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High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells

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World Journal of Gastroenterology 2009年第17期15卷 2089-2096页

作者： Carl Christoph Schimanski Kirsten Frerichs Fareed Rahman Martin Berger Hauke Lang Peter R Galle Markus Moehler Ines Gockel First department of Internal Medicine Johannes Gutenberg University of Mainz 55131 Mainz Germany Unit of Toxicology and Chemotherapy GermanCancer Research Centre 69120 Heidelberg Germany department of general and abdominal surgery Johannes Gutenberg University of Mainz 55131 Mainz Germany

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.

关键词：大肠癌细胞逆转录聚合酶链反应 AKT信号通路 microRNA 表型致癌 SW480 转移模型

Endoscopic findings in patients with Schatzki rings:Evidence for an association with eosinophilic esophagitis

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World Journal of Gastroenterology 2012年第47期18卷 6960-6966页

作者： Michaela Müller Alexander J Eckardt Annette Fisseler-Eckhoff Susanne Haas Ines Gockel Till Wehrmann department of Gastroenterology German Diagnostic ClinicD-65191 WiesbadenGermany department of Pathology Dr.Horst-Schmidt-Kliniken65199 WiesbadenGermany department of general and abdominal surgery University Medical CenterThe Johannes Gutenberg University55131 MainzGermany

AIM:To investigate endoscopic findings in patients with Schatzki rings(SRs) with a focus on evidence for eosinophilic esophagitis(EoE).METHODS:We consecutively approached all adult patients scheduled for elective outpatient upper endoscopy for a variety of indications at the German Diagnostic Clinic,Wiesbaden,Germany between July 2007 and July *** patients with endoscopically diagnosed SRs,defined as thin,symmetrical,mucosal structures located at the esophagogastric junction,were prospectively *** endoscopic findings,clinical information and histopathological findings with a focus on esophageal eosinophilia(≥ 20 eosinophils/high power field) were *** criteria for active EoE were defined as:(1) eosinophilic tissue infiltration ≥ 20 eosinophils/hpf;(2) symptoms of esophageal dysfunction;and(3) exclusion of other causes of esophageal *** reflux disease was excluded by proton pump inhibitor treatment prior to *** presence of ≥ 20 eosinophils/hpf in esophageal biopsies in patients that did not fulfil the criteria of EoE was defined as esophageal ***:A SR was diagnosed in 171(3.3%;128 males,43 females,mean age 66 ± 12.9 years) of the 5163 patients that underwent upper *** of the 116 patients(17%) from whom esophageal biopsies were obtained showed histological hypereosinophilia(≥ 20 eosinophils/hpf).Nine of these patients(8 males,1 female,mean age 49 ± 10 years) did not fulfill all diagnostic criteria of EoE,whereas in 11(9%) patients with ≥ 20 eosinophils/hpf,a definite diagnosis of EoE was *** of the 11 patients(27%) with definite EoE had no suspicious endoscopic features of *** contrast,in the 25 patients in whom EoE was suspected by endoscopic features,EoE was only confirmed in 7(28%) *** with EoE were younger(mean age 41.5 ± 6.5 vs 50.5 ± 11.5 years,P = 0.012),were more likely to have a history of allergies(73% vs 29%,P = 0.007

关键词：嗜酸性粒细胞食管癌患者证据平均年龄组织病理学关联质子泵抑制剂

Is the schatzki ring a unique esophageal entity?

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World Journal of Gastroenterology 2011年第23期17卷 2838-2843页

作者： Michaela Müller Ines Gockel Philip Hedwig Alexander J Eckardt Kathrin Kuhr Jochem Knig Volker F Eckardt department of Gastroenterology German Clinic for Diagnostics Wiesbaden65191 WiesbadenGermany department of general and abdominal surgery University Medical Center of the Johannes Gutenberg University Mainz55131 MainzGermany Institute of Medical Statistics Informatics and EpidemiologyUniversity of Cologne50924 CologneGermany Institute of Medical Biostatistics Epidemiology and InformaticsUniversity Medical Center of the Johannes Gutenberg University Mainz55131 MainzGermany

