蛋白质芯片在胰腺癌研究中的应用现状

胰腺癌是一种进展迅速的恶性肿瘤.临床迫切需要寻找胰腺癌的早期诊断标志物和发现新的治疗靶点.蛋白质芯片技术的发展,带来了很多机遇和挑战.此文对蛋白质芯片在胰腺癌中的应用现状作一综述,包括早期诊断、肿瘤标志物、治疗靶点及良恶性胰腺疾病的鉴别等.     

胰腺癌基国诊断研究进展

胰腺癌是人类恶性程度较高的肿瘤之一,目前常规的诊断技术难以早期发现.同所有肿瘤一样,胰腺癌的发生、发展是多种基因表达异常的结果.基因诊断是胰腺癌早期诊断的发展方向,尤其是基因芯片技术的应用,可快速检测胰腺癌细胞全部基因表达情况,为胰腺癌的早期诊断展现了新的曙光.     

SELDI-TOF MS技术在胰腺癌早期诊断中的应用

胰腺癌是目前预后最差的恶性肿瘤,早期诊断被认为是改善胰腺癌预后的重要出路之一.表面增强激光解吸电离飞行时间质谱(SELDI- TOF MS)技术,是近年来发展起来一种新的高通量蛋白质组学研究方法,本文就SELDI-TOF MS技术相关的原理、特点,在胰腺癌早期诊断中的应用新进展和未来的发展趋势作一综述.     

蛋白质指纹谱在胰腺癌诊断中的意义

尽管胰腺癌影像学诊断水平明显提高,但是早期患者往往缺乏临床症状而没有进行影像学检查.目前常用的肿瘤标志物CA19-9在胰腺癌的筛查中敏感性和特异性不高,尤其对于早期胰腺癌诊断价值不大[1-2],所以胰腺癌的早期诊断仍然是个难题.随着分子牛物学技术迅猛发展,蛋白质组学应运而生.本文应用SELDI-TOF-MS技术探测胰腺癌患者血清蛋白质组学的变化,以期发现特异的蛋白类肿瘤标志物,从而实现胰腺癌的早期诊断.     

胰腺癌影像诊断新进展

目前,胰腺癌的早期诊断受到关注.传统影像诊断技术有CT、MR和超声.新的技术已经发展起来,比如PET/CT融合和MRS,尤其是分子影像的实验研究,为今后胰腺癌的早期诊断提供新的技术手段.     

磁性纳米颗粒制备技术的进展及其在胰腺癌诊断中的应用

胰腺癌和胰腺上皮内瘤变的临床早期诊断十分困难,磁性纳米颗粒是一种具有超顺磁特性的新型磁共振增强造影剂,在肿瘤早期诊断方面有巨大的发展潜力.此文就磁性纳米颗粒制备技术的进展及其在胰腺癌诊断中的应用现状和前景作一综述.     

蛋白质组学在胰腺癌早期诊断中的应用

蛋白质组学的提出及其相关技术的发展为胰腺癌的早期诊断奠定了基础.其直接定位于蛋白质水平,从整体、动态、定量的角度研究基因功能,有助于发现用于早期临床诊断的肿瘤标志物,同时也可应用于寻找新的治疗靶标和进一步揭示胰腺癌发生、发展机制.本文就近年来蛋白质组学在胰腺癌早期诊断中的应用做一概述.     

超声内镜在胰腺癌诊断中的应用及进展

目前传统影像学技术对早期胰腺癌的诊断缺乏足够的敏感性,因此胰腺癌的早期诊断是目前国际上精准医疗方面最大的挑战。经过大量的临床实践和技术的发展,超声内镜在胰腺癌特别是胰腺癌早期诊断方面优势逐步体现。阐述了超声内镜在胰腺癌早期诊断中的应用及进展。     

胰腺癌的综合治疗

全球每年约有15万人,欧洲约有4万人死于胰腺癌[1],胰腺癌的发病率在全球范围内呈上升趋势.尽管影像学诊断技术和外科手术技术在不断提高,但其术后生存率并没有突破性改变.早期胰腺癌手术切除率为90%～100%,5年生存率可达70%～100%,但胰腺癌具有早期浸润血管,早期"围胆管"侵犯,早期神经束侵犯及早期缺乏特征性症状与体征的生物学特性,致使近90%的患者就诊时已属晚期,手术切除率仅为10%,5年生存率不足4%.     

