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陆舜:肺癌个体化治疗进展

陆舜:上海交通大学附属胸科医院,主任医师,博士研究生导师。

近年来,基于肺癌发病机制的深入认识以及癌基因组学的研究成果,肺癌靶向治疗取得了突破性进展。非小细胞肺癌的治疗已经由“化疗”时代高速进入了以靶向治疗为主要手段的综合性“个体化治疗“时代。根据分子标志筛选特定的疾病人群,应用阻断此标志的化合物来抑制肿瘤生长已成为治疗肺癌的新思路。

目前已知的具有显著分子特征的标志有表皮生长因子受体(EGFR)突变、间变性淋巴瘤激酶(ALK)突变和ROS1突变等。

2015-08-20 课时:56分钟

欧阳冬生:遗传药代与个体化治疗

欧阳冬生,博士,教授,博士研究生导师,中南大学临床药理研究所副所长,国家药物临床试验I期临床研究室主任。

遗传药理学的发展,根据年龄和体重等确定药物剂量的时代将逐步被根据患者的遗传特点选择剂量所代替。也就是根据患者的药物代谢酶和药物作用靶点的基因型对所用药物代谢动力学参数和对药物的敏感性的影响来选择药物剂量。

这样可以最大限度地减少药物不良反应和毒性作用,同时也最大限度地提高药物治疗效应。以特定基因型患者为研究对象进行的临床试验结果是根据患者基因型选择药物剂量的依据。

但是,迄今这样的依据少之又少。目前只能根据具有遗传多态性的药物代谢酶在药物代谢中的贡献大小来调整剂量。

研究表明携带CYP2C9变异基因的患者在用华法林治疗期间出现出血的几率较高,在确定华法林的给药剂量时基因型起着非常重要的作用;可待因在体内需通过CYP2D6经氧位去甲基代谢生成吗啡而产生镇痛作用,CYP2D6的PM个体在体内不能使其代谢生成吗啡,因此在这类患者中应用可待因不能产生镇痛作用。

2015-08-25 课时:48分钟

翟所迪:制定中国万古霉素治疗药物监测指南

翟所迪,北京大学第三医院药剂科主任,北京大学治疗药物监测和临床毒理中心主任。中国药学会医院药学专业委员会副主任委员、中国药理学会治疗药物监测研究会副主任委员、卫生部合理用药专家委员会临床药学组组长。

2009年美国ASHP(卫生系统药师协会)颁发了美国的万古霉素TDM(治疗药物监测)指南,2013年日本颁发了日本的万古霉素TDM指南,这两个指南虽然对中国的万古霉素TDM有一定的指导作用,但还是与国内的万古霉素TDM现状有较大的差异,细菌的耐药性不尽相同。

重要的是美国、日本的万古霉素TDM指南的证据系统不是依据目前更规范的GRADE证据系统建立的。我们使用WHO的指南建立方法,首先用DELPHE方法优选了指南推荐意见的16个PICO,针对16个PICO制作了16个系统评价或meta分析。

对患者相关的一些推荐意见,采用问卷调查的方法了解了患者的意愿,我们尊重患者依据自己的价值观做出的选择。万古霉素TDM指南的形成对于指导国内万古霉素TDM工作具有重要的临床指导意义,是万古霉素个体化给药的规范,也是循证药学证据应用的高级阶段。

2015-09-08 课时:26分钟

胡苹:肌肉干细胞与肌肉损伤个体化治疗

胡苹,中国科学院上海生物化学与细胞生物学研究所研究员,于北京大学生命科学院获得学士学位,美国纽约州立大学Stony Brook分校-冷泉港实验室获得博士学位。

成体干细胞负责哺乳动物出生后组织和器官的再生。这些细胞通常处于静息状态,在损伤等外界条件刺激下进入增殖和分化状态,并最终再生出需要修复的组织。

成体干细胞是再生医学治疗中很重要的细胞来源,但是成体干细胞移植在临床应用中面临着一个严重的问题,即干细胞在植入体内后很快进入静息状态,无法再生出所需要的组织。成体干细胞是如何在静息、增殖、分化状态之间相互转换,从而满足生物体组织再生的要求的,目前还所知甚少。

