肿瘤抑制基因与大肠癌

近年来的研究表明,大肠癌的易感性和发病机制均与遗传机制有关,家族性腺瘤息肉病(FAP)和遗传性非息肉病结肠癌(HNPCC)均为常染色体显性遗传,其发病率分别占大肠癌的1％和5％。散发性大肠癌中遗传因素虽不甚重要,但是大肠癌和腺瘤患者的亲属发病率高于普通人群,亦反映了遗传     

遗传性非息肉病性大肠癌的临床研究进展

遗传性非息肉病性大肠癌(hereditary nonpolyposis colorectal cancer,HNPCC)又称Lynch综合征,是一种由错配修复基因(mismatch repair gene,MMR)突变引起的常染色体显性遗传病[1].作为大肠癌的一个重要临床亚型,HNPCC约占全部大肠癌的5%～15%.相对于散发性大肠癌,HNPCC的遗传病因特殊、临床病理特点突出.是目前大肠癌和遗传性肿瘤的一个研究热点.     

遗传性非息肉病性大肠癌临床病理特点与预后的关系分析

目的研究遗传性非息肉病性大肠癌的临床病理特点与预后的关系。方法选取2000年1月至2010年6月,在多地通过临床家系调查,筛选出18个遗传性非息肉病性大肠癌家系,其中肿瘤患者共70例,分为典型组(A组)和非典型组(B组),将同期调查中的其余无家族遗传背景的大肠癌68例患者作为对照组(C组)。回顾分析两组的临床病理和随访资料,比较两组的临床病理特点和预后关系差异。结果 A组和B组与C组在性别方面无显著差异,但在发病年龄、肿瘤情况、病理类型和预后方面差异显著。遗传性非息肉病性大肠癌发病年龄早、病理分化不佳、结肠癌和多原发癌常见的特点,但其5年以上的存活率优于无家族遗传背景的大肠癌。结论遗传性非息肉病性大肠癌的临床病理特点明显,与散发性大肠癌生物行为有显著的差异,预后较无家族遗传背景的大肠癌佳。     

遗传性非息肉病性结直肠癌患者的病理特点以及临床意义分析

目的探讨遗传性非息肉病性结直肠癌患者的病理特点以及临床意义。方法 80例大肠癌患者,其中40例散发性结直肠癌患者作为对照组, 40例遗传性非息肉病性结直肠癌患者作为试验组。对比两组患者的性别、肿瘤部位、肿瘤分期及病理类型及3、5年生存情况。结果两组患者的性别比较,差异无统计学意义(P>0.05);两组患者的肿瘤部位、肿瘤分期和病理类型比较,差异均有统计学意义(P<0.05)。试验组患者的3、5年生存率分别为87.5%、65.0%,均高于对照组的67.5%、42.5%,差异均有统计学意义(P<0.05)。结论遗传性非息肉病性结直肠癌患者的病理特点显著,且预后比散发性结直肠癌要好,值得临床推广。     

胃与大肠癌家系调查的结果比较

遗传性非息肉病性大肠癌（hereditary nonpolyposis colorectal cancer，HNPCC）因其遗传病因特殊和临床病理特点突出成为大肠癌研究的一个热点。依据是否伴发大肠外肿瘤，HNPCC分为两种临床亚型。目前认为胃癌是HNPCC最常见大肠外肿瘤之一。现将我院2001年1月-2005年12月收治并手术的胃癌与大肠癌患者的家系调查资料进行总结分析，以了解胃癌与大肠癌家族遗传背景及差异情况，提高诊断治疗水平。     

遗传性非息肉病性结直肠癌1个家系

遗传性非息肉病性结直肠癌(hereditarynon polyposiscolorectalcancer ,HNPCC)是一种常染色体显性遗传的家族性肿癌综合症,占总的结直肠癌(colorectalcancer ,CRC)的5 %～10 % [1] 。由于该综合症具有显著的家族特性,典型的临床特征,早期出现结直肠癌(平均确诊年龄4 5岁) ,近侧     

北京社区结直肠癌筛查的初步结果分析

目的探索城市居民中老年人群结直肠癌的发病情况,并通过积极干预降低社区结直肠癌的发病率。方法北京丰台区东高地居民区16个单位50～80岁共10740人接受大肠癌筛查,9843人(91.65%)接受连续3次的便隐血(免疫法)检查,阳性患者2709人(占受检者的27.52%),其中260人(占便隐血阳性者的9.60%)接受了电子肠镜检查。结果260例接受电子肠镜检查的患者中,检出大肠癌12例,男性8例,女姓4例,年龄66～77岁。其中息肉癌变2例,直肠类癌2例(均为早期),DukeⅡ期大肠癌4例,DukⅢA期大肠癌1例。检出结肠腺瘤127例。结直肠癌的检出率为121.9/105。结论城市居民中老年人群结直肠癌的发病率呈直线上升。通过便隐血检查后,阳性患者接受肠镜检查可以发现早期结直肠癌。建议此项工作应在城市居民中广泛开展以改善结直肠癌的预后。     

3431例电子结肠镜检查结果的回顾性分析

目的 探讨电子结肠镜检查对大肠病变的临床意义,为临床合理应用电子结肠镜检查手段提供临床依据.方法 回顾性分析本院2010年1月～2011年12月收治的3431例电子结肠镜检查患者,其中检测出大肠疾病患者1594例,分析发病年龄、性别、主要病变的差异.结果 大肠疾病中结直肠息肉、结直肠炎、结直肠癌检出率较高.1594例大肠疾病患者中,老年组结肠癌的检出率明显高于中年组和青年组.结直肠癌和结直肠息肉的检出率随年龄增长而逐渐增加.男性大肠患病率高于女性.结论 电子结肠镜对大肠病变的诊断有重要意义,有助于结直肠癌、结直肠炎和结直肠息肉的早期防治,从而提高患者的生活质量.     

上海某镇173例大肠息肉的特点分析

目的:了解洞泾镇大肠癌初筛阳性居民中大肠息肉的患病特点.方法:在大肠癌初查阳性并进行结肠镜检查的522例对象中,收集到173例被诊断为大肠息肉患者的信息,分析大肠息肉患病的性别和年龄分布以及大肠息肉类型与患病部位的关系.结果:在173例大肠息肉患者中,男性检出率42.25％,女性检出率24.24％,差异有统计学意义(P<0.05),50岁及以上受检者的大肠息肉检出率高于50岁以下受检者(34.7％ 比12.1％,P<0.05).类型以腺瘤性息肉最多(75.14％),发病部位以直肠(32.95％)和乙状结肠(23.70％)为主.结论:大肠息肉的发病与年龄和性别有关,腺瘤型息肉居多,好发部位为直肠和乙状结肠.     

不同年龄结直肠癌患者临床及内镜特点分析

目的探讨不同年龄结直肠癌患者临床及内镜特点，以提高结直肠癌早期诊断率。方法结直肠癌患者按年龄分为青年组（≤35岁）、中年组（36～59岁）、老年组（≥60岁），比较不同年龄组结直肠癌患者临床表现、内镜表现、病理资料。结果结直肠癌以中、老年人多见（占全部结直肠癌的89．8％），临床首发症状均为便血，青年组腹痛比中、老年组常见（P〈0．05）；各组均以左半结肠癌多见，共占76％，右半结肠癌占24％：中、老年组结直肠癌合并息肉的发生率高于青年组；青年组低分化腺癌较中、老年组多见。结论结直肠癌以中、老年多见，左半结肠癌较右半结肠癌多见，青年人结直肠癌低分化腺癌多见，恶性程度高，预后不良。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.