumor. Mean fluorescence signal-to-background ratio of SLNs was 4.4(range 1.4-19.8). In 8 of the 21 patients, SLNs outside the standard resection plane were identified, that contained malignant cells in 2 patients.CONCLUSION: This study shows successful use of ICG:Nanocoll as lymphatic tracer for SLN detection in gastric cancer. Moreover, tumor-containing LNs outside the standard dissection planes were identified. | Quirijn RJG Tummers Leonora SF Boogerd Wobbe O de Steur Floris PR Verbeek Martin C Boonstra Henricus JM Handgraaf John V Frangioni Cornelis JH van de Velde Henk H Hartgrink Alexander L Vahrmeijer | 2016 | World Journal of Gastroenterology2016，22，13： | 9 |
| 4 | Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine显示文摘AIM: To evaluate whether pyrrolidine dithiocarbamate (PDTC), an enhancer of HO production, attenuates intestinal IR injury.METHODS: Eighteen male rats were randomly allocated into three groups: (a) sham; (b) IR, consisting of 30 min of intestinal ischemia, followed by 2-h period of reperfusion; and (c) PDTC treatment before IR. Intestinal microvascular perfusion (IMP) was monitored continuously by laser Doppler fiowmetry. At the end of the reperfusion, serum samples for lactate dehydrogenase (LDH) levels and biopsies of ileum were obtained. HO activity in the ileum was assessed at the end of the reperfusion period.RESULTS: At the end of the reperfusion in the IR group,IMP recovered partially to 42.5% of baseline (P<0.05vs sham), whereas PDTC improved IMP to 67.3% of baseline (P<0.01 vs IR). There was a twofold increase in HO activity in PDTC group (2 062.66±106.11) as compared to IR (842.3±85.12) (P<0.001). LDH was significantly reduced (P<0.001) in PDTC group (585.6±102.4)as compared to IR group (1 973.8±306.5). Histological examination showed that the ileal mucosa was significantly less injured in PDTC group as compared with IR group.CONCLUSION: Our study demonstrates that PDTC improves the IMP and attenuates IR injury of the intestine possibly via HO production. Additional studies are warranted to evaluate the clinical efficacy of PDTC in the prevention of IR injury of the small intestine. | Ismail H Mallick Wen-Xuan Yang Marc C Winslet Alexander M Seifalian | 2005 | World Journal of Gastroenterology2005，11，46： | 8 |
| 5 | Signaling pathways involved in the inhibition of epidermal growth factor receptor by erlotinib in hepatocellular cancer显示文摘瞄准:在肝细胞癌(HCC ) 检验导致 erlotinib 的生长抑制的内在的机制。方法:在基因表示的导致 Erlotinib 的改变用 cDNA 数组技术被评估;在蛋白质表示或蛋白质激活的变化用西方的弄污由于象 IGF-1-induced EGFR transactivation 一样的 erlotinib 治疗被调查。结果:Erlotinib 治疗禁止了 mitogen 激活和抄写(STAT ) 的激活的蛋白质(地图)-kinase 小径和信号变换器调停了表明哪个导致了调整由 cDNA 数组技术示威了的基因的 apoptosis 和房间周期的一个改变的表达式。象与象 Bcl-2, Bcl-X (L) 或 jun D 一样的 antiapoptotic 因素的一条下面规定联系的 caspases 和 gadds 一样的 proapoptotic 因素的 Overexpression 说明了让 erlotinib 的力量导致 apoptosis。支持 G1/S-transition 的房间周期管理者并且在 cyclin 依赖的激酶禁止者和 gadds 的表示上的 Downregulation 响应 erlotinib 贡献了 G1/G0-arrest 的正式就职。而且,我们显示了由 IGF-1-receptor 的调停 EGFR 的发信号的 transactivation 并且在受体受体十字谈话显示出 erlotinib 的禁止的效果。结论:我们的学习在 HCC 房间和 thus 使 EGFR-TK-inhibition 的行动的机制的理解清楚些可能便于 additively 或 synergistically 行动的联合治疗的设计。而且,我们对 erlotinib 处理作出回应的小径上的数据能在以后预言肿瘤的应答的海角到 EGFR-TKIs 是有用的。 | Alexander Huether Michael Hpfner Andreas P Sutter Viola Baradari Detlef Schuppan Hans Scherübl | 2006 | World Journal of Gastroenterology2006，12，32： | 7 |
