乳腺肿瘤中nm23-H1、MTA1蛋白表达与癌浸润转移的关系

目的探讨nm23-H1、MTA1蛋白在乳腺肿瘤中的表达情况,研究其在乳腺癌发生、发展中的生物学意义并观察其与乳腺癌浸润及转移的内在关系。方法采用免疫组化SP法检测50例乳腺肿瘤组织中nm23-H1和MTA1蛋白的表达情况。结果乳腺浸润性导管癌组织nm23-H1蛋白阳性表达率明显低于乳腺纤维腺瘤(P<0.05);乳腺浸润性导管癌组织MTA1蛋白阳性表达率明显高于乳腺纤维腺瘤(P<0.05);乳腺肿瘤中nm23-H1和MTA1蛋白表达呈负相关(P<0.05)。结论MTA1蛋白高表达及nm23-H1蛋白低表达与乳腺癌发生浸润转移有关,二者在乳腺癌发生浸润转移过程中可能起着正负调控作用。联合检测此指标的表达状况将有助于乳腺癌的早期诊断和预后判断。     

乳腺浸润性导管癌中Ezrin和CD44v6的表达及临床意义

目的:探讨Ezrin和CD44v6在乳腺浸润性导管癌中的表达情况,探讨其与临床病理特征的关系。方法:应用免疫组化En Vision法检测95例乳腺浸润性导管癌和30例正常乳腺组织中Ezrin和CD44v6的表达情况。结果:Ezrin和CD44 v6在乳腺癌中的阳性率分别为62.1%和58.9%,明显高于正常乳腺组织中的23.3%和16.7%(P<0.05)。Ezrin和CD44v6在乳腺癌中的表达与淋巴结转移、临床分期密切相关(P>0.05),与患者的年龄、肿瘤大小、组织分级无关(P>0.05)。在乳腺癌中Ezrin和CD44v6的表达呈正相关(P<0.05)。结论:Ezrin和CD44v6可能在乳腺浸润性导管癌的发展和转移中起协同作用,联合检测其表达情况有助于判断乳腺癌的恶性程度和转移潜能。     

Bmi-1在乳腺浸润性导管癌中的表达及临床意义

目的探讨Bmi-1在乳腺浸润性导管癌中的表达及其与临床病理特征之间的关系。方法采用免疫组织化学法检测60例乳腺浸润性导管癌组织中Bmi-1及Her-2、ER、PR的表达情况,并检测了30例乳腺增生症中Bmi-1表达情况。结果 60例乳腺浸润性导管癌中,Bmi-1蛋白高表达29例(48.3%),30例乳腺增生症中Bmi-1蛋白高表达6例(20.0%),两组之间差异有显著性(P<0.05)。Bmi-1蛋白阳性表达与乳腺浸润性导管癌的淋巴结转移及TNM分期密切相关(P<0.05),而与患者的年龄、肿瘤大小、组织学分级、Her-2、ER、PR等无显著性相关(P>0.05)。结论 Bmi-1蛋白在乳腺浸润性导管癌中的高表达与肿瘤进展相关,提示Bmi-1可能成为预测乳腺癌转移的新分子标志物。     

