幽门螺旋杆菌与肝癌相关性的研究进展

幽门螺旋杆菌被认为是胃炎、消化性溃疡、胃癌的主要致病因素,然而近年来,诸多实验研究指出它还与肝脏肿瘤之间有密切联系,现就近几年的相关研究进展进行综述,主要涉及侵袭肝脏途径、入侵肝脏细胞病理机制与肝炎肝硬化的关系等方面。     

酒精性脂肪肝的线粒体作用机制研究进展

酒精性脂肪肝是世界范围内肝脏相关疾病发病和死亡的主要驱动因素之一。酒精摄入会负向调控肝脏正常的脂质代谢，而肝脏对酒精最早和最常见的不良反应是肝脏脂肪变性，其严重程度被认为与酒精性肝病中晚期进展密切相关。线粒体作为内源性活性氧的主要生成位点和生物能量代谢的关键场所之一，在调节肝细胞氧化还原和脂质代谢方面起着重要作用。然而，酒精诱导线粒体内活性氧的大量生成会直接或间接导致线粒体功能障碍，进而抑制线粒体β氧化，造成大量脂肪酸在肝内异常累积，最终导致酒精性脂肪肝。本文主要从酒精诱导肝脏线粒体氧化应激、线粒体β氧化、线粒体自噬、缺氧和线粒体靶向抗氧化剂等角度探讨了其与酒精性脂肪肝相关的潜在发病机制，并回顾了与线粒体相关的其他转录因子对酒精诱导的肝脏脂质累积的作用。     

肝脏病理损伤对肝转移癌发生的影响

早在一百多年前，就有学者发现肝脏损伤与肝转移癌存在着一定的关系。近年来，随着研究肿瘤转移发生、发展机制技术的不断更新，有关肝脏损伤与肝转移癌关系的研究亦再次受到人们的关注。以下就近期国内外有关肝脏主要良性损伤与肝转移癌的关系作一综述。     

结肠癌肝脏转移前微环境形成机制及作用的研究进展

结肠癌肝转移是临床治疗难题,研究发现,肿瘤细胞转移至肝脏前,通过释放相关细胞因子在肝脏内部形成转移前微环境,从而利于循环肿瘤细胞在肝脏定植。转移前微环境的形成主要与结肠原发癌、肝脏局部微环境以及机体免疫状况相关,其中涉及多种机制,包括肿瘤分泌外泌体、细胞因子、肿瘤上皮间质转化、肝脏细胞外基质重塑等。研究结肠癌肝转移前微环境形成机制,将有助于结肠癌肝转移的早诊早治以及降低肝转移发生、改善患者预后。本文就结肠癌肝转移前微环境的形成及相关机制进行综述。     

基因芯片技术研究抗病毒药物Bay41-4109的肝毒性机制

背景与目的:研究新型抗乙肝病毒药物Bay41-4109的肝毒性机制.材料与方法:用典型诱导剂苯巴比妥作为对照,观察大鼠连续5d灌胃给予Bay41-4109后肝脏脏器系数的变化,并对肝脏进行组织学检查;用MTT比色法进行HepG2细胞毒性实验.然后利用大鼠和人的全基因组芯片,分析Bay41-4109对大鼠肝脏和人肝细胞基因表达谱的影响,并对基因芯片数据进行聚类分析和初步功能分析,采用RT-PCR对部分差异表达的基因进行验证.结果:Bay41-4109和苯巴比妥均引起大鼠肝脏脏器系数显著增高(P＜0.05),肝组织局部出现小的灶性坏死;Bay41-4109引起大鼠肝脏发生差异表达的基因主要与药物代谢及脂肪和能量代谢有关,其中有26个基因的改变与苯巴比妥一致.体外研究发现Bay41-4109在IC20和IC50浓度下引起HepG2细胞发生差异表达的基因主要与脂肪、氨基酸、能量代谢有关,与大鼠肝脏基因芯片结果一致.差异表达基因用RT-PCR能得到验证.结论:Bay41-4109的肝毒性与药物代谢酶表达异常以及脂肪能量代谢异常有关.     

胆固醇代谢的调控参与肝癌发生发展的研究进展

胆固醇是机体细胞膜性结构的重要组分和合成甾体类激素的主要原料，肝脏是机体胆固醇代谢的核心器官，司职胆 固醇合成、摄取、转运和排泄等重要功能。肝脏胆固醇代谢的失调参与一系列肝脏疾病的发生发展，尤其与肝癌的发生发展密切 相关。因此，探索肝脏尤其是肝细胞中胆固醇代谢的分子调控机制，阐明胆固醇在肝癌中的作用，并寻求干预肝脏胆固醇代谢的 潜在靶点，是目前广受关注的重要科学问题。本文就肝脏胆固醇代谢调控参与肝癌发生发展及其生物治疗方面的研究进展作一 综述。     

