Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Endomembrane system wikipedia , lookup
Extracellular matrix wikipedia , lookup
Tissue engineering wikipedia , lookup
Cell growth wikipedia , lookup
Cell encapsulation wikipedia , lookup
Cytokinesis wikipedia , lookup
Signal transduction wikipedia , lookup
Cell culture wikipedia , lookup
Cellular differentiation wikipedia , lookup
The Phenotype of "Cancer" Cells Folder : CellProp(NoTP) Updated: February 26, 2017 In the First Third of Biology of Cancer Weinberg Book: 2nd Edition Chapter One: Cell Biology and Genetics Review Chapter Two: The Nature of Cancer (pp. 31 to 69) What is Cancer Like? (501 Intro) What are the clinical distributions of cancers? (Clinical) What are the patterns of cancer appearance and spread? What are Environmental Cancer Causative Agents(Epidemiology) How do we classify and define different kinds of cancers? (Definitions and Classifications) What do we study when we want to understand cancer biology? (Models) In the Second Third of Biology of Cancer: How Do Cancers Get that Way? What are cancer cells like? (Cell Properties; Immortalization) Chapter 2 (Parts); Chapter 10 , pp 391 - 437 How do cancer cells interact and diverge? (Heterogeneity) Chapter 13: Heterotypic Interactions. pp 577 – 640) How do cancer develop and change? (Progression) Chapter 11: Multi-step Tumorigenesis. pp 439 - 510 How do cancer cells and cancerous neoplasms grow? Chapter 5: Growth Factors and Receptors, pp 131 - 174 How do cancer cells become invasive and become able to spread? (Invasion and Metastasis) Chapter 14: Moving Out: Invasion and Metastasis, pp 641 - 722 What do we study in order to understand metastatic cancers? (Met Models) Chapter 14 What We Want to Know about the Biology of the "Cancer Cell" What are "Cancer Cells" Like? (See Next Slide) How are those features consistent with the natural history and pathology of cancer? What are the molecular-genetic and biochemical bases for these phenomena? What is the environmental impact on these properties? What does this tell us about how cancers start and progress? How do cancer cells interact with each other and with host cells and tissues to advance the pathology? How can we use these cellular properties for diagnosis of cancer? Can we use these cellular properties in the design of therapeutic intervention? Part 1, Section 2 of Biology of Cancer The Biology of the Cancer Cell: What are cancer cells like? What Makes a Cell “Neoplastic” How do they differ from normal cells of comparable tissue origin? How does a leukemic leukocyte differ from a normal white blood cell? How does a breast carcinoma cell differ from the epithelial cell type of origin? How does a sarcoma differ from a carcinoma, a leukemia, or a neurological neoplasm? Comparing Normal vs Neoplastic Cells What Cancer Cell Type? • Leukemia? Carcinoma?, Sarcoma?, ? • At What Point in Progression? What is the Appropriate Normal Cell of Origin with Which to Make the Comparison? What Features are Fundamental & Causal? What Features are Necessary to Maintain the Neoplastic State? What Features are Incidental, or a Necessary Consequence of being a Neoplastic Cell, but are not causative for the pathology? What cancer-specific features can we exploit for diagnosis and for therapy? Structural Characteristics of Cancer Cells in Vivo and in Cell Culture: Features of Cellular Anaplasia Resemble Primitive, Undifferentiated, Embryonic Cells Lose Differentiated Functions: Look more like embryonic cells Large Nucleus, Excess Chromatin Can become enlarged and multinucleated Aberrant Cytoskeletal Structures and Function Acquire Abnormal Chromosomal Numbers & Structures Aneuploid Translocations, Deletions, Amplifications Loss of Heterozygosity Exhibit Aberrant Mitoses Characteristic Behavior of Cancer Cells in Culture: Morphological Phenotype of the Transformed Cell (part 1) • • • • • • Easily Converted to Continuous Culture Colony Formation in Soft Agar High Cloning Efficiency Growth in Suspension Culture for Some Lines Anchorage-Independent Growth Grows in Low Serum Medium Low requirement for exogenous growth factors May be able to produce its own growth factors and to produce altered growth-factor receptors that don’t need an exogenous growth signal • Altered Density-dependent Inhibition of Mitosis Grows to High Density • Altered Contact-inhibition of Cell Movement Characteristic Behavior of Cancer Cells in Culture: Morphological Phenotype of the Transformed Cell (part 2) • Can be Sub-cultured