靶向药物不良反应的认识与思考

新的靶向药物出现提高了抗癌疗效.降低了毒性,使转移性恶性肿瘤患者从治疗中获益.靶向药物耐受性好.通常出现轻微或中度的毒副反应.尽管大多数不良反应是可以得到迅速处理的,但是严重的甚至危及生命的不良反应仍能够发生.因此.为更好地指导临床实践工作.该文综述了实体瘤治疗中常用靶向药物的主要不良反应和安全数据,并按照药物的作用靶点和信号通路进行了组织分类.     

应用分子靶向治疗的时机选择

分子靶向药物的出现显示出肿瘤治疗传统模式的重要进展。与传统放疗、化疗相比,分子靶向治疗因其特异性高、不良反应轻微,在恶性肿瘤个体化治疗中扮演重要角色。十五年来,分子靶向药物的出现,给肿瘤的治疗模式带来重大改变,也给临床医生带来新的挑战。准确把握分子靶向药物应用时机,获得最大临床效果,已成为肿瘤治疗领域关注热点。本文就非小细胞肺癌、消化系统肿瘤、乳腺癌、肾癌治疗中分子靶向药物如何选择应用时机进行阐述。     

晚期结直肠癌的分子靶向治疗

对于晚期结直肠癌(mCRC)的靶向治疗,目前正在研究和临床应用的主要有:(1)针对肿瘤细胞表面的表皮生长因子受体(EGFR)的药物;(2)针对血管内皮生长因子(VEGF)信号传导通路的药物;(3)针对受体酪氨酸激酶及其下游级联反应的药物;(4)免疫靶向治疗药物,例如PD-1/PD-L1抑制剂。但在我国经CFDA批准应用于临床的仅有抗EGFR的西妥昔单抗和抗VEGFR的贝伐单抗。怎么用好这两个靶向药物,让mCRC患者得到最合理、最有效的治疗,让患者生存时间尽可能延长且生活质量高。2016年ESMO共识指南,将患者的治疗按治疗目标来考虑,比较具有可操作性。肿瘤部位因为分子水平的差异,对靶向药物可能有选择倾向。免疫靶向药物的出现,它的作用特点,也许对我们的mCRC的治疗会是另外一种策略。     

怎样正确对待药物的不良反应

药物是诊断疾病、治疗疾病、预防疾病不可缺少的重要部分。药物是用来调节机体生理功能的特殊物质。药物对机体产生药效的同时 ,机体对药物在体内的过程也产生一种动力学的作用。药效学与药代动力学是药物治疗疾病过程中的统一体。它们之间的矛盾贯穿始终 ,只有当两方面的作用相互协调 ,治疗疾病才能达到最佳效果。否则 ,在治疗疾病的过程中就会产生不同程度的不良反应。正是出现了不良反应 ,不仅影响治疗而且也影响机体正常的生理功能 ,造成健康的损害。怎样处理好药物治疗作用与不良反应的关系 ,是临床药学工作者必须要研究的问题 ,也是现…     

超声微泡介导靶向治疗研究进展

载药超声微泡的靶向治疗是当前医药领域中的研究热点。超声微泡破坏技术介导的靶向药物和基因治疗是一种最新的靶向治疗方法。超声微泡不仅可以作为一种超声造影剂增强成像对比度,更可以通过各种物理、化学修饰携带各种药物或基因在超声场强破坏作用下进行靶向治疗。超声微泡造影剂靶向治疗包括超声介导载药微泡的治疗及超声介导靶向载药微泡的治疗。本文就超声微泡特性、超声靶向微泡破坏(UTMD)技术机制、超声微泡介导靶向治疗三方面进行综述。     

非小细胞肺癌靶向治疗的前途与困惑

靶向治疗是运用抗肿瘤药物靶向性与肿瘤的不同特异性住点结合发生作用从而抑制肿瘤细胞生长的一种治疗手段。针对恶性肿瘤中的非小细胞肺癌,其在临床中取得了一定成效。然而,其中仍存在很多问题。本文针对吉非替尼在非小细胞肺癌中的运用,及其优点和所面临的问题,阐述如何应对完善靶向治疗的挑战。     

非小细胞肺癌靶向药物治疗争论热点

非小细胞肺癌作为全球和我国发病率最高、死亡人数最多的恶性肿瘤,其药物治疗始终是临床肿瘤学界高度关注的焦点之一。肿瘤的药物治疗模式从单纯以细胞毒药物杀伤肿瘤逐步向调节信号传导通路转变,分子靶向药物日益成为治疗肿瘤的重要武器。回顾肺癌靶向治疗的进展,诸多问题需要解决。     

非小细胞肺癌靶向治疗的前途与困惑

靶向治疗是运用抗肿瘤药物靶向性与肿瘤的不同特异性住点结合发生作用从而抑制肿瘤细胞生长的一种治疗手段.针对恶性肿瘤中的非小细胞肺癌,其在临床中取得了一定成效.然而,其中仍存在很多问题.本文针对吉非替尼在非小细胞肺癌中的运用,及其优点和所面临的问题,阐述如何应对完善靶向治疗的挑战.     