超声造影在局灶性脂肪肝与肝脏良性肿瘤鉴别诊断中的应用价值

目的:探讨超声造影在局灶性脂肪肝与肝脏良性肿瘤鉴别诊断中的应用价值.方法:收集在我院手术或行肝脏穿刺组织病理检查确诊的肝脏良性肿瘤及局灶性脂肪肝共患者156例(156个主要病灶),均有完整病史、常规超声、超声造影检查,病理结果,回顾性分析超声及超声造影检查结果.结果:超声造影检查对局灶性脂肪肝与肝脏良性肿瘤诊断的灵敏度为82.61%、特异度为92.73%、阳性预测值为82.61%、诊断准确率为89.74%,明显高于常规超声检查的63.04%、82.73%、60.42%、76.92%,比较差异有统计学意义(P<0.05);局灶性脂肪肝的46个病灶表现为与肝组织同步增强及消退,肝血管瘤、肝脏腺瘤、肝局限性结节增生在动脉相、门脉相时表现各有不同.结论:超声造影用于局灶性脂肪肝及肝脏良性肿瘤诊断时灵敏度及特异度均明显高于常规超声检查,可根据动脉相及门脉相的表现对局灶性脂肪肝与肝脏良性肿瘤进行鉴别诊断.     

原发性肝脏间质瘤1例报告并文献复习

目的:探讨肝脏间质瘤的临床、病理特点.方法:对1 例原发于肝脏的巨大间质瘤,应用免疫组化S-P法观察,进行临床病理分析.结果:免疫组化染色提示CD117(+)、Vimentin(+)、CD34(-)、S-100(-)、SMA(-)、Hepatocyte(-)、AFP(-)、HMB45(-).结论:胃肠道外间质瘤发生在肝脏极为罕见,需要与多种肝脏原发肿瘤进行鉴别,正确诊断主要依赖组织病理及免疫组化结果.     

肝脏树突状细胞与肝细胞癌

近年来随着对肝脏DC免疫生物学研究的不断深入，人们更深入地了解了肝脏DC的免疫学特性及其与肝脏疾病尤其是肝细胞癌（hepatocellular carcinoma, HCC）的关系，并据此设计有针对性的治疗策略。在肝脏微环境的作用下，肝脏DC处于非成熟状态，具有数量相对不足、显著的异质性、抗原摄取能力及T细胞活化能力低下等特点，它可表达特殊的CC和CCR。上述因素使肝脏DC在肝脏免疫调节中起重要作用，主要体现在大量肝脏非成熟DC无法活化T细胞，尤其在肝细胞癌的状态下，非成熟肝脏DC进一步增加，伴随着免疫活化因子IL12分泌的减少，不利于机体抗肿瘤免疫的产生，而肝细胞癌自身可通过AFP、IL10、IL8及HBV/HCV的作用抑制肝脏DC。但也有观点认为，肝脏DC为成熟状态，可通过调节T细胞活化的途径最终引起肝脏免疫耐受的产生。     

磁共振功能成像在肝脏疾病的诊断及疗效评价方面的应用进展

磁共振功能成像在肝脏应用主要包括弥散成像、灌注成像、波谱显像三方面。目前,弥散成像和灌注成像已广泛应用于肝脏肿瘤和弥漫性疾病的诊断、鉴别诊断和治疗后疗效评价。波谱分析从探测活体组织化合物浓度入手,为肝脏疾病的更早期、更特异诊断和疗效监测方面提供了新方法。本文综述了近年来磁共振功能成像在肝脏疾病的诊断及疗效评价方面的应用进展。     

胃癌影响因素研究进展

胃癌一直以来都严重威胁着人类的健康生活。近年来已经对胃癌的影响因素进行了大量研究,且已经证实了幽门螺杆菌感染、抽烟、饮酒等因素在胃癌的发生发展过程中起着非常重要的作用,但影响胃癌发展形成的因素是多方面的。随着医疗技术的发展,我们对胃癌的认识不能仅局限于几个单方面因素。因此,本文介绍了胃癌的流行病学,同时回顾了过去研究中的新发现。     

Helicobacter pylori and gastric cancer prevention is possible

Epidemiological data gathered during the past few years have shown an association between Helicobacter pylori infection and gastric carcinoma. This association is considered to be causal because of its biological plausibility and the existence of an animal model, even though the positive consequences of eradication on cancer prevention have not yet been definitely proven. The limited proportion of H. pylori infected subjects who develop a gastric cancer can be explained by host factors (certain alleles of IL-1beta) and bacterial factors (cag positive strains), and to a lesser extent by environmental factors (diet). Arguments in favor of the prevention of gastric carcinoma by eradicating H. pylori are now stronger than before, given the availability of simple and accurate diagnostic tests (serology) and treatment follow-up (urea breath test), as well as a 7-day treatment which is usually sufficient for eradication.     

