中山大学循证医学3TranslationalMedicine-ZSU-FS.ppt

1、Translational Medicine clinical scientists working in strong laboratories and with cutting-edge technology; a supportive infrastructure within the institution.,T2: the “laboratory” for T2 research is the community and ambulatory care settings mastery of the “implementation science” of fielding and e

2、valuating interventions in real world settings mastery of the disciplines such as clinical epidemiology and evidence synthesis, communication theory, behavioral science, public policy, financing, organizational theory, informatics, and mixed methods/qualitative research.,Challenges,T1: struggles mor

3、e with biological and technological mysteries, trial recruitment, and regulatory concerns,T2: struggles more with human behavior and organizational inertia, infrastructure and resource constraints, and the messiness of proving the effectiveness of “moving targets” under conditions that investigators

4、 cannot fully control,Investigators,T1: Basic scientists cooperate with clinical doctors,T2: Population-based investigators and epidemiologists and health policy makers, etc.,More effective collaboration between lab scientists and clinical doctors,Translational Medicine,Dissemination of the innovati

5、on Adoption of the innovation Maintaining the innovation Refining and evolving as body of knowledge expands,The Translation Continuum,Source: National Cancer Institute,Translational Medicine,Translate the success in genomic medicine into clinical applications Evidence-based medicine develop rational

6、e and theory for drug design and therapeutic intervention Develop personal medicine and preventive medicine,Translational Medicine,Translational Research -hot spot Genomic and gene diagnosis and treatment基因组研究及基因诊断治疗 Phase I trial for drugs 药物一期临床试验 Genomic Pharmocology and personalized medicine 基因组

7、药理学与个体化医学 Biomarks 生物标记物 Signal transducting pathway and clinical applications 信号传导通路的研究及其临床应用 Stem cell干细胞,Translational Medicine,The heart of translational research resides in Phase I trials where novel treatments are ： tested for feasibility and toxicity preparation for a Phase II trial in which

8、therapeutic effectiveness is tested Marincola, FM Translational Medicine: A two -w ay road, JTM, 2006,Clinical Research Training Program,Computer Skills Clinical Research Methods Biostatistics: Statistical Approach in Clinical Research Measurements in Clinical Research Ethics and Regulations of Clin

9、ical Research Research Design and Development Cost-effectiveness Analysis Regression and ANOVA Logistic Regression Clinical Trials,The process of Translation,Choose a research topic related to your clinical practice,Early study on nitric oxide Synthase,Uses for a cloned gene,Homology comparison Quan

10、titate gene expression Chromosomal mapping Determine transcriptional regulation Prepare recombinant protein Antibody development Tissue localization Develop transgenic/knockout animals Gene transfer/gene therapy studies Intellectual property / technology transfer,Explore Gene and Diseases,Physiopath

11、ological Study,Bench:Vasoprotective Properties of Nitric Oxide Inhibits platelet aggregation Inhibits leukocyte chemotaxis Inhibits VSMC proliferation Inhibits VSMC migration Promotes EC growth Inhibits EC apoptosis Potent vasodilator,Cell and Animal,Adenoviral Vector (type 5, E1-, E3-)腺病毒载体,Small A

12、nimals,Bigger Animals,Animal Experiment,2005年,PhaseClinical Trial,Clinical Trial: AdiNOS gene therapy to block AV fistula neointimal hyperplasia in hemodialysis patients 2006,Current State of Translational Medicine,17 year innovation adoption curve from discovery into accepted standards of practice

13、Even if a standard is accepted, patients have a 50:50 chance of receiving appropriate care, a 5-10% probability of incurring a preventable, anticipatable adverse event The market is balking at healthcare inflation, new diagnostics and therapeutics will find increasing resistance for reimbursement,Pe

14、rsonalized Medicine,Clinic,Lab,Population,T1,T2,T1:applying basic science findings from lab research in clinical studies of patients,T2:applying the findings of clinical studies to alter health practices in the community,EBM,Tranaslational Medicine,Personalized Medicine,Personalized medicine,the app

15、lication of genomic and molecular data to better target the delivery of health care, facilitate the discovery and clinical testing of new products, and help determine a persons predisposition to a particular disease or condition a patients protein, gene or metabolite profile could be used to tailor

16、medical care to that individuals needs,Imatinib for GIST,GIST genesis Key process： c-kit mutation-KIT TK activation PDGFR mutation 86% GIST kit mutation，prognosis factor Imatinib Oral small molecule TKI Inhibit TK activation抑制酪氨酸激酶活化 Design for chronic myeloid leukemia (CML),Imatinib for GIST,Imatin

17、ib for GIST,Joensuu H，et al. 2001,Pretreatment,One month of therapy,H344:1052-1056.,The First GIST Patient: Histology,Imatinib for GIST,Imatinib for GIST,Joensuu H，et al. 2001 Theory：Imatinib could target GIST Easy Detected tumor marker：CD117 Tissue from the patient Response confirmed by pathology D

18、ynamic monitored by tumor marker Ethics： IRB,Imatinib 治疗 GIST,2000.3： Joensuu H. first case 2000.7： phase II study(B2222) 2001 autumn：phase II study (S0033,EORTC) 2002.2：FDA,Imatinib for GIST,5-year survival Kit mutation predict Imatinib response,Imatinib for GIST,Imatinib for GIST,Imatinib resistance cliniclab Overcome Imatinib resistance lab clinic Mechanism of Imatinib resistance clinicl