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Core signaling pathways and new therapeutic targets in pancreatic cancer

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Chinese Medical Journal 2010年第9期123卷 1210-1215页

作者： YOU Lei CHEN Ge zhao yu-pei Department of General Surgery Peking Union Medical College HospitalBeijing 100730China

Objective Pancreatic cancer is a highly aggressive malignancy that has been resistant to treatment. Advances in cancer genetics have improved our understanding of this disease, but the genetics of pancreatic cancer remain poorly understood. A better understanding of the pathogenic role of specific gene mutations and core signaling pathways would propel the development of more effective treatments. The objective in this review was to highlight recent research that shows promise for new treatments for pancreatic cancer. Data sources All articles cited in this review were mainly searched from PubMed, which were published in English from 1993 to 2009. Study selection Original articles and critical reviews selected were relevant to the molecular mechanisms of pancreatic cancer. Results Dysregulation of core signaling pathways and processes through frequently genetic alterations can explain the major features of pancreatic tumorigenesis. New therapeutic targets based on recent research are emerging that hold promise for the future management of pancreatic cancer. Conclusion New agents used in conjunction with standard radiotherapy and chemotherapy might help to overcome drug resistance by targeting multiple signaling pathways to induce responsiveness of pancreatic cancer cells to death signals.

关键词： pancreatic cancer signaling pathway therapeutic target

Combined detection of serum tumor markers for differential diagnosis of solid lesions located at the pancreatic head

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Hepatobiliary & Pancreatic Diseases International 2007年第6期6卷 641-645页

作者： Liao, Quan zhao, yu-pei Yang, Ying-Chi Li, Li-Jun Long, Xiao Han, Shao-Mei Beijing Union Med Coll Hosp Dept Gen Surg Beijing 100730 Peoples R China

BACKGROUND: The differential diagnosis of solid lesions located at the pancreatic head is very important for choosing therapies and setting up surgical tactics. This study was designed to evaluate the clinical significance of combined measurement of multiple serum tumor markers and the application of the receiver-operating characteristic (ROC) curves in the differential diagnosis of solid lesions located at the pancreatic head. METHODS: The serum levels of CA19-9, CA242, CA50 and carcinoembryonic antigen (CEA) in 112 patients with carcinoma of the pancreatic head and 38 patients with focal chronic pancreatitis in the pancreatic head were measured with ELISA. The sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of the four serum tumor markers were calculated. The ROC curves for the four serum tumor markers were constructed and the area under the curve (AUC) was calculated. RESULTS: The AUCs of CA19-9, CA242, CA50 and CEA were 0.805, 0.749, 0.738 and 0.705; the PLRs were 1.91, 3.43, 5.09 and 5.46; and the NLRs were 0.41, 0.56, 0.59 and 0.71, respectively. Combined measurements increased the diagnostic specificity, and parallel combined testing increased the diagnostic sensitivity. CONCLUSIONS: Combined measurement of serum tumor markers CA19-9, CA242, CA50 and CEA is valuable in differential diagnosis of solid lesions located at the pancreatic head, and CA19-9 has the best diagnostic ability. Combined measurements can increase the specificity of diagnosis. Evaluation with the ROC curve is better than the sensitivity or specificity alone and the results are more integrated and objective.

关键词： pancreatic neoplasm tumor markers ROC curve differential diagnosis

On multiple testing,validation of gene expression profiling,and translational research

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中华医学杂志(英文版) 2008年第13期121卷 1247-1248页

作者： zhao yu-pei CHEN Ge Departmem of General Surgery Peking Union Medical College Hospital Beijing 100730 China）

To the editor:With great interest,we read the recent article by zhao et al,in which the authors performed a genome-wide screen for genes that are associated with multi-drug resistance *** authors concluded that construction of a chemoresistance prediction rule,based on gene expression patterns, is practical and that their results may be useful for the detection and treatment of MDR in pancreatic cancer patients.

