Virchow s Hypothesis lymphorecticular infiltration of cancer reflected the origin of cancer at sites of inflammation
|
|
- Julian Norton
- 6 years ago
- Views:
Transcription
1 Virchow s Hypothesis 1863 lymphorecticular infiltration of cancer reflected the origin of cancer at sites of inflammation
2 Barrett s esophagus/ Esophageal adenocarcinoma PSC / Cholangiocarcinoma Viral hepatitis / Hepatocellular cancer Gastritis/ Gastric cancer Colitis / Colon cancer
3 Gastrointestinal Cancers and Chronic Infection EBV nasopharyngeal cancer H. Pylori gastric adenocarcinoma MALT Clonorchis Sinesis cholangiocarcinoma HPV anogenital cancer
4 A Generalized Scheme of Chronic Inflammation Pathogens Physical injury Normal microflora Epithelial layer Toxins PAMPs Host cell apoptosis Host cell necrosis PRRs + Endogenous ligands + Macrophage Genetic factors Chemokines Cytokines Lymphocytes Anti-inflammatory controls Karin, M Cell, 2006 Persistent inflammation CP
5 Angiogenesis (VEGF) Hallmarks of Cancer (Intrinsic Genetic Process) Uncontrolled selfsufficiency in growth (oncogenes) Death signals (tumor suppressor genes p53) Limitless replication (? stem cell) Tissue invasion Hanoham D: Cell 100:57, 2000 CP
6 Survival factors Growth factors Genetic mutations Oxidative stress Cytokines Inflammatory Cells Tissue remodeling Migration, invasion Angiogenic factors CP
7
8 Incidence of Cholangiocarcinoma Incidence of Cholangiocarcinoma Years since PSC diagnosis CP Cumulative incidence of cholangiocarcinoma (%)
9 Survival factors Growth factors Oxidative, nitrosative stress Genetic mutations Cytokines Inflammatory Cells Tissue remodeling Migration, invasion Angiogenic factors CP
10 inos Expression is Upregulated in PSC and CCA Normal PSC Cholangiocarcinoma inos positive 0/30 inos positive 30/30 inos positive 20/20 Jaiswal et al. Cancer Res, 2000
11 Oxidative DNA Lesion H H 2 N O N 6 N H N N deoxyribose Oxidative Stress ROS H 2 N OH H N 6 N o N N deoxyribose Deoxyguanosine dg 8-oxo-deoxyguanosine 8-oxo-dG
12 inos Expression in PSC and Cholangiocarcinoma is Associated with Oxidatively Damaged DNA Normal PSC Cholangiocarcinoma 8-oxodG Positive: 0/10 8-oxodG Positive: 10/10 8-oxodG Positive: 10/10 Jaiswal et al, Gastroenterology,120, , 2001
13 p16 Point Mutations in PSC-associated Cholangiocarcinoma Promoter/ Enhancer 5 Exon 1 Exon 2 Exon 3 3 8/10 3/10 None None A A G A G G T C Patients T C A G A G A G A G A G A G T C T C T C A G A G A G A G
14 Survival factors Growth factors Genetic mutations Oxidative stress Cytokines Inflammatory Cells Tissue remodeling Migration, invasion Angiogenic factors CP
15 IL-6 Increases Expression of the Anti-Apoptotic Protein Mcl-1 Autocrine/paracrine pathway IL-6 Nucleus Cholangiocarcinoma cell Mcl-1 Kobayashi S et al, Gastroenterology 2005;128:
16 Normal Mcl-1 is Overexpressed in PSC and Cholangiocarcinoma ALC 8%(2/25) 20%(3/15) PSC CCA 48%(14/29) 70%(23/33)
17 anti-il (Hours) Mcl-1 actin
18 Survival factors Growth factors Genetic mutations Oxidative stress Cytokines Inflammatory Cells Tissue remodeling Migration, invasion Angiogenic factors CP
19 Developmental Signaling Pathways and Cancer Notch Wnt Hedgehog
20 Notch Signaling Pathway Sending cell Jagged Notch Receiving cell γ-secretase NICD (Intracellular domain) Cytoplasm Notch precursor Golgi CSL Nucleus Target Genes
21 Cholangiocyte Inflammation inos NO Notch Cancer phenotype Cell proliferation Anti-apoptosis Angiogenesis
22 Notch-1 Protein is Enhanced in PSC and CCA Normal Liver PSC CCA Staining Intensity (% of 2) Normal PSC CCA (n=15) (n=16) (n=12)
23 Notch-1 Expression in Cholangiocyte is inos dependent Immunoblot analysis 250K 150K 100K 603B 603B-iNOS AS Notch-1 (FL) NICD * Actin Notch-1 / 18S ratio Real-time PCR ** 603B ** p< B-iNOS AS Non-specific band
24 Cellular Mechanisms Linking Inflammation to Cholangiocarcinoma Inflammation COX-2 Bile duct inos Cholangiocarcinoma COX-2; Sirica AE, et al. Semin Liver Dis, 2002 inos; Jaiswal M, et al. Gastroenterology, 2001
25 β-catenin Pathway Activation in Response to PGE2 COX-2 EP2 PGE2 Axin α s GTP γ β P13K PIP 3 AKT PDK1 -P β- catenin β- catenin GSK-3β -P Science, 2005 Tcf Lef β- catenin Gene expression cell growth CP
26 Survival factors Growth factors Genetic mutations Oxidative stress Cytokines Inflammatory Cells Tissue remodeling and Oncogenesis Angiogenic factors CP