我们利用肌肉干细胞为模式系统,研究信号传导系统与转录调控系统之间的相互作用,及其与成体干细胞命运决定的关系。最终能够促使更多的成体干细胞在临床移植后进入增殖、分化状态,实现组织器官的再生。

2015-09-15 课时:40分钟

李苏:化疗药物监测与抗肿瘤药物个体化治疗

李苏,广州中山大学附属肿瘤医院药物临床试验中心副主任兼I药理室主任。并任广东药学会理事,中国药学会成员等职位。主要研究方向:抗癌药物的I期临床试验和抗癌药物的TDM。

化学治疗是肿瘤三大治疗手段之一,化学类抗癌药物由于其治疗窗窄、个体差异大、毒性大临床给药要求需用对药物、用对时间、用对剂量。治疗药物监测或目标浓度干预的治疗策是通过测定体液中的药物浓度,根据患者的药代动力学-生理学模型(PK-PD)或群体药代动力学数据调整后续的给药剂量,此方式已经应用于5-FU、紫杉醇、MTX、泰素帝等临床治疗。但TCI在肿瘤个体化应用仍存在一定的阻碍包括:

 缺乏浓度(AUC)与临床疗效的关系的数据
 未建立最大耐受剂量(MTD)与浓度的关系
 联合给药影响疗效和毒性的评估
 检测方法的局限性
 最佳时间点的选择
 取样点和检测时间的不一致
测定大剂量氨甲喋呤给药后MTX浓度不仅可以调整解毒剂的剂量,也能通过计算AUC调整后续MTX剂量,从而减少复发的风险。5-FU不仅可通过测定其代谢酶DPD酶基因多态性进行初始剂量的制定,也能通过测定血药浓度调整后续给药剂量,从而减少毒副反应,增加患者依从性;同时通过测定其靶酶TS酶的SNP筛选适合5-FU的患者。紫杉醇通过测定给药后30h的血药浓度,通过高于0.05μM的时间调整给药剂量,从而降低骨髓毒性而不改变疗效。

2015-09-21 课时:31分钟

刘宝瑞:液体活检与肿瘤实时个体化药物治疗

刘宝瑞:主任医师、教授、博士生导师,担任南京大学医学院附属鼓楼医院肿瘤中心主任、南京大学临床肿瘤研究所所长,是南京大学、南京医科大学、南京中医药大学博士生导师。

刘宝瑞教授先后荣获 “中国医师奖”、“全国医药卫生系统先进个人”、“江苏省有突出贡献专家”、江苏省优秀重点人才”、“南京市科技功臣”等称号,享受国务院特贴。现为国家自然科学基金委员会评审专家,国家科技奖及教育部科技奖评审专家,中华医学会肿瘤专科分会胃肠学组委员,中国生物医学工程学会肿瘤靶向治疗技术委员会主任委员,江苏省中西医结合肿瘤专业委员会主任委员,江苏省医学会肿瘤化疗与生物治疗分会副主任委员,江苏省抗癌协会肿瘤标志委员会副主任委员,江苏省抗癌协会化疗专业委员会副主任委员等学会工作。为16种中文医学统计源杂志编委或特约编委,为10种外文医学杂志特约审稿专家。

2015-09-24 课时:48分钟

肿瘤免疫学与免疫治疗的新进展

This animation created by Nature Reviews Cancer and Nature Reviews Immunology illustrates how tumour cells are sensed and destroyed by cells of the immune system and how tumours can evolve to evade immune-mediated elimination. Scientists are developing new immunotherapies that help the immune system to ‘fight back’ — the animation explains how these exciting new drugs work.