肝细胞生长因子 /酪氨酸蛋白激酶 MET信号通路与乳腺癌侵袭转移的相关性分析

目的 探讨分析肝细胞生长因子(HGF)/酪氨酸蛋白激酶MET(c-met)信号通路与乳腺癌侵袭转移的相关性.方法 选择2018年3月至2019年3月承德医学院附属医院临床术后经病理证实的乳腺癌标本75例、乳腺纤维腺瘤标本60例以及癌旁正常乳腺组织标本50例.采用SP免疫组化法以及逆转录聚合酶链反应(RT-PCR)法检测各组织标本HGF、c-met、β连环素(β-catenin)蛋白表达和mRNA表达情况.结果 HGF[82.67％(62/75)比48.33％(29/60)比14.00％(7/50)]、c-met[86.67％(65/75)比55.00％(33/60)比20.00％(10/50)]、β-catenin[78.67％(59/75)比41.67％(25/60)比6.00％(3/50)]在乳腺癌组织、乳腺纤维腺瘤组织以及癌旁正常乳腺组织中的表达均差异有统计学意义(P<0.05).在乳腺癌、乳腺纤维腺瘤以及癌旁正常乳腺组织中HGF、c-met mRNA相对表达量差异有统计学意义(P<0.05),其中乳腺癌相对表达量最高、乳腺纤维腺瘤相对表达量次之;而乳腺癌、乳腺纤维腺瘤以及癌旁正常乳腺组织中β-catenin mRNA相对表达量比较差异无统计学意义(P>0.05).HGF表达阳性率与病人TNM分期、淋巴结转移、肿瘤大小、ER表达、HER-2表达有关(P<0.05).c-met蛋白表达阳性率与病人肿瘤TNM分期、淋巴结转移密切相关(P<0.05).β-catenin蛋白表达异常率与病人TNM分期、淋巴结转移、肿瘤大小密切相关(P<0.05).结论 乳腺癌组织中HGF、c-met蛋白高表达而β-catenin蛋白异常表达,且HGF/c-met信号通路及β-catenin蛋白与乳腺癌侵袭转移密切相关.     

乳腺浸润性导管癌组织中血管内皮细胞生长因子与增殖细胞核抗原的表达及临床病理意义

目的探讨血管内皮细胞生长因子(VEGF)和增殖细胞核抗原(PCNA)在乳腺浸润性导管癌(IDC)组织中的表达及其与临床病理的相关性。方法应用免疫组化SP法检测43例乳腺浸润性导管癌组织及其癌旁正常乳腺组织中VEGF和PCNA的表达。结果VEGF、PCNA在乳腺浸润性导管癌组织中的阳性表达率为72.10%和83.72%,癌旁正常乳腺组织中则为23.26%和18.60%,两者在IDC和正常乳腺组织中的阳性表达差异均有显著性(P<0.01);VEGF的阳性表达与乳腺癌病理学分级、淋巴结转移有关(P<0.01,P<0.05),PCNA的阳性表达与淋巴结转移有关(P<0.05),但两者的表达均与病人年龄、肿瘤大小无关(P>0.05)。结论VEGF、PCNA的同时表达有助于乳腺癌病理诊断;亦可将其作为有无淋巴结转移的生物学标志,对判断预后和术后的治疗有一定的指导意义。     

C-erbB-2在乳腺浸润性导管癌中的表达及意义

目的:探讨C-erbB-2蛋白在乳腺浸润性导管癌中的表达与淋巴结转移的关系。方法:采用免疫组织化学方法(SP法)检测60例乳腺浸润性导管癌组织中C-erbB-2蛋白、雌激素受体(ER)和孕激素受体(PR)的表达,分析其与临床病理指标的关系。结果:60例乳腺癌组织中C-erbB-2蛋白阳性表达占45.00%(27/60),阳性表达率与肿瘤直径、淋巴结转移、组织学分级比较差异有统计学意义,并与ER、PR呈负相关(P<0.05)。结论:C-erbB-2蛋白与乳腺浸润性导管癌侵袭和转移密切相关,可作为判断乳腺癌预后的一个重要指标。     

The expression and significance of MMP-7 and E-cad proteins in breast carcinoma

目的 研究基质金属蛋白酶-7(MMP-7)和钙黏附素-E(E-cad)在乳腺导管原位癌和浸润性导管癌中的表达及意义.方法 采用免疫组化SP法检测MMP-7和E-cad 在25例乳腺导管原位癌 (DCIS)、68例浸润性导管癌(IDC)和17例正常乳腺组织 (Control) 中的表达,并进行相关分析.结果 与对照组比较,MMP-7在乳腺导管原位癌和浸润性导管癌中的表达显著增高(P<0.05);而E-cad的表达明显减低(P<0.05),且MMP-7与E-cad间无相关关系(χ2＝0.00,P=1.00);MMP-7及E-cad均与乳腺癌肿瘤分化程度及淋巴结转移密切相关(P<0.05).结论 MMP-7和E-cad与乳腺导管原位癌和浸润性导管癌的发生发展相关.     