| 6 | Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal metastases显示文摘AIM:To systematically review the available evidence regarding cytoreductive surgery(CRS) and intraperitoneal chemotherapy(IPC) for colorectal peritoneal metastases(CPM).METHODS:An electronic literature search was carried out to identify publications reporting oncological outcome data(overall survival and/or disease free survival and/or recurrence rates)following CRS and IPC for treatment of CPM.Studies reporting outcomes following CRS and IPC for cancer subtypes other than colorectal were only included if data were reported independently for colorectal cancer-associated cases;in addition studies reporting outcomes for peritoneal carcinomatosis of appendiceal origin were excluded.RESULTS:Twenty seven studies,published between1999 and 2013 with a combined population of 2838patients met the predefined inclusion criteria.Included studies comprised 21 case series,5 case-control studies and 1 randomised controlled trial.Four studies provided comparative oncological outcome data for patients undergoing CRS in combination with IPC vs systemic chemotherapy alone.The primary indication for treatment was CPM in 96%of cases(2714/2838)and recurrent CPM(rCPM)in the remaining 4%(124/2838).In the majority of included studies(20/27)CRS was combined with hyperthermic intraperitoneal chemotherapy(HIPEC).In 3 studies HIPEC was used in combination with early post-operative intraperitoneal chemotherapy(EPIC),and 2 studies used EPIC only,following CRS.Two studies evaluated comparative outcomes with CRS+HIPEC vs CRS+EPIC for treatment of CPM.The delivery of IPC was performed using an'open'or'closed'abdomen approach in the included studies.CONCLUSION:The available evidence presented in this review indicates that enhanced survival times can be achieved for CPM after combined treatment with CRS and IPC. | Reza Mirnezami Brendan J Moran Kate Harvey Tom Cecil Kandiah Chandrakumaran Norman Carr Faheez Mohamed Alexander H Mirnezami | 2014 | World Journal of Gastroenterology2014，20，38： | 6 |
| 7 | Primary squamous cell carcinoma of the rectum: An update and implications for treatment显示文摘AIM: To provide an update on the aetiology, pathogenesis, diagnosis, staging and management of rectal squamous cell carcinoma(SCC).METHODS: A systematic review was conducted according to the preferred reporting items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of Ovid MEDLINE was performed with the reference list of selected articles reviewed to ensure all relevant publications were captured. The search strategy was limited to the English language, spanning from 1946 to 2015. A qualitative analysis was undertaken examining patient demographics, clinical presentation, diagnosis, staging, treatment and outcome. The quantitaive analysis was limited to data extracted on treatment and outcomes including radiological, clinical and pathological complete response where available. The narrative and quantitative review were synthesised in concert.RESULTS: The search identified 487 articles in total with 79 included in the qualitative review. The quantitative analysis involved 63 articles, consisting of 43 case reports and 20 case series with a total of 142 individual cases. The underlying pathogenesis of rectal SCC while unclear, continues to be defined, with increasing