联合检测ERCC1和生存素在非小细胞肺癌个体化治疗中的意义

目的探讨联合检测肿瘤组织中核苷酸切除修复交叉互补基因1(ERCC1)和生存素蛋白的表达指导非小细胞肺癌(NSCLC)个体化治疗的价值。方法确诊为NSCLC患者151例,随机进入个体化治疗(A组,101例)和标准治疗(B组,50例)两组。A组依据活检组织标本中ERCC1及生存素蛋白表达情况选择个体化方案化疗:两种蛋白表达均为阴性的患者采用含铂一线化疗方案;其他患者则选用非铂化疗方案。B组均选择含铂一线化疗方案。比较两组患者化疗有效率和总生存期。结果 A组化疗有效率高于B组(49.5%vs.32.0%)(P<0.05);A组中位生存时间比B组长(13.81个月vs.11.50个月)(P<0.05)。结论联合检测肿瘤组织中ERCC1和生存素蛋白指导NSCLC患者个体化治疗可以提高化疗效果,延长生存时间。     

核苷酸切除修复交叉互补基因1、核苷酸还原酶M1亚基及β-微管蛋白Ⅲ表达与非小细胞肺癌术后含铂类化疗方案治疗疗效的关系

目的 探讨晚期非小细胞肺癌（NSCLC）患者肿瘤组织内核苷酸切除修复交叉互补基因1（ERCC1）、核苷酸还原酶M1亚基（RRM1）和β-微管蛋白Ⅲ（β-tubulinⅢ）表达与铂类标准化疗方案疗效的关系.方法 回顾性分析96例晚期NSCLC病例,采用实时荧光定量聚合酶链反应法检测ERCC1、RRM1和β-tubulinⅢ的表达量,分析患者的基因表达水平与化疗疗效的关系.结果 晚期NSCLC患者肿瘤组织内ERCC1低表达化疗有效率为75.0%,明显高于高表达的11.4%（χ^2 =15.762,P＜0.01）;RRM1低表达化疗有效率为72.6%,明显高于高表达的11.1%（χ^2 =14.986,P＜0.01）;β-tubulinⅢ低表达化疗有效率为76.6%,明显高于高表达的12.2%（χ^2=15.419,P＜0.01）.ERCC1、RRM1和β-tubulinⅢ的表达水平分别与铂类联合吉西他滨（GP方案）、铂类联合紫杉醇（TP方案）等化疗药物的疗效有相关性.结论 晚期NSCLC患者ERCC1、RRM1和β-tubulinⅢ表达不同,可能是标准化疗方案药物敏感性差异的重要因素,可为晚期NSCLC患者个体化用药提供参考依据.     

非小细胞肺癌患者ERCC1表达与铂类药物化疗敏感性的相关性的系统分析

目的 分析非小细胞肺癌患者ERCC1表达与对铂类药物治疗敏感性的相关性。 方法 电子检索Medline（1991~2009.12）、Pubmed、CBMDisc等数据库,对回顾性病例研究和随机对照临床试验进行总结分析。 结果 共纳入10篇文献,包括9篇回顾性病例研究和1篇随机对照临床试验。9篇回顾性病例研究资料结果表明,ERCC1表达阴性患者对铂类药物的联合化疗方案的反应率明显高于阳性患者（P=0.02）;1篇文献报道化疗后肿瘤进展时间ERCC1阴性组患者显著长于ERCC1阳性组患者（P〈0.05）;化疗后中位生存期具有统计学差异的2篇报道均为ERCC1阴性组高于ERCC1阳性组 （P〈0.05）。RCT研究结果表明辅助化疗可以明显延长ERCC1阴性患者的生存期,但不能延长ERCC1阳性患者的生存期。 结论 非小细胞肺癌患者中ERCC1低表达者可以从铂类化疗方案中受益,高表达者对铂类药物的化疗敏感性差,需要更好的辅助治疗方案。ERCC1作为预测NSCLC对铂类药物化疗方案敏感性的指标并指导临床个体化治疗具有临床意义。     