2015-11-25 课时:6分钟

卵巢癌:治疗新突破

卵巢癌是第七大最常见的癌症,也是最难治疗的癌症之一。正如动画显示,这在很大程度上是因为许多肿瘤的发展能抵抗一线治疗:以铂为基础的化疗。好消息是,实验疗法的发展可能提供一种更好的方法,来击败致死性肿瘤。

2015-11-27 课时:3分钟

为什么基因治疗能成为消灭HIV的合理工具 - David Baltimore P2

本视频由科普中国和生物医学大讲堂出品

David Baltimore (Caltech) Part 2: Why Gene Therapy Might be a Reasonable Tool for Attacking HIV

Lecture Overview:
In this set of lectures, I describe the threat facing the world from the human immunodeficiency virus (HIV) and a bold proposal on how we might meet the challenge of eliminating this disease by engineering the immune system.

In part 1, I provide a broad introduction to viruses, describing their basic properties and my own history of studying the replication of RNA viruses which led to the discovery of reverse transcriptase. I also illustrate the distinguishing features of equilibrium viruses (e.g. the common cold) that have adapted to co-exist with their host and non-equilibrium viruses (e.g. HIV) that have recently jumped from another species, are not adapted to the new host, and which can lead to disastrous outcomes (e.g. loss of immune function with potential lethality in the case of HIV).

In part 2, I describe the growing health problem that is facing the world with the spread of HIV and the limitations of current drug therapies and vaccine strategies. We need new ideas for tackling this problem. Here and in the next segment, I describe bold strategies of using gene therapy to conquer HIV, The approach that I describe in this segment involves gene therapy to produce short hairpin RNAs (siRNA) that target the destruction of a critical co-receptor of HIV, which the viruses that needs to infect cells. I discuss initial proof-of-principle experiments that suggest this approach might be feasible and the next steps needed to develop this idea into a real therapy.

In this last segment, I describe another gene therapy strategy for HIV in which we propose to develop antibody-like proteins that can be expressed by a patient's B cells and will target the HIV virus for destruction. To achieve this objective, hematopoietic (blood) stem cells must to be targeted with the gene, which will ultimately develop into B cells that express the therapeutic molecule. The ultimate goal is to produce a life-long supply of anti-HIV neutralizing antibodies. In this lecture, I describe the molecular methods underlying this strategy and a development path from proof-of-principle studies in mouse to safe trials in humans. This project receives funding from the Bill and Melinda Gates Foundation.

Speaker Bio: After serving as President of the California Institute of Technology for nine years, in 2006 David Baltimore was appointed President Emeritus and the Robert Andrews Millikan Professor of Biology. Born in New York City, he received his B.A. in Chemistry from Swarthmore College in 1960 and a Ph.D. in 1964 from Rockefeller University, where he returned to serve as President from 1990-91 and faculty member until 1994.

For almost 30 years, Baltimore was a faculty member at Massachusetts Institute of Technology. While his early work was on poliovirus, in 1970 he identified the enzyme reverse transcriptase in tumor virus particles, thus providing strong evidence for a process of RNA to DNA conversion, the existence of which had been hypothesized some years earlier. Baltimore and Howard Temin (with Renato Dulbecco, for related research) shared the 1975 Nobel Prize in Physiology or Medicine for their discovery, which provided the key to understanding the life-cycle of HIV. In the following years, he has contributed widely to the understanding of cancer, AIDS and the molecular basis of the immune response. His present research focuses on control of inflammatory and immune responses as well as on the use of gene therapy methods to treat HIV and cancer in a program called "Engineering Immunity".

Baltimore played an important role in creating a consensus on national science policy regarding recombinant DNA research. He served as founding director of the Whitehead Institute for Biomedical Research at MIT from 1982 until 1990. He co-chaired the 1986 National Academy of Sciences committee on a National Strategy for AIDS and was appointed in 1996 to head the National Institutes of Health AIDS Vaccine Research Committee.

In addition to receiving the Nobel Prize, Baltimore's numerous honors include the 1999 National Medal of Science, election to the National Academy of Sciences in 1974, the Royal Society of London, and the French Academy of Sciences. For 2007/8, he is President of the AAAS. He has published more than 600 peer-reviewed articles.

2015-12-14 课时:31分钟

杜弈奇:益生菌在炎症性肠病(IBD)治疗上的研究-第2段

炎症性肠病(IBD)易复发,免疫抑制剂效果差。本短片介绍了,益生菌在溃疡性结肠炎治疗上的研究。

2016-01-21 课时:5分钟