evidence of a metaplasia-dysplasia-carcinoma sequence and a possible role for human papilloma virus in this progression. The presentation is similar to rectal adenocarcinoma, with a diagnosis confirmed by endoscopic biopsy. Many presumed rectal SCC's are in fact an extension of an anal SCC, and cytokeratin markers are a useful adjunct in this distinction. Staging is most accurately reflected by the tumour-nodemetastasis classification for rectal adenocarcinoma. It involves examining locoregional disease by way of magnetic resonance imaging and/or endorectal ultrasound, with systemic spread excluded by way of computed tomography. Positron emission tomography is integral in the workup to exclude an external siteof primary SCC with metastasis to the rectum. While the optimal treatment remains as yet undefined, recent studies have demonstrated a global shift away from surgery towards definitive chemoradiotherapy as primary treatment. Pooled overall survival was calculated to be 86% in patients managed with chemoradiation compared with 48% for those treated traditionally with surgery. Furthermore, local recurrence and metastatic rates were 25% vs 10% and 30% vs 13% for the chemoradiation vs conventional treatment cohorts.CONCLUSION: The changing paradigm in the treatment of rectal SCC holds great promise for improved outcomes in this rare disease. | Glen R Guerra Cherng H Kong Satish K Warrier Andrew C Lynch Alexander G Heriot Samuel Y Ngan | 2016 | World Journal of Gastrointestinal Surgery2016，8，3： | 5 |
| 8 | Nonalcoholic fatty liver disease is associated with benign gastrointestinal disorders显示文摘AIM:To explore associations between nonalcoholic fatty liver disease(NAFLD)and benign gastrointestinal and pancreato-biliary disorders.METHODS:Patient demographics,diagnoses,and hospital outcomes from the 2010 Nationwide Inpatient Sample were analyzed.Chronic liver diseases were identified using International Classification of Diseases,the 9thRevision,Clinical Modification codes.Patients with NAFLD were compared to those with other chronic liver diseases for the endpoints of total hospital charges,disease severity,and hospital mortality.Multivariable stepwise logistic regression analyses to assess for the independent association of demographic,comorbidity,and diagnosis variables with the event of NAFLD(vs other chronic liver diseases)were also performed.RESULTS:Of 7800441 discharge records,32347(0.4%)and 271049(3.5%)included diagnoses of NAFLD and other chronic liver diseases,respectively.NAFLD patients were younger(average 52.3 years vs55.3 years),more often female(58.8%vs 41.6%),less often black(9.6%vs 18.6%),and were from higher income areas(23.7%vs 17.7%)compared to counterparts with other chronic liver diseases(all P<0.0001).Diabetes mellitus(43.4%vs 28.9%),hypertension(56.9%vs 47.6%),morbid obesity(36.9%vs 8.0%),dyslipidemia(37.9%vs 15.6%),and the metabolic syndrome(28.75%vs 8.8%)were all more common among NAFLD patients(all P<0.0001).The average total hospital charge($39607 vs$51665),disease severity scores,and intra-hospital mortality(0.9%vs6.0%)were lower among NALFD patients compared to those with other chronic liver diseases(all P<0.0001).Compared with other chronic liver diseases,NAFLD was significantly associated with diverticular disorders[OR=4.26(3.89-4.67)],inflammatory bowel