关键词： gene expression cancer patients

Synthesis,characterization,and tunable wettability of poly (ionic liquid) brushes via nitroxide-mediated radical polymerization (NMP)

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Chinese Science Bulletin 2010年第31期55卷 3562-3568页

作者： YAG Wu HE XiaoJing GAO JinZhang GUO Hao HE XiaoYan WAN Fei zhao XiuLi yu Yan pei Ben College of Chemistry and Chemical Engineering Northwest Normal University Lanzhou 730070 China

Well-defined poly(ionic liquid) brushes with tunable wettability are successfully synthesized via nitroxide-mediated radical polymerization.X-ray photoelectron spectroscopy,attenuated total reflection infrared spectroscopy and static water contact angle measurements are used to monitor each ***,nuclear magnetic resonance(1H and 13C) spectra and gel permeation chromatographic measurements reveal that there is a linear increase in polymer film thickness with polymerization time,indicating that chain growth from the surface is a controlled/"living" *** surface morphology was measured by atomic force ***,the surfaces of the poly(ionic liquid) brushes with tunable wettability and reversible switching between hydrophilicity and hydrophobicity can be easily achieved by counteranion exchange.

关键词：自由基聚合离子液体润湿性可调谐合成 NMP 表面形貌测量 X射线光电子能谱

Risk factors for postoperative pancreatic fistula in patients with insulinomas:analysis of 292 consecutive cases

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Hepatobiliary & Pancreatic Diseases International 2012年第1期11卷 102-106页

作者： zhao, yu-pei Zhan, Han-Xiang Cong, Lin Zhang, Tai-Ping Liao, Quan Dai, Meng-Hua Cai, Li-Xing Zhu, yu Chinese Acad Med Sci Peking Union Med Coll Hosp Peking Union Med Coll Dept Gen Surg Beijing 100730 Peoples R China

BACKGROUND: Pancreatic fistula (PF) remains the most challenging complication in pancreatic surgery, yet few published studies have focused on the risk factors for postoperative PF in patients undergoing surgery for insulinomas. METHODS: From January 1990 to February 2010, a total of 292 patients with insulinomas underwent surgery at Peking Union Medical College Hospital. Demographic data, intraoperative procedures, and postoperative data were collected. Particular attention was paid to variables associated with PF as defined by the International Study Group of Pancreatic Fistula (ISGPF). Univariate and multivariate analyses were used to identify possible risk factors for PP. RESULTS: PF was found in 132 (45.2%) patients, of whom 90 were classified into ISGPF grade A, 33 grade B, and 9 grade C. Multivariate analysis showed that male patients (OR=2.56; P=0.007) and operative time > 180 minutes (OR=3.756; P 180 minutes were independent risk factors for clinical PF, while pancreatic resection with a stapler was a protective factor. Whether body mass index (BMI) and other variables during operation are risk factors of PF needs further study. (Hepatobiliary Pancreat Dis Int 2012;11:102-106)

关键词： insulinoma pancreatic fistula risk factors

Pancreatic duct stones in patients with chronic pancreatitis:surgical outcomes

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Hepatobiliary & Pancreatic Diseases International 2010年第4期9卷 423-427页

作者： Liu, Bo-Nan Zhang, Tai-Ping zhao, yu-pei Liao, Quan Dai, Meng-Hua Zhan, Han-Xiang Peking Union Med Coll Peking Union Med Coll Hosp Dept Gen Surg Beijing 100730 Peoples R China Chinese Acad Med Sci Beijing 100730 Peoples R China

BACKGROUND: Pancreatic duct stone (PDS) is a common complication of chronic pancreatitis. Surgery is a common therapeutic option for PDS. In this study we assessed the surgical procedures for PDS in patients with chronic pancreatitis at our hospital. METHOD: Between January 2004 and September 2009, medical records from 35 patients diagnosed with PDS associated with chronic pancreatitis were retrospectively reviewed and the patients were followed up for up to 67 months. RESULTS: The 35 patients underwent ultrasonography, computed tomography, or both, with an overall accuracy rate of 85.7%. Of these patients, 31 underwent the modified Puestow procedure, 2 underwent the Whipple procedure, 1 underwent simple stone removal by duct incision, and 1 underwent pancreatic abscess drainage. Of the 35 patients, 28 were followed up for 4-67 months. There was no postoperative death before discharge or during follow-up. After the modified Puestow procedure, abdominal pain was reduced in patients with complete or incomplete stone clearance (P>0.05). Steatorrhea and diabetes mellitus developed in several patients during a long-term follow-up. CONCLUSIONS: Surgery, especially the modified Puestow procedure, is effective and safe for patients with PDS associated with chronic pancreatitis. Decompression of intraductal pressure rather than complete clearance of all stones predicts postoperative outcome.

