2018年肿瘤免疫研究热点回眸

 肿瘤免疫疗法已成为肿瘤治疗的重要手段，是肿瘤研究领域的焦点和热点。肿瘤免疫治疗相关药物相继问世，而2018年度诺贝尔生理学或医学奖授予两位在肿瘤免疫治疗中有突出贡献的免疫学家，更是确立了肿瘤免疫治疗时代的到来。本文概述了2018年肿瘤免疫治疗研究的热点及进展，包括新的肿瘤免疫检查点的发现、T细胞耗竭的深入探究、新的肿瘤免疫抑制细胞亚群的发现以及肿瘤免疫治疗新策略的探索。     

Cancer epidemiology in the last century and the next decade

By the early 1980s, epidemiologists had identified many important causes of cancer. They had also proposed the 'multi-stage' model of cancer, although none of the hypothesized events in human carcinogenesis had then been identified. The remarkable advances in cell and molecular biology over the past two decades have transformed the scope and methods of cancer epidemiology. There have been a few new discoveries based purely on traditional methods, and many long-suspected minor risks have been estimated more precisely. But modern epidemiological studies often depend on genetic, biochemical or viral assays that had not been developed 20 years ago.     

肿瘤精准药物治疗研究进展

 随着新一代基因测序技术以及癌生物学的迅猛发展，基于基因组生物标志物的抗肿瘤精准药物开发成为药物研发的重要方向。介绍了抗肿瘤精准药物在非小细胞肺癌、乳腺癌、黑色素瘤以及白血病等肿瘤领域表现出的优异治疗效果，剖析了目前已上市以及处于研发阶段的“泛癌种”药物，表明基于生物标志物而非肿瘤组织的治疗药物将成为抗肿瘤药物研发的方向之一。介绍了以“篮子试验”和“雨伞试验”为代表的抗肿瘤药物新型临床试验设计以及PROTACs药物开发新技术，指出新理念新技术的出现将进一步推动抗肿瘤精准药物发展，促进针对耐药或“不可成药靶点”的靶向药物的开发。     

Role of FGF-2／FGFR signaling pathway in cancer and its signification in breast cancer

Fibroblast growth factor-2 (FGF-2) is a member of a large family of proteins that bind heparin and heparan sulfate and modulate the function of a wide range of cell types. It has been proved that FGF-2 stimulates the growth and development of new blood vessels (angiogenesis) that contribute to the pathogenesis of several diseases (i.e. cancer, atherosclerosis). However, many of the biological activities of FGF-2 have been found to depend on its receptor抯 intrinsic tyrosine kinase activity and second messengers such as the mitogen activated protein kinases. This review will focus on the mechanism of FGF-2/FGFR induced signaling pathway in tumor and human breast cancer.     

Necroptosis——一种新型程序性死亡机制的研究进展

坏死在众多生理和病理进程中都扮演着重要的作用.最近,一种新型的被称为"necroptosis"的细胞坏死程序受到了人们的普遍关注.从形态学上来讲,necroptosis表现出和坏死相同的特征;然而,它却有自己独特的信号通路,这种通路需要受体相互作用蛋白激酶RIP1和RIP3的参与,形成诱导死亡信号复合体,从而促进细胞程序性坏死,但可以被necrostatins特异性地抑制.Necroptosis有助于免疫系统的调节,癌症的治疗以及多种压力下细胞的应答.本篇综述中我们将总结这种特殊的程序性死亡的信号通路、生物学效应和病理学意义.     

汶川地震对图书馆界的启示

“5·12”汶川大地震给四川灾区带来了严重的破坏,当地的图书馆也遭受了巨大的人员伤亡和经济损失。如今,重建工作已经积极展开,新图书馆会在“科学规划、统筹兼顾”的前提下进行选址、设计、建设。同时,新图书馆的建设将站在全局的高度,突出功能、地位特点,加强安全管理,提高公共服务和社会管理水平,建立并完善突发事件应急机制。     

氯化两面针碱抗肿瘤作用机制研究进展

传统中药两面针（Zanthoxylum nitidum（Roxb．）DC）有效成分氯化两面针碱主要通过抑制拓扑异构酶活性、阻滞细胞周期、诱导肿瘤细胞凋亡、逆转肿瘤细胞多药耐药等几种作用机制达到抗肿瘤作用。作为传统中药的新用法,氯化两面针碱抗肿瘤作用具有很大的开发应用价值,建议今后重点对氯化两面针碱系统的构效关系和结构优化,为研究开发新药提供目的化合物或候选药物分子;同时通过合成和建立天然活性物质类似物的化合物库来研发新药。     

