Click to edit Master title style,,Click to edit Master text styles,,Second level,,Third level,,Fourth level,,Fifth level,,,,*,Translational Medicine & Personalized Medicine,转化医学和个体化医学,EBP Models,Traditional practice Model,(,×,),,Model 1: Use the highest quality information to guide clinical decisions,,Model 2: Search, evaluate, and make available specialty specific Level 1 information,,Model 3: Create original research or systematic reviews,,Model 4: Translational research,……,Background,In the past 30 years,，,NCI $200 Billions,,Results,：,1.56million articles,,80,％,on mice, fruit fly and round worm,。
No change on cancer related mortality rate,Background,Background,New biotechnology,,Genomics(,基因组,), Proteomics(,蛋白质组,),,Bioinformatics(,生物信息学,),,Increasing complexity of clinical research,Definition,Translational research, “transforms scientific discoveries arising from the laboratory, clinical, or population studies into clinical applications…〞,,Include：,,bench to bedside(根底研究到临床应用),,bedside to bench(临床治疗结果促进根底研究),,Source: National Cancer Institute, National Institutes of Health,Definition,,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,Goals/Purpose,T1:,,The production of a promising,new treatment/method,that can be used clinically or commercialized.,T2:,,Ensure that new treatments and research knowledge actually reach the,patients or populations,for whom they are intended and are implemented correctly,Research content,T1:,,to test, in humans, the novel therapeutic strategies developed through experimentation (,ex vivo or from-bench-to-bedside,),,T2:,,to test how can efficiently use clinical results to optimize health practices and improve guidelines and health policy (,from-bedside-to-population,),Settings/knowledge background,T1:,,requires mastery of molecular biology, genetics, and other basic sciences;,,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 evaluating 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 more 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 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 innovation,,Adoption of the innovation,,Maintaining the innovation,,Refining and evolving as body of knowledge expands,The Translation Continuum,Basic Scientific Discovery,Early Translation,Late Translation,Dissemination,Adoption,Promising gene,,Basic epidemiological finding,Partnerships,,Intervention development,Phase III trials,,Regulatory approval,,Partnerships,,Health services research to support dissemination and adoption,To community providers,,To patients and public,Adoption of advance by providers, patients, and public,,Payment mechanisms to enable adoption,,,,,,Source: National Cancer Institute,Translational Medicine,Translate the success in genomic medicine into clinical applications,,Evidence-based medicine,develop rationale 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 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 Clinical,,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,,Quantitate 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,,,,Physiopathological 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 Animals,,Bigger Animals,,Animal Experiment,2005,年,,,PhaseⅠClinical 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,,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,Personalized 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 application 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 person's predisposition,to a,particular disease or condition,,a patient's protein, gene or metabolite profile could be used to tailor medical care to that individual's 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,Imatinib for GIST,Joensuu H,，,et al.,2001,Pretreatment,One month,,of therapy,H&E,(at diagnosis),,,,H&E,,,,Ki 67,,,,CD117,,Joensuu H et al.,N Engl J Med,. 2001;344:1052-1056.,,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,,Dynamic 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,clinic→lab,,Overcome Imatinib,,resistance,,lab →,,clinic,,Mechanism of Imatinib,,resistance,,clinic→lab,Imatinib for GIST,Surgery in advance GIST,,When to stop?,,Choi’s,,Imatinib for GIST,Choi et al, J Clin Oncology, 2007;25:1753-1759,Imatinib for GIST,C-kit activation normally associated with KIT mutations,,C-kit activation sometimes without KIT mutations,,Some c-kit negative tumors have KIT mutations,,Some c-kit negative GISTs have activating mutations in a different TK (tyrosine kinase), PDGFRa,,……,Summary,Clinical expertise is important,,EBM: improve clinical practice and research,,Translational Medicine&Personalized Medicine: new trend,,Integration of EBM and Translational Medicine,。