ERCC1蛋白的表达与晚期食管癌含顺铂方案化疗疗效的临床观察

目的:探讨晚期食管癌患者癌组织中切除修复交叉互补基因1(ERCCl)蛋白的表达与含顺铂方案联合化疗疗效的相关性.方法:回顾性检测98例晚期食管癌患者肿瘤组织中ERCC1蛋白的表达,观察患者接受含顺铂方案的联合化疗的疗效,分析ERCC1表达与客观有效率、疾病控制率、无进展生存期、总生存期之间的关系.结果:98例患者ERCC1表达阳性率为56.1％ (55/98),总疾病控制率为70.4％(69/98),ERCC1表达阴性组的客观有效率(76.7％)优于表达阳性组(38.2％),差异有统计学意义(x2=14.506,P=0.000);ERCC1表达阴性组的疾病控制率(88.4％)优于表达阳性组(56.4％),差异有统计学意义(x2=11.867,P=0.001);ERCC1表达阳性和阴性的两组无进展生存期和总生存期变化相近(P＞0.05).结论:晚期食管癌病理组织中ERCC1阴性表达患者疗效近期有效率优于ER-CC1阳性表达患者.     

白介素-2与顺铂胸腔内给药治疗肺癌胸腔积液

恶性胸腔积液是晚期肺癌的一个常见并发症，预后极差。有效的治疗不但可改善患者的临床症状，提高生存质量，且配合全身化疗可适当延长患者的生存期。2001年2月～2004年12月采用胸腔置管引流胸腔积液并胸腔内予顺铂或白介素-2(IL-2)治疗肺癌胸腔积液47例，取得了较好的效果，尤以白介素-2(IL-2)治疗取得了较好效果。报告如下：     

多西他赛不同给药方案治疗非小细胞肺癌的效果

目的:综述多西他赛不同给药方案治疗晚期非小细胞肺癌的优化效果。方法:汇总多西他赛单药和联合方案单周和3周方案一线和二线治疗晚期非小细胞肺癌(NSCLC)20个大型临床试验,比较多西他赛不同给药周期的不同方案的生存期(率)、生活质量和药物安全性的效果。结果:①Ⅳ期非小细胞肺癌患者[躯体功能评分(PS)为1～2]的老年病人(>75岁),一线治疗可选用多西他赛单药3周方案,二线治疗可选多西他赛单药每周方案。②Ⅳ期非小细胞肺癌患者(PS评分为0～1),如果基因ERCC1 mRNA表达水平低(或无ERCC1数据),可选择多西他赛联合顺铂3周方案。③Ⅳ期非小细胞肺癌患者,如果ERCC1高表达,可选择多西他赛联合吉西他滨方案治疗。④Ⅳ期非小细胞肺癌患者(PS评分为1～2)的病人(<75岁),可考虑选用多西他赛联合顺铂的每周方案。结论:多西他赛针对不同患者化疗组合,给药计划和化疗剂量的个体化选择将是晚期非小细胞肺癌的治疗所必需的。     

ERCC1基因表达与晚期非小细胞肺癌铂类化疗方案疗效的前瞻性研究

目的探讨核苷酸切除修复交叉互补组基因1（ERCC1）基因表达与晚期非小细胞肺癌铂类化疗方案的疗效。方法入组40例晚期非小细胞肺癌患者,实验组选取化疗前采用分支DNA-液相芯片技术检测确定为ERCC1 mRNA低表达的患者,对照组为同期住院的非ERCC1 mRNA低表达患者,每组各20例。每组患者行至少4个周期的含铂的化疗方案治疗,评价两组的化疗反应率、疾病进展时间。结果实验组患者的化疗有效率、疾病进展时间分别为85.0%、11.6个月;对照组的化疗有效率、疾病进展时间分别为30.0%、7.9个月,差异有统计学意义。结论ERCC1基因表达可作为预测晚期非小细胞肺癌对含铂化疗方案的敏感性的指标。     

