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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 | 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 |
| 3 | 微通道内气-液传质研究显示文摘以CO2-H2O为模型体系,实验考察了当量直径为667 μm的单通道和16个并行通道内的气-液传质行为.实验发现,液体表观速度增加,单通道内液侧体积传质系数明显提高;同一液体表观速度下,液侧体积传质系数随气体表观速度增加而增加;在实验数据基础上关联了液侧体积传质系数与气-液两相流参数间的关系.微通道内的液侧体积传质系数较常规尺度气-液接触设备至少高1~2个数量级.并讨论了并行微通道内气-液两相流分配特性对整体传质性能的影响,表明合理设计气、液流动分布结构,可保证微通道内优异的传质特性. | 乐军 陈光文 袁权 罗灵爱 LE GALL Hervé | 2006 | 化工学报2006，57，6： | 23 |
| 4 | Genetics of hepatocellular carcinoma显示文摘The completely assembled human genome has made it possible for modern medicine to step into an era rich in genetic information and high-throughput genomic analysis. These novel and readily available genetic resources and analytical tools may be the key to unravel the molecular basis of hepatocellular carcinoma (HCC). Moreover, since an efficient treatment for this disease is lacking, further understanding of the genetic background of HCC will be crucial in order to develop new therapies aimed at selected targets. We report on the current status and recent developments in HCC genetics. Special emphasis is given to the genetics and regulation of major signalling pathways involved in HCC such as p53, Wnt- signalling, TGFβ, Ras, and Rb pathways. Furthermore, we describe the influence of chromosomal aberrations as well as of DNA methylation. Finally, we report on the rapidly developing field of genomic expression profiling in HCC, mainly by microarray analysis. | Andreas Teufel Frank Staib Stephan Kanzler Arndt Weinmann Henning Schulze-Bergkamen Peter R Galle | 2007 | World Journal of Gastroenterology2007，13，16： | 21 |
| 5 | 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 |
| 6 | Update on autoimmune hepatitis显示文摘Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features,hyperglobulinemia (IgG),and the presence of circulating autoantibodies,as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years,a couple of new insights into the genetic aspects,clinical course and treatment of AIH have been reported,which will be the focus of this review. In particular,we concentrate on genome-wide microsatellite analysis,a novel mouse model of AIH,the evaluation of a large AIH cohort for overlap syndromes,suggested novel criteria for the diagnosis of AIH,and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil. | Andreas Teufel Peter R Galle Stephan Kanzler | 2009 | World Journal of Gastroenterology2009，15，9： | 17 |
| 7 | Laparoscopic vs open approach to resection of hepatocellular carcinoma in patients with known cirrhosis:Systematic review and meta-analysis显示文摘AIM: To review the currently available literature comparing laparoscopic to open resection of hepatocellular carcinoma(HCC) in patients with known liver cirrhosis.METHODS: A literature search of MEDLINE, EMBASE, and Cochrane databases was conducted. The search terms used included(laparoscopic OR laparoscopy) AND(hepatic or liver) AND(surgery or resection) AND 'hepatocellular carcinoma' AND(cirrhosis or cirrhotic). Furthermore, to widen the search, we also used the 'related articles' section. Studies reporting a comparison of outcomes and methods of open vs laparoscopic hepatic resection for HCC in patients with liver cirrhosis were included. Meta-analysis of results was