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Transcript
Genes and Cancer
Prof. Arnaldo Ferreira
Impacts, Issues: Between You and
Eternity
 Cancer strikes one in three people in the United
States
• Kills one in four
 Overall more males than females get cancer
• Pattern varies depending upon the type of cancer
 Gene mutations and cancer
• BRCA1 and BRCA2: “breast cancer susceptibility
genes”
The Characteristics of Cancer
 As genes switch on and off, they determine
when and how fast the cell will grow and divide,
when it will stop dividing, and even when it will
die
 Cancer can result when controls over cell
division are lost
Some Tumors Are Cancer, Others Are Not
Hyperplasmia
 Cells in a tissue overgrow
 Resulting defined mass: tumor (neoplasm)
• Benign, e.g., moles
• Slow growth
• Expands in the same tissue; does not spread
• Cells look nearly normal
• Malignant
• Rapid growth
• Invades surrounding tissue and metastasizes
• Cell differentiation usually poor
Some Tumors Are Cancer, Others Are Not
Dysplasia
 Abnormal change in the size, shape, and
organization of cells in a tissue
 Often an early step toward cancer
• Microscopic characteristics of cancer cells
• Behave differently from normal cells
Cancer Cells Are Abnormal in Their
Growth and Appearance
Normal Moles Are Common Examples of
Benign Growths
Main Features of Benign and Malignant
Tumors
A Cancer Cell’s Structure Is Abnormal
 Cancer is a result of a series of mutations in the
cell’s genes
•
•
•
•
Larger cell nucleus and less cytoplasm
Loss of structural specialization
Cytoskeleton shrinks
Plasma membrane proteins could be lost or
altered
• New plasma membrane proteins may appear
• Changes passed on to cell’s descendants
Cancer Cells Also Do Not Divide Normally
 Cancer cells don’t necessarily divide faster than
normal cells; more cancer cells are dividing than
dying
 Cancer cells do not respond to crowding; loss of
contact inhibition
• Leads to a disorganized mass; cells may have
extensions
• May produce HCG and angiogenin
• Metastasis: makes a cancer malignant
Threadlike “False Feet” Are a Common
Feature of Cancerous Cells
Cancer Spreads Step-by-Step
Cancer is a Genetic Disease
 Cancer is a genetic disease that develops in a
predictable sequence of steps
 Carcinogenesis
• Transformation of a normal cell into a cancerous
cell
• Step-by-step transformation
Carcinogenesis Occurs in Predictable Steps
A Common Type of Colorectal Cancer
May Develop by These Steps
Colon cancer results from genetic
alterations in multiple genes
Inherited mutations in the APC gene dramatically increase
risk of colon cancer
Cancer Usually Involves Several Genes
 Proto-oncogenes
• In normal cells
• Code for proteins involved in the stimulus of cell
division
• If altered, may form oncogenes
• Alone, do not cause malignant cancer
• Require other mutations, including one in a tumor
suppressor gene
Cancer Usually Involves Several Genes
 Tumor suppressor genes
• Stop cell growth and division; prevent cancer
formation
• May prevent expression of oncogenes
Types of cancer genes
Type of gene Normal function Mutated function Types of proteins
Oncogene
Promotes division Promotes division Growth factors
- abnormal time or
cell type
Tumor
suppressor
gene
Suppresses cell
division
DNA repair
Repair DNA
gene mutation mutations
Fails to suppress
division
Checkpoint
molecules
Fail to repair DNA
mutations
Enzymes for
mismatch or
excision repair
Other Factors Also May Lead to Cancer
 Inherited susceptibility to cancer
• ~5% of cancers
 Viruses
• Viral DNA may be inserted into a host cell’s DNA
• May switch on a proto-oncogene
• May carry oncogenes
Other Factors Also May Lead to Cancer
 Chemical carcinogens
• Carcinogens: cancer-causing substances that
can lead to a mutation in DNA
• Asbestos, vinyl chloride, and benzene
• Hydrocarbons in cigarette smoke
• Aflatoxin: fungal product
 Radiation
• UV from the sun and tanning lamps
• X-rays: medical and dental
• Radon, cosmic rays, and gamma radiation
Cruciferous vegetables can lower cancer
risk
Other Factors Also May Lead to Cancer
 Breakdowns in immunity
• Healthy immune system can target and destroy
cancer cells
• When cancer cells have altered proteins at its
surface, cells are not destroyed
• Risk of cancer increases:
• With age
• When an immune system has been suppressed for
a long time
• HIV infection
• Immunosuppressant drugs
• Anxiety and depression
Focus on Environment: Cancer Risk from
Environmental Chemicals
 Exposure to pesticides
• Agricultural chemicals in food and airborne
chemicals due to spraying programs
• Reduce exposure; how?