Indefinitely: Immortalized • Do Not Show Cellular Senescence • Possible Maintenance of Chromosomal Telomeres (ends of chromosomes) • Altered Pathways to Apoptosis (Geneticallyprogrammed Cell Death) Forms Tumors in Genetically Appropriate Hosts with Low Cell Challenge Number: Tumorigenic Senescence of Normal Human Fibroblasts Passaged Beyond 60 Cell Doublings In Cell Culture Figure 10.2 The Biology of Cancer (© Garland Science 2007) p. 359 Protective Effect of Telomeres on Chromosome Integrity Telomere Shortening with Successive Cell Divisions in Normal Cells Telomeres* on normal cells protect chromosome ends * Telomeres labelled green by Fluorescence in situ hybridization with DNA probe that recognizes repeated nucleotide base sequence in telomeric DNA p. 369 Cells with blocked telomere formation show extensive chromosme fusion leading to cell death Figure 10.11 The Biology of Cancer (© Garland Science 2007) Please put all books and papers on the floor so they cannot be referred to. No hand-held devices other than the blue or tan XR Response Cards are allowed. (No inter-student texting) These quizzes are relatively easy but they constitute 40% of the numerical score from which class standing and letter grades are determined. Therefore the quizzes have to be fair and honest. Response Counter Response Counter Response Counter Biochemical Characteristics of Cancer Cells (Part 1) Enhanced Energy Metabolism; Decreased Storage of Energy-rich Metabolites Enhanced Biosynthesis of Macromolecules Altered Cytoskeletal Elements Altered Plasma Membrane Components Altered Membrane-Cytoskeletal-Cytosolic Interactions Altered Cell-Adhesion Sites Altered Transport Altered Immunogenicity Biochemical Characteristics of Cancer Cells (Part 2) • Altered Isoenzyme and Isoprotein Patterns: (Oncofetal Isoenzymes and Isoproteins) • Increased Plasminogen-activator and Increased Clotting Ability • Loss of Membrane-Cytosolic Growth Regulation and Control of Gene Expression • Secretion of Proteases • Increasing genetic anomalies To Here Class 11: February 23, 2017 Characteristics of Neoplastic Tissue in Vivo • Can Be Transplanted Indefinitely: Immortalized • Exhibits Positional Anaplasia and Aberrant Inter-cellular Interactions • Altered and Reduced Cell Adherence Cell to Cell Cell to Connective Tissue • Disordered Cell:Cell Interaction and Alignment • Induction of Host Tissue Infiltration Connective Tissue, Nerves, Blood Supply • Can Infiltrate Host Tissue: Invasion What Underlies, Generates, Maintains, and Extends These Multiple Anomalies in Cancer Cells and Cancer Tissues? Accumulating Cell Signaling Anomalies in Cancer Introduction (Transfection) of cancer-inducing genetic elements; Activation of endogenous pre-existing cancer-inducing genetic elements (See Chapter 3 on Viruses and Cancer) Perturbation of Cell-Signaling Pathways (See Chapters 4 and 5– Signaling in Normal Cells) Cellular Oncogenes (Chapter 4) Growth Factors and Receptors (Chapter 5) Aberrant Cell Signaling in Cancer (Chapter 6) Loss of Tumor Suppressor Elements (Chapters 7, 8, 9) Aberrant Cell Cycle Entry – “Control of the Cell Cycle Clock”) Failure to Invoke Apoptosis Deficiency in DNA Repair Genetics Underlying Immortalization and Tumorigenesis (Chapter 10) From Science, February 3, 2012: Visualization in Science Full Science Article on Visualization http://www.sciencemag.org/site/special/vis2011/?utm_content=special%20issue&utm_ medium=all&utm_campaign=science&utm_source=shortener You should be able to get to these by clicking on them or you can copy and paste this URL to your Explorer or Mozilla browser. Click on the second active “Slideshow” above the word “Illustration. You will see the label “Death Receptors”. You should be able to hear and see this presentation. Use the left and right arrows to go from one slide to the next. You also could try: http://scim.ag/y41Bht Also select the “Slideshow” option above the word “Video”. We will try this in class Video of pancreatic cell (Text Only. Video and Audio of Pancreatic Cell is seen in the above link) http://www.sciencemag.org/content/335/6068/534.full Cell Signaling in Normal and Neoplastic Growth Control Next Three Slides Transport into and out of a cell. Author: Insuhana Signal transported to inside the cell by a membrane vesiclel Signal passes directly into cell Signaling from outside cell through membrane receptor RTK = Through Receptor membrane receptor Ras Pathway Signaling from outside to inside of the cell Tyrosine Kinase Growth Factors Ras = Rat Sarcoma Virus Oncoprotein TCR = T-Cell Receptor PMA GAP GTP GRB2 SOS P CD-GEGII Ras GEF GDP P P Ras PLC-ε p120GAP PI3K RalGDS P Raf Rac Rap1A p190-B Ral GTP P MEKs PAKs PLD RalBP1 Rho PLD Pathway MEKK1 ERKs CDC42 P Stress Fibers and Focal Adhesions JNKK ERKs JNK JNK Elk1 c-Jun ATF2 Gene Expression GTPase will affect actvitity of RAS c-Fos 2009 ProteinLounge.com C External Cytokine Signaling Intra-cellular signaling Note integrin signaling 12 Different Cellsignaling pathways potentially containing aberrant protein components in 24 different patients with pancreatic cancers. Affects RAS Signalling From Science, Sept. 26, 2008 DNA Repair Cell cycle control Cell Death Control Jones et al. pp 1801-1806 How Do We Make Sense out of these complex signaling pathways? Show: Cold Spring Harbor Site Inside Cancer: Viewing Cancer Cells from Inside ( Linked on Course Web-site under OnLine Scientific Materials) Links given on the next slide Hallmarks of Cancer: Characteristics of Cancers Pathways to Cancer: Shows Cellular Pathways Functioning Diagnosis & Treatment: Different kinds of cancers Causes and Prevention From Course Web-site: tpfondy.syr.edu/bio501 OnLine Scientific Materials (CxSciInfo.htm) On-Line Links to Web-sites Relating to Cancer biology and Cancer Medicine Caring Bridge: Stories of People and Cancer Inside Cancer: Viewing Cancer Cells from Inside (Cold Spring Harbor Laboratory). Superb View of Cancer Pathways, Diagnosis, and Treatment www.insidecancer.com View For This Part of the Course: “Hallmarks of Cancer” Links 1,2,3,4,5 involving Properties of Cancer Cells For Later Parts of the Course View: Link 6 involves Invasion and Metastasis Link 7 involves Tumor immunology Link 8 Involves Cancer Genetics Later Sections in Inside Cancer: “Pathways to Cancer” = Cell Signaling and Cancer “Causes and Prevention” “Diagnosis and Treatment” Inside Cancer: Viewing Cancer Cells from Inside (Cold Spring Harbor Laboratory). Pathways to Cancer Shows transfer of extracellular signals via Cell Membrane Receptors to initiate messenger RNA synthesis in the nucleus, ribosomal RNA synthesis, protein synthesis, protein modification in the Golgi apparatus, protein packaging, and export of newly synthesized proteins. Note where “Growth Factor” is being used to identify the newly synthesized protein, this does not mean that it is acting as a growth factor yet. It is being used an example (in this case a bad example because of the confusion) of a newly synthesized protein. Stories of People, Tumors, Blindness, and Childhood Death The Story of the Africa Mercy 60 Minutes, February 17, 2013 12 Minute Video https://www.youtube.com/watch?v=TfjYeQzCwzU Click on this link of Copy this youtube link to your browser These links will require signing up for an account Africa Mercy: Hospital of hope - 60 Minutes - CBS News ►► www.cbsnews.com/video/watch/?id=50141230n Please put all books and papers on the floor so they cannot be referred to. No hand-held devices other than the blue or tan XR Response Cards are allowed. (No inter-student texting) These quizzes are relatively easy but they constitute 40% of the numerical score from which class standing and letter grades are determined. Therefore the quizzes have to be fair and honest. Rank 1 Responses 2 3 4 5 6 Response Counter Non-Response Response Counter Response Counter This one is not graded. We will switch to anonymous for this Turning Point Poll On a scale of -2 to +2 rate (Use Keys 1 to 5 as indicated): 5 4 5 1 = -2 = I’m totally snowed 2 == -1 = I’m having a hard time following 3 = 0 = I’m doing OK with most of it. I can figure the rest out later 4 = +1 = I’m not having any problem following this 5 = + 2 = This is a breeze. Please get moving! 4 3 3 2 2 1 1 Duration: 0 Seconds To Here at the end of Presentation 12, Tuesday March 1, 2016 Rank 1 2 3 4 5 6 Responses 0% 0% 1 2 0% 0% 3 4 0% 0% 5 6 A Note on Cancer and the Cancer Cell Phenotype: The Genotype, the Proteome, the Metabolome, the Signal Transduction Anomalies , the Epigenetic modifications of Gene Expression produce, and sustain the Neoplastic Phenotype. The Phenotype is what kills. How the cell got to that phenotype is important, but in the end target for therapy is the pathological phenotype, regardless of how the cell got to that phenotype. e.g. The earliest clinically active anti-neoplastic agents were agents directed against cell proliferation, before anyone knew what caused the aberrant cell proliferation in cancers. Sydney Farber and Leukemia Therapy 1945