消化道肿瘤蛋白质组学研究进展

近年来，蛋白质组学技术在肿瘤中的研究和应用越来越广泛。蛋白质组学在消化系统肿瘤的筛查和早期诊断、预后检测、复发后预测等方面发挥重要作用。本文总结了蛋白质组学技术进展及在食管癌、胃癌、结直肠癌、胰腺癌、肝癌等消化道肿瘤中的研究进展。     

蛋白质组学在消化系肿瘤中的应用

蛋白质组学是以双向凝胶电泳和质谱技术为核心, 从整体的角度研究生物机体、组织、细胞甚至细胞器基因编码的全部蛋白质, 在更贴近生命本质的层次上发现和理解生命活动的规律.作为肿瘤研究的新平台, 蛋白质组学对食管癌、胃癌、肝癌、胰腺癌、结直肠癌等消化系肿瘤的早期诊断, 寻找新标志物, 治疗以及药物开发的新靶点等方面有重要意义, 具有潜在、广阔的应用前景.     

蛋白质组学在结直肠癌中的研究进展

结直肠癌是最常见的恶性肿瘤之一,高居癌症致死病的第4位.早期不易发现、预后差,因此需要寻找新型的分子标志物来提高早期诊断,并发现有效的治疗新靶点.蛋白质组学技术的发展,有助于在蛋白质水平上更好的阐述结直肠癌的发病机制、进而提高早期诊断和治疗能力.近年来,蛋白质组学通过提供大规模高通量的蛋白质分析技术手段,在组织、血清、细胞等不同水平鉴定出多种结直肠癌的差异表达蛋白,并发现新的潜在诊断标志物和临床药物治疗靶点.本文就近年来结直肠癌蛋白质组学研究进展进行简要介绍.     

SELDI-TOF-MS联合蛋白质组学实验数据库对结直肠癌血清标志物的鉴定

目的:探讨表面增强激光解析离子化飞行时间质谱仪(SELDI-TOF-MS)联合蛋白质组学实验数据库方法研究结直肠癌患者血清标志物的可行性.方法:应用SELDI-TOF-MS对169例结直肠癌患者与83例正常人血清进行了蛋白质谱检测.通过Biomarker WizardTM与BiomarkerPatternsTM软件分析发现差异蛋白,建立结直肠癌诊断模型;用蛋白质组学实验数据库检索鉴定出有意义的差异蛋白,并用ELISA法对结直肠癌患者及正常人血清样本中差异蛋白表达进行验证.结果:发现34种差异蛋白,以质荷比(m/z)为2873,3163,6121,7778的4种差异蛋白组成的分类树诊断模型.在学习模式下其诊断结直肠癌的灵敏度为91.57%,特异度为90.53%:在测试模式下分别为82.25%.80.72%.其中m/z为7778的蛋白峰强度在结直肠癌患者血清中明显高于正常人(p<0.01),数据库检索结果提示该蛋白为血小板因子4(PF4).ELISA法测定结直肠癌患者血清PF4水平显著高于正常人(p<0.01),其灵敏度及特异度分别为61.1%,76.9%.结论:SELDI-TOF-MS联合蛋白质组学实验数据库的方法简便可行.可为蛋白芯片研究提供新思路;PF4(m/z=7778)在结直肠癌患者血清中明显升高,是结直肠癌患者新的血清学标志物.     

肠道菌群在结直肠癌发病与治疗中的研究进展

结直肠癌是常见的消化道恶性肿瘤.近年来有关肠道菌群的研究结果显示,肠道菌群结构、丰度和功能的改变与很多疾病密切相关,如炎症性肠病、自身免疫性疾病、消化道肿瘤等.肠道菌群失调可通过菌群移位、"驱动-乘客"模型、"毒性"肠道细菌模型等机制导致结直肠癌的发生发展.而补充膳食纤维与益生菌,应用肠道微生物移植技术可通过抑制肿瘤血...     