胰腺癌分子诊断的研究进展

近年胰腺癌的发病率呈逐年上升趋势,本病恶性程度较高,与其早期局部侵犯和转移有关,因此早期诊断胰腺癌是实施根治性切除、延长患者生存期的关键。目前临床上尚缺乏有效的非创伤性早期筛查手段,多数患者确诊时已不能行手术切除。随着近年分子生物学和高通量测序技术的发展,在全基因组、转录组、蛋白质组水平筛选胰腺癌分子标记物成为了可能,可有效提高本病的早期诊断率。本文就胰腺癌分子诊断的研究进展作一综述。     

Pancreatic cancer proteome: the proteins that underlie invasion, metastasis, and immunologic escape

BACKGROUND & AIMS: Pancreatic cancer is a highly lethal disease that has seen little headway in diagnosis and treatment for the past few decades. The effective treatment of pancreatic cancer is critically relying on the diagnosis of the disease at an early stage, which still remains challenging. New experimental approaches, such as quantitative proteomics, have shown great potential for the study of cancer and have opened new opportunities to investigate crucial events underlying pancreatic tumorigenesis and to exploit this knowledge for early detection and better intervention. METHODS: To systematically study protein expression in pancreatic cancer, we used isotope-coded affinity tag technology and tandem mass spectrometry to perform quantitative proteomic profiling of pancreatic cancer tissues and normal pancreas. RESULTS: A total of 656 proteins were identified and quantified in 2 pancreatic cancer samples, of which 151 were differentially expressed in cancer by at least 2-fold. This study revealed numerous proteins that are newly discovered to be associated with pancreatic cancer, providing candidates for future early diagnosis biomarkers and targets for therapy. Several differentially expressed proteins were further validated by tissue microarray immunohistochemistry. Many of the differentially expressed proteins identified are involved in protein-driven interactions between the ductal epithelium and the extracellular matrix that orchestrate tumor growth, migration, angiogenesis, invasion, metastasis, and immunologic escape. CONCLUSIONS: Our study is the first application of isotope-coded affinity tag technology for proteomic analysis of human cancer tissue and has shown the value of this technology in identifying differentially expressed proteins in cancer.     

Proteomics of pancreatic cancer

Pancreatic cancer is a devastating disease, with a mortality rate almost identical with its incidence. Late diagnosis and limited therapeutic options make early detection of pancreatic cancer a pressing clinical problem. In this context, the investigation of the pancreatic cancer proteome has recently gained considerable attention because profiles of proteins may be able to more accurately identify disease states, such as cancer. Recent pancreatic cancer proteome studies may be categorized into basic studies cataloguing the pancreatic proteome, studies investigating differential protein expression patterns, and studies searching for proteome-based biomarkers for early cancer detection and differentiation. Although these studies clearly demonstrate that a range of biological samples are suitable for proteomic analyses, comparison of different studies is problematic due to the diversity of methodologies, sample sources, and characterization of patient populations. Reproducibility between studies has rarely been investigated, and no investigation has compared the different methods of proteomic research. The results of this review have shown that more stringent requirements concerning the design and the analysis of future studies should be implemented. These include an adequate patient number, obligatory histological examination of tissues, appropriate control groups, identification of proteins and peaks, validation of differential expression using independent cohorts and/or a second methodology, and, finally, demonstration of result reproducibility. This will hopefully lead to the discovery of prognostic and predictive biomarkers that help to improve prognosis of pancreatic cancer patients.     

胰腺腺管内上皮瘤的研究进展

胰腺癌的早期诊断与综合治疗目前缺乏有效的措施，80％的胰腺癌在诊断时已丧失手术机会，5年生存率仅为0．4％～4％。胰腺癌生存时间的延长取决于早发现、早治疗。故充分认识胰腺癌的癌前病变一胰晾腺管内上皮瘤（PanlN），了解其病理分级及与之相关的各级分子生物学水平的改变，讨论PanlN红胰腺癌形成中的作用，对胰腺癌的早期诊断及综合治疗有重要意义。     

Staging and treatment for patients with pancreatic cancer. How small is an early pancreatic cancer?

To determine the tumor size that constitutes early pancreatic cancer, we reviewed and analyzed the English-language and Japanese literature (a total of 25 publications) on small pancreatic cancers less than 2 cm in diameter and/or stage 1 cancers. Reports on in situ carcinoma and intraductal carcinoma of the pancreas were also evaluated. The results were: (1) A total of 302 cases of small pancreatic cancer less than 2 cm in diameter reported at separate institutions were pooled from 15 reports. The rates for patients in stage I and those with no lymph node metastasis averaged 41.7% and 57.9%, respectively. The 5-year postoperative cumulative survival rate (5Y-PCR) was less than 50% in almost all these reports. Similar data were shown in the 7 collective reviews. (2) Another 33 cases of small pancreatic cancer of 1 cm or less in diameter were collected from three reports. The rates for stage I tumor and 5Y-PCR at one institution with two reports were 100% and 100% and the rates in the other report were 85% and 78%, respectively. (3) Twelve cases of in situ carcinoma and intraductal carcinoma of the pancreas were collected from four reports. All of the patients were stage I and were alive with no evidence of tumor recurrence for periods ranging from 6 to 78 months. Small pancreatic cancer less than 1 cm in diameter is better viewed as an early pancreatic cancer, and in situ carcinoma and intraductal carcinoma of the pancreas with minimal invasion to the pancreatic parenchyma may be defined as early pancreatic cancer, regardless of size.     

