大肠癌靶向药物治疗进展评述

21世纪以来,靶向药物如抗VEGF的人源化单克隆抗体(Bevacizumab,贝伐单抗)和抗EGFR单克隆抗体(人鼠嵌合性单抗Cetuximab,C225,西妥昔单抗和全人源化单抗EGFR抗体,Panitumumab,帕尼单抗)的临床应用,已使复发转移性结直肠癌患者的总生存取得了长足的进步,但临床上应如何更加合理有效地使用这些药物,仍有许多亟待解决的问题.     

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。     

乳腺癌前哨淋巴结活检术新型荧光靶向示踪剂的研发进展

前哨淋巴结活检术是临床腋窝淋巴结阴性的早期乳腺癌患者腋窝的标准处理模式,但由于传统示踪剂(蓝染料、核素和荧光示踪剂等)定位特异性差及药物准入等问题,限制了其在临床的推广应用。蓝染料和荧光示踪剂由于分子颗粒较小导致其易通过前哨淋巴结使次级淋巴结显像。核素示踪剂虽然可以特异性定位前哨淋巴结,但存在药品准入和放射安全性等问题。利妥昔单抗是一种针对淋巴结中B淋巴细胞膜上CD20分子的特异性人源化单克隆抗体,新型荧光靶向示踪剂将吲哚菁绿偶联于利妥昔单抗,将兼顾荧光显像与靶向定位的优点,其单抗的分子完整性和免疫活性无破坏,为无菌、无致热原、无急性毒性的示踪剂。     

贝伐单抗治疗实体肿瘤的临床研究进展

血管内皮生长因子(vascular endothelial growth factor,VEGF)在肿瘤的发病机制中起着关键作用,其作为抗肿瘤治疗的重要靶点,已得到越来越多的关注.贝伐单抗(Bevacizumab,BEV)是一种血管内皮生长因子的单克隆抗体,是目前最受关注的分子靶向药物之一,自2004年经美国FDA批准上市以来,BEV已被用于多种实体肿瘤的治疗.本文就BEV关于治疗几类实体肿瘤的临床研究进展作一综述.     

治疗用抗体研究中的几个关键问题

抗体用于疾病的治疗已经有百余年历史了 ,从最初的多克隆抗血清到杂交瘤技术制备的单克隆抗体 ,都曾对生物医学的进步做出了突出的贡献 ,并因此而获得诺贝尔生理学和医学奖。目前治疗用抗体的研究已经发展到基因工程抗体阶段 ,一些关键性问题的逐步解决将使该领域的前景越来越广阔。1　技术平台治疗用抗体的研制依赖于不同的技术平台。杂交瘤技术使单克隆抗体的制备研究发生了飞跃性的进步 ,一大批针对不同抗原的单抗先后问世。但是 ,来源于鼠、兔等动物的单抗用于人体治疗存在众所周知的异源性问题 ,而人杂交瘤的制备由于种种原因未取得根…     

食管癌的分子靶向治疗进展

食管癌是消化道常见肿瘤,大多数患者在就诊时已属晚期。尽管多学科综合治疗不断发展,食管癌的预后及整体生存仍较差。食管癌的分子靶向治疗通过干扰相关信号通路抑制细胞增殖,促进其凋亡。目前主要是应用单克隆抗体和酪氨酸酶抑制剂干扰EGFR、HER-2、VEGFR、C-MET、AXL受体介导的信号传导通路。其中针对HER-2、AXL与AURKA的靶向药物显现出巨大发展潜力。本文对食管癌分子靶向治疗的现况和进展简单综述。     

EGFR靶向治疗中敏感性预测指标的启示

EGFR抗肿瘤靶向治疗药物临床疗效存在明显个体差异,与其疗效敏感性相关的预测标志物能指导临床用药,成为临床关注的热点,本文从哲学的角度思考靶向治疗敏感性预测指标与恶性肿瘤的关系,试图以此为指导,更好地加强临床用药的预见性.     