27 Cytokines Bacterial/viral infection Stress Cytoplasm IKK complex IKK1 IKK2 NEMO NEMO P P IKK1 IKK2 P P NF-κB:IκB P65 P50 IκB P65 P50 IκB P P Ub-Ub-Ub-Ub-Ub-Ub NF-κB P65 P proteasome IκB P P Ub-Ub-Ub-Ub-Ub-Ub P65 NF-κB responsive gene Nucleus P50 J Clin Inves 107(2):140, 2001 Cytokines Chemokines Adhesion molecules Receptors Cell hb proteins, etc Cell proliferation Cell growth Cell ditherentiation CP
28 Nuclear Factor-κB B has Various Tumour-Promoting Functions Depending on Cell Type in Which it is Activated Growth factors (such as TNF and IL-1) Inflammatory cell TNF TNFR IL-1 IL-1R IκB p50 p65 NF-κB- binding site TNF IL-1 IL-6 CXCL8 VEGF CSF1 Tumour cell Classical pathway NF-κB activation p50 p65 NF-κB- binding site Survival BCL-X L GADD45β BFL1 SOD2 Survival factors Karin M et al Nature Reviews in Immunology, 2005 CP
29 Cytokines Bacterial/viral infection Stress Cytoplasm IKK complex IKK1 IKK2 NEMO NEMO P P IKK1 IKK2 P P NF-κB:IκB P65 P50 κb P65 P50 IκB P P Ub-Ub-Ub-Ub-Ub-Ub NF-κB P65 P proteasome IκB P P Ub-Ub-Ub-Ub-Ub-Ub P65 NF-κB responsive gene Nucleus P50 J Clin Inves 107(2):140, 2001 Cytokines Chemokines Adhesion molecules Receptors Cell hb proteins, etc Cell proliferation Cell growth Cell ditherentiation CP
30 Colitis-Associated Cancer Is Reduced By Deleting IKKß From Intestinal Epithelial Cells Greten et al Cell, 2004 Model of AOM plus DSS tumorigenesis
31 NF-κB B and Tumorigenesis in Colitis Enterocyte NF-κB intact Cancer Genetic mutations IKKβ deficient Greten FR et al: Cell, 2004 Apoptosis CP
32 AN Mitosis AB Inflammatory cells
33 HCC is increased in DEN Treated Mice Deficient in Hepatocyte IKKß DEN and WT Mice DEN and Hepatocyte IKKß Δ Mice Maeda et al. Cell, 2005
34 DEN Hepatocarcinogenesis and Hepatocye NF-κB Hepatocyte Cancer IKK-β deficiency Genetic mutations Growth/survival factors Kupffer cell cell death NF-κB activation CP
35 DEN Hepatocarcinogenesis and Kupffer Cell NF-κB Hepatocyte cancer Genetic mutations NF-κB IKK-β deficient cell death Kupffer cell activation CP
36 Cytokines Bacterial/viral infection Stress Cytoplasm IKK complex IKK1 IKK2 NEMO NEMO P P IKK1 IKK2 P P NF-κB:IκB P65 P50 IκB P65 P50 IκB P P Ub-Ub-Ub-Ub-Ub-Ub NF-κB P65 P proteasome IκB P P Ub-Ub-Ub-Ub-Ub-Ub P65 NF-κB responsive gene Nucleus P50 J Clin Inves 107(2):140, 2001 Cytokines Chemokines Adhesion molecules Receptors Cell hb proteins, etc Cell proliferation Cell growth Cell ditherentiation CP
37 Arrows indicate large tumors Cancer Cell 11:119, 2007 CP
38 AN Mitosis AB Inflammatory cells
39 Fas N TNF-R1 N TRAIL-R1/2 N C C C Extracellular Cysteine-rich Domain Transmembrane Domain Cytoplasmic Death Domain
40 FasL/CD95L Fas/CD95 The Fas DISC Pro-Caspase 8 DED DED DED DD FADD DD DD DD DED DD DED FADD DED Pro-Caspase 10 DD DED Death Domain Death Effector Domain Active Caspase 8 Active Caspase 10
41 NEMO LPC-KO NEMO/FADD LPC-KO Tunel (LPS 10 hr) Cancer Cell 11:119, 2007 CP
42 Serum ALT 1, P< Cancer Cell 11:119, 2007 NEMO LPC-KO NEMO/ FADD LPC-KO CP
43 NF-κB B in Different Cancer Models NFκB hi M S CP
44 NF-κB B in Different Cancer Models Tonic signals Inflammatory signals NFκB hi IKK NFκB Kupffer cells M S CP
45 NF-κB B in Different Cancer Models JNK hi IKK NFκB Kupffer cells IKK NFκB TNF IL-6 JNK hi ROS hi M S Cancer CP
46 A Generalized Scheme of Chronic Inflammation Pathogens Physical injury Normal microflora Epithelial layer Toxins PAMPs Host cell apoptosis Host cell necrosis PRRs + Endogenous ligands + Macrophage Genetic factors Chemokines Cytokines Lymphocytes Anti-inflammatory controls Karin, M Cell, 2006 Persistent inflammation CP
47 Survival factors Growth factors Genetic mutations Oxidative stress Cytokines Inflammatory Cells Tissue remodeling Migration, invasion Angiogenic factors CP
48 Tumor Associated Macrophages (TAM)
49 Macrophage Condeelis, J et al Cell, 2006 Common functions Angiogenic factors Tissue remodeling and repair Growth and migration factors Macrophogenesis Ductal invasion Normal epithelial cells Tumor cells Metastasis Tumor invasion Blood vessel CP
50 Contribution of Macrophages to Metastasis Blood vessel EGF EGF CSF-1 CSF-1 CSF-1 CSF-1 EGF EGF CC Wang Wang et et al: al: Trends Trends in in cell cell biology biology 15:141, 15:141, Paracrine chemotaxis CP CP
51 The Cancer Ecosystem Neoangiogenesis TAM TIL APC Connective tissue Fibroblasts CP
52 CP
53 Dead snake CP
T cell maturation. T-cell Maturation. What allows T cell maturation?