diseases[OR=3.64(3.10-4.28)],gallstone related diseases[OR=3.59(3.40-3.79)],and benign pancreatitis[OR=2.95(2.79-3.12)]on multivariable logistic regression(all P<0.0001)when the latter disorders were the principal diagnoses on hospital discharge.Similar relationships were observed when the latter disorders were associated diagnoses on hospital discharge.CONCLUSION:NAFLD is associated with diverticular,inflammatory bowel,gallstone,and benign pancreatitis disorders.Compared with other liver diseases,patients with NAFLD have lower hospital charges and mortality. | Srinevas K Reddy Min Zhan H Richard Alexander Samer S El-Kamary | 2013 | World Journal of Gastroenterology2013，19，45： | 4 |
| 9 | Long-term survival of a patient after resection of a gastrointestinal stromal tumor arising from the pancreas显示文摘BACKGROUND:Gastrointestinal stromal tumors (GISTs) may arise in any part of the gastrointestinal tract;extragastrointestinal locations are extremely rare.Only a few cases of extragastrointestinal stromal tumor arising from the pancreas were reported.None of the reports described a long-term follow-up of the patients.METHOD:This report describes an interesting and unusual case of GIST arising from the pancreas.RESULTS:A 74-year-old female presented with a palpable abdominal mass.CT scan showed a large mass 11×8×4 cm originating from the tail of the pancreas.Percutaneous biopsy revealed a GIST predominantly with spindle cells,but some parts also contained epitheloid cells.The patient was treated by distal pancreatic resection with splenectomy.Immunohistochemistry of the tumor showed a staining pattern characteristic of GIST.The patient has achieved a long-term survival of five years and six months without any sign of recurrence of the disease.CONCLUSION:This is the first reported case of an extragastrointestinal stromal tumor arising from the pancreas treated surgically,with a long-term survival. | Filip eka Bohumil Jon Alexander Ferko Zdeněk ubrt Dimitar H Nikolov Věra Tyová | 2011 | Hepatobiliary & Pancreatic Diseases International2011，10，3： | 3 |
| 10 | High Hepatic SCD1 Activity Is Associated with Low Liver Fat Content in Healthy Subjects under a Lipogenic Diet显示文摘 | Günther Silbernagel Marketa Kovarova Alexander Cegan Jürgen Machann Fritz Schick Rainer Lehmann Hans-Ulrich H?ring Norbert Stefan Erwin Schleicher Andreas Fritsche Andreas Peter | 2012 | The Journal of Clinical Endocrinology & Metabolism2012，，12： | 3 |
| 11 | Fondaparinux预防老年急性内科患者发生静脉血栓形成的效果与安全性:随机安慰剂对照研究显示文摘目的:观察 Fondaparinux 对具有中高度静脉血栓发生危险的老年急性内科住院患者的抗凝效果与安全性。设计:双盲随机安慰剂对照研究。背景:8个国家的35个中心。参与者:849例≥60岁内科患者,住院原因分别为充血性心力衰竭、慢性肺病合并急性呼吸系统疾患、急性炎症性或感染性疾病,预期至少住院4天以上。干预:2.5 mg Fondaparinux 或安慰剂,每天1次皮下注射,持续6~14天。观察指标:主要指标为静脉血栓形成(治疗后15天内采用双侧静脉造影检查)及有症状的静脉血栓;次要指标为死亡与出血。患者随访时间为1个月。结果:Fondaparinux 治疗组425例患者和安慰剂组414例患者接受了安全性分析(10例未治疗)。644例患者(75.9%)可接受主要指标分析。静脉血栓检出率在 Fondaparinux 治疗组为5.6%(18/321),安慰剂组为10.5%(34/323),相对危险减少46.7%(95% CI 7.7%~69.3%)。安慰剂组5例患者发生有症状的静脉血栓,Fondaparinux治疗组无患者发生有症状的静脉血栓(P=0.029)。两组均有1例(0.2%)患者发生严重出血。随访结束时,安慰剂组、Fondaparinux 治疗组分别死亡25(6.0%)、14(3.3%)例患者。结论:Fondaparinux 可有效预防急性内科老年患者无症状性及有症状的静脉血栓。严重出血几率两组相似。 | Alexander T Cohen Bruce L Davidson Alexander S Gallus Michael R Lassen Martin H Prins Witold Tomkowski Alexander G G Turpie Jan F M Egberts Anthonie W A Lensing 石汉平(译) 王深明(校) | 2006 | 英国医学杂志中文版2006，9，5： | 3 |