EGFR靶向治疗中敏感性预测指标的启示

EGFR抗肿瘤靶向治疗药物临床疗效存在明显个体差异,与其疗效敏感性相关的预测标志物能指导临床用药,成为临床关注的热点,本文从哲学的角度思考靶向治疗敏感性预测指标与恶性肿瘤的关系,试图以此为指导,更好地加强临床用药的预见性。     

EGFR突变NSCLC二线TKIs治疗优化选择

恶性肿瘤的治疗已经进入驱动基因指导下的个体治疗时代,肺癌患者应该进行多基因检测,特别是表皮生长因子受体（EGFR）基因突变。EGFR基因突变的非小细胞肺癌（NSCLC）患者,如果一线接受了化疗,二线应该选择表皮生长因子受体一酪氨酸酶抑制剂（EGFR—TKIs）。EGFR基因突变的NSCLC患者一线EGFR—TKIs治疗失败后,二线治疗应该是个体化合理选择,包括局部放疗、化疗和继续EGFR—TKIs。目前一代和二代EGFR—TKIs药物之间未见到显著疗效差别。第三代EGFR—TKIs是目前的EGFR—TKIs耐药后的最有希望的选择,特别是针对T790M突变耐药。     

抗血小板药物在冠心病中的临床应用进展

近些年来,冠心病的发病率逐年增高,发病人群也趋向于年轻化,严重威胁着人类的健康和利益。斑块破裂和血栓形成是导致冠心病急剧变化以及发生心脏病事件的基本病理改变。抗血小板药物能通过几种不同的途径抑制血小板的聚集,进而抑制冠脉中的血栓形成。因此,在临床上,抗血小板治疗一直在冠心病的防治中发挥着关键的作用。本文将阐述典型的四大类抗血小板药物在冠心病中的临床应用进展,即:血栓素A2抑制剂、P2Y12受体拮抗剂、糖蛋白(GP)Ⅱb/Ⅲa受体抑制剂和磷酸二酯酶抑制剂。     

原发性肝癌分子靶向治疗的进展

不能手术和已转移的原发性肝细胞癌（hepatocellular carcinoma,HCC）预后很差,放化疗难以使患者受益。近年来,分子靶向治疗对一些肿瘤已取得突破性进展,肝癌的分子靶向治疗也在临床试验中取得了令人鼓舞的结果。目前的肝癌临床研究主要针对EGFR、VEGF／VEGFR、HGF、MMP、乙肝表面抗原等靶点。本文针对肝癌的分子靶向治疗的研究进展进行了综述。     

超声联合微泡剂介导的肿瘤靶向治疗研究进展

包被气体的微泡剂作为超声造影剂不仅显著提高了临床超声显像诊断能力,而且其作为一种新型药物载体的靶向治疗作用正逐步被揭示。携带基因或药物的超声微泡剂介导肿瘤靶向治疗已经成为超声研究领域中的研究热点。这种微泡剂在超声能量作用下因空化效应导致自身破裂并定向释放所携带的药物或者基因,使特定肿瘤组织或细胞部位浓度大大提高,从而起...     

肿瘤诊治相关肾损伤的防治决策

肿瘤患者在诊治过程中可能会引起肾脏损伤,如造影剂、化疗和靶向药物的使用等等。如何平衡肿瘤患者在诊治过程中的疗效及安全性,使患者能够接受并完成治疗,延长患者无进展生存和总生存,是肿瘤学界所面临的挑战。     

Situation-evoking stimuli,domain of reference,and the incremental interpretation of lexical ambiguity

In two experiments, we examined the influence of situation-evoking stimuli on the resolution of lexical ambiguity. In Experiment 1, we examined situation-evoking stimuli at an early NP position. Readers were asked to establish whether specific entities were likely to participate as agents in contextually defined situations. Naming latencies demonstrated that defined situations headed by likely agents evoked a domain of reference that included only the situation-appropriate meaning of a targeted lexical ambiguity. In contrast, defined situations headed by unlikely agents evoked a domain of reference that did not include either meaning of the intended ambiguous word. In Experiment 2, we examined situation-evoking stimuli at a later direct object position. The specificity of the theme/patient role filler was manipulated, where the linguistic expressions were either specific or general with respect to a given contextual situation. The results showed that contexts with specific situation-evoking stimuli were rated as strongly biased and provided a domain of reference for the immediate resolution of lexical ambiguity, whereas contexts with nonspecific role fillers were rated as ambiguous and provided a domain of reference that was supportive of both meanings of an ambiguous word. The results were discussed within a contextual-feature-sensitive model of language processing.     