T-cell Maturation What allows T cell maturation? Direct contact with thymic epithelial cells Influence of thymic hormones Growth factors (cytokines, CSF) T cell maturation T cell progenitor DN DP SP 2ry
More informationInnate Immunity. Chapter 3. Connection Between Innate and Adaptive Immunity. Know Differences and Provide Examples. Antimicrobial peptide psoriasin
Chapter Know Differences and Provide Examples Innate Immunity kin and Epithelial Barriers Antimicrobial peptide psoriasin -Activity against Gram (-) E. coli Connection Between Innate and Adaptive Immunity
More informationVIII Curso Internacional del PIRRECV. Some molecular mechanisms of cancer
VIII Curso Internacional del PIRRECV Some molecular mechanisms of cancer Laboratorio de Comunicaciones Celulares, Centro FONDAP Estudios Moleculares de la Celula (CEMC), ICBM, Facultad de Medicina, Universidad
More informationCANCER IMMUNOPATHOLOGY. Eryati Darwin Faculty of Medicine Andalas University
CANCER IMMUNOPATHOLOGY Eryati Darwin Faculty of Medicine Andalas University Padang 18 Mei 2013 INTRODUCTION Tumor: cells that continue to replicate, fail to differentiate into specialized cells, and become
More informationMolecular biology :- Cancer genetics lecture 11
Molecular biology :- Cancer genetics lecture 11 -We have talked about 2 group of genes that is involved in cellular transformation : proto-oncogenes and tumour suppressor genes, and it isn t enough to
More informationAlcoholic hepatitis is a drug-induced disorder
Alcoholic hepatitis is a drug-induced disorder Gyongyi Szabo, MD, PhD Professor of Medicine University of Massachusetts Medical School Source: 2 Sobernation.com Clinical Progression of ALD Mortality Acute
More informationSupplemental Table 1. Primers used for RT-PCR analysis of inflammatory cytokines Gene Primer Sequence
Supplemental Table 1. Primers used for RT-PCR analysis of inflammatory cytokines Gene Primer Sequence IL-1α Forward primer 5 -CAAGATGGCCAAAGTTCGTGAC-3' Reverse primer 5 -GTCTCATGAAGTGAGCCATAGC-3 IL-1β
More informationIL-24 AND ITS ROLE IN WOUND HEALING
IL-24 AND ITS ROLE IN WOUND HEALING Nancy J. Poindexter, Ryan Williams, Garth Powis, Sunil Chada, and Elizabeth A. Grimm & Introgen Therapeutics, Inc., Houston, TX IL-24/MDA 24/MDA-77 is a Tumor Suppressor
More informationThe Hallmarks of Cancer
The Hallmarks of Cancer This illustration encompasses the six hallmark capabilities originally proposed in our 2000 perspective. The past decade has witnessed remarkable progress toward understanding the
More informationPancreatic intraepithelial
Pancreatic intraepithelial neoplasia (PanIN) Markéta Hermanová St. Anne s University Hospital Brno Faculty of Medicine, Masaryk University Precursor lesions of invasive pancreatic cancer Pancreatic intraepithelial
More informationulcer healing role 118 Bicarbonate, prostaglandins in duodenal cytoprotection 235, 236
Subject Index Actin cellular forms 48, 49 epidermal growth factor, cytoskeletal change induction in mucosal repair 22, 23 wound repair 64, 65 polyamine effects on cytoskeleton 49 51 S-Adenosylmethionine
More informationImmune surveillance hypothesis (Macfarlane Burnet, 1950s)
TUMOR-IMMUNITÄT A.K. Abbas, A.H. Lichtman, S. Pillai (6th edition, 2007) Cellular and Molecular Immunology Saunders Elsevier Chapter 17, immunity to tumors Immune surveillance hypothesis (Macfarlane Burnet,
More informationNeoplasia 18 lecture 6. Dr Heyam Awad MD, FRCPath
Neoplasia 18 lecture 6 Dr Heyam Awad MD, FRCPath ILOS 1. understand the role of TGF beta, contact inhibition and APC in tumorigenesis. 2. implement the above knowledge in understanding histopathology reports.
More informationThe Hallmarks of Cancer
The Hallmarks of Cancer Theresa L. Hodin, Ph.D. Clinical Research Services Theresa.Hodin@RoswellPark.org Hippocrates Cancer surgery, circa 1689 Cancer Surgery Today 1971: Nixon declares War on Cancer
More informationInflammatory Cells and Metastasis
Inflammatory Cells and Metastasis Experimentelle Krebsforschung SS 07 Gerhard Christofori Institute of Biochemistry and Genetics Department of Clinical-Biological Sciences Center of Biomedicine University
More information1. The metastatic cascade. 3. Pathologic features of metastasis. 4. Therapeutic ramifications. Which malignant cells will metastasize?