performed using a random effects model to compute relative risk(RR) and for dichotomous variablesand standard mean differences(SMD) for continuous variables.RESULTS: A total of 420 patients from 4 cohort studies were included in final analysis. Patients undergoing laparoscopic procedures had statistically less blood loss compared to the open cohort, SMD of-1.01(95%CI:-1.23-0.79), P < 0.001, with a reduced risk of transfusion, RR = 0.19(95%CI: 0.09-0.38), P < 0.001. A wider clearance at tumour resection margins was achieved following a laparoscopic approach, SMD of 0.34(95%CI: 0.08-0.60), P = 0.011. No significant difference was noted between laparoscopic and open resection operative times, SMD of-0.15(95%CI: 0.35-0.05), P = 0.142. The overall RR of suffering from postoperative morbidity is 0.25 in favour of the open surgery cohort(95%CI: 0.17-0.37), P < 0.001. Patients under-going laparoscopic surgery had significantly shorter length of stays in hospital compared to the open cohort, SMD of-0.53(95%CI:-0.73 to-0.32), P < 0.001.CONCLUSION: This review suggests that laparoscopic resection of hepatocellular carcinoma in patients with cirrhosis is safe and may provide improved patient outcomes when compared to the open technique. | Ahmed Twaij Philip H Pucher Mikael H Sodergren Tamara Gall Ara Darzi Long R Jiao | 2014 | World Journal of Gastroenterology2014，20，25： | 16 |
| 8 | Treatment of nonalcoholic fatty liver disease显示文摘不含酒精的脂肝疾病(NAFLD ) 是为在发达国家的提高的肝酶的最普通的原因。在因为超重孩子的增加的数字,具有特别兴趣的预防节目以外,处理应该集中于最重要的风险因素,肥胖和抗胰岛素性。作为阐明的后果 NAFLD 的 pathomechanisms,潜在的治疗学的选择的数字增加了。然而,调查治疗学的效果的许多研究在至少一个下列点显示出缺点:连续的肝活体检视,治疗的短术语和包括的病人的有限数字的缺乏。第二产生胰岛素抗体 pioglitazone 和 rosiglitazone 为注意在 NAFLD,而是重量获得和潜在的 hepatotoxicity 电话显示出最有希望的改进。在结论,为特定的药的应用程序的一个一般建议不能被给。在肥胖的病人改进胰岛素敏感度的而且控制的临床的试用,体重减轻和物理活动应该是优先级目的。 | Juergen Siebler Peter R Galle | 2006 | World Journal of Gastroenterology2006，12，14： | 16 |
| 9 | 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 |
| 10 | 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 |
| 11 | TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies显示文摘AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resistance in hepatocellular carcinoma(HCC)and to study the efficacy of agonistic TRAIL antibodies,as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS:Surface expression of TRAIL receptors (TRAIL-R1-4)and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting,respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNAs.HCC cellswere treated with kinase inhibitors and chemotherapeutic drugs.Apoptosis induction and cell viability were analyzed via flow cytometry and 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS:TRAIL-R1 and-R2 were profoundly expressed on the HCC cell lines Huh7 and Hep-G2. However,treatment of Huh7 and Hep-G2 with TRAIL and agonistic antibodies only induced minor apoptosis rates.Apoptosis resistance towards TRAIL could be considerably reduced by adding the chemotherapeutic drugs 5-fluorouracil and doxorubicin as well as the kinase inhibitors LY294002[inhibition of phosphoinositol- 3-kinase(PI3K)],AG1478(epidermal growth factor receptor kinase),PD98059(MEK1),rapamycin(mam- malian target of rapamycin)and the multi-kinase inhibitor Sorafenib.Furthermore,the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL play a