Agents' self‐esteem moderates the effectiveness of negative‐direct partner regulation strategies

Prior research suggests that trying to change partner's attitudes and behaviors in hostile and demanding ways can successfully produce desired changes in targeted partners. The current research investigated whether the effectiveness of negative‐direct partner regulation strategies depends on the self‐esteem of regulation agents. Two longitudinal studies, involving individuals (N = 156) and couples (N = 174) in ongoing relationships, assessed agents' partner regulation attempts, the regulation strategies agents enacted, and the success of regulation attempts across time. Regulation agents who were low in self‐esteem and engaged in negative‐direct regulation strategies experienced lower regulation success over time. Lower regulation success in turn predicted decreases in relationship quality. These results indicate that negative‐direct regulation strategies are not beneficial when engaged by agents low in self‐esteem.     

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。     

Neuropharmacological treatment of mental dysfunction in Parkinson's disease

Many patients with Parkinson's Disease (PD) experience significant cognitive and mood impairment -even early in the course of the disease. These mental impairments are only partially responsive to levodopa treatment and are often as disabling as the motor impairment, particularly in mid and late stages of the disease. Investigators have recently begun a search for new agents that can effectively treat mental dysfunction of PD. Although there have been only a handful of properly controlled clinical trials of interventions targeted at amelioration of mental dysfunction in PD, progress has been made. Based on the available evidence, targeting catecholaminergic and cholinergic function may be an effective strategy for amelioration of cognitve, mood and psychiatric disturbances in PD.     

Stop the blame game: An analysis of blaming on Weibo during the early days of the COVID-19 pandemic in rice and wheat areas in China

In the pandemic era, social media has provided the public with a platform to make their voice heard. One of the most important public opinions online during a pandemic is blame. Blame can lead to stigma towards patients as well as potential patients and decrease social cooperation, which might impede prevention and control measures during epidemics. Thus, studying online blame during the early days of COVID-19 can facilitate the management and control of future pandemics. By analyzing 3791 posts from one of the most popular social media sites in China (Weibo) over the 10 days immediately after COVID-19 was declared to be a communicable disease, we found that there were four main agents blamed online: Individuals, corporations, institutions, and the media. Most of the blame targeted individual agents. We also found that there were regional-cultural differences in the detailed types of blamed individual agents, that is, between rice- and wheat-farming areas in China. After controlling influence of distance from the epicenter of Wuhan, there were still stable differences between regions: people in wheat areas had a higher probability of blaming agentic, harmful individuals, and people in rice areas had a higher probability of blaming individuals with low awareness of social norms for preventive health behavior. Findings have implications for preventing and predicting blame across cultures in future pandemics.     

Suicide Prevention in Adolescents (Age 12–18)

The epidemiology of adolescent suicide is summarized with particular emphasis on temporal trends by age and gender. “First-generation” prevention programs, as reviewed and critiqued by the Centers for Disease Control and Prevention, are then examined. In the absence of compelling empirically based behavioral outcome data, selective targeted “second-generation” prevention efforts are then described across the primary-secondary-tertiary continuum. These efforts are focused toward targets of individual predisposition, the social milieu, or proximal agents associated with high risk for suicidal behaviors. Finally, with an eye toward the future, current obstacles and unanswered questions are explored as they relate to opportunities and hopes for change in effecting reduced rates of these behaviors.     

Positive Affective Priming: A Behavioral Technique to Facilitate Therapeutic Engagement by Families,Caregivers, and Teachers

Affective priming is a technique used in experimental psychology to investigate the organization of emotional schemata not fully available to conscious awareness. The presentation of stimuli (the prime) with strong positive emotional valence alters the accessibility of positive stimuli within the individual's emotionally encoded cognitive system. By altering the valence of internal stimuli, it offers a method for influencing families, caregivers, and teachers serving as mediators in child behavior therapy. The need for priming is greatest where adults involved in therapy as agents of child behavior change have such negative feelings toward the targeted client, or to the therapeutic context, that acceptance and engagement with therapy are compromised. Examples of how positive affective priming might be used clinically are provided.