1. The metastatic cascade 3. Pathologic features of metastasis 4. Therapeutic ramifications Sir James Paget (1814-1899) British Surgeon/ Pathologist Paget s disease of Paget s disease of the nipple (intraductal
More informationThe death receptors: signaling and modulation
The death receptors: signaling and modulation 1 1 The extrinsic cell death pathway 2 Nat Rev Drug Discov. 2008 Dec;7(12):1001-12. 2 Death receptors Belong to the tumor necrosis factor (TNF) receptor gene
More informationCYTOKINE RECEPTORS AND SIGNAL TRANSDUCTION
CYTOKINE RECEPTORS AND SIGNAL TRANSDUCTION What is Cytokine? Secreted popypeptide (protein) involved in cell-to-cell signaling. Acts in paracrine or autocrine fashion through specific cellular receptors.
More informationT-cell activation T cells migrate to secondary lymphoid tissues where they interact with antigen, antigen-presenting cells, and other lymphocytes:
Interactions between innate immunity & adaptive immunity What happens to T cells after they leave the thymus? Naïve T cells exit the thymus and enter the bloodstream. If they remain in the bloodstream,
More informationT-cell activation T cells migrate to secondary lymphoid tissues where they interact with antigen, antigen-presenting cells, and other lymphocytes:
Interactions between innate immunity & adaptive immunity What happens to T cells after they leave the thymus? Naïve T cells exit the thymus and enter the bloodstream. If they remain in the bloodstream,
More informationNewly Recognized Components of the Innate Immune System
Newly Recognized Components of the Innate Immune System NOD Proteins: Intracellular Peptidoglycan Sensors NOD-1 NOD-2 Nod Protein LRR; Ligand Recognition CARD RICK I-κB p50 p65 NF-κB Polymorphisms in Nod-2
More informationCell Cell Communication
IBS 8102 Cell, Molecular, and Developmental Biology Cell Cell Communication January 29, 2008 Communicate What? Why do cells communicate? To govern or modify each other for the benefit of the organism differentiate
More informationINFLAMMATION & REPAIR
INFLAMMATION & REPAIR Lecture 7 Chemical Mediators of Inflammation Winter 2013 Chelsea Martin Special thanks to Drs. Hanna and Forzan Course Outline i. Inflammation: Introduction and generalities (lecture
More informationApoptotic Pathways in Mammals Dr. Douglas R. Green
Apoptotic Pathways in Mammals Douglas R. Green 1 Apoptosis A form of cell death that is defined morphologically, and features a number of biochemical events Programmed cell death Cell death that occurs
More informationCancer and Oncogenes Bioscience in the 21 st Century. Linda Lowe-Krentz
Cancer and Oncogenes Bioscience in the 21 st Century Linda Lowe-Krentz December 1, 2010 Just a Few Numbers Becoming Cancer Genetic Defects Drugs Our friends and family 25 More mutations as 20 you get older
More informationPATHOBIOLOGY OF NEOPLASIA
PATHOBIOLOGY OF NEOPLASIA Department of Pathology Gadjah Mada University School of Medicine dr. Harijadi Blok Biomedis, 6 Maret 2009 [12] 3/17/2009 1 The pathobiology of neoplasia Normal cells Malignant
More informationBihong Zhao, M.D, Ph.D Department of Pathology
Bihong Zhao, M.D, Ph.D Department of Pathology 04-28-2009 Is tumor self or non-self? How are tumor antigens generated? What are they? How does immune system respond? Introduction Tumor Antigens/Categories
More informationGenome of Hepatitis B Virus. VIRAL ONCOGENE Dr. Yahwardiah Siregar, PhD Dr. Sry Suryani Widjaja, Mkes Biochemistry Department
Genome of Hepatitis B Virus VIRAL ONCOGENE Dr. Yahwardiah Siregar, PhD Dr. Sry Suryani Widjaja, Mkes Biochemistry Department Proto Oncogen and Oncogen Oncogen Proteins that possess the ability to cause
More information1.The metastatic cascade. 2.Pathologic features of metastasis. 3.Therapeutic ramifications
Metastasis 1.The metastatic cascade 2.Pathologic features of metastasis 3.Therapeutic ramifications Sir James Paget (1814-1899) British Surgeon/ Pathologist Paget s disease of bone Paget s disease of the
More informationTargeting Inflammation in Breast Cancer Pathogenesis
Targeting Inflammation in Breast Cancer Pathogenesis Clifford Hudis, M.D. Chief, Breast Cancer Medicine Service Attending Physician, MSKCC Professor of Medicine, Weill Cornell Medical College August 7,
More informationTCR, MHC and coreceptors
Cooperation In Immune Responses Antigen processing how peptides get into MHC Antigen processing involves the intracellular proteolytic generation of MHC binding proteins Protein antigens may be processed
More informationInnate immunity. Abul K. Abbas University of California San Francisco. FOCiS
1 Innate immunity Abul K. Abbas University of California San Francisco FOCiS 2 Lecture outline Components of innate immunity Recognition of microbes and dead cells Toll Like Receptors NOD Like Receptors/Inflammasome
More informationIntroduction to pathology lecture 5/ Cell injury apoptosis. Dr H Awad 2017/18
