biology of cancer 134 l1 karobi moitra
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Biology of Cancer 134 , lecture 1TRANSCRIPT
WHAT IS CANCER AND HOW DOES IT AFFECTTHE HUMAN CONDITION ?
Karobi Karobi Moitra (Ph.D)Moitra (Ph.D)NCI Frederick , NIHNCI Frederick , NIHCancer Inflammation ProgramCancer Inflammation ProgramHuman Genetics SectionHuman Genetics SectionFrederick MD.Frederick MD.
Is cancer a single disease
or
a group of diseases ?
Cancer is a group of related diseases which arecharacterized by uncontrolled cellular growth
and division
Earliest signs of cancer : 3000 BC
Origin of the word “Cancer”
The origin of the word cancer is credited to the Greek physician Hippocrates(460–370 B.C.), considered the "Father of Medicine." Hippocrates used theterms carcinos and carcinoma to describe non-ulcer forming and ulcer-formingtumors. In Greek, these words refer to a crab, most likely applied to thedisease because the finger-like spreading projections from a cancer called tomind the shape of a crab.
The Roman physician, Celsus (28-50 B.C.), later translated the Greek terminto cancer, the Latin word for crab.
Galen (130-200 A.D.), another Roman physician, used the word oncos (Greekfor swelling) to describe tumors. Galen's term is now used as a part of thename for cancer specialists -- oncologists.
Cancer is associated with abnormal cellularproliferation
Cells divide when they should not divide and theylack the normal control systems to shut off unwanted
cell division
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Loss of Normal Growth Control
Cancer cell division
Fourth orlater mutation
Thirdmutation
Secondmutation
Firstmutation
Uncontrolled growth
Cell Suicide or Apoptosis
Cell damage—no repair
Normal cell division
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In most cases to form a contiguous cell masscalled a tumor
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Example of Normal Growth
Cell migration
Dermis
Dividing cellsin basal layer
Dead cellsshed from
outer surface
Epidermis
Each time one of these basal cells divides, it produces two cells. One remains in the basal layer andretains the capacity to divide. The other migrates out of the basal layer and loses the capacity todivide. The number of dividing cells in the basal layer, therefore, stays the same.
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The Beginning of Cancerous Growth
During the development of skin cancer, the normal balance between cell division and cell loss is disrupted.The basal cells now divide faster than is needed to replenish the cells being shed from the surface of theskin. Each time one of these basal cells divides, the two newly formed cells will often retain the capacity todivide, thereby leading to an increase in the total number of dividing cells.
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Cell death =Cell growth
Cell death <Cell growth
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Tumors (Neoplasms)
Underlying tissue
This gradual increase in the number of dividing cells creates a growing mass of tissue called a “tumor” or “neoplasm.”
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Melanoma
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Types of cancer / precancerous subtypes:
According to growth type:
Neoplasia - growth of cells to form a new structure eg: a tumor
Hyperplasia - excessive no. of cells.
Dysplasia - loss of normal arrangement of tissue (precancerous)
Carcinoma-in-situ - uncontrolled growth of cells that remains at the same place (non-invasive).
Invasive carcinoma - can invade surrounding tissue and also undergo metastasis.
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Hyperplasia
HyperplasiaNormal
Excessive growth
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Dysplasia
Hyperplasia Mild dysplasiaNormal
Excessive growth Loss of cellular structure& tissue arrangement
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Normal to Invasive
Milddysplasia
Carcinoma insitu (severedysplasia) Cancer
(invasive)
Normal Hyperplasia
Excessive growth Loss of cellular structure& tissue arrangement
Excessive growth in place
Invades
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Types of cancer / precancerous subtypes:
According to growth type:
Neoplasia - growth of cells to form a new structure eg: a tumor
Hyperplasia - excessive no. of cells.
Dysplasia - loss of normal arrangement of tissue (precancerous)
Carcinoma-in-situ - uncontrolled growth of cells that remains at the same place (non-invasive).
Invasive carcinoma - can invade surrounding tissue and also undergo metastasis.
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According to tissue type affected :
Carcinoma - tumors made up of principally epithelial cells (cells that line inner and outer surfaces). eg: cervical and skin cancers.
Sarcoma - made up principally of connective tissue cells (cartilage, bone etc.) eg: osteosarcoma.
Leukemia - Neoplastic growth of leucocytes (WBC) .
Lymphoma - excessive production of lymphocytes by lymph nodes and spleen. eg: Hodgkins disease.
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Different Kinds of Cancer
Lung
Breast (women)
Colon
BladderProstate (men)
Some common sarcomas:FatBone
Muscle
Lymphomas:Lymph nodes
Leukemias:BloodstreamSome common
carcinomas:
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According to tissue type affected :
Carcinoma - tumors made up of principally epithelial cells (cells that line inner and outer surfaces). eg: cervical and skin cancers.
Sarcoma - made up principally of connective tissue cells (cartilage, bone etc.) eg: osteosarcoma.
Leukemia - Neoplastic growth of leucocytes (WBC) .
Lymphoma - excessive production of lymphocytes by lymph nodes and spleen. eg: Hodgkins disease.
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According to metastasis (invading capacity)
Benign tumor - these tumors have restricted growth and tend to remain localized. eg: wart.
Malignant tumor - these tumors do not remain localized but invade other tissue and give rise to secondary tumors in other parts of the body (metastasis).