非小细胞肺癌靶向药物治疗争论热点

非小细胞肺癌作为全球和我国发病率最高、死亡人数最多的恶性肿瘤,其药物治疗始终是临床肿瘤学界高度关注的焦点之一.肿瘤的药物治疗模式从单纯以细胞毒药物杀伤肿瘤逐步向调节信号传导通路转变,分子靶向药物日益成为治疗肿瘤的重要武器.回顾肺癌靶向治疗的进展,诸多问题需要解决.     

抗血管生成靶向药物相关性高血压

高血压是抗血管生成靶向药物最常见的副作用之一,其机制和管理受到重视。本文就靶向药物导致高血压的机制进行了探讨,考虑可能与抗血管生成药物的作用靶点有关,即影响了血管内皮生长因子的功能所致;介绍临床如何进行高血压管理并建议在抗血管生成靶向药物使用过程中规范地监测、控制血压,开展相关研究。     

超声引导介入治疗在老年原发性肝癌中的应用

超声引导介入治疗是一种微创靶向治疗,具有操作简单、安全性高等优点,已成为临床肝癌非手术领域不可缺少的新技术。治疗手段主要包括微波消融、局部注射无水酒精、抗肿瘤生物反应调节剂等。在老年人这个特殊人群中的应用得到较多重视。本文就超声引导介入治疗在老年原发性肝癌中的应用做一讨论。     

体像障碍的认知机制及治疗

体像障碍是一种对想象的或轻微外表缺陷的先占观念, 这种先占观念给个体带来极大的痛苦。其负性的自我认知框架, 影响个体对信息的选择、组织及评估。因此结合心理实验范式和神经生理综合分析体像障碍的认知过程, 对深化体像障碍认知机制和优化其认知行为治疗具有重要意义。     

Welcome to the ‘Paradigm War’: the case of antidepressant medication

Mindfulness-based therapies are a recent development within the cognitive-behavioural tradition and an important element of the third wave cognitive behavioural therapy models. A number of these therapies could be considered to have mindfulness as a major component of the therapy. There has been a considerable growth of interest in these therapies with an accompanying increase in their evidence base. While a number of reviews have been conducted, these therapies were not comprehensively appraised. The most prominent of these therapies, mindfulness-based cognitive therapy, was developed to reduce relapse in recurrent depression. We conducted a meta-analysis which looked at therapies considered to have mindfulness as a major component. We investigated whether this group of therapies was effective in reducing current depressive symptomatology as measured by the Beck depression inventory (BDI). A total of 11 studies were included in the analysis. We found a significant mean reduction score in current depressive symptomatology, as measured by the BDI, of 8.73 points (95% confidence interval?=?6.61, 10.86). We found evidence for the effectiveness of these major-component therapies in reducing levels of active depression. The robustness of these findings is discussed alongside the implications for research and practice within the context of the current literature.     

临床肿瘤免疫的研究近况

免疫系统具有特异性破坏肿瘤而不损伤正常组织的能力,并且可以产生长久记忆从而阻止肿瘤复发。过去30年的肿瘤免疫研究充分证明肿瘤可以被免疫系统识别,并且机体免疫监视可以阻止肿瘤的发展或长期控制。目前的临床试验提示免疫治疗可能成为肿瘤治疗非常重要的一部分,试验中发现免疫相关的毒性、疗效评价标准以及观察终点与传统的细胞毒药物及靶向治疗均存在很大的差别。为了充分发挥免疫治疗的疗效,研究者需要更深入地了解肿瘤与宿主免疫反应之间动力学关系以及肿瘤的免疫逃逸机制,识别、评价及处理免疫相关反应。     

Neurocognitive mechanisms of anxiety: an integrative account

Anxiety can be hugely disruptive to everyday life. Anxious individuals show increased attentional capture by potential signs of danger, and interpret expressions, comments and events in a negative manner. These cognitive biases have been widely explored in human anxiety research. By contrast, animal models have focused upon the mechanisms underlying acquisition and extinction of conditioned fear, guiding exposure-based therapies for anxiety disorders. Recent neuroimaging studies of conditioned fear, attention to threat and interpretation of emotionally ambiguous stimuli indicate common amygdala-prefrontal circuitry underlying these processes, and suggest that the balance of activity within this circuitry is altered in anxiety, creating a bias towards threat-related responses. This provides a focus for future translational research, and targeted pharmacological and cognitive interventions.     