Introduction to pathology lecture 5/ Cell injury apoptosis Dr H Awad 2017/18 Apoptosis = programmed cell death = cell suicide= individual cell death Apoptosis cell death induced by a tightly regulated
More informationCytokines modulate the functional activities of individual cells and tissues both under normal and pathologic conditions Interleukins,
Cytokines http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter22/animation the_immune_response.html Cytokines modulate the functional activities of individual cells and tissues both under
More informationPBS Class #2 Introduction to the Immune System part II Suggested reading: Abbas, pgs , 27-30
PBS 803 - Class #2 Introduction to the Immune System part II Suggested reading: Abbas, pgs. 15-25, 27-30 Learning Objectives Compare and contrast the maturation of B and T lymphocytes Compare and contrast
More informationTargeting tumour associated macrophages in anti-cancer therapies. Annamaria Gal Seminar Series on Drug Discovery Budapest 5 January 2018
Targeting tumour associated macrophages in anti-cancer therapies Annamaria Gal Seminar Series on Drug Discovery Budapest 5 January 2018 Macrophages: Professional phagocytes of the myeloid lineage APC,
More informationSUPPLEMENTARY INFORMATION
b 350 300 250 200 150 100 50 0 E0 E10 E50 E0 E10 E50 E0 E10 E50 E0 E10 E50 Number of organoids per well 350 300 250 200 150 100 50 0 R0 R50 R100 R500 1st 2nd 3rd Noggin 100 ng/ml Noggin 10 ng/ml Noggin
More informationPrediction of invasiveness of hepatic tumor cells
Prediction of invasiveness of hepatic tumor cells (Overexpression of Romo1 Promotes Production of Reactive Oxygen Species and Invasiveness of Hepatic Tumor Cells) (Romo1 : Reactive Oxygen Species Modulator
More information2. Innate immunity 2013
1 Innate Immune Responses 3 Innate immunity Abul K. Abbas University of California San Francisco The initial responses to: 1. Microbes: essential early mechanisms to prevent, control, or eliminate infection;
More informationPrinciples of Genetics and Molecular Biology
Cell signaling Dr. Diala Abu-Hassan, DDS, PhD School of Medicine Dr.abuhassand@gmail.com Principles of Genetics and Molecular Biology www.cs.montana.edu Modes of cell signaling Direct interaction of a
More informationSignaling Through Immune System Receptors (Ch. 7)
Signaling Through Immune System Receptors (Ch. 7) 1. General principles of signal transduction and propagation. 2. Antigen receptor signaling and lymphocyte activation. 3. Other receptors and signaling
More informationCytokines, adhesion molecules and apoptosis markers. A comprehensive product line for human and veterinary ELISAs
Cytokines, adhesion molecules and apoptosis markers A comprehensive product line for human and veterinary ELISAs IBL International s cytokine product line... is extremely comprehensive. The assays are
More informationContents. Preface XV Acknowledgments XXI List of Abbreviations XXIII About the Companion Website XXIX
Contents Preface XV Acknowledgments XXI List of Abbreviations XXIII About the Companion Website XXIX 1 General Aspects of Signal Transduction and Cancer Therapy 1 1.1 General Principles of Signal Transduction
More informationKinase-independent functions of RIPK1 regulate hepatocyte survival and liver carcinogenesis
The Journal of Clinical Investigation Kinase-independent functions of RIPK1 regulate hepatocyte survival and liver carcinogenesis Trieu-My Van, 1,2,3 Apostolos Polykratis, 1,2,3 Beate Katharina Straub,
More informationEarly cell death (FGF) B No RunX transcription factor produced Yes No differentiation
Solution Key - Practice Questions Question 1 a) A recent publication has shown that the fat stem cells (FSC) can act as bone stem cells to repair cavities in the skull, when transplanted into immuno-compromised
More informationNFκB What is it and What s the deal with radicals?
The Virtual Free Radical School NFκB What is it and What s the deal with radicals? Emily Ho, Ph.D Linus Pauling Institute Scientist Department of Nutrition and Food Management Oregon State University 117
More informationT Cell Effector Mechanisms I: B cell Help & DTH
T Cell Effector Mechanisms I: B cell Help & DTH Ned Braunstein, MD The Major T Cell Subsets p56 lck + T cells γ δ ε ζ ζ p56 lck CD8+ T cells γ δ ε ζ ζ Cα Cβ Vα Vβ CD3 CD8 Cα Cβ Vα Vβ CD3 MHC II peptide
More informationInnate Immunity II. Integration. Lindsay Nicholson Advanced Immunology L2
Innate Immunity II Integration Lindsay Nicholson Advanced Immunology L2 l.nicholson@bristol.ac.uk Lecture 1 Defining Innate Immunity Recognition and effector mechanisms (I) Lecture 2 Recognition and effector
More informationACTIVATION OF T LYMPHOCYTES AND CELL MEDIATED IMMUNITY
ACTIVATION OF T LYMPHOCYTES AND CELL MEDIATED IMMUNITY The recognition of specific antigen by naïve T cell induces its own activation and effector phases. T helper cells recognize peptide antigens through
More informationShould the tumor necrosis factor (TNF) pathway be activated or silenced in the treatment of triple-negative breast cancer?