肾上腺髓质素在乳腺癌组织的表达及与临床病理特征的关系

目的:探讨肾上腺髓质素(adrenomedullin,ADM)在乳腺癌组织中的表达情况及其与临床病理指标的关系。方法:采用流式细胞术对32例乳腺癌组织、癌旁2cm及癌旁5cm乳腺组织和10例乳腺纤维腺瘤组织的ADM蛋白表达进行定量检测。结果:乳腺癌组织的ADM表达水平(1.234±0.456)高于癌旁2cm乳腺组织(1.011±0.336,P<0.05)和癌旁5cm乳腺组织(0.981±0.397,P<0.05),而癌旁2cm和癌旁5cm组织之间比较差异无统计学意义(P>0.05);乳腺癌组织的ADM表达水平也明显高于乳腺纤维腺瘤(0.930±0.141,P<0.01)。ADM在乳腺癌组织的表达水平与肿瘤的组织学分级相关(rs=0.552,P<0.01),组织学Ⅲ级的ADM表达水平(1.516±0.579)明显高于Ⅱ级(1.072±0.186,P<0.01)和Ⅰ级(0.956±0.223,P<0.05),Ⅱ级和Ⅰ级比较差异无统计学意义(P>0.05);乳腺癌组织的ADM表达水平与肿瘤大小、TNM分期、病理类型、淋巴结转移状况、ER/PR和C-erbB-2等临床病理指标无关联(P>0.05)。结论:ADM在乳腺癌组织的表达明显增高,肿瘤的组织学分化差者表达增强。     

乳腺癌中Survivin蛋白的表达与细胞凋亡的关系

目的探讨Survivin蛋白在乳腺癌中的表达及其与浸润、转移、细胞凋亡的关系。方法采用免疫组化S-P法检测12例正常乳腺、7例乳腺导管内癌、41例乳腺浸润性导管癌组织中Survivin蛋白的表达(其中24例有淋巴结转移,24例无淋巴结转移),并用TUNEL法测定细胞凋亡指数。结果正常乳腺、乳腺导管内癌、乳腺浸润性导管癌中Survivin蛋白表达的阳性率分别为25%(3/12)、57.14%(4/7)、70.73%(29/41)。在三种组织中Survivin蛋白的表达有上升趋势,但缺乏统计学意义(P>0.05)。Survivin蛋白的表达与乳腺癌的淋巴结转移有密切关系(P<0.05),与组织学类型、年龄无明显关系(P>0.05)。乳腺癌中Survivin蛋白的表达水平与癌细胞的凋亡指数成负相关(P<0.05)。结论Survivin参与乳腺癌的发生发展,Survivin蛋白的异常表达对细胞凋亡起一定抑制作用,其过度表达提示乳腺癌预后不良。Survivin蛋白表达在有淋巴结转移的乳腺癌中比无淋巴结者明显增高,有统计学意义(P<0.05)。     

S100A4、CB在乳腺癌中的表达及意义

目的探讨S100A4、CB蛋白在乳腺癌中的表达情况及二者与乳腺浸润性导管癌的浸润、转移的关系。方法应用免疫组织化学SP法分别检测20例正常乳腺组织、20例乳腺良性病变组织和40例乳腺浸润性导管癌中S100A4、CB蛋白的表达。结果 20例正常乳腺组织中S100A4及CB蛋白的阳性表达率分别为25.0%(5/20)及15.0%(3/20),20例乳腺良性病变组织中S100A4蛋白阳性表达率30.0%(6/20)及35.0%(7/20),40例乳腺浸润性导管癌组织中S100A4及CB蛋白阳性表达率为67.5%(27/40)及72.5%(29/40),在乳腺浸润性导管癌组织中,S100A4蛋白的表达与患者年龄、肿瘤的组织学分级无关(P>0.05),而与淋巴结转移密切相关(P<0.05),CB蛋白的表达与患者年龄无关(P>0.05),而与淋巴结转移、肿瘤的组织学分级密切相关(P<0.05),S100A4蛋白与CB蛋白的表达呈正相关(P<0.05)。结论 S100A4及CB蛋白在乳腺浸润性导管癌中均高表达,且与乳腺的浸润和淋巴结转移密切相关。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.