major role in TRAIL resistance:knock-down by RNA interference increased TRAIL-induced apoptosis of HCC cells.Additionally, knock-down of MCL-1 and BCL-xL led to a significant sensitization of HCC cells towards inhibition of both c-Jun N-terminal kinase and PI3K.CONCLUSION:Our data identify the blockage of survival kinases,combination with chemotherapeutic drugs and targeting of antiapoptotic BCL-2 proteins as promising ways to overcome TRAIL resistance in HCC. | Bruno Christian Koehler Toni Urbanik Binje Vick Regina Johanna Boger Steffen Heeger Peter R Galle Marcus Schuchmann Henning Schulze-Bergkamen | 2009 | World Journal of Gastroenterology2009，15，47： | 9 |
| 12 | 3D numerical parametric study of the influence of open-pit mining sequence on existing tunnels显示文摘The development of open-pit mines can adversely affect and even damage existing access tunnels. To ensure the safety and serviceability of them, it is essential to know potential adverse effects of the mining sequence on existing tunnels such as displacements of the lining and additional loads on the lining. In this paper, three-dimensional numerical parametric study is performed to explore this complex interaction.This study investigates the effects of different parameters that may affect the tunnel response. These parameters are: excavation sequence method, horizontal/vertical stress ratio, slope angle, and tunnel diameter. This study shows that the mining sequence affects the stability of the tunnels. The open-pit mining activities lead to both higher axial forces in rock bolts and normal forces and bending moments in the lining. The results of the analysis also demonstrate that the mining sequence causes tunnel heave and significant tensile forces in the lining. Based on the study in this paper a better understanding of the interaction between open-pit mining sequence and tunnels will be obtained. | Beyabanaki Amir Reza Gall Vojtech | 2017 | International Journal of Mining Science and Technology2017，27，3： | 8 |
| 13 | 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 |
| 14 | Heterogeneity of Patients with Intermediate (BCLC B) Hepatocellular Carcinoma: Proposal for a Subclassification to Facilitate Treatment Decisions显示文摘 | Luigi Bolondi Andrew Burroughs Jean-Fran?ois Dufour Peter Galle Vincenzo Mazzaferro Fabio Piscaglia Jean Raoul Bruno Sangro | 2012 | Semin Liver Dis2012，，04： | 7 |
| 15 | 轮胎模态试验及在轮胎结构设计中的应用研究显示文摘分析了轮胎模态分析的试验方法及其在轮胎设计中的应用 ,并建立了轮胎模态分析试验系统。测量了各类型轮胎的固有频率特性 ,分析了轮胎气压、胎面花纹和轮胎质量对轮胎的固有频率特性的影响规律、模态振型与振动和噪声的关系 ,得出结论 :轮胎气压增大 ,轮胎的固有频率也随之增高 ;同型号、同规格光面轮胎的基频低于有花纹轮胎 ;轮胎刚度变化对轮胎固有频率的影响大于轮胎质量的影响。此外 。 | 葛剑敏 王卫防 孙世铭 Rolf Gall | 2001 | 轮胎工业2001，21，4： | 7 |
| 16 | Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Subanalyses of a phase III trial显示文摘 | Jordi Bruix Jean-Luc Raoul Morris Sherman Vincenzo Mazzaferro Luigi Bolondi Antonio Craxi Peter R. Galle Armando Santoro Michel Beaugrand Angelo Sangiovanni Camillo Porta Guido Gerken Jorge A. Marrero Andrea Nadel Michael Shan Marius Moscovici Dimitris Vo | 2012 | Journal of Hepatology2012，，4： | 6 |