Should the tumor necrosis factor (TNF) pathway be activated or silenced in the treatment of triple-negative breast cancer? Sonja Kesselmans. S2242362. Bachelorscriptie. 20-06-2014 Supervisor: Marcel van
More informationDetermination Differentiation. determinated precursor specialized cell
Biology of Cancer -Developmental Biology: Determination and Differentiation -Cell Cycle Regulation -Tumor genes: Proto-Oncogenes, Tumor supressor genes -Tumor-Progression -Example for Tumor-Progression:
More informationThe Enhancement of Toxin-Induced Liver Fibrosis in Fatty Liver Disease. Ekihiro Seki, M.D.,Ph.D. University of California San Diego
The Enhancement of Toxin-Induced Liver Fibrosis in Fatty Liver Disease Ekihiro Seki, M.D.,Ph.D. University of California San Diego - A manufactured chemical. - Does not exist naturally. Carbon tetrachloride
More informationMechanisms of Tumor Suppressor Gene Demethylation in Colon Cancer by Berries
Mechanisms of Tumor Suppressor Gene Demethylation in Colon Cancer by Berries Li-Shu Wang, PhD Assistant Professor Department of Medicine Medical College of Wisconsin Cancer Center Ten Leading Cancer Types
More informationInnate Immunity. Connection Between Innate and Adaptive Immunity. Know Differences and Provide Examples Chapter 3. Antimicrobial peptide psoriasin
Know Differences and Provide Examples Chapter * Innate Immunity * kin and Epithelial Barriers * Antimicrobial peptide psoriasin -Activity against Gram (-) E. coli Connection Between Innate and Adaptive
More informationEffector Mechanisms of Cell-Mediated Immunity
Effector Mechanisms of Cell-Mediated Immunity Dr. Julia Rempel Section of Hepatology 789-3825 jdrempel@cc.umanitoba.ca 804D JBRC Topics: I. Types of Cell-Mediated Immunity II. Migration of Effector T Lymphocytes
More informationDeregulation of signal transduction and cell cycle in Cancer
Deregulation of signal transduction and cell cycle in Cancer Tuangporn Suthiphongchai, Ph.D. Department of Biochemistry Faculty of Science, Mahidol University Email: tuangporn.sut@mahidol.ac.th Room Pr324
More informationBasic tumor nomenclature
Jonas Nilsson jonas.a.nilsson@surgery.gu.se Sahlgrenska Cancer Center Bilder gjorda av Per Holmfeldt och Jonas Nilsson Benign tumor Basic tumor nomenclature Malignant tumor = cancer Metastasis Carcinoma:
More informationC H A R A C T E R I Z A T I O N O F T H E N O V E L D O M A I N W I T H N O N A M E G E N E I N C O L O N C A N C E R
C H A R A C T E R I Z A T I O N O F T H E N O V E L D O M A I N W I T H N O N A M E G E N E I N C O L O N C A N C E R Charleen Rupnarain A dissertation submitted to the Faculty of Science, University of
More informationCell Cell Communication
IBS 8102 Cell, Molecular, and Developmental Biology Cell Cell Communication January 29, 2008 Communicate What? Why do cells communicate? To govern or modify each other for the benefit of the organism differentiate
More informationRIPK1-TRAF2 interplay on the TNF/NF-κB signaling, cell death, and cancer development in the liver
Editorial RIPK1-TRAF2 interplay on the TNF/NF-κB signaling, cell death, and cancer development in the liver Satomi Yamamoto, Tomoo Iwakuma Department of Cancer Biology, University of Kansas Medical Center,
More informationTransformation of Normal HMECs (Human Mammary Epithelial Cells) into Metastatic Breast Cancer Cells: Introduction - The Broad Picture:
Transformation of Normal HMECs (Human Mammary Epithelial Cells) into Metastatic Breast Cancer Cells: Introduction - The Broad Picture: Spandana Baruah December, 2016 Cancer is defined as: «A disease caused
More informationThink Tank on Molecular Targets: Survival and Death Pathways in Cancer
Think Tank on Molecular Targets: Survival and Death Pathways in Cancer Oncogenes Induce Cell Proliferation & Cell Death Proliferation Mitogens ONCOGENES Apoptosis Adapted from G Evan Survival Signals Block
More informationCELL BIOLOGY - CLUTCH CH CANCER.
!! www.clutchprep.com CONCEPT: OVERVIEW OF CANCER Cancer is a disease which is primarily caused from misregulated cell division, which form There are two types of tumors - Benign tumors remain confined
More informationApoptosis in chronic hepatitis C
Apoptosis in chronic hepatitis C Dr med. Anna Parfieniuk-Kowerda Department of Infectious Diseases and Hepatology Medical University of Bialystok Poland APOPTOSIS Apoptosis - type I programmed cell death
More informationCancer. The fundamental defect is. unregulated cell division. Properties of Cancerous Cells. Causes of Cancer. Altered growth and proliferation
Cancer The fundamental defect is unregulated cell division. Properties of Cancerous Cells Altered growth and proliferation Loss of growth factor dependence Loss of contact inhibition Immortalization Alterated
More informationACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS. Choompone Sakonwasun, MD (Hons), FRCPT
ACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS Choompone Sakonwasun, MD (Hons), FRCPT Types of Adaptive Immunity Types of T Cell-mediated Immune Reactions CTLs = cytotoxic T lymphocytes
More informationIntroduction. Cancer Biology. Tumor-suppressor genes. Proto-oncogenes. DNA stability genes. Mechanisms of carcinogenesis.
Cancer Biology Chapter 18 Eric J. Hall., Amato Giaccia, Radiobiology for the Radiologist Introduction Tissue homeostasis depends on the regulated cell division and self-elimination (programmed cell death)
More informationGeneration of post-germinal centre myeloma plasma B cell.
