FDA最新药物

已批准新药IRESSA获批用于冶疗NSCLC AstraZeneca制药公司宣布,美国FDA于5月5日批准该公司的新药IRESSA(gefitinib)用于治疗晚期非小细胞肺癌(NSCLC)。这一批准给了晚期非小细胞肺癌患者带来了新的生存机会。     

晚期非鳞非小细胞肺癌的药物治疗研究进展

肺癌是我国乃至全世界发病率和死亡率最高的恶性肿瘤,严重威胁人类的健康。非鳞非小细胞肺癌占其中的绝大多数,由于缺乏有效的、特异性强的早期筛查方法,许多患者被确诊时已属晚期。近年来随着多学科综合治疗的开展,其治疗效果有了很大的提高,但1年生存率仍不理想。目前针对晚期非鳞非小细胞肺癌的治疗,仍以化疗、分子靶向治疗及生物免疫治疗等综合治疗为主。本文对晚期非鳞非小细胞肺癌常用的药物治疗进展作一综述。     

晚期非小细胞肺癌的中西医结合药物治疗现状

近年来,肺癌在内科药物治疗方面有较大进展,传统化疗、分子靶向药物、靶向药物耐药的后续治疗,以及免疫疗法在晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的综合治疗中扮演着不可替代的角色,但也存在一些不足之处,如化疗及靶向药物的毒副作用和耐药等,5年生存率仍然很低。诸多临床工作者为尽可能的延长晚期NSCLC患者的生存时间、提高患者的生活质量而采用中西医结合的治疗手段,效果明显。该文就晚期非小细胞肺癌的中西医结合药物治疗现状作一综述。     

晚期非小细胞肺癌的药物治疗进展

肺癌目前仍是死亡率较高的恶性肿瘤。近年来随着分子靶向治疗的进展,非小细胞肺癌的治疗已经取得了长足的进步。许多转化性临床研究结果带来近期疗效、生活质量尤其是生存的显著提高。传统的化疗是非小细胞肺癌治疗的基石,是野生型以及突变未知患者治疗的首选;分子靶向治疗则为敏感突变的患者带来了革命性的转变,是目前治疗的中流砥柱;而免疫治疗在免疫检查点抑制剂上的突破也结束了长期混沌的状态,成为非小细胞肺癌治疗的新兴力量。而无论是化疗、靶向治疗还是免疫治疗,基于肿瘤分子病理改变的精确治疗是目前非小细胞肺癌治疗发展的趋势。     

化疗联合帕博利珠单抗治疗晚期肺腺癌患者20例观察

<正>肺癌目前仍然是全世界男女癌症相关死亡的主要原因。铂类化疗是晚期或转移性非小细胞肺癌的标准一线治疗。然而,对于有靶向基因组改变的患者,包括突变的表皮生长因子受体(EGFR)基因和重排的间变性淋巴瘤激酶(ALK)基因,特异性靶向治疗可能导致延长总生存时间(OS)。相比之下,对于无靶向遗传异常的非小细胞程序性细胞死亡1(PD-1)肺癌,1年的OS仅为30%～40%,中位生存期为8～10个月[1]。     

晚期非小细胞肺癌维持化疗的新进展

化疗是晚期肺癌的主要治疗手段．第三代新药联合铂类的两药化疗方案是初治晚期非小细胞肺癌（NSCLC）的标准一线治疗方案,与最佳支持治疗比较,中位生存期延长2个月,1年生存率提高10％。     

血清肿瘤标志物水平与晚期非小细胞肺癌患者靶向治疗有效性的相关分析

目的:探讨血清肿瘤标志物水平与晚期非小细胞肺癌患者靶向治疗有效性。方法:选取52例晚期非小细胞肺癌患者作为研究对象,研究时间为2017年10月～2018年12月,均实施靶向治疗。观察治疗后有效率,且评估癌胚抗原、CA125、Cyfra21-1、SCCAg、NSE水平。结果:52例晚期非小细胞肺癌患者经靶向治疗后有效率为71.15%。治疗前有效组患者的癌胚抗原、CA125、Cyfra21-1、SCCAg、NSE高于治疗后数据,统计学存在差异(P0.05);治疗前无效组患者的癌胚抗原、CA125、Cyfra21-1、SCCAg、NSE与治疗后相比,无明显差异(P0.05)。结论:晚期非小细胞肺癌患者经靶向治疗后血清肿瘤标志物水平发生显著改变,可为判断治疗效果及评估预后提供客观依据,值得应用及推广。     

延续护理在非小细胞肺癌患者出院后口服靶向药物治疗中的临床效果研究

<正>肺癌是近年来发病率增长最快、对人群健康和生命威胁最大的恶性肿瘤之一~([1])。临床上将肺癌分为小细胞肺癌和非小细胞肺癌,非小细胞肺癌主要包括腺癌、鳞癌、大细胞癌,约占全部肺癌的85%左右。大部分患者就诊时已属于晚期,失去了手术机会,化疗和放疗成了这些患者的主要治疗方法。肺癌患者一般年龄大、伴发疾病多,对全身放化疗耐受性差,治疗以姑息、支持、辅助及对症处理为主,生存质量和寿命均受到影响。最新的研究进展表明分子靶向药物给非小细胞肺癌晚期患者提供了新的治疗方向,分子靶向药物治疗比传统的化疗具有更高的选择性,毒副反应更少,患者易接受。吉非替尼作为晚期非小细胞肺癌常用的分子靶向药物,它与     

吉西他滨单药治疗老年晚期非小细胞肺癌疗效观察

目的观察吉西他滨单药治疗老年晚期非小细胞肺癌的疗效和不良反应。方法对46例ⅢB～Ⅳ期老年晚期非小细胞肺癌患者采用吉西他滨1000mg/m2,第1、8天,3周重复,2个周期后评价疗效,共4～6周期。结果 44例可评价疗效,总有效率(CR+PR)为25%(11/44),中位生存期6.8个月,1a生存率为27%,不良反应以白细胞和血小板下降为常见,但均可耐受。结论吉西他滨单药治疗老年晚期非小细胞肺癌有较好疗效,可明显改善患者生存质量,延长生存时间,不良反应轻,患者易于耐受。     

新型抗肿瘤药物治疗肺癌的研究进展

新型抗肿瘤药物不断推陈出新,彻底改写晚期肺癌的治疗格局,延长了患者的生存,推进了肺癌慢病化进程。本文拟对肺癌治疗领域包括靶向治疗、免疫治疗及抗血管生成治疗中的新型抗肿瘤药物及相关研究进展进行梳理汇总,旨在为临床用药提供参考。     

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.