 Industrial chemicals
 Ames test
• Assess chemical’s ability to cause mutations
Some Industrial Chemicals Linked to
Cancer
Some Major Types of Cancer
 In general, a cancer is named according to the
type of tissue in which it first forms
 Sarcomas: cancer of connective tissue
 Carcinomas: cancer arising from epithelium
 Lymphomas: cancer of lymphoid tissue
 Leukemias: cancer of stem cells
 Gliomas: cancer of brain glial cells
Cancer Is Named for the Site in the Body
Where It First Develops
In the U.S., More than 1 Million People
Are Diagnosed with Cancer Each Year
Cancer Screening and Diagnosis
 Early and accurate diagnosis of cancer is important to
maximize the chances that a cancer can be cured
Blood Tests Can Detect Chemical
Indications of Cancer
 Tumor markers
• Produced by particular types of cancer cells
• Produced by certain cells in response to cancer
• Detected by blood tests
• HCG
• PSA: prostate-specific antigen
Medical Imaging Can Reveal the Site and
Size of Tumors
 Medical imaging
• MRI (magnetic resonance imaging):
reveals tumors obscured by bone
• X-rays
• Ultrasound
• CT (computerized tomography)
Medical Imaging Can Reveal the Site and
Size of Tumors
 Radioactive tracers
• Tracked using a PET scanner
• Diagnosis of thyroid cancer using radioactive
iodine
 Radioactively labeled monoclonal antibodies
• Useful in the location and size of certain tumors in
the colon, brain, and bone
 DNA probe: locates mutated genes, e.g., p53
Radioactive Tracers Also Can Reveal
Cancer Tumors
Biopsy Is the Only Sure Way to Diagnose
Cancer
 Biopsy
• Removal and microscopic examination of tissue
 Seven common cancer signs: CAUTION
Light Microscope Image Shows
Cancerous Cells in Breast Tissue
Cancer Treatment and Prevention
 When a person is diagnosed with cancer, a
variety of weapons are available to combat it
 Chemotherapy drugs
 Radiation therapy
 Surgery
Chemotherapy and Radiation Kill Cancer
Cells
 Chemotherapy
• Drugs used to kill cancer cells; disrupt some
aspect of cell division
• Toxic to healthy cells; hair, bone marrow,
lymphocytes, and epithelial cells of intestinal lining
• Side effects include hair loss, nausea, vomiting,
and reduced immune responses
• Genetic approach to chemo in the future
Chemotherapy and Radiation Kill Cancer
Cells
 Radiation therapy
• Used when cancer is small or has
not spread
• Radioisotopes used, e.g., Ra-226
and Co-60
 Chemotherapy and radiation
destroy healthy cells
 More precise treatments
• Monoclonal antibody treatment
• Interferon treatment; limited at
present
Good Lifestyle Choices Can Limit
Cancer Risk
 Avoid tobacco completely
 Maintain a desirable weight; eat a low-fat diet with
plenty of fruits and vegetables
 Drink alcohol in moderation
 Make sure your living and work environment is
safe from carcinogens
 Protect your skin from the sun’s UV rays
This Cancer Cell Is Surrounded by White
Blood Cells
Cancer Causes and Contributing Factors
Types of Cancer
• Skin Cancer
• Colon Cancer
• Prostate Cancer
• Lung Cancer
• Liver Cancer
• Brest Cancer
• Bladder Cancer