Generation of post-germinal centre myeloma. DNA DAMAGE CXCR4 Homing to Lytic lesion activation CD38 CD138 CD56 Phenotypic markers Naive Secondary lymphoid organ Multiple myeloma is a malignancy of s caused
More informationBL-8040: BEST-IN-CLASS CXCR4 ANTAGONIST FOR TREATMENT OF ONCOLOGICAL MALIGNANCIES. Overview and Mechanism of Action Dr.
BL-8040: BEST-IN-CLASS CXCR4 ANTAGONIST FOR TREATMENT OF ONCOLOGICAL MALIGNANCIES Overview and Mechanism of Action Dr. Leah Klapper, CSO 88 BL-8040: Novel CXCR4 Antagonist For Hematological Cancers Indications:
More informationCancer. The fundamental defect is. unregulated cell division. Properties of Cancerous Cells. Causes of Cancer. Altered growth and proliferation
Cancer The fundamental defect is unregulated cell division. Properties of Cancerous Cells Altered growth and proliferation Loss of growth factor dependence Loss of contact inhibition Immortalization Alterated
More informationIntracellular MHC class II molecules promote TLR-triggered innate. immune responses by maintaining Btk activation
Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining Btk activation Xingguang Liu, Zhenzhen Zhan, Dong Li, Li Xu, Feng Ma, Peng Zhang, Hangping Yao and Xuetao
More informationThe Adaptive Immune Response: T lymphocytes and Their Functional Types *
OpenStax-CNX module: m46560 1 The Adaptive Immune Response: T lymphocytes and Their Functional Types * OpenStax This work is produced by OpenStax-CNX and licensed under the Creative Commons Attribution
More informationUNIVERSITY OF MEDICINE AND PHARMACY CRAIOVA PhD SCHOOL. PhD THESIS
UNIVERSITY OF MEDICINE AND PHARMACY CRAIOVA PhD SCHOOL PhD THESIS THE IMPORTANCE OF TUMOR ANGIOGENESIS IN CEREBRAL TUMOR DIAGNOSIS AND THERAPY ABSTRACT PhD COORDINATOR: Prof. univ. dr. DRICU Anica PhD
More informationCancer and Oncogenes Bioscience in the 21 st Century. Linda Lowe-Krentz October 11, 2013
Cancer and Oncogenes Bioscience in the 21 st Century Linda Lowe-Krentz October 11, 2013 Just a Few Numbers Becoming Cancer Genetic Defects Drugs Our friends and family 200 180 160 140 120 100 80 60 40
More informationOncolytic Virotherapy: Targeting Cancer Stem Cells
Oncolytic Virotherapy: Targeting Cancer Stem Cells Cancer Stem Cells (CSCs) or Cancer Initiating Cells (CICs) A consensus of five defining criteria has been established to affirm the existence of CICs:
More informationCell Polarity and Cancer
Cell Polarity and Cancer Pr Jean-Paul Borg Email: jean-paul.borg@inserm.fr Features of malignant cells Steps in Malignant Progression Cell polarity, cell adhesion, morphogenesis and tumorigenesis pathways
More informationInnate Immunity, Inflammation and Cancer
Innate Immunity, Inflammation and Cancer Willem Overwijk, Ph.D. Melanoma Medical Oncology Center for Cancer Immunology Research MD Anderson Cancer Center, Houston, TX SITC/MDACC -6/14/2013 www.allthingsbeautiful.com
More informationCOURSE: Medical Microbiology, PAMB 650/720 - Fall 2008 Lecture 16
COURSE: Medical Microbiology, PAMB 650/720 - Fall 2008 Lecture 16 Tumor Immunology M. Nagarkatti Teaching Objectives: Introduction to Cancer Immunology Know the antigens expressed by cancer cells Understand
More informationD2 inhibits TLR2- initiated 12p40 transcription (-) TLR2 PGN MDP. MyD88 IRAK ECSIT TRAF6 NIK. Smallest unit of PGN muramyl dipeptide IKK.
D2 inhibits TLR2- initiated 12p40 transcription CARD CARD NOD2 LRR RICK/Rip2 NIK MDP TRAF6 PGN TLR2 MyD88 IRAK ECSIT (-) IKK Smallest unit of PGN muramyl dipeptide IκB NF-κB atanabe et al, 2004 NF-κB IL-12p40
More informationChapter 10 (pages ): Differentiation and Functions of CD4+ Effector T Cells Prepared by Kristen Dazy, MD, Scripps Clinic Medical Group
FIT Board Review Corner September 2015 Welcome to the FIT Board Review Corner, prepared by Andrew Nickels, MD, and Sarah Spriet, DO, senior and junior representatives of ACAAI's Fellows-In-Training (FITs)
More informationImmunology. T-Lymphocytes. 16. Oktober 2014, Ruhr-Universität Bochum Karin Peters,
Immunology T-Lymphocytes 16. Oktober 2014, Ruhr-Universität Bochum Karin Peters, karin.peters@rub.de The role of T-effector cells in the immune response against microbes cellular immunity humoral immunity
More informationG-Protein-Coupled Receptors
Cellular Signalling Cells must be ready to respond to essential signals in their environment. These are often chemicals in the extracellular fluid (ECF) from distant locations in a multicellular organism
More informationTHE HALLMARKS OF CANCER
THE HALLMARKS OF CANCER ONCOGENES - Most of the oncogenes were first identified in retroviruses: EGFR (ErbB), Src, Ras, Myc, PI3K and others (slightly more than 30) - Mutated cellular genes incorporated
More informationMCB 4211 Basic Immunology 2nd Exam; 10/26/17 Peoplesoft #:
For this first section, circle the letter that precedes the best answer for each of the following multiple-choice questions. LOOK AT ALL ALTERNATIVES BEFORE CHOOSING YOUR ANSWER. 1. The TcR (T cell receptor)
More informationnumber Done by Corrected by Doctor Maha Shomaf
number 19 Done by Waseem Abo-Obeida Corrected by Abdullah Zreiqat Doctor Maha Shomaf Carcinogenesis: the molecular basis of cancer. Non-lethal genetic damage lies at the heart of carcinogenesis and leads
More informationInnate Immunity. Hathairat Thananchai, DPhil Department of Microbiology Faculty of Medicine Chiang Mai University 2 August 2016
Innate Immunity Hathairat Thananchai, DPhil Department of Microbiology Faculty of Medicine Chiang Mai University 2 August 2016 Objectives: Explain how innate immune system recognizes foreign substances
More informationFollicular Lymphoma. ced3 APOPTOSIS. *In the nematode Caenorhabditis elegans 131 of the organism's 1031 cells die during development.