iRGD肽协同奥沙利铂逆转结直肠肿瘤耐药的研究进展

结直肠癌是世界上常见的恶性肿瘤,奥沙利铂（oxaliplatin）是常用于结直肠肿瘤化疗的第三代铂类药物,以其为基础的化疗方案现已成为结直肠癌化疗的标准方案。结直肠癌化疗无效的一个重要原因是肿瘤细胞对化疗药物产生耐药,最近研究发现,具有靶向能力的修饰物与化疗药物结合,能提高肿瘤组织内化疗药物的局部浓度。iRGD肽作为一种靶向肽与化疗药物结合,能增强化疗效果,血管内注射与iRGD肽偶联修饰过的化疗药物,能导致化疗药物与肿瘤血管结合,并能扩散到血管外的肿瘤实质。本文就iRGD肽协同奥沙利铂逆转结直肠肿瘤耐药的研究进展做详尽综述。     

5-LOX mRNA和COX-2 mRNA在结直肠癌中的表达及二者的相互关系

目的 研究5脂氧合酶(5-LOX)和环氧合酶2(COX-2)在结直肠癌中的表达及二者的相互关系.方法 用RT-PCR检测39例结直肠癌标本中5-LOX mRNA和COX-2 mRNA的表达.结果 5-LOX mRNA和COX-2 mRNA在结直肠癌组织中的表达率分别为84.6%(33/39)及76.9%(30/39),均与结直肠癌临床分期、肿瘤大小、肿瘤分化程度有关.但两者无相关性(P＞0.05).结论 5-LOX mRNA和COX-2 mRNA在结直肠癌组织中表达增高,提示了在研究结直肠癌治疗和预防时可采取对代谢途径抑制这一新方向.     

遗传性结直肠肿瘤研究进展

结直肠癌是我国最常见的消化系恶性肿瘤之一,其发病率和死亡率都居全部恶性肿瘤的前列.约有1/3的结直肠癌是由遗传性结直肠肿瘤引起.遗传性结直肠肿瘤包括遗传性非息肉病性结直肠癌和遗传性结肠息肉病两大类.本文简要总结了近年来国内外学者在遗传性结直肠肿瘤的研究中所取得的共识与进展,并就其临床诊治进行讨论和展望.以期加深人们对他的认识,提高医务人员对上述疾病的临床诊治能力.     

结直肠癌预后与肿瘤细胞DNA组成的关系

已有学者报告:在实体肿瘤细胞中观察到非整倍体细胞提示预后不良.本文研究的目的是探讨在结直肠癌患者中,非整倍体细胞是否是一项与病期和病理无关的独立的预后检测指标.材料与方法:原发性已切除的结直肠癌77例参与本研究,研究对象均符合下列标准:早先无其它肿瘤病史,无溃疡性结肠炎或家族性结直肠息肉史,原发肿瘤已根治.有下列情况者不列入本研究:1.结直肠癌以往曾经其它方式治疗; 2.复发性结直肠癌;3.肿瘤已有转移;4.起于结直肠息肉的原位癌,未侵犯息肉蒂;5.肿瘤已致肠穿孔.以下临床特征应予注意:年龄、性别、肿瘤部位、手术前血清CEA浓度、邻近器官侵犯情况、     

大肠癌APC基因研究进展

肿瘤的发生发展除了与饮食、环境等因素有关外,还与多个癌基因的激活和肿瘤抑制基因的失活有关。结直肠癌的发生发展为肿瘤分子生物学的研究提供了极好的模式。遗传性结直肠癌包括家族性腺瘤性息肉病结直肠癌及遗传性非息肉性结直肠癌,总发病率约占结直肠癌的15%左右。遗传性结直肠癌的基因定位是     

蛋白质组学在胰腺癌中的研究进展

胰腺癌是一种常见的恶性肿瘤,迫切需要早期诊断及治疗。快速发展的蛋白质组学技术为探讨胰腺癌发生的分子机制、发现新的肿瘤标记物及治疗靶点提供了新的手段,在胰腺癌研究中显示出巨大的前景。     