Strategies for early detection of resectable pancreatic cancer

Pancreatic cancer is difficult to diagnose at an early stage and generally has a poor prognosis. Surgical resection is the only potentially curative treatment for pancreatic carcinoma. To improve the prognosis of this disease, it is essential to detect tumors at early stages, when they are resectable. The optimal approach to screening for early pancreatic neoplasia has not been established. The International Cancer of the Pancreas Screening Consortium has recently finalized several recommendations regarding the management of patients who are at an increased risk of familial pancreatic cancer. In addition, there have been notable advances in research on serum markers, tissue markers, gene signatures, and genomic targets of pancreatic cancer. To date, however, no biomarkers have been established in the clinical setting. Advancements in imaging modalities touch all aspects of the clinical management of pancreatic diseases, including the early detection of pancreatic masses, their characterization, and evaluations of tumor resectability. This article reviews strategies for screening high-risk groups, biomarkers, and current advances in imaging modalities for the early detection of resectable pancreatic cancer.     

Early detection and screening of pancreatic cancer. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011

Pancreatic cancer presents at an advanced stage in majority of the patients, hence resulting in a very dismal prognosis. Novel and effective methods to detect and screen pancreatic cancer and its precursors are warranted. The U.S. Multi-Society Task Force recommends against routine screening for pancreatic cancer in asymptomatic adults using abdominal palpation, ultrasonography, or serologic markers. Moreover, the screening for persons with hereditary predisposition to develop pancreatic cancer has not been validated. Herein, the authors summarize the data presented at the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in detecting early stage pancreatic cancer (Abstracts #187 and #193).     

Imaging diagnosis of pancreatic cancer:A state-of-the-art review

Pancreatic cancer(PC)remains one of the deadliest cancers worldwide,and has a poor,five-year survival rate of 5%.Although complete surgical resection is the only curative therapy for pancreatic cancer,less than20%of newly-diagnosed patients undergo surgical resection with a curative intent.Due to the lack of early symptoms and the tendency of pancreatic adenocarcinoma to invade adjacent structures or to metastasize at an early stage,many patients with pancreatic cancer already have advanced disease at the time of their diagnosis and,therefore,there is a high mortality rate.To improve the patient survival rate,early detection of PC is critical.The diagnosis of PC relies on computed tomography(CT)and/or magnetic resonance imaging(MRI)with magnetic resonance cholangiopancreatography(MRCP),or biopsy or fine-needle aspiration using endoscopic ultrasound(EUS).Although multi-detector row computed tomography currently has a major role in the evaluation of PC,MRI with MRCP facilitates better detection of tumors at an early stage by allowing a comprehensive analysis of the morphological changes of the pancreas parenchyma and pancreatic duct.The diagnosis could be improved using positron emission tomography techniques in special conditions in which CT and EUS are not completely diagnostic.It is essential for clinicians to understand the advantages and disadvantages of the various pancreatic imaging modalities in order to be able to make optimal treatment and management decisions.Our study investigates the current role and innovative techniques of pancreatic imaging focused on the detection of pancreatic cancer.     

Management of patients at high risk for pancreatic cancer

Opinion statement Because pancreatic cancer patients seldom exhibit disease-specific symptoms until the cancer is at an advanced stage, its diagnosis is a virtual death sentence. Therefore, to make a significant impact on long-term survival for subjects with pancreatic cancer, asymptomatic individuals would have to be screened for premalignant precursors of pancreatic cancer or for asymptomatic pancreatic cancer. A number of formidable obstacles limit the ability of healthcare providers to screen for early neoplastic changes and to make a very early and specific diagnosis of pancreatic cancer. These include lack of a high-risk population for sporadic pancreatic cancer and lack of a simple, noninvasive test sensitive enough to detect small cancers. However, progress is being made in defining various high-risk groups for pancreatic cancer, and improvements in imaging modalities make detection of premalignant lesions and small cancers possible in such individuals. The protocols currently being studied, including use of endoscopic ultrasound and endoscopic retrograde cholangiopancreatography to detect precancerous lesions and small pancreatic cancer in high-risk patients, are still in the research arena and not yet ready for clinical practice.     

Molecular detection of pancreatic neoplasia: Current status and future promise

Pancreatic cancer is usually diagnosed at an advanced stage and curative resection is feasible in only a small minority of patients at the time of diagnosis. Diagnosis at an early stage is unequivocally associated with better long-term survival. Several candidate molecular markers for early detection are currently under investigation in different phases of discovery and validation. Recent advances in the technology for whole genome,methylome,ribonucleome,and proteome interrogation has enabled rapid advancements in the field of biomarker discovery. In this review we discuss the current status of molecular markers for detection of pancreatic cancer in blood,pancreatic cyst fluid,pancreatic juice and stool and briefly highlight some promising preliminary results of new approaches that have the potential of advancing this field in the near future.