AIM:To study,whether the association of Schatzki rings with other esophageal disorders support one of the theories about its ***:From 1987 until 2007,all patients with newly diagnosed symptomatic Schatzki rings (SRs) were prospectively registered and *** of them underwent structured interviews with regards to clinical symptoms,as well as endoscopic and/or radiographic *** and radiographic studies determined the presence of an SR and additional morphological ***:One hundred and sixty-seven patients (125 male,42 female) with a mean age of 57.1±14.6 years were *** patients complained of intermittent dysphagia for solid food and 113 (79.6%) patients had a history of food *** experienced symptoms for a mean of 4.7±5.2 years before *** in 23.4% of the 64 patients who had endoscopic and/or radiological examinations before their first presentation to our clinic,was the SR previously *** presentation,the mean ring diameter was 13.9±4.97 *** hundred and sixty-two (97%) patients showed a sliding hiatal *** reflux esophagitis was found in 47 (28.1%) ***-six (15.6%) of 167 patients showed single or multiple esophageal webs;five (3.0%) patients exhibited eosinophilic esophagitis;and four (2.4%) had esophageal *** (7%) of 57 patients undergoing esophageal manometry had nonspecific esophageal motility ***:Schatzki rings are frequently associated with additional esophageal disorders,which support the assumption of a multifactorial *** typical symptoms,SRs might be overlooked.

关键词：食管实体临床症状平均年龄嗜酸性粒细胞 SRS 运动障碍非特异性

Intrahepatic cholangiocarcinoma: Introducing the preoperative prediction score based on preoperative imaging

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Hepatobiliary & Pancreatic Diseases International 2021年第3期20卷 262-270页

作者： Fabian Bartsch Felix Hahn Lukas Müller Janine Baumgart Maria Hoppe-Lotichius Roman Kloeckner Hauke Lang department of general Visceral and Transplant SurgeryUniversity Medical Center of the Johannes Gutenberg-University MainzLangenbeckst155131 MainzGermany department of Diagnostic and Interventional Radiology University Medical Center of the Johannes Gutenberg-University MainzLangenbeckst155131 MainzGermany

Background: Intrahepatic cholangiocarcinoma(ICC) still has a poor long-term outcome, even after complete resection. We investigated different parameters gathered in preoperative imaging and analyzed their influence on resectability, recurrence, and survival. Methods: All patients who underwent exploration due to ICC between January 2008 and June 2018 were analyzed retrospectively. Kaplan-Meier model, log-rank test and Cox regression were used. Results: Out of 184 patients, 135(73.4%) underwent curative intended resection. Median overall survival(OS) was 22.2 months with a consecutive 1-, 3-and 5-year OS of 73%, 29%, and 17%. Median recurrencefree survival(RFS) was 9.3 months with a consecutive 1-, 3-and 5-year RFS of 36%, 15%, and 11%. Site of tumor, parenchymal localization, tumor configuration/dissemination, and estimated tumor volume had significant influence on resectability. Univariate analyses showed that site of tumor, tumor configuration/dissemination, number of nodules, and estimated tumor volume had predictive values for OS and RFS. Together with tumor size the preoperative prediction(POP) score was created showing significance for OS and RFS(all P<0.001). In multivariate analysis, POP score(HR=1.779;95% CI: 1.26 8-2.4 95;P=0.001), T stage(HR=1.255;95% CI: 1.040-1.514;P=0.018) and N stage(HR=1.334;95% CI: 1.081-1.645;P=0.007) were the independent predictors for OS. For RFS, POP score(HR=1.733;95% CI: 1.30 0-2.311;P<0.0 01) and M stage(HR=3.036;95% CI: 1.376-6.697;P=0.006) were the independent predictors. Conclusions: The POP score showed to have a highly significant influence on OS and RFS. The score is easy to assess through preoperative imaging. For patients in the high risk group at least staging laparoscopy or preoperative chemotherapy should be evaluated, because they showed equal outcome compared to the irresectable group.

关键词： Intrahepatic cholangiocarcinoma Cholangiocarcinoma Liver surgery Preoperative imaging Survival

MRI versus 64-row MDCT for diagnosis of hepatocellular carcinoma

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World Journal of Gastroenterology 2009年第48期15卷 6044-6051页

作者： Michael Bernhard Pitton Roman Kloeckner Sascha Herber Gerd Otto Karl Friedrich Kreitner Christoph Dueber department of Diagnostic and Interventional Radiology Johannes Gutenberg-University department of Transplantation and Hepatobili-opancreatic surgery University of Mainz

AIM:To compare the diagnostic capability of multidetector computed tomography(MDCT) and magnetic resonance imaging(MRI) for the detection of hepatocellular carcinoma(HCC) tumour nodules and their effect on patient ***:A total of 28 patients(25 male,3 female,mean age 67±10.8 years) with biopsy-proven HCC were investigated with 64-row MDCT(slice 3 mm native,arterial and portal-venous phase,120 mL Iomeprol,4 mL/s,delay by bolus trigger) and MRI(T1fs fl2d TE/ TR 2.72/129 ms,T2tse TE/TR 102/4000 ms,5-phase dynamic contrast-enhanced T1fs fl3d TE/TR 1.56/4.6,Gadolinium-DTPA,slice 4 mm).Consensus reading of both modalities was used as *** nodules were analyzed with respect to number,size,and ***:In total,162 tumour nodules were detected by consensus *** detected signifi cantly more tumour nodules(159 vs 123,P20 *** missed 2 nodules ≤10 mm and 1 nodule ≤15 *** MRI,nodule diameters were greater than on CT(29.2±25.1 mm,range 5-140 mm vs 24.1±22.7 mm,range 4-129 mm,P<0.005).In 2 patients,MDCT showed only unilobar tumour spread,whereas MRI revealed additional nodules in the contralateral *** of these nodules could have changed the therapeutic ***:Contrast-enhanced MRI is superior to 64-row MDCT for the detection of HCC *** should be allocated to interventional or operative treatment according to a dedicated MRI-protocol.

关键词：磁共振成像螺旋CT 肝癌诊断

Significance of preoperative C-reactive protein as a parameter of the perioperative course and long-term prognosis in squamous cell carcinoma and adenocarcinoma of the oesophagus

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World Journal of Gastroenterology 2006年第23期12卷 3746-3750页

作者： Ines Gockel Kathrin Dirksen Claudia M Messow Theodor Junginger department of general and abdominal surgery Johannes Gutenberg-UniversityMainzGermany Institute of Biostatistics and Documentation Johannes Gutenberg-UniversityMainzGermany

瞄准：C 反应的蛋白质(CRP ) 是尖锐阶段的反应物和瘤的恶意的潜力的已知的指示物。这研究的目的是作为起作用的仙子的一个参数调查外科手术前的 CRP 的意义在有有鳞的房间癌和食道的腺癌的病人的路线和长期的预后。方法：浆液 CRP 在从... 详细信息

瞄准：C 反应的蛋白质(CRP ) 是尖锐阶段的反应物和瘤的恶意的潜力的已知的指示物。这研究的目的是作为起作用的仙子的一个参数调查外科手术前的 CRP 的意义在有有鳞的房间癌和食道的腺癌的病人的路线和长期的预后。方法：浆液 CRP 在从 1989 年 12 月为癌症经历 oesophagectomy 到 2004 年 3 月的 371 个病人中的 291 个外科手术前地被决定。中部的耐心的年龄是 59 (28-79 ) 年， 82.5% 病人是男性。有鳞的房间癌在 151 被诊断(51.9%) 并且在 122 个病人的腺癌。Transhiatal oesophagectomy 在 151 被做(51.9%) 病人并且 134 (46.0%) 病人们经历了腹胸的过程。结果：(43.6%) 在 127，外科手术前的浆液 CRP 集中在正常以内的病人变化(< 5 mg/dL ) ，提高的 CRP 层次在 164 被测量(56.4%) 病人。瘤扩展(P < 0.0005 ) 并且淋巴节点的数字由变形传播影响了(P = 0.015 ) 显著地与提高的 CRP 层次在这个组被增加。在起作用的仙子之中参数两输血的数字(P = 0.006 ) 并且一般复杂并发症率(P = 0.002 ) 在有提高的外科手术前的 CRP 层次的病人是更高的。13.6 的长期的幸存率(0-109.8 ) 瞬间在有与 18.9 相比的提高的 CRP 层次的组是更差的(0-155.4 ) 在有正常 CRP 的组的瞬间铺平(木头等级测试：P = 0.107 ) 。有向后的变量选择的 Multivariate 分析与食道的癌在病人作为长期的预后的一个独立预示的因素识别了外科手术前的 CRP，与 1.182 的危险比率(95% 信心间隔：1.030-1.356 ) 。结论：外科手术前的浆液 CRP 水平是在有有鳞的房间癌和食道的腺癌的病人的一个容易坚定的独立预示的标记。

关键词： C-反应蛋白手术治疗牙周炎鳞状细胞癌食管

VEGF-D expression correlates with colorectal cancer aggressiveness and is downregulated by cetuximab

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World Journal of Gastroenterology 2008年第26期14卷 4156-4167页

作者： 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 1st department of Medicine Johannes Gutenberg University Mainz 55101 Germany department of general and abdominal surgery johannes gutenberg university Mainz 55101 Germany

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.