A novel concept of identifying precancerous cells to enhance anti-cancer therapies

Cancer is the leading cause of death worldwide and mortality due to cancer continues to rise. Cancer cell resistance to chemoradiotherapy is hindering treatment efforts in clinics. Prevention strategies and early detection thus may reduce mortality. In this study, we have proposed the concept of using precancerous cells and their progeny in cancer therapy, which could provide unique insights for early cancer diagnosis, treatment, and preventive therapy. In addition to discussing the nature and characteristics of precancerous cells and their progeny, we have also introduced an effective precancerous cell-targeted therapy based on an animal model of hepatocellular carcinoma. Anti-precancerous cell drug development should be a major target during cancer elimination and it may lead to preventive therapies for individuals with a high risk of developing cancer.     

Toward the discovery of new biomarkers of hepatocellular carcinoma by proteomics.

Primary liver cancer is the fifth most frequent neoplasm and the third most common cause of cancer-related death, with more than 500,000 new cases diagnosed yearly. The outcome for hepatocellular carcinoma (HCC) patients still remains dismal, partly because of our limited knowledge of its molecular pathogenesis and the difficulty in detecting the disease at its early stages. Therefore, studies aimed at the definition of the mechanisms associated with HCC progression and the identification of new biomarkers leading to early diagnosis and more effective therapeutic interventions are urgently needed. Proteomics is a rapidly expanding discipline that is expected to change the way in which diseases will be diagnosed, treated, and monitored in the near future. In the last few years, HCC has been extensively investigated using different proteomic approaches on HCC cell lines, animal models, and human tumor tissues. In this review, state-of-the-art technology on proteomics is overviewed, and recent advances in liver cancer proteomics and their clinical projections are discussed.     

基于蛋白质组学筛选获得的乙型肝炎病毒相关肝癌诊断标志物的研究进展

肝癌是世界上死亡率最高的恶性肿瘤之一,乙型肝炎病毒（HBV）是主要的致病原,然而,HBV感染相关的肝癌发病机制不明,早期诊断非常困难。蛋白质组学为肝癌研究开辟了新的途径,受到研究者的关注。本文对近3年在HBV相关肝癌发病机制、肝癌标志物筛选研究方法及已发现的肝癌诊断标志物方面取得的研究成果进行了综述。     

缺氧诱导因子-1α在食管鳞状细胞癌中的研究

食管癌是常见的消化系统恶性肿瘤,我国90%以上的食管癌为食管鳞状细胞癌,其病因和发病机制尚未明确。近年来研究表明,肿瘤微环境参与食管鳞状细胞癌的发生、发展。肿瘤的快速生长导致肿瘤微环境缺血缺氧,而缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)作为细胞对缺氧环境适应的重要调节因子,在食管鳞状细胞癌的血管生成、增殖、侵袭、转移及放化疗敏感性等方面发挥重要作用。本文通过探讨HIF-1α对食管鳞状细胞癌发生、发展及预后的影响,评估HIF-1α在食管鳞状细胞癌治疗中的作用,为研究食管鳞状细胞癌的机制、治疗及预后提供新思路。     

Future direction of nanomedicine in gastrointestinal cancer]

Cancer is one of the leading causes of death in human, and among various cancers, gastrointestinal cancers occupy more than 55%. Gastric cancer is the first leading cause of cancer-related mortality in the world and the number of pancreas and colon cancers are increasing remarkably during last two decades which will continue to increase in the future. Even though the clinical importance of gastrointestinal cancers is very high and endless efforts has been made to develop novel diagnostic and therapeutic methods to improve the patient's quality of life and survival, the realistic advance in the actual survival benefit of the cancer patients are still strongly required. Nanotechnology has the power to radically change the way of cancer diagnosis and treatment. Currently, there is a lot of researches on novel nanodevices capable of detecting cancer at its earliest stage, pinpointing its location within the body, and delivering anticancer drugs specifically to the malignant cells. Nanoscale devices can readily interact with biomolecules both on the cell surface and within the cell. In addition, nanoscale devices are already proven that they can deliver therapeutic agents to target cells even within specific organelles. Major areas in which nanomedicine is being developed in cancer include early detection and proteomics, imaging diagnostics and multifunctional therapeutics. Because nanotechnology would provide a technical power and tool that enable new diagnostics, therapeutics, and preventives to keep pace with today's explosion in knowledge in the future, it would be very useful to know the perspectives in the direction of nanotechnology as a major clinician responsible for the patients with gastrointestinal malignancies.     