Harvard-MIT Division of Health Sciences and Technology HST.176: Cellular and Molecular Immunology Course Director: Dr. Shiv Pillai Follicular Lymphoma 1. Characterized by t(14:18) translocation 2. Ig heavy
More informationContribution of microglia to tissue injury and repair in MS
Contribution of microglia to tissue injury and repair in MS MS disease course histologic features Courtesy of Samuel Ludwin I ACUTE CHRONIC s ACTIVE CHRONIC Clinical Course Intra CNS Extra CNS Imaging
More informationDr Rodney Itaki Lecturer Anatomical Pathology Discipline. University of Papua New Guinea School of Medicine & Health Sciences Division of Pathology
Neoplasia Dr Rodney Itaki Lecturer Anatomical Pathology Discipline University of Papua New Guinea School of Medicine & Health Sciences Division of Pathology General Considerations Overview: Neoplasia uncontrolled,
More informationScott Abrams, Ph.D. Professor of Oncology, x4375 Kuby Immunology SEVENTH EDITION
Scott Abrams, Ph.D. Professor of Oncology, x4375 scott.abrams@roswellpark.org Kuby Immunology SEVENTH EDITION CHAPTER 11 T-Cell Activation, Differentiation, and Memory Copyright 2013 by W. H. Freeman and
More informationIntroduction: 年 Fas signal-mediated apoptosis. PI3K/Akt
Fas-ligand (CD95-L; Fas-L) Fas (CD95) Fas (apoptosis) 年 了 不 度 Fas Fas-L 力 不 Fas/Fas-L T IL-10Fas/Fas-L 不 年 Fas signal-mediated apoptosis 度降 不 不 力 U-118, HeLa, A549, Huh-7 MCF-7, HepG2. PI3K/Akt FasPI3K/Akt
More informationReview (V1) - The Hallmarks of Cancer
Review (V1) - The Hallmarks of Cancer Robert A. Weinberg 1 Review (V1) - The Hallmarks of Cancer 2 Review (V1) - Number of somatic mutations in human cancers Top: children vs. adults Numbers in parentheses
More informationCigarette Smoke Exposure and HIV-Related Neurologic Disease Progression Basic Mechanisms and Clinical Consequences
Cigarette Smoke Exposure and HIV-Related Neurologic Disease Progression Basic Mechanisms and Clinical Consequences Walter Royal, III, MD Professor of Neurology University of Maryland School of Medicine
More information7/6/2009. The study of the immune system and of diseases that occur as a result of inappropriate or inadequate actions of the immune system.
Diseases of Immunity 2009 CL Davis General Pathology Paul W. Snyder, DVM, PhD Purdue University Acknowledgements Pathologic Basis of Veterinary Disease, 4 th Ed Veterinary Immunology, An Introduction 8
More informationSupplementary Figures
Supplementary Figures Figure S1. Validation of kinase regulators of ONC201 sensitivity. Validation and screen results for changes in cell viability associated with the combination of ONC201 treatment (1
More informationEBV infection B cells and lymphomagenesis. Sridhar Chaganti
EBV infection B cells and lymphomagenesis Sridhar Chaganti How EBV infects B-cells How viral genes influence the infected B cell Differences and similarities between in vitro and in vivo infection How
More information1. Activated receptor tyrosine kinases (RTKs) phosphorylates themselves
Enzyme-coupled receptors Transmembrane proteins Ligand-binding domain on the outer surface Cytoplasmic domain acts as an enzyme itself or forms a complex with enzyme 1. Activated receptor tyrosine kinases
More informationThe Role of Chemokines in Hepatitis C Virus-Mediated Liver Disease
Int. J. Mol. Sci. 2014, 15, 4747-4779; doi:10.3390/ijms15034747 Review OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms The Role of Chemokines in Hepatitis
More informationDevelopment of Carcinoma Pathways
The Construction of Genetic Pathway to Colorectal Cancer Moriah Wright, MD Clinical Fellow in Colorectal Surgery Creighton University School of Medicine Management of Colon and Diseases February 23, 2019
More informationFigure S1 Generation of γ-gt DTR transgenic mice. (A) Schematic construct of the transgene. (B)
Figure S1 Generation of γ-gt DTR transgenic mice. (A) Schematic construct of the transgene. (B) PCR identified expected hhb-egf band (left panel) and HA tag band (right) in kidneys of transgenic (TG) mice
More information