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Malignant versus Benign Tumors
Malignant (cancer)cells invadeneighboring tissues,enter blood vessels,and metastasize todifferent sites
Time
Benign (not cancer)tumor cells growonly locally and cannotspread by invasion ormetastasis
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Invasion and Metastasis
3Cancer cellsreinvade and growat new location
1Cancer cells invadesurrounding tissuesand blood vessels
2Cancer cells aretransported by thecirculatory systemto distant sites
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According to tissue type affected :
Carcinoma - tumors made up of principally epithelial cells (cells that line inner and outer surfaces). eg: cervical and skin cancers.
Sarcoma - made up principally of connective tissue cells (cartilage, bone etc.) eg: osteosarcoma.
According to growth type:
Neoplasia - growth of cells to form a new structure eg: a tumor
Hyperplasia - excessive no. of cells.
Dysplasia - loss of normal arrangement of tissue (precancerous)
Carcinoma-in-situ - uncontrolled growth of cells that remains at the same place (non-invasive).
Invasive carcinoma - can invade surrounding tissue and also undergo metastasis.
Leukemia - Neoplastic growth of leucocytes (WBC) .
Lymphoma - excessive production of lymphocytes by lymph nodes and spleen. eg: Hodgkins disease.
According to metastasis (invading capacity)
Benign tumor - these tumors have restricted growth and tend to remain localized. eg: wart.
Malignant tumor - these tumors do not remain localized but invade other tissue and give rise to secondary tumors in other parts of the body (metastasis).
Different kinds of cancer
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Why Cancer Is Potentially Dangerous
Melanomacells travelthroughbloodstream
Melanoma(initial tumor)
Brain
Liver
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If left untreated cancer can result in death……..
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Naming Cancers
Prefix Meaningadeno- glandchondro- cartilageerythro- red blood cellhemangio- blood vesselshepato- liverlipo- fatlympho- lymphocytemelano- pigment cellmyelo- bone marrowmyo- muscleosteo- bone
Cancer Prefixes Point to Location
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Microscopic Appearance of Cancer Cells
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Cancer cell Normal cell
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Characteristic adaptive features of cancer cells :
1. Loss of contact inhibition
Normal cells stop growing when their plasma membranescome into contact with one another - normal cells stop moving when they contact each other this is called contact inhibition, cancer cells lose the property of contact inhibition. Transformed cells do not stop dividingafter forming a monolayer division continues until severallayers of cells are formed.
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2. Unrestrained control of growth
Cancer cells lack the normal control systems to shutoff unwanted growth.
3. Metastasis
Metastasis is the spread of cancer cells from a primarysite of origin to other tissues where they grow as secondary tumors.
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Some biochemical properties of cancer cells :
1. Increased glycolysis (Warburg effect)Otto Warburg observed that virtually every type of cancercells that form solid tumors excrete much larger quantities oflactic acid than its normal counterpart. This is known as the‘Warburg effect’.Unlike normal cells, which break down sugar using oxidativepathways (or the Krebs cycle), tumor cells used non-oxidative pathways (glycolysis) to generate energy fromsugar.
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2. Alterations in cytoskeletal proteins
Less organized/ disorganized arrangement of cytoskeletal proteins - such as myosin , tubulin etc.
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3. Loss of anchorage dependence
Cancer cells in culture can grow suspended in media while most normal cells need to attach to a substratum to grow (anchored).
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4. Cancer cells are seemingly immortal
Cancer cells in culture can continue to grow indefinitely.
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The Somatic Mutation TheoryOf Cancer
Theodore Boveri 1914
He stated that the fundamentalcause of cancer was in chromatinimbalance in the cells from which cancer arises.
Evidence : Many cancers havechromosomal abnormalities
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The cell cycle
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What Causes Cancer?
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What Causes Cancer?Some viruses or bacteria
HeredityDiet
Hormones
RadiationSome chemicals
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Population-Based Studies
CANADA:Leukemia
Regions of Highest Incidence
BRAZIL:Cervicalcancer
U.S.:Coloncancer
AUSTRALIA:Skincancer
CHINA:Livercancer
U.K.:Lungcancer
JAPAN:Stomachcancer
A striking finding to emerge from population studies is that cancers arise with different frequenciesin different areas of the world. For example, stomach cancer is especially frequent in Japan, coloncancer is prominent in the United States, and skin cancer is common in Australia. What is thereason for the high rates of specific kinds of cancer in certain countries?
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Heredity? Behaviors? Other Factors?
100
50
50
Stomach Cancer(Number of new cases
per 100,000 people)
U.S.Japan Japanesefamiliesin U.S.
100
70
70
Colon Cancer(Number of new cases
per 100,000 people)
U.S.Japan Japanesefamiliesin U.S.
In theory, differences in heredity or environmental risk factors might be responsible for the different cancerrates observed in different countries. Studies on people who have moved from one country to anothersuggest that exposure to risk factors for cancer varies by geographic location. For example, in Japan, therate of colon cancer is lower, and the rate of stomach cancer is higher, than in the United States. But thisdifference has been found to gradually disappear in Japanese families that have moved to the United States.This suggests that the risk of developing the two kinds of cancer is not determined primarily by heredity. Thechange in risk for cancer for Japanese families could involve cultural, behavioral, or environmental factorspredominant in one location and not in the other.
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Tobacco Use and CancerSome Cancer-Causing Chemicals in Tobacