5 US Mortality, 2004 No. of deaths % of all deaths Rank Cause of Death 1. Heart Diseases 652,2. Cancer ,3. Cerebrovascular diseases 150,4. Chronic lower respiratory diseases 121,5. Accidents (Unintentional injuries) 112,6. Diabetes mellitus 73,7. Alzheimer disease ,Influenza & pneumonia 59,Nephritis ,10. Septicemia ,Source: US Mortality Public Use Data Tape 2004, National Center for Health Statistics, Centers for Disease Control and Prevention, 2006.
6 2007 Estimated US Cancer Deaths* Men 289,550Women 270,100Lung & bronchus 31%Prostate 9%Colon & rectum 9%Pancreas 6%Leukemia 4%Liver & intrahepatic 4% bile ductEsophagus 4%Urinary bladder 3%Non-Hodgkin % lymphomaKidney 3%All other sites %26% Lung & bronchus15% Breast10% Colon & rectum6% Pancreas6% Ovary4% Leukemia3% Non-Hodgkin lymphoma3% Uterine corpus2% Brain/ONS2% Liver & intrahepatic bile duct23% All other sitesLung cancer is, by far, the most common fatal cancer in men (31%), followed by prostate (9%), and colon & rectum (9%). In women, lung (26%), breast (15%), and colon & rectum (10%) are the leading sites of cancer death.The most abundant cancer in male is prostate, the most abundant cancer in women is breast (both= ~33%)ONS=Other nervous system.Source: American Cancer Society, 2007.
7 This Lecture properties of cancer cells tumor progression what causes cancer?accumulation of mutationsoncogenes and tumor-suppressor genes
8 Cancer: an Aberration of Normal Development Cancer cells exhibit behaviors found in normal cells during development & differentiation.However, these behaviors are separated from developmental controls.
9 Most normal cells have a limited potential to divide. Properties of Cancer CellsMost normal cells have a limited potential to divide.senescent cells
10 Normal Stem Cells can Divide Indefinitely, but Under Tight Control
11 Properties of Cancer Cells Cancer cells are "immortalized”,just like stem cells, but w/o control.tumor
19 Normal cells can be invasive at the right time and place. Dave McClaySeward Hung
20 Properties of Cancer Cells Cancer cells are "immortalized”.Cancer cells are not under contact inhibition.Cancer cells do not form differentiated tissues.Cancer cells avoid apoptosis.Cancer cells are invasive.
31 Molecular Changes Required for Metastasis Cells need to lose cell-cell adhesion contacts.Cells need to penetrate through the matrix.
32 Molecular Changes Required for Metastasis Loss of cadherins is detected in all tumors.Metastatic cells produce high concentrations of MMPs (matrix-metalloproteinases).
33 Cancer : Accumulation of Mutations What Causes Cancer?Cancer : Accumulation of Mutationsrandom mutations (mistakes at the assembly line)inherited mutations (pre-disposition)viral infectionsenvironmental factors (chemical;physical)
34 The first Association Between Occupation and Cancer Percivall Pott found that chimney sweeps show substantially higher rates of skin cancer.
35 British chimney sweeps didn’t do anything about it. Danish chimney sweeps : a daily bath after work.A sad British chimney sweepResult: significantly lower rates of skin cancer amongst Danish chimney sweeps, compared with British, even a century later.
36 A happy Danish Chimney Sweep at workwith the family
39 + = Carcinogens are not always mutagens. Specifically alarming: many of these carcinogens are found in cigarette smokeIn many cases Carcinogens are also mutagens, but there are also other cases. Carcinogens can “help” a cancerous cell without creating a mutation. For example, the risk of getting certain mouth and throat cancers is increase a 100 fold if a person is a serious smoker and consumes distilled alcohols. Ethanol is not a mutagen, but it has toxic effects on the epithelial cells lining the mouth and the throat. The reaction of the body: stimulating proliferation. The problem: if a cell is already mutant and over proliferative, it will be the first to react to this stimulus. As a result, there will be a clonal expansion of this cell and its descendants and more possibilities for one of them to acquire more mutationsCarcinogens are not always mutagens.100 fold increased risk for head and neck cancers+=
40 A Process of Natural Selection One Mutation is Not Enough !!A Process of Natural SelectionAccumulation of mutations
43 A Process of Natural Selection One Mutation is Not Enough !!A Process of Natural Selection
44 Cancer at the Molecular Level Signal transduction moves information from the cell surface to the nucleus& other cellular targets.
45 What Types of Genes are Mutated in Cancers? Two Broad CategoriesOncogenesmutational activation of proteinsTumor suppressor genesmutational inactivation of proteins
46 They are similar, but NOT identical. Oncogenesproto-oncogeneoncogeneThey are similar, but NOT identical.A proto-oncogene: a normal cellular gene that can become an oncogene, upon DNA damage.
47 An Oncogene Acts in a Dominant Fashion If oncogenes are dominant,what is the normal functions of the proto-oncogenes?
48 cellular signaling machinery stuck in the ON State Oncogenescellular signaling machinery stuck in the ON Stateone mutated copy = over active protein = over proliferation, over-survival, etc.
49 cell proliferation The c-myc Proto-oncogene is a Transcription Factor. Normally, c-myc is stimulated by growth factors.c-mycc-mycc-mycc-mycc-myccell proliferationActa Cytologica, 05Gene amplification turns myc into an oncogene.
50 What Types of Genes are Mutated in Cancers? Two Broad Categories Oncogenesmutational activation of proteinsTumor suppressor genesmutational inactivation of proteins
51 The good guys become bad guys. OncogenesThe good guys become bad guys.Tumor suppressor genesWe are losing the good guys.
54 no cell cycle arrest (over-proliferation) angiogenesis no apoptosis Without 2 copies of P53:no cell cycle arrest (over-proliferation)angiogenesisno apoptosisno DNA repair (more mutations)
55 How to read a Paper Before We Summarize for the paper, as well as for each figure1) What is the question addressed here?2) How did the researchers address this question?3) what are the results?4) what are the conclusions?
56 SummaryCancer cells exhibit behaviors found in normal cells, but in cancer these behaviors are not under control.tumorCancer develops through gradual changes in cell properties.Various factors lead to accumulation of DNA damage- cancer.Oncogenes and tumor-suppressor genes are the molecules behind cancer.