Hiwi基因在耐药MCF-7/ADM乳腺癌细胞株中的表达

目的探讨Hiwi基因在耐阿霉素人乳腺癌MCF-7/ADM细胞和非耐药MCF-7细胞的表达.方法应用实时定量PCR与Western blot技术进行Hiwi基因在耐阿霉素人乳腺癌MCF-7/ADM细胞和非耐药MCF-7细胞株表达水平检测.结果 Hiwi基因在耐阿霉素人乳腺癌MCF-7/ADM细胞中的表达明显高于正常乳腺细胞(P0.01)及非耐药MCF-7细胞(P0.05).结论 Hiwi基因在耐阿霉素人乳腺癌MCF-7/ADM细胞株的高表达为耐药乳腺癌细胞的靶向治疗指出新的研究方向,对乳腺癌治疗预后评估具有临床指导性.     

试论游泳运动对癌症的影响

癌症是威胁人类健康的大敌，游泳运动为康复体育的重要手段，对癌症的康复有着积极的作用，原因在于游泳运动可使血液中自细胞大量增多，循环于血液中的淋巴细胞，巨噬细胞和直接杀伤细胞（K细胞）明显增加，它们能利用吞噬作用使人体内可能有的癌细胞难以逃脱厄运，同时可减轻化疗的副作用。     

Xenogeneic homologous genes, molecular evolution and cancer therapy

Cancer is one of the main causes for death of human beings to date, and cancer biotherapy (mainlyimmunotherapy and gene therapy) has become the most promising approach after surgical therapy, radiotherapy andchemotherapy. However, there are still many limitations on cancer immunotherapy and gene therapy; therefore great ef-fort is being made to develop new strategies. It has been known that, in the process of evolution, a number of genes, theso-called xenogeneic homologous genes, are well-conserved and show the structural and/or functional similarity betweenvarious species to some degree. The nucleotide changes between various xenogeneic homologous genes are derived frommutation, and most of them are neutral mutations. Considering that the subtle differences in xenogeneic homologousgenes can break immune tolerance, enhance the immunogenicity and induce autologous immune response so as to elimi-nate tumor cells, we expect that a strategy of inducing autoimmune response using the property of xenogeneic homologousgenes will become a new therapy for cancer. Moreover, this therapy can also be used in the treatment of other diseases,such as autoimmune diseases and AIDS. This article will discuss the xenogeneic homologous genes, molecular evolutionand cancer therapy.     

A high-resolution map of human evolutionary constraint using 29 mammals

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ～4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ～60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.     

Role of ion flux in the control of c-fos expression

There has been much interest in the biochemical and biophysical processes that couple extracellular signals to alterations in gene expression. While many early events associated with the treatment of cells with growth factors have been described (for example, ion flux and protein phosphorylation), it has proved difficult to establish biochemical links to gene expression. Recently, the study of such genomic control signals has been facilitated by the demonstration that the c-fos proto-oncogene is rapidly and transiently induced by treatment of several cell types with polypeptide growth factors and other growth modulating substances. In one particular system it has been shown that nerve growth factor (NGF) causes a transient induction of c-fos in the phaeochromocytoma cell line PC12, within 15 min. Furthermore, the magnitude of this induction can be modulated with pharmacological agents such as peripheral-type benzodiazepines (BZDs). Thus, the study of c-fos expression in PC12 cells could yield valuable clues to the coupling mechanisms linking cell surface activation to genomic events. Here we demonstrate that c-fos is induced in PC12 cells either by receptor-ligand interaction or by agents or conditions that effect voltage-dependent calcium channels.     