| 17 | In vivo subsurface morphological and functional cellular and subcellular imaging of the gastrointestinal tract with confocal mini-microscopy显示文摘瞄准:为在活体内评估一根最新发达的手持的共焦的探针在啮齿类动物的完全的胃肠道的显微镜的成像。方法:一根新奇僵硬共焦的探针(直径 7 公里) 为 fluorophore 刺激用 488 nm 单身者线激光在人为使用与类似于灵活 endomicroscopy 系统的光特征被设计。轻排放在 505 ~ 750 nm 被检测。看法的地多样地是 475 妈妈 475 妈妈。光片厚度是有 0.7 妈妈的侧面的分辨率的 7 妈妈。在不同深度(到 250 妈妈的表面) 的表面下的连续图象多样地在 1024 点在实时被产生由在轻轻的、稳定的接触把探查放到织物上的 1024 个象素(0.8 frames/s ) 。织物标本为组织病理学说的关联被取样。结果:食管,胃,小并且大肠和中央,肝,胰和胆囊是在在 n = 的高分辨率的视觉 ised 在活体内 48 个鼠标。有共焦的微型显微镜学探查的实时显微镜的成像是容易的完成。不同染色协议(荧光黄,吖啶黄,标记 FITC 的葡聚糖和 L。可食用嗯植物凝血素) 织物的每个加亮的特定的方面,和在活体内成像与常规组织学最优地相关。在活体内血流监视把功能的质量加到词法成像。结论:共焦的显微镜学是在甚至表面下的织物结构的高分辨率允许完全的官方补给的道的可视化的可行在活体内。在这研究评估的新共焦的探查设计与腹腔镜检查兼容并且显著地扩展可能的应用的地到 intra 腹的机关。它允许新在活体内染色和申请选择的立即的测试因此在病人从动物研究允许快速的转移到临床的使用。 | Martin Goetz Beena Memadathil Stefan Biesterfeld Constantin Schneider Sebastian Gregor Peter R Galle Markus F Neurath Ralf Kiesslich | 2007 | World Journal of Gastroenterology2007，13，15： | 6 |
| 18 | Hepatocellular carcinoma in patients with autoimmune hepatitis显示文摘AIM: To evaluate and confirm the low incidence of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH). At present only very few cases of HCC in patients with AIH and definite exclusion of chronic viral hepatitis have been published, suggesting that HCC due to AIH is rare. METHODS: In order to further investigate the incidence of HCC in patients with AIH, we reviewed our large cohort of 278 patients with AIH. RESULTS: Eighty-nine patients (32%) were diagnosed with liver cirrhosis, a preneoplastic condition for HCC. We studied a total of 431 patient years of cirrhosis in these patients, an average 4.8 years per patient. During this period none of the patients of our own study cohort developed HCC. However, three patients with HCC due to AIH associated liver cirrhosis were referred to our department for further treatment of HCC. In all three patients chronic viral hepatitis was excluded. CONCLUSION: We conclude that HCC may under rare circumstances develop due to chronic AIH dependent liver cirrhosis. Compared to other causes of liver cirrhosis such as chronic viral hepatitis, alcohol, or hemochromatosis, the incidence of HCC is significantly lower. Pathophysiological differences between AIH and chronic viral hepatitis responsible for differences in the incidence of HCC are yet to be further characterized and may lead to new therapeutic concepts in prevention and treatment of liver cancer. | Andreas Teufel Arndt Weinmann Catherine Centner Anja Piendl Ansgar W Lohse Peter R Galle Stephan Kanzler | 2009 | World Journal of Gastroenterology2009，15，5： | 5 |
| 19 | 肾包膜下种植建立人前列腺癌异种移植动物模型显示文摘目的 采用肾包膜下种植方案建立人前列腺癌异种移植动物模型.方法 15只SCID雄鼠按随机表分组法随机分为3组,每组5只.应用组织重组技术,将人前列腺癌新鲜组织和新出生BALB/c雄鼠精囊间质(SVM)在体外重组,显微外科条件下种植于SCID鼠肾包膜下,4周后观察肿瘤种植率并称重、计算体积.检测血清前列腺特异性抗原(PSA)值.用细胞角蛋白(CK)8/18、波形蛋白(vimentin)单克隆抗体特异标记人前列腺上皮和基质成纤维细胞,用P63单克隆抗体标记上皮基底膜证实其是否为前列腺癌组织.另将人前列腺癌新鲜组织单独种植于SCID鼠肾包膜下作为对照.结果 15只SCID鼠78只次组织种植中无一只死亡.4周后,重组种植组成瘤率为100%(39/39),单独种植组为94.1%(37/39),差异无统计学意义(P>0.05).新生瘤体为实体状、不规则、黄/白色,隆出肾脏表面和(或)嵌入肾实质.重组种植组瘤体生长旺盛,单独种植组瘤体较为平坦,肿瘤大小及重量在两组间差异有统计学意义[(9.7±3.1)mm^3比(6.8±2.0)mm^3;(12.1±3.6)μg比(8.2±2.2)μg,均P<0.01].重组种植组血清PSA值高于单独种植组,但两组间差异无统计学意义(P>0.05).CK8/18、vimentin单抗标记证实新生瘤体为人源性前列腺组织,P63单抗标记显示上皮基底膜消失证实为前列腺癌.结论 肾包膜下种植可高效率建立人前列腺癌异种移植动物模型.本模型含有肿瘤基质成分,可为体内研究前列腺癌发病和病程演变中间质-上皮细胞相互作用提供技术平台. | 孙宏斌 WANG Hong Renea A Taylor Gall P Risbridger | 2010 | 中华医学杂志2010，90，30： | 4 |
| 20 | 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 |
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