抗肿瘤血管新药的研究进展

目前肿瘤血管靶向治疗新药的研究主要集中在两个方向,即肿瘤血管生成抑制剂(tumor angiogenesis inhibitor,TAI)和肿瘤血管靶向制剂(vascular targeting agent,VTA).TAI类旨在抑制肿瘤血管生成的过程,近年来研究较多的为血管内皮生长因子(VEGF)类、基质金属蛋白酶(MMP)类、血管抑素类、内皮抑素类等;而VAT类则是通过破坏肿瘤组织中已存在的血管从而使肿瘤坏死,主要包括小分子类VTA和生物类VTA.对近年来各类抗肿瘤血管治疗新药的种类、作用机制及各自的临床研究进展进行综述.     

以血管内皮生长因子及其受体为靶点的肿瘤血管生成抑制剂的研究进展

肿瘤的生长和转移依赖于新生血管的形成,血管内皮生长因子(VEGF)在肿瘤新生血管形成中起关键作用。以VEGF及其受体为靶点,通过抑制肿瘤血管生长,从而遏制肿瘤的生长和转移的研究已经取得了一定的成果,在此对肿瘤血管生成抑制剂(TAI)的研究进展进行综述。     

31种中药材的乙醇提取物抑制血管生成的活性研究

目的筛选具有抑制肿瘤新生血管生成作用的药物。方法建立抑制人血管内皮细胞(HMEC1)生长的高通量筛选模型,采用75%乙醇为溶剂浸提药材,研究提取物对HMEC1生长和鸡胚尿囊血管生成的抑制活性,筛选具有抑制HMEC1增殖活性和鸡胚尿囊血管生成的中药。结果 31种中药中对HMEC1增殖具有明显抑制活性的药材有7种,其中对鸡胚尿囊血管生成有明显抑制活性的有4种。结论五倍子、钩藤、黄芩、蒲黄等4种中药具有潜在的研究开发的价值。     

在肿瘤研究中转基因小鼠模型的研究进展

随着基因工程技术的飞速发展,转基因小鼠模型对研究肿瘤基因特征、肿瘤抑制基因的表达和功能有着重要的作用。近年来,肿瘤血管生成理论成为肿瘤研究的新热点。与肿瘤血管生成相关的调控基因的研究也越来越受到重视。该文对转基因小鼠模型在肿瘤研究中的进展作了综述,并着重介绍了关于肿瘤血管生成调控基因转基因小鼠模型的研究情况。     

血管生成实验模型研究进展

抗血管生成已经成为治疗肿瘤转移、糖尿病视网膜病变、风湿性关节炎等疾病的重要策略之一。血管生成模型作为一种研究工具在探讨血管形成机制、发现促进或抑制血管生成药物等研究中发挥十分积极的作用。如何寻找适合的血管生成模型是研究人员在研究中常遇到的问题。该文就主要常用模型做较全面的介绍,并对其优缺点进行评价。     

超声靶向微泡破裂增强恩度凝胶抑制裸鼠乳腺癌移植瘤血管生成作用

目的:探讨超声靶向微泡破裂对恩度凝胶瘤体内注射抑制裸鼠乳腺癌移植瘤血管生成作用的影响。方法:制备载恩度的PLGA-PEG-PLGA温度敏感型凝胶,检测恩度凝胶体外释放及超声辐照对药物释放的影响;建立荷人乳腺癌裸鼠移植瘤模型,分为模型组、恩度凝胶瘤体内注射组、恩度凝胶联合超声靶向微泡破裂组,每周治疗1次,连续3次后行肿瘤超声造影,测定肿瘤组织微血管密度,评价各种处理对肿瘤血管生成的抑制作用。结果:恩度凝胶在体外平稳释放约1周时间,超声辐照可提高恩度凝胶的释放速率;恩度凝胶瘤体内注射联合超声靶向微泡破裂处理具有明显的抑制肿瘤血管生成作用,肿瘤超声造影峰值强度及微血管密度均明显低于对照组及单纯恩度凝胶治疗组(P0.05)。结论:恩度凝胶联合超声靶向微泡破裂可阻断肿瘤微循环,并有效控制缓释载体的药物释放速率,使更多释放药物作用于血管内皮细胞,具有明显的抑制肿瘤血管生成作用。     

肿瘤血管生成的靶向调控及其药物研究进展

肿瘤血管生成(Tumor Angiogenesis)对大多数实体瘤的生长和转移具有重要意义,是多步骤多因素参与复杂的病理过程.选择肿瘤血管生成中的一些关键环节或参与的重要因子作为靶点,研制应用特异性肿瘤血管生成抑制剂或抗体,以靶向调控肿瘤血管生成,控制肿瘤的生长和转移,达到治疗肿瘤的目的.本文对近年来肿瘤血管生成机制和肿瘤血管生成抑制剂的研究进展进行综述.     

现代鲜药抗肿瘤血管生成的研究进展

目的对肿瘤血管生成的机制及现代鲜药抗肿瘤血管生成作用的研究进展进行综述。方法本文以金龙胶囊多年来在肿瘤血管生成方面的实验结果为基础,总结介绍了现代鲜药在肿瘤血管生成方面的研究进展。结果与结论现代鲜药制剂在肿瘤防治中发挥着重要的作用,其抗肿瘤作用机制涉及抑制肿瘤新生血管生成因素。     

沙利度胺对小鼠恶性黑色素瘤生长及血管生成模式的影响

目的:观察沙利度胺对恶性黑色素瘤(恶黑)生长及血管生成模式的影响,为对其治疗提供实验依据.方法:B16黑色素瘤移植瘤模型C57小鼠35只,随机分为实验组20只,对照组15只,分别给予沙利度胺及0.5%羧甲基纤维素钠溶液灌胃.计数肿瘤组织中内皮依赖性血管、马赛克血管和血管生成拟态数目及肿瘤细胞坏死情况,并进行血管内皮细胞生长因子(VEGF)、核因子(NF)-κB、基质金属蛋白酶(MMP)-2、MMP-9和增殖细胞核抗原(PCNA)的免疫组化染色.结果:给药9d后.实验组小鼠的肿瘤体积明显小于对照组(P＜0.05).实验组内皮依赖性血管、马赛克血管和血管生成拟态数量显著低于对照组(P＜0.05),且实验组VEGF、NF-κB、PCNA、MMP-2及MMP-9的表达也明显低于对照组(P＜0.05).实验组肿瘤组织中坏死细胞数明显高于对照组(P＜0.05).结论:沙利度胺可以抑制恶黑血管生成.促进肿瘤细胞的坏死,抑制肿瘤的生长.     

肿瘤血管生成的分子机制及其治疗前景

肿瘤血管生成在肿瘤的生长和转移中起着重要的作用。众多肿瘤血管生成生长因子和抑制因子参与了对肿瘤血管生成的调控。因此 ,研究肿瘤血管生成相关分子在肿瘤血管生成中的作用机制 ,及其对肿瘤血管生成的调控 ,来达到控制肿瘤血管生长和转移的目的 ,已成为肿瘤治疗的新途径。该文对肿瘤血管生成的分子机制及其治疗前景的研究作一评述。     

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.