如何回复SCI期刊给出修改意见.ppt

CARCINOGENESIS:MOLECULAR BASIS OF CANCER DAVID LEWIN MD OVERVIEW BASIC CONCEPTS OF ONCOGENES, TUMOR SUPPRESSOR GENES, APOPTOSIS, DNA REPAIR TELOMERES HOW THEY ARE ASSOCIATED WITH MALIGNANCY PROPOSED FUNCTIONS GENETIC ALTERATIONS ASSOCIATED WITH THEIR ACTIVATION OR LOSS FUNDAMENTAL PRINCIPLES Non-Lethal genetic damage (Mutations) Acquired Environment (next lecture) Inherited (Germ line) Tumors arise from a single progenitor cell Monoclonal (X-linked isoenzyme) Target Genes Proto-oncogenes, TSG, Apoptosis, DNA repair Multistep Process MONOCLONALITY:X-Linked Isoenzyme Simplified Cancer Pathogenesis ONCOGENES PROTO-ONCOGENES NORMAL CELLULAR GENE ALTERATIONS GIVE ONCOGENE MUTATIONS, AMPLIFICATION, RETROVIRAL TRANSFER DEFINE MOLECULAR BASIS FOR CANCER EXPLAIN MUTAGENS EFFECT ON CANCER DEVELOPMENT LABORATORY IDENTIFICATION OF ONCOGENES ACUTE RETROVIRAL TRANSDUCTION ACUTE TRANSFORMING VIRUSES (V-ONC) INSERTIONAL MUTAGENESIS SLOW TRANSFORMING VIRUSES DNA TRANSFECTION (IN VITRO) NOT ASSOCIATED WITH VIRUSES Protein Products of Oncogenes Oncoproteins Resemble normal products except: Devoid of regulatory elements Production does not depend on growth factors or external signals Effect key proteins Cell growth Development Differentiation Cell Death PROTO-ONCOGENES Growth Factors sis, hst-1, int-2 Over expressed Growth Factor Receptors ret, c-erb B-2 (Her2/neu) Mutated “on” Signal Transducers ras: Most common abnormality Mutated “on” Nuclear Transcription Proteins myc Control transcription genes, Bind DNA Cyclin and Cyclin-Dependent Kinases Mutations favor proliferation Model of Action of ras Gene Role of Cyclins and Cyclin-Dependant Kinases (CDK) PROTO-ONCOGENE ACTIVATION POINT MUTATIONS ras - COLON CANCER GENE REARRANGEMENTS t(8;14) - BURKITT’S t(9;22) – Chronic myelogenous leukemia (CML) GENE AMPLIFICATION N-myc - NEUROBLASTOMA BURKITT’S LYMPHOMA ONCOGENE ACTIVATION BY CHROMOSOME REARRANGEMENT TRANSLOCATION OF 8 AND 14 [t(8,14)] c-myc (chr 8) to immunoglobulin heavy