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Differential c-erbB-1 and c-erbB-2 mRNA expression in cancer of the pancreas compared with cancer of the papilla of Vater

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World Journal of Gastroenterology 2006年第3期12卷 437-442页

作者： KlausLPrenzel utewarnecke-eberz JanBrabender StephanEBaldus ElfriedeBollschweiler ChristianAGutschow UtaDrebber ArnulfHHoelscher PaulMSchneider Department of Visceral and Vascular Surgery University of Cologne50931 CologneGermany Institute of PathologyUniversity of Cologne50931 CologneGermany

AIM： We examined quantitative mRNA expression of growth factor receptors （c-erbB-1, c-erbB-2） and the anti-apoptosis gene survivin known to be regulated in pancreatic adenocarcinomas and compared the expression pattern with that in carcinomas of the papilla of Vater. METHODS： Quantitative real-time reverse transcriptase- PCR （QRT-PCR, Taqman^TM） was performed to analyze mRNA expression levels of c-erbB-1, c-erbB-2 and survivin in normal and corresponding tumor samples of 31 pancreatic adenocarcinomas and 8 cancers of the papilla of Vater. RESULTS： The overall median mRNA expression of survivin was significantly increased in both adenocarcinoma of the pancreas （P〈0.01） and papilla of Vater （P〈0.008） compared with uninvolved normal control tissue. In pancreatic cancer, expression of c-erbB-1 was significantly decreased compared with the normal pancreatic tissue （P〈0.03）, whereas in the cancer of the papilla of Vater expression of c-erbB-2 was significantly downregulated （P〈0.05） compared with the paired normal samples. Gene expression was not associated with tumor stage, differentiation or prognosis. CONCLUSION： The common anti-apoptosis gene survivin is overexpressed both in the cancer of the papilla of Vater and pancreas. In contrast, the growth factor receptor genes c-erbB-1 and c-erbB-2 are differentially regulated in both tumor entities adding further evidence that pancreatic cancer is biologically different from the cancer of papilla of Vater.

关键词： Pancreatic cancer Ampullary cancer Growth factor receptor Gene expression RT-PCR Survivin

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Prediction of Response to Multimodality Treatment inEsophageal Cancer

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The Chinese-German Journal of Clinical Oncology 2004年第4期3卷 253-256页

作者： RalfMetzger HuanXi FutoshiMiyazono HiroshiHigashi utewarnecke-eberz StephanE.Baldus JanBrabender PaulM.Schneider DepartmentofVisceral-andVascularSurgery UniversityofCologneCologneGermany DepartmentofGeneralSurgery BeijingHospitalBeijingChina FirstDepartmentofSurgery UniversityofKagoshimaSchoolofMedicineKagoshimaJapan InstituteofPathology UniversityofCologneCologneGermany

Patients with locally advanced esophageal cancer have a dismal prognosis when treated exclu- sively by surgery. This fact prompted many investigators to apply neoadjuvant treatment strategies in an e?ort to improve survival. Results from phase III randomized trials are encouraging however, they revealed 五笔字型计算机汉字输入技术 that only patients with major histopathological response will bene?t from treatment. Therefore, predic- tive molecular markers indicating response or non-response to neoadjuvant treatment would be extremely helpful in selecting patients for current and future treatment protocols. In this paper we review the role of the molecular markers ERCC1 (excision repair cross-complementing 1 gene) and c-erbB-2 (synonym: HER2/neu) in predicting response to radiochemotherapy and outcome for patients with locally advanced resectable esophageal cancers (cT2-4, Nx, M0). The results are promising and it appears that we might expect to unequivocally identify with ERCC1 and c-erbB-2 respectively, approximately up to one third of patients who ful?l the criteria for neoadjuvant treatment for locally advanced esophageal cancer but will not bene?t from our treatment protocol. Integration of such markers in the clinical setting might prevent a substantial number of patients from expensive, non-e?ective and potentially harmful therapies, and could lead to a more individualized type of combined multimodality treatment in the near future.

关键词： esophageal cancer response prediction multimodality therapy neoadjuvant radiochemotherapy ERCC1 c-erbB-2

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Neoadjuvant treatment for advanced esophageal cancer: response assessment before surgery and how to predict response to chemoradiation before starting treatment

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Chinese Journal of Cancer Research 2015年第3期27卷 221-230页

作者： Elfriede Bollschweiler Arnulf H.Hlscher Matthias Schmidt Ute Warnecke-eberz Department of General Visceral and Cancer SurgeryUniversity of Cologne Institute of Nuclear Medicine University of Cologne

Patients with advanced esophageal cancer（T3-4, N） have a poor prognosis. Chemoradiation or chemotherapy before esophagectomy with adequate lymphadenectomy is the standard treatment for patients with resectable advanced esophageal carcinoma. However, only patients with major histopathologic response（regression to less than 10% of the primary tumor） after preoperative treatment will have a prognostic benefit of preoperative chemoradiation. Using current therapy regimens about 40% to 50% of the patients show major histopathological response. The remaining cohort does not benefit from this neoadjuvant approach but might benefit from earlier surgical resection. Therefore, it is an aim to develop tools for response prediction before starting the treatment and for early response assessment identifying responders. The current review discusses the different imaging techniques and the most recent studies about molecular markers for early response prediction. The results show that [^18F]-fluorodeoxyglucose-positron emission tomography（FDGPET） has a good sensitivity but the specificity is not robust enough for routine clinical use. Newer positron emission tomography detector technology, the combination of FDG-PET with computed tomography, additional evaluation criteria and standardization of evaluation may improve the predictive value. There exist a great number of retrospective studies using molecular markers for prediction of response. Until now the clinical use is missing. But the results of first prospective studies are promising. A future perspective may be the combination of imaging technics and special molecular markers for individualized therapy. Another aspect is the response assessment after finishing neoadjuvant treatment protocol. The different clinical methods are discussed. The results show that until now no non-invasive method is valid enough to assess complete histopathological response.

关键词： Esophageal cancer squamous cell carcinoma adenocarcinoma neoadjuvant chemoradiation response prediction response assessment

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Neoadjuvant chemoradiation changes podoplanin expression in esophageal cancer patients

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World Journal of Gastroenterology 2020年第23期26卷 3236-3248页

作者： Ute Warnecke-eberz Patrick Plum Viola Schweinsberg Uta Drebber Christiane J Bruns Dolores T Müller Arnulf H Holscher Elfriede Bollschweiler Department of General Visceral and Cancer SurgeryUniversity Hospital of CologneCologne 50937Germany Department of Dermatology University Hospital of CologneCologne 50937Germany Institute of Pathology University Hospital of CologneCologne 50937Germany Agaplesion Markus Hospital Frankfurt 60431Germany

BACKGROUND Locally advanced adenocarcinoma of the esophagus(EAC) and squamous cell carcinoma(ESCC) result in a worse prognosis. Neoadjuvant treatment improves survival, however, only for responders. The transmembrane glycoprotein podoplanin is overexpressed in squamous cell carcinomas, mi RNA-363 is associated to its regulation in head and neck *** To predict therapy response and prognosis markers, and targets for novel therapies would individualize treatments leading to more favourable *** Expression of podoplanin protein has been visualized by immunohistochemistry in surgical specimens of 195 esophageal cancer patients who underwent transthoracic esophagectomy: 90 ESCC and 105 EAC with clinical T2-3, Nx, *** hundred and six patients received neoadjuvant chemoradiation. RNA was extracted from paraffin-embedded tissue, and mi RNA-363 quantified by realtime Taq Man-real-time-PCR. D2-40 mab staining of > 5% was scored as high podoplanin expression(HPE). We related podoplanin and mi RNA-363 expression to histopathologic response after neoadjuvant treatment and clinicopathological characteristics, such as histological tumor type, survival rate or clinical tumor *** confirmed expression of membrane-bound podoplanin in 90 ESCC patients.26% showed HPE of > 5%. In addition, absence in EAC patients(only 2% with HPE) was shown. Lower podoplanin expression has been detected in resectionspecimen of 58 ESCC patients after neoadjuvant(RTx/CTx) treatment, only 11% with HPE, compared to 50% HPE of 32 non-pretreated primary surgery patients,P = 0.0001. This difference of podoplanin expression was confirmed comparing pre-treatment biopsies with matching post-treatment surgical specimens, P <0.001. Podoplanin has been identified as a prognostic marker in 32 patients that underwent primary surgery without neoadjuvant treatment. Low(0-5%)podoplanin expression was associated with better prognosis compared to patients with HPE, P = 0.013. Podoplanin e

