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Cancer things to know pptx


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Things to know about cancer

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Cancer things to know pptx

  1. 1. Cancer Manash K. Paul, PhD University of California Los Angeles This presentation is for teaching purpose only
  2. 2. Cancer – incurable suffering ? This presentation is for teaching purpose only
  3. 3. What is Cancer ?  Cancer – cells divide without control and are able to invade other tissues  14.1 million adults in the world were diagnosed with cancer in 2012  8.2 million deaths from cancer in the world in 2012  Is the top cause of cell death after heart diseases  $216.6 billion: The overall costs of cancer in 2009, according to the National Institutes of Health (NIH). This presentation is for teaching purpose only
  4. 4. Most dangerous Cancer 0 5 10 15 20 25 30 Lung&bronchus Prostate Colon&rectum Pancreas Liver&bileduct Leukemia Esophagus Urinarybladder Non-Hodgkinlymphoma Kidney&renalpelvis Lung&bronchus Breast Colon&rectum Pancreas Ovary Leukemia Uterinecorpus Non-Hodgkinlymphoma Liver&bileduct Brain&othernervoussystem Male Female Lung cancer accounts for 1.6 million deaths in 2012. Lung cancer is the most common cancer worldwide
  5. 5.  Most cancers are named for the organ or type of cell in which they start How are cancer named ? Thispresentationisforteachingpurposeonly
  6. 6. Cancer types: classified by tissue of origin  Carcinoma – cancer of skin or in tissues that line or cover internal organs.  Sarcoma – cancer of bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.  Leukemia – cancer of blood-forming tissue such as the bone marrow and causes large numbers of abnormal blood cells.  Lymphoma and myeloma – cancers of the cells of the immune system.  Central nervous system cancers – cancers of the tissues of the brain and spinal cord. This presentation is for teaching purpose only
  7. 7. Self renewal: The ability of a stem cell to divide and produce copies of itself for an indefinite period of time. Differentiation: The process by which cells become specialized to perform particular tasks. Apoptosis: Is the process of programmed cell death. Ref: Cell Death/ Apoptosis Self renewal Self renewal check Differentiation Block 2 Block 3 Block 1 Life of a cell: Basics of cancer
  8. 8. Normal cells Well-behaved- stop growing when they cover the dish (monolayer). Cancer cell Not well-behaved- keep growing after they cover the dish (clumps). Basic Properties of cancer cells  Uncontrolled growth  Invasive  Immortal- no senescence- telomerase is 1 factor  Chromosomal abnormalities- aneuploid Images: Cell and Molecular Biology, 2004/e, John Wiley
  9. 9. Origin of Cancer  Cells grow and divide in a controlled way to produce more cells  The genetic material (DNA) of a cell can become damaged or changed, producing mutations that affect normal cell growth and division  Mutated genes that cause cancer are called oncogenes. It is thought that several mutations need to occur to give rise to cancer  A factor which brings about a mutation is called a mutagen. Any agent that causes cancer is called a carcinogen, and the process called carcinogenesis  Cancerous cells do not self destruct and continue to divide and form a mass of tissue called a tumor
  10. 10. Cancer and the cell cycle checkpoints G1 checkpoint M checkpoint Control system G2 checkpoint G0  Growth factors bind to specific receptors on the plasma membrane to trigger cell division  Signals affecting critical checkpoints determine whether the cell will divide (cyclins, kinases)  Ignores STOP signal
  11. 11. Cancer and the cell cycle checkpoints
  12. 12. Oncogene Deletion Duplication Inversion Homologous chromosomes  Mutations can activate an oncogene or inactivate a tumor suppressor  Deletion: FIG-ROS protein in Astrocytoma  Duplication: Myc in small cell lung cancer  Inversion: CBFB-MYH11 in Acute Myeloid Leukemia  Chromosomal translocation: Philadelphia chromosome in Chronic myelogenous leukemia  The DNA has a mutation that causes the cell to replicate abnormally  Deletion, Duplication, Inversion, Reciprocal translocation are the major types of genetic mutations
  13. 13. Tumor suppressor  Genes in the body that can suppress or block the development of cancer  Need TWO bad copies before problems occur- recessive  Homozygous loss of p53 is found in 65% of colon cancers, 30–50% of breast cancers, and 50% of lung cancers.
  14. 14. Carcinogenesis  Carcinogenesis: A process by which normal cells gets transformed into cancer cells  Hyperplasia: Abnormal proliferation of normal cells within a tissue and may result in the enlargement of an organ or formation of a benign tumor  Dysplasia: Condition characterized by an abnormal expansion of immature cells within a tissue, suggestive of an early neoplastic process.  Neoplasia: Abnormal, uncoordinated proliferation of cells, usually causes a lump or tumor. Neoplasms may be benign, pre-malignant or malignant
  15. 15. Tumors ? Tumor: or neoplasm, is an abnormal mass of tissue, may/ may not be cancer Benign Tumors: Slow growing expansive masses often with a “Pushing margin” and enclosed within a fibrous capsules. Malignant Tumors: rapidly growing, invading local tissue and spreading to distant sites.
  16. 16. Angiogenesis and Metastasis  Angiogenesis is the recruitment of blood vessels from the network of neighbouring vessels  Without blood and the nutrients it carries, a tumour would be unable to continue growing. With the new blood supply, the tumour growth accelerates  Individual cells from the tumour enter into the network of newly formed blood vessels, using these vessels as highways by which they can move to other parts of the body  What makes most tumours so lethal is their ability to metastasize -- that is, establish new tumour sites (Secondary tumours) at other locations pathway-uncovered_09.html
  17. 17. The Etiology of cancer  Viruses (papilloma, Epstein-Barr, hepatitis B, retrovirus)  Radiation exposure  Environmental/Industrial carcinogens: * Asbestos * Aromatic amines * Bischloromethyl ethers * Beta napthalene and benzedrine * Polycyclic hydrocarbons * Drug induced cancers (alkylators such as melphaian and cyclophophamide) * Nickel * Vinyl chloride * Isopropyl alcohol * Diet and nutrition  Tobacco and alcohol consumption  Immnodeficiency syndromes: Central nervous system cancers: HIV is associated with Kaposi’s sarcoma, non-Hodgkin’s lymphoma  Genetic susceptibility syndromes
  18. 18. Clinical symptoms or signs of cancer
  19. 19.  Cancer is now the top causes of death in India, after heart attack  India has some of the world's highest incidences of cancer, like Cervical, gall bladder, oral, pharynx and lung  3.3 million cancer patient (WHO report)  Cost of treatment, a burden World Cancer Day: Indians ignore warning signs at their own peril. India Today: Jan 31, 2014 Cancer Country: India
  20. 20. What do we actually use to study Cancer Biology and Cancer Medicine?  Neoplastic and Normal Cell Lines in Culture  Transformed Normal Cells  Freshly-derived Cancer Cells  Genetically Engineered Cells  Animal Models in Cancer Research (“Pre-Clinical Trials”) Inbred Animal Models Veterinary Animals Animal-Human Engineered Hybrid Models  Clinical Cancer in Patients (Phase I, Phase II, and Phase III) A B C A549 lung cancer cell line in culture Primary lung squamous cancer cells in culture Mouse lung with adenocarcinoma H and E staining of Left lung with adenocarcinoma H and E staining of mouse lung with squamous carcinoma High magnification of C 50µm50µm 100µm
  21. 21.  Problem is Cancer cells are part of our body  Local therapy:  Surgery  Radiation therapy  Systemic treatment:  Chemotherapy  Hormonal therapy  Monoclonal antibodies  Radioactive material  Supportive care  Non-conventional therapy Modalities of treatment: Surgery  Method of choice  Can remove entire tumor  Debulking  Absence of distant metastases Radiation  high-energy particles or waves, such as x-rays, gamma rays, electron beams, or protons, to destroy or damage cancer cells.  Causes small break in the DNA of cancer cells  Kill tumor without damage to surrounding tissues  Tumor must be accessible
  22. 22. Cancer Therapy: Systemic treatment  Chemotherapy  Cytotoxic drugs + body defenses  Single agent  Combination chemotherapy  E.g. Cisplatin, Paclitaxel, Etoposide  Gleevec: Inhibits the receptor protein kinase activity of Abl- one of the receptor oncogenes-in Chronic myelogenous Leukemia.  Revolutionized treatment of this disease.  Typical chemotherapy or radiation therapy has severe drawbacks  Immunotherapy passive : Antibodies against a protein that is unique or overexpressed on cancer cells, can kill the cells. Herceptin, Rituxan Active: Cytokines produced during a bacterial infection include Tumor necrosis factor Monocyte Mediated Antibody- Dependent Cell-mediated Cytotoxicity Gleevec: Mecahanism of action ATP
  23. 23. Cancer Therapy: New Approaches Cancer Vaccines  Majority used for treatment not prevention  May offer method that can enhance the immune response against cancer  Cancer Vaccines: Different than HPV vaccine and traditional vaccines  At this time, cancer vaccines are only available in clinical trials.  Main types: Dendritic cell vaccines, Tumor cell vaccines, Antigen vaccines, Anti-Idiotype vaccines and DNA vaccines Key players  Dendritic Cell: ~Remarkable ability to capture and process antigen. ~ APC presents antigen to T-cell to mount an immune response.  T-Cell: ~ Mediates immune response. Gene therapy  Replaces a faulty gene or adds a new gene in an attempt to cure disease or improve your body's ability to fight disease (cancer)  modified version of the herpes simplex 1 virus which kills melanoma cells
  24. 24. Dendritic Cell Vaccines  Dendritic cells can be generated outside of the body  Dendritic cells are made capable of recognizing antigen by gene therapy and exposure to antigen  Dendritic cells injected into the individual stimulating an immune response  Being studied in: prostate, melanoma, breast, lung, colorectal, kidney, leukemia, and non-Hodgkin lymphoma.  Sipuleucel-T (Provenge) by Dendreon in clinical trials for the treatment of asymptomatic Androgen-Independent Prostate Cancer
  25. 25. Cancer and Bioengineering  Drug design and discovery, computer modelling  Generating more predictive models for cancer research both invitro and invivo  Non-invasive intravital imaging of drug response in live tissue and tumor growth  Designing tumor detection kit  Production of chemotherapeutic drugs  Production of therapeutic antibody  Production of facilities for palliative care  Facial or other organ reconstruction using different scaffold  Drug delivery method
  26. 26. As a general background source  Alberts B. et al., The Molecular Biology of the Cell Garland Science Press, ISBN 0-8153-3218-1 is recommended. As a detailed source  Robert A. Weinberg, The Biology of Cancer Garland Science Press, ISBN 0-8153-4078-8.  Lauren Pecorino, Molecular Biology of Cancer, Oxford University Press. ISBN 978-0-19-921148-7.  M. Molls, P. Vaupel, C. Nieder, M.S. Anscher. The impact of tumor biology on cancer treatment and multidisciplinary strategies, Springer. ISBN 978-3-540-74385-9.  Yi Lu, R. I.Mahato, Pharmaceutical perspectives of cancer therapeutics, Springer. ISBN 978-1-4419-0130-9. Textbook & Readings:
  27. 27. Regulation of Gene Expression by Transcription Factors:
  28. 28. Have you heard of cancer of RBC ? Have you heard of cancer of heart ? Thank you