非小细胞肺癌组织表达ERCC1与顺铂耐药的相关性分析

目的：探讨非小细胞肺癌（NSCLC）组织表达切除修复交叉互补基因1（ERCC1）与顺铂耐药的相关性。方法以2010年4月-2013年7月江西省肿瘤医院收治的79例NSCLC患者作为研究对象,采用免疫组化法检测上述研究对象新鲜肿瘤组织标本的ERCC1表达水平,给予所有研究对象2个疗程的化疗,化疗方案为长春瑞滨联合顺铂。化疗2个周期后,采用《实体瘤的疗效评价标准》（RECIST）进行疗效评价。结果（1）79例NSCLC患者,37例ERCC1呈阳性表达,42例ERCC1呈阴性表达。（2）ERCC1阳性表达组与ERCC1阴性表达组之间的性别、年龄、病理类型、TNM分期、吸烟史相比差异无统计学意义（P＞0.05）。 ERCC1阴性表达组的化疗疗效显著优于ERCC1阳性表达组,两者相比差异有统计学意义（P＜0.05）。结论NSCLC患者检测ERCC1有助于预测患者对顺铂的耐药性。     

联合检测蛋白ERCC1、Rad51和P53的表达与预测晚期非小细胞肺癌铂类药物化疗疗效的相关性研究

目的 检测ERCC1、Rad5 1和P53在晚期非小细胞肺癌中的表达,探讨其临床意义和与铂类药物化疗疗效的相关性。方法 选取我院2012年6月~2013年6月诊断为晚期非小细胞肺癌的68例患者病理学标本,采用免疫荧光组织化学染色法检测晚期非小细胞肺癌患者标本和外周淋巴血细胞中ERCC1、Rad51和P53的表达,观察ERCC1、Rad51和P53在晚期非小细胞肺癌患者标本和外周淋巴血细胞中表达的相关性;给予患者2~4个疗程铂类为基础的标准化疗方案,评价ERCC1、Rad51和P53蛋白的表达与化疗疗效相关性。结果 晚期非小细胞肺癌患者标本和外周淋巴血细胞中ERCC1、Rad51和P53阳性率(分别为42.6%、35.3%和45.6%)和阴性表达率(分别为33.8%、27.9%和38.2%)相同,呈显著正相关(均P<0.05);ERCC1、Rad51和P53蛋白表达在患者年龄、性别、TNM分期、病理类型间无统计学意义(P<0.05);ERCC1阳性表达患者铂类药物化疗后总有效率为41.2%,显著低于阴性患者化疗后总有效率73.9%(P<0.05);Rad51阳性表达患者化疗后总有效率33.3%显著低于阴性表达患者化疗后总有效率63.2%(P<0.05);P53阳性表达患者铂类药物化疗后总有效率为29.0%,显著低于阴性患者化疗后总有效率53.8%(P<0.05)。结论 检测晚期非小细胞肺癌患者外周淋巴血细胞中ERCC1、Rad51和P53表达可很好反映其在癌组织中的表达情况;ERCC1、Rad51和P53表达较低的患者铂类药物治疗有效率更好,ERCC1、Rad51和P53对化疗疗效的预测为负相关。     

非小细胞肺癌化疗药物耐药性及其与ERCC1、RRM1表达的相关性

目的探讨原代培养非小细胞肺癌(NSCLC)细胞对化疗药物的耐药性,及其与非小细胞肺癌组织中ERCC1、RRM1基因表达的关系。方法取手术切除的新鲜非小细胞肺癌组织标本,制备成活细胞浓度为(2~3)×10~5/ml的单细胞悬液,分别加入10倍血浆峰值药物浓度顺铂(CDDP)、吉西他滨(GEM)、培美曲塞、依托泊苷(VP-16)。用MTT法检测经上述药物作用后肿瘤细胞活力及代谢活性的变化;同时取非小细胞肺癌组织制成石蜡切片,用免疫组化检测ERCC1、RRM1蛋白的表达。结果 (1)ERCC1和RRM1在80例NSCLC组织中的表达均高于癌旁组织,差异有统计学意义(P值均<0.05)。(2)ERCC1的阳性表达与顺铂的耐药性有统计学意义(P<0.05);RRM1的阳性表达与吉西他滨的耐药性有统计学意义(P<0.05)。结论 ERCC1、RRM1蛋白可能成为NSCLC患者化疗耐药的预测因子,二者联合检测有助于NSCLC患者个体化治疗方案的选择。     

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.