呼出气体冷凝物的蛋白质组学研究用于肺癌早期诊断的探讨

蛋白质组学研究的新方法、新技术的出现使其在肿瘤的研究中展现出广阔的应用前景。呼出气体冷凝物是一种尚处于研究阶段的无创、简易的新型检测肺癌的方法,包含了一系列来源于下呼吸道的生物标志物,如蛋白质。从这一视角分析以呼出气体冷凝物为样本、蛋白质组学技术为研究手段,来检测肺癌肿瘤标志物的潜力及面临的局限,论述其用于肺癌早期诊断...     

Cancer of pancreas

Cancer of the pancreas is the tenth most frequent cancer in Europe, accounting for some 3% of cancer in both sex. Smoking has been clearly established as a major risk factor affecting the carcinogenesis of pancreatic carcinoma. Diet has also been associated with pancreatic cancer, although no conclusive data are yet available. Different genetic alterations have been observed in pancreatic neoplasms. Typical symptoms of pancreatic cancer are: jaundice, abdominal pain and weight loss. The prognosis of pancreatic carcinoma depends mainly on radical surgery and the presence of negative resection margins, as well as on the biological tumour stage, which also influences the treatment strategy. The treatment of pancreatic cancer is undertaken with two aims. Radical surgery is indicated for patients with early stage of disease, mainly stage I and partially II. In all other cases, the aim of treatment is the palliation of different very distressing symptoms related to this neoplasm.     

Clinicopathologic impact of colloid in colorectal carcinoma

The overall incidence of colloid (mucinous) carcinoma in patients with colorectal cancer is 17 percent, and its influence on patterns of failure and survival in patients with colorectal cancer varies throughout the literature. The presence of colloid carcinoma may have a real but small impact on the patterns of failure or survival in colorectal cancer. The data are conflicting and, furthermore, by proportional hazards analysis, colloid carcinoma is not an independent prognostic factor for survival. Therefore, despite it being common clinical practice, a change in treatment recommendations based solely on the presence or absence of colloid cancer is not recommended. Treatment recommendations should be based primarily on the tumor stage and site. However, given the trend toward increased failure and decreased survival compared with adenocarcinoma, colloid carcinoma should be reported separate from other histological patterns to better understand its natural history.Recipient of American Cancer Society Clinical Oncology Career Development Award.     

Pancreatic intraepithelial neoplasia

Great efforts have been devoted to detecting preinvasive precursors to ductal carcinoma of the pancreas in the hope of improving the currently bleak prognosis of invasive pancreatic cancer. Intensive investigations of the pancreas have led to the recognition of intraductal papillary mucinous neoplasms (IPMNs) and the detection of preinvasive precursors to conventional ductal carcinoma. The pancreatic intraepithelial neoplasia (PanIN) nomenclature for precursor lesions of ductal carcinoma was developed at the "Pancreatic Cancer Think Tank" held in the United States in 1999. However, some reports of precursor lesions have suggested that these definitions do not encompass the full spectrum of precursors of ductal carcinoma, and these issues were the subject of the "Forum on Carcinoma In Situ of the Pancreas" held in Japan in 2002. After this forum, it became clear that the existing definitions of PanINs needed to be revised and expanded. Both participants of the Pancreatic Cancer Think Tank and the Forum gathered together at a meeting on precursor lesions of pancreatic cancer in 2003, and an international consensus on the diagnostic criteria for PanINs and IPMNs was created. We describe herein the current understanding of precursor lesions of pancreatic cancer.