HPA axis and sleep: identifying subtypes of major depression

It is increasingly acknowledged that the diagnosis of major depression encompasses patients who do not necessarily share the same disease biology. Though the diagnostic criteria allow the specification of different subtypes, e.g. melancholic and atypical features, a consensus still has to be reached with regard to the clinical symptoms that clearly delineate these subtypes. Beside clinical characteristics, biological markers may help to further improve identification of biologically distinct endophenotypes and, ultimately, to devise more specific treatment strategies. Alterations of the hypothalamus-pituitary-adrenal (HPA) axis and sleep architecture are not only commonly observed in patients with major depression, but the nature and extent of these alterations can help to identify distinct subtypes. Thus, a HPA overdrive, due to enhanced secretion of corticotropin-releasing hormone (CRH) and an impaired negative feedback via glucocorticoid receptors, seems to be most consistently observed in patients with melancholic features. These patients also show the clearest sleep-electroencephalogram (EEG) alterations, including disrupted sleep, low amounts of slow wave sleep (SWS), a short rapid eye movement (REM) latency and a high REM density. In contrast, patients with atypical features are characterized by reduced activity of the HPA axis and ascending noradrenergic neurons in the locus coeruleus. Though sleep-EEG alterations have been less thoroughly examined in these patients, there are data to suggest that SWS is not reduced and that REM sleep parameters are not consistently altered. While the atypical and melancholic subtypes of major depression may represent the extremes of a spectrum, the distinct clinical features provide an opportunity to further explore biological markers, as well as environmental factors, contributing to these clinical phenotypes. Moreover, dysregulations of the HPA axis and sleep-EEG alterations can also be induced in rodents, thereby allowing alignment of critical biological aspects of a human disease subtype with an animal model. Such "Translational Research" efforts should help to develop targeted therapies for distinct patient populations.     

Psychological treatment of depression: a review

The available empirical evidence on the efficacy of psychological intervention in depressive disorders is reviewed. No fully adequate study has yet appeared; but there seems sufficient consensus to justify the conclusion that psychological treatment can be effective in alleviating current depressive states and that more complex therapies involving both behavioural and cognitive elements appear the most promising. However, it remains to be seen whether the success of these techniques depends upon the type of depressive disorder manifested; and whether they are applicable across a full range of verbal reasoning ability and socio-economic class.     

The NICE guidelines are misleading,unscientific, and potentially impede good psychological care and help

NICE guidelines have been given the authority to determine what psychological therapies can be provided within the UK National Health Service. This also has implications for private practice. The guidelines are based on a medical model and consider psychotherapy as analogous to a drug. Psychological thinking is discouraged by this approach. A large amount of psychotherapy research evidence is ignored by NICE, particularly the persistent finding that differences in effectiveness between therapies are minimal and elusive. Differences between the skills of therapists are a more significant factor. Practice-based evidence, and learning from the patient's feedback (both conscious and unconscious) may be a better approach. For most forms of psychological distress, none of the main psychological therapies studied in randomized controlled trials can be considered to be clinically effective, even though they facilitate some degree of statistically significant change.     

Informed Consent in Emergency Research: A Contradiction in Terms

Improving the treatment of life threatening emergency illness or disease requires that new or novel therapies be assessed in clinical trials. As most subjects for these trials will be incapacitated there is some controversy about they might best protected whilst still allowing research to continue. Recent European and UK clinical trials legislation, which has effectively stopped research into emergency conditions, is discussed. Possible changes to these regulations are proposed.     

The impact of “non-targeted traits” on personality test faking,hiring, and workplace deviance

Evidence suggests that job applicants often “fake” on pre-employment personality tests by attempting to portray an exceedingly desirable impression in order to improve the likelihood of being selected. In the current research we shed light on the personality characteristics of those individuals who seem most likely to engage in faking. We refer to these personality variables as non-targeted traits when they are not directly targeted by the organization’s pre-employment personality test. These traits, however, may have an influence on targeted scores used for employment decision making through their effect on faking. Findings suggest that individuals will be more likely to be hired if they are low on non-targeted traits including Honesty–Humility, Integrity, and Morality, and high on Risk Taking. Such individuals also reported higher levels of workplace deviance in their current jobs. Thus, it seems that individuals low on Honesty–Humility, Integrity, and Morality, and individuals high on Risk Taking, may be most likely to engage in personality test faking, be hired, and participate in workplace deviant behaviors if these traits are not directly targeted in selection.