关键词： Esophageal cancer Response prediction Prognosis D2-40 Posttranscriptional regulation miRNA-363

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Association of the GNAS1 T393C polymorphism with tumor stage and survival in gastric cancer

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World Journal of Gastroenterology 2009年第48期15卷 6061-6067页

作者： Hakan Alakus Stefan P Mnig Ute Warnecke-eberz Gül Alakus Günther Winde Uta Drebber Klaus J Schmitz Kurt W Schmid Kathrin Riemann Winfried Siffert Elfriede Bollschweiler Arnulf H Hlscher Ralf Metzger Department of General Visceral and Cancer SurgeryCenter for Integrated OncologyUniversity of Cologne Department of Gastrointestinal Surgery Klinikum Herford Institute of Pathology University of Cologne Institute of Pathology and Neuropathology University Hospital of EssenUniversity of Duisburg-Essen Institute of Pharmaco-genetics University Hospital of EssenUniversity of Duisburg-Essen

AIM： To analyze the impact of the GNAS1 T393C polymorphism on prognosis and histopathology of gastric cancer. METHODS： Genomic DNA was extracted from paraffinembedded tissues of 122 patients with primary gastric carcinoma and from the blood of 820 healthy white individuals. Allelic discrimination was performed by quantitative real-time polymerase chain reaction. Genotyping was correlated with histopathologic parameters and with overall survival according to the Kaplan-Meier approach and with multivariate analysis by multiple stepwise regression. RESULTS： Thirty-nine （32%） patients displayed a CC genotype, 57 （46.7%） a CT genotype and 26 （21.3%） a TT genotype. The frequency of the C allele （fC） in the patient group was 0.55, which was not significantly different from that of healthy blood donors. The distribution was compatible with the Hardy-Weinberg equilibrium. Analysis of clinicopathological parameters did not show any significant correlation of the T393C genotype with gender （P = 0.50）, differentiation （P = 0.29）, pT-category （P = 0.19）, pN-category （P = 0.30）, pM-category （P = 0.25）, R-category （P = 0.95）, the classifications according to WHO （P = 0.34）, Lauren （P = 0.16）, Goseki （P = 1.00） and Ming （P =0.74）. Dichotomization between C＋（CC＋CT） and C-genotypes （FI）, however, revealed significantly more advanced tumor stages （P = 0.023） and lower survival rates （P = 0.043） for C allele carriers. CONCLUSION： The present study provides strong evidence to suggest that the GNAS1 T393C allele carrier status influences tumor progression and survival in gastric cancer with higher tumor stages and a worse outcome for C allele carriers.

关键词： Gastric cancer G Protein Polymorphism Prognosis Tumor stage

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由侵位后的结晶分异作用、扩散作用及交代作用形成的包体岩浆的化学演化

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国外火山地质 1990年第4期 53-64页

作者： Gunter W.eberz 吴礼道

东南澳大利亚斯威夫兹克里克深成岩体中的含角闪石微花岗状包体,从边缘到中心显示出矿物和结构的变化.包体边缘呈细粒状、淬火结构,相对于包体粗粒中心富含闪石、黑云母;在某些情况下,还富含磁铁矿.为了研究与这些矿物变化相伴生的化学... 详细信息

东南澳大利亚斯威夫兹克里克深成岩体中的含角闪石微花岗状包体,从边缘到中心显示出矿物和结构的变化.包体边缘呈细粒状、淬火结构,相对于包体粗粒中心富含闪石、黑云母;在某些情况下,还富含磁铁矿.为了研究与这些矿物变化相伴生的化学变化,将这种类型的包体及其邻接的花岗岩类主岩制成0.3—1.0cm厚的板片.富集在细粒边缘中的Ti、Al、Mg、Fe、K、Rb、Ba、Nb、Y、Sc、V、Ni及稀土元素是包体中心的3倍.这种富集是通过Si和Zr的亏损来补偿的.而Ca、Na、和Sr等元素从边缘到中心则显示出不连续的变化.和这些包体紧邻的主岩,相对于未出露包体的主岩来说,其Mg、Na、K、Rb和Ba等元素则是亏损的.没有一种单一的作用能够解释所有这些变化.因此,我们认为这些化学变化是与孤立包体岩浆原地结晶分导作用、扩散作用及交代作用有关.

关键词：包体花岗细粒岩浆黑云母结晶分异作用富集系数交代作用变质作用扩散作用化学演化侵位

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