关键词：结肠直肠癌淋巴管X射线血管内皮细胞生长因子 VEGF-D 基因表达

Image cytometric DNA analysis of mucosal biopsies in patients with primary achalasia

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World Journal of Gastroenterology 2006年第19期12卷 3020-3025页

作者： I Gockel P K(a|¨)mmerer J Brieger UR Heinrich WJ Mann F Bittinger VF Eckardt T Junginger department of general and abdominal surgery johannes gutenberg-university Mainz Laboratory of Tumor Biology department of Otolaryngology Johannes Gutenberg-UniversityMainz Institute of Pathology johannes gutenberg-university Mainz department of Gastroenterology German Diagnostic Clinic Wiesbaden

瞄准：为随后的快速的诊断在弛缓不能病人的粘膜活体检视决定 DNA 非整倍性。方法：从中间的活体检视第三根食管与弛缓不能在 15 个病人被获得。染色的 Immunohistochemical 为 p53 为 Ki67 和 PAb 1801 与单音的同种细胞的抗体 MIB-1 ... 详细信息

瞄准：为随后的快速的诊断在弛缓不能病人的粘膜活体检视决定 DNA 非整倍性。方法：从中间的活体检视第三根食管与弛缓不能在 15 个病人被获得。染色的 Immunohistochemical 为 p53 为 Ki67 和 PAb 1801 与单音的同种细胞的抗体 MIB-1 被执行，除了为发育异常的常规 histologic 考试。新鲜活体检视材料的原子核是酶的联盟者并且机械地孤立，并且 DNA 内容在福尔根的染色以后与图象血细胞计数被决定。恶意分级的 DNA 根据 Boecking 被估计决定在正常双山峰附近注意的 DNA 价值的可变性。测量的进一步的索引包括了整倍体的率，和 5c- ， 7c-exceeding 和 9c-exceeding 评价。结果：组织学的考试没表明发育异常；当时 MIB-1 (基础) 在 8/15 弛缓不能标本显示出阳性反应， p53 在所有标本是否定的。图象 cytometric DNA 分析在 4/15 (26.7%) 检测了非整倍性标本。从有象标本一样的有鳞的房间癌的 15 个病人的样品只获得了 2 对作为参考测试服务的肿瘤厘米近似。象 9 件 peritumoral 样品(9/15 ) 一样的所有癌(15/15 ) 是一整倍体。从有 peritumoral 和癌标本的弛缓不能病人的活体检视的比较统计上揭示了有效差量考虑整倍体的率(双：P < 0.0001；四倍的：P = 0.001 ) ，根据 Boecking 恶意分级(P < 0.0001 ) 并且 5c-(P < 0.0001 ) ， 7c-(P < 0.0001 ) ，并且 9c-(P = 0.0001 ) 在各自的顺序与 progredient DNA 改变超过率。结论：发现那 DNA 非整倍性被图象血细胞计数与弛缓不能在病人的食道的标本识别，它可能由于在 27% 病人作为癌前期损害介绍的特定的染色体改变，导致我们断定图象血细胞计数代表一个珍贵屏蔽工具。

关键词：黏膜活体检验弛缓不能癌症前期食管癌

Boosting T cell immunity against cytomegalovirus:a potential strategy combating human aging and age-related diseases

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Signal Transduction and Targeted Therapy 2023年第10期8卷 4417-4418页

作者： Matthias Wirth Walburgis Brenner Oliver H.Kramer department of Hematology Oncology and Cancer ImmunologyCampus Benjamin FranklinCharite-Universitatsmedizin Berlincorporate member of Freie Universitat Berlin and Humboldt-Universitat zu BerlinBerlinGermany university Medical Center Gottingen Department of GeneralVisceral and Pediatric SurgeryGottingenGermany German Cancer Consortium(DKTK) German Cancer Research Center(DKFZ)HeidelbergGermany Clinic for Obstetrics and Women's Health University Medical CenterJohannes Gutenberg University MainzLangenbeckstr.155131 MainzGermany department of Toxicology University Medical CenterMainzGermany

In a recent publication in Cell,Hasegawa and colleagues reveal that cytotoxic CD4-positive cytotoxic T lymphocytes(CD4+CTLs)eliminate senescent fibroblasts with a surface expression of the immunologically important human leukocyte antigen class Il(HLA-)and the human cytomegalovirus glycoprotein B(HCMV-gB).1 This implies that a virome-immune cell interaction controls the fate of human skin cells that are linked to the aging process and associated diseases.

关键词： immunity cytomegalovirus cytotoxic