关键词： pancreatic duct stone chronic pancreatitis surgical management modified Puestow procedure

Assessment of pancreatic carcinoma cell chemosensitivity using a three-dimensional culture system

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Chinese Medical Journal 2010年第14期123卷 1871-1877页

作者： LIAO Quan HU Ya zhao yu-pei ZHOU Tao ZHANG Qiang Department of General Surgery Peking Union Medical College Hospital National Laboratory of Medical Molecular Biology Chinese Academy of Medical Sciences Beijing 100730 China

Background Monolayer cell culture models are the traditional culture models used for in vitro research of pancreatic carcinoma chemosensitivity. However, these models neglect the interactions between tumor cells and the impact of the tumor microenvironment. Such tumor cell monolayers poorly mimic the solid tumor microenvironment. The present study aimed to investigate the chemosensitivity characteristics of pancreatic cancer cells in a three-dimensional culture system by analyzing the differences in drug sensitivity between a scattered cell culture model and a multicellular spheroid culture model. Methods Three pancreatic cancer cell lines （SW1990, ASPC-1 and PCT-3） were cultured in three-dimensional collagen gels as well as in traditional two-dimensional monolayers. The chemosensitivities of the pancreatic carcinoma cells to 5-fluorouracil （5-FU）, gemcitabine, and oxaliplatin in vitro were detected by both the Cell Counting Kit-8 test and the collagen gel droplet-embedded culture drug-sensitivity test. Results In the two-dimensional culture model, differences in the chemosensitivities of the cloned pancreatic carcinoma cells and scattered cells existed for some concentrations of 5-FU, gemcitabine and oxaliplatin. In the three-dimensional culture model, there were significant differences in the chemosensitivities of the pancreatic cancer cells between the scattered cells and multicellular spheroids （P 〈0.05）. Conclusion Pancreatic carcinoma cells exhibit multicellular resistance in three-dimensional cultures.

关键词： pancreatic carcinoma cell chemosensitivity three-dimensional culture

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加强胰腺癌诊断和治疗的规范化

中国医学科学院学报 2005年第5期27卷 553-555页

作者：赵玉沛中国医学科学院中国协和医科大学北京协和医院基本外科北京100730

重视早期诊断,准确进行术前评估,合理切除范围和积极开展综合治疗,是胰腺癌诊治规范化的关键环节,对改善其整体预后至关重要。

关键词：胰腺癌早期诊断可切除性评估手术辅助治疗

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再谈新时期青年外科医生的成长

中华外科杂志 2009年第1期47卷 2-3页

作者：赵玉沛中华外科杂志总编辑中国医学科学院北京协和医院外科 100730

如果用“一日千里”来形容当今医学发展的速度恐怕并不为过。外科学作为临床医学的一个重要分支，正伴随着时代跃动的节拍突飞猛进地发展。外科医生，尤其是年轻的外科医生，在惊叹学科的发展空间越来越广阔的同时，也时常会因为一些问... 详细信息

如果用“一日千里”来形容当今医学发展的速度恐怕并不为过。外科学作为临床医学的一个重要分支，正伴随着时代跃动的节拍突飞猛进地发展。外科医生，尤其是年轻的外科医生，在惊叹学科的发展空间越来越广阔的同时，也时常会因为一些问题感到茫然，譬如怎样处理全面发展与专业化，如何使临床与科研工作同步协调发展，怎样才能写出高质量的学术论文，等等。针对这些问题简要地谈谈自己的一些认识和建议。

关键词：青年外科医生临床医学医学发展协调发展科研工作学术论文外科学专业化