器官发育及细胞程序化死亡的基因调节研究

用线虫实验模型系统研究调节器官发育及细胞程序化死亡的基因，且发现这种基因在人体中也存在，这一成果获得了2002年诺贝尔生理学医学奖。“程序性细胞死亡”机理的发现为艾滋病、肿瘤和癌症等疾病的治疗提供了寻找新方法的可能，将在人类战胜疾病过程中发挥重要作用。     

2019年无人机热点回眸

 在科技创新牵引和管控政策的推动下,无人机产业焕发出新的活力。2019年,无人机自主控制及应用技术又取得长足发展,呈现出一些新的发展态势。从无人机新战略、无人机赛事、技术革新、实战化等多个角度,对2019年无人机的科技热点及发展趋势进行了总结。分析表明,无人机集群智能作为一项颠覆性技术和作战理念,将成为未来无人机研究发展的重要方向。     

PM2.5引起的肿瘤新生血管形成和转移研究进展

 PM_2.5指直径≤2.5 μm 的颗粒物质,它很容易穿过呼吸道屏障,进入血液循环,可诱发肺癌等多种恶性肿瘤,已成为恶性肿瘤新的诱因。近年研究揭示,PM_2.5可刺激肿瘤细胞合成和分泌血管内皮生长因子（VEGF）,促进血管内皮细胞介导的肿瘤血管新生;并可激活肿瘤细胞,使其通过血管生成拟态直接形成肿瘤血管;还能使肿瘤干细胞向肿瘤内皮细胞转化,促进肿瘤新生血管形成。此外,PM_2.5可促进肿瘤细胞及其他多种细胞分泌趋化因子和白细胞介素,招募骨髓和血液中白细胞进入肿瘤组织,诱发局部慢性炎症反应,诱导上皮细胞-间充质细胞转化（EMT）的发生,增加肿瘤细胞干性、迁移和转移能力;还可破坏血管稳态,增加血管通透性,为肿瘤细胞的转移打开方便之门。PM_2.5在肿瘤的新生血管形成和转移中起了重要作用,然而,至今对其作用机制知之甚少。因此,进一步深入研究PM_2.5诱导的肿瘤新生血管形成及转移机制,能为PM_2.5引起的恶性肿瘤防治提供可靠的理论依据和新的应对策略。     

The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells

Syk is a protein tyrosine kinase that is widely expressed in haematopoietic cells. It is involved in coupling activated immunoreceptors to downstream signalling events that mediate diverse cellular responses including proliferation, differentiation and phagocytosis. Syk expression has been reported in cell lines of epithelial origin, but its function in these cells remains unknown. Here we show that Syk is commonly expressed in normal human breast tissue, benign breast lesions and low-tumorigenic breast cancer cell lines. Syk messenger RNA and protein, however, are low or undetectable in invasive breast carcinoma tissue and cell lines. Transfection of wild-type Syk into a Syk-negative breast cancer cell line markedly inhibited its tumour growth and metastasis formation in athymic mice. Conversely, overexpression of a kinase-deficient Syk in a Syk-positive breast cancer cell line significantly increased its tumour incidence and growth. Suppression of tumour growth by the reintroduction of Syk appeared to be the result of aberrant mitosis and cytokinesis. We propose that Syk is a potent modulator of epithelial cell growth and a potential tumour suppressor in human breast carcinomas.     

肿瘤生物免疫治疗研究进展

 肿瘤免疫编辑理论的提出阐述了免疫系统在肿瘤发生发展中不可忽视的作用。靶向肿瘤免疫负调控的单克隆抗体在临床的成功应用,更确定了调控免疫系统对有效治疗肿瘤的重要性。未来大有发展潜力的联合免疫治疗手段主要有抗体、细胞因子、肿瘤疫苗、过继免疫细胞治疗和溶瘤病毒等。免疫治疗联合传统的肿瘤治疗包括手术、放疗和化疗,是今后提高肿瘤治疗效果的重要研究和应用方向。本文主要综述抗体治疗、肿瘤疫苗治疗、细胞过继免疫治疗、溶瘤病毒治疗的研究进展,提出相关研究中存在的问题,并对其进行展望。     

实时无标记肿瘤细胞迁移筛选技术体系的建立

肿瘤转移是导致肿瘤患者死亡的最主要原因。细胞迁移在多步骤、多阶段的肿瘤转移过程中发挥着重要的作用。尽管有许多迁移相关分子的研究,但细胞迁移的分子机制仍不清楚。研究将xCELLigence细胞分析系统和RNA干扰技术结合,初步建立了实时无标记的肿瘤细胞迁移筛选技术体系。该技术体系的建立将为大规模的肿瘤细胞迁移筛选工作奠定基础,还将有助于发现肿瘤细胞迁移信号通路中新的调控分子,揭示肿瘤转移的分子机制。