| 12 | Plant-promoted pyrene degradation in soil显示文摘 | Liste H H Alexander M | 2000 | Chemosphere2000，40，： | 2 |
| 13 | Some 7-Substituted 4-aminoquinoline derivatives显示文摘 | Alexander R S Henry F H | 1946 | J Am Chem Soc1946，18，： | 2 |
| 14 | Risk factors associated with major cerebrovascular complications after intracranial stenting显示文摘 | F Nahab M J. Lynn S E. Kasner M J. Alexander R Klucznik O O. Zaidat J Chaloupka H Lutsep S Barnwell M Mawad B Lane M I. Chimowitz | 2009 | Neurology2009，，23： | 2 |
| 15 | Effect of Preparation Procedure on the Catalytic Properties of Fe-ZSM-5 as SCR Catalyst显示文摘 | Alexander Shishkin Per-Anders Carlsson Hanna H?relind Magnus Skoglundh | 2013 | Topics in Catalysis2013，，9： | 2 |
| 16 | Right Portal Vein Ligation Combined With In Situ Splitting Induces Rapid Left Lateral Liver Lobe Hypertrophy Enabling 2-Staged Extended Right Hepatic Resection in Small-for-Size Settings显示文摘 | Andreas A. Schnitzbauer Sven A. Lang Holger Goessmann Silvio Nadalin Janine Baumgart Stefan A. Farkas Stefan Fichtner-Feigl Thomas Lorf Armin Goralcyk Rüdiger H?rbelt Alexander Kroemer Martin Loss Petra Rümmele Marcus N. Scherer Winfried Padberg Alfred K? | 2012 | Annals of Surgery2012，，3： | 2 |
| 17 | Acute ischaemic stroke interventions: large vessel occlusion and beyond显示文摘Care for acute ischaemic stroke is one of the most rapidly evolving fields due to the robust outcomes achieved by mechanical thrombectomy.Large vessel occlusion(LVO)accounts for up to 38%of acute ischaemic stroke and comes with devastating outcomes for patients,families and society in the pre-intervention era.A paradigm shift and a breakthrough brought mechanical thrombectomy back into the spotlight for acute ischaemic stroke;this was because five randomised controlled trials from several countries concluded that mechanical thrombectomy for acute stroke offered overwhelming benefits.This review article will present a comprehensive overview of LVO management,techniques and devices used,and the future of stroke therapy.In addition,we review our institution experience of mechanical thrombectomy for posterior and distal circulation occlusion. | Ahmad Sweid Batoul Hammoud Sunidhi Ramesh Daniella Wong Tyler D Alexander Joshua Harrison Weinberg Maureen Deprince Jaime Dougherty Dimitri Jean-Mickael Maamari Stavropoula Tjoumakaris Hekmat Zarzour Michael R Gooch Nabeel Herial Victor Romo David M Hasan Robert H Rosenwasser Pascal Jabbour | 2020 | Stroke & Vascular Neurology2020，5，1： | 2 |
| 18 | 新产品的定价方法显示文摘这项研究的目的是确定产品在其发展初期的定价问题,并分析制定价格上限的主要方法。因此,早期的产品价格上限计算方法需要考虑产品本身价格和影响价格的劳动力成本。同时,不仅要考虑消费者特征,而且还要考虑现行税制和通货膨胀水平。 | TATYANA A.SAKHNOVIСH ALEXANDER V.РLYASUNKOV | 2018 | 中国商论2018，0，24： | 2 |
| 19 | Intraoperative laser fluorescence angiography in colorectal surgery: a noninvasive analysis to reduce the rate of anastomotic leakage显示文摘 | Stefanie Kudszus Christian Roesel Alexander Schachtrupp J?rg J. H?er | 2010 | Langenbeck’s Archives of Surgery2010，，8： | 2 |
| 20 | Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial显示文摘 | Caroline AH Klazen Paul NM Lohle Jolanda de Vries Frits H Jansen Alexander V Tielbeek Marion C Blonk Alexander Venmans Willem Jan J van Rooij Marinus C Schoemaker Job R Juttmann Tjoen H Lo Harald JJ Verhaar Yolanda van der Graaf Kaspar J van Everdingen Al | 2010 | 2010 (9746)2010，，9746： | 2 |
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