Oxidative stress in gastric carcinogenesis

There is still high stomach cancer though its mortality rate Helicobacter pylori has tended to decrease for the past several years. Study of Helicobacter pylori become more active as the relation between the stomach cancer and Helicobacter pylori has been clarified. In the present study, we added considerations from the literature in terms of oxidation stress with Helicobacter pylori about the underlying mechanism of the stomach cancer. Moreover, we referred to the relation between adenocarcinoma at the oesophagogastric junction and the oxide of nitrogen as clarified by recent study. Additionally, the role of anti-oxidant biofactors such as vegetables and fruits were considered from the viewpoint of cancer prevention in light of recent findings.     

解放军总医院胃癌住院患者临床资料分析

目的总结近一年以来胃癌住院患者临床资料特点、变化趋势,对比各项检查结果针对性筛查幽门螺杆菌感染患者,研究与胃癌患病的关系。方法回顾性分析经病理诊断并收治入院的胃癌患者(共计1461例),对其平均年龄、性别比例、病理类型、发生部位、TNM分期等进行统计;二筛选病例资料里幽门螺杆菌感染检测患者(共265例),对这类患者的胃癌指标变化进行统计学分析。结果1461例胃癌中,男性占70.77%(1034例),女性占29.23%(427例),平均年龄(59.29±11.30)岁(中位年龄60岁)。病理类型以低分化乳头状腺癌居多(408例),占57.3%。发生部位以贲门居多(232例),占28.29%。取得幽门螺杆菌粪便抗原检查结果的病例为265例(男性192例,女性73例),阳性患者90例,阴性患者175例,胃癌相关检查指标人胃蛋白酶原Ⅰ、Ⅱ在幽门螺杆菌感染与非感染患者之间的统计结果P值均小于0.05。结论胃癌患者的发病年龄有逐年增高的趋势;病理类型以腺癌居多;人胃蛋白酶原Ⅰ、Ⅱ作为胃癌风险评估的指标,在胃癌检测筛查中具有很高的评定价值。     

Helicobacter pylori seropositivity as a risk factor for pancreatic cancer.

BACKGROUND: Pancreatic cancer is among the most fatal cancers worldwide and one for which few preventable risk factors have been established. Gastric carriage of Helicobacter pylori, particularly cytotoxin-associated gene-A-positive (CagA+) strains, is known to be a risk factor for peptic ulcer disease and gastric cancer and may have a similar etiologic relationship with pancreatic cancer. METHODS: We investigated the association of H. pylori carriage and exocrine pancreatic cancer in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 29 133 male Finnish smokers aged 50-69 years at baseline. Case subjects (n = 121) were matched on date of baseline serum collection, study center, age, trial intervention, and completion of the dietary questionnaire to 226 control subjects who were alive at the time the matching case subject was diagnosed and who remained free of cancer, during up to 10 years of follow-up. Levels of immunoglobulin G antibodies to H. pylori whole-cell and CagA+ antigens from stored baseline serum were measured by enzyme-linked immunosorbent assay. Smoking-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of conditional logistic regression. Statistical tests were two-sided. RESULTS: Seroprevalence of H. pylori was 82% and 73% among case and control subjects, respectively. Compared with seronegative subjects, those with H. pylori or CagA+ strains were at statistically significantly elevated risk of pancreatic cancer (OR = 1.87 [95% CI = 1.05 to 3.34]; OR = 2.01 [95% CI = 1.09 to 3.70], respectively). CONCLUSIONS: Our findings support a possible role for H. pylori carriage in the development of exocrine pancreatic cancer.     

Gene therapy for liver metastases

Although resection is currently the only curative approach for metastatic liver cancer, only a small number of cases are suitable for this procedure. In the past few years, gene therapy has emerged as an appealing treatment option for liver cancer. Phase I and II clinical trials have been conducted in patients with either primary or secondary liver cancer using a variety of genes including tumor-suppressor gene p53, suicide genes, immune genes, and replication-competent oncolytic adenoviruses. The results have shown that, although gene therapy has been well tolerated and toxicity has been low, the clinical benefit has so far been marginal. Gene therapy as a definitive treatment for liver metastases remains limited, at least for the time being, but it may be useful as an adjuvant treatment in combination with radiotherapy, chemotherapy, and/or surgery to achieve disease-free survival.     

肿瘤低发区苍山县肝癌死亡率的变化趋势和对病因研究的启示

目的观察肿瘤低发区苍山县２５年肝癌死亡率的动态变化。方法采用全死因历年检测登记的方法获取资料，统计分析采用中国１９６４年人口构成进行标化死亡率的计算。结果２５年的动态观察资料显示肝癌的死亡率显著增加。结论同期山东省和全国的死因调查结果也显示肝癌死亡率上升，这一现象表明肝癌的危险因素并非高发区所特有，而是在很多地区环境中普遍存在的     

肝癌干细胞研究进展

近几年,肿瘤起源于干细胞的假说正在人类各种肿瘤中得到证实,包括肝癌。目前认为肿瘤干细胞对肿瘤发生、转移和预后起了关键作用,因此如何分离和鉴定肝癌干细胞对于改善预防方法、促进早期检测以及研发新的治疗方法都是一个非常紧迫的课题。本文就有关肝癌干细胞存在的依据、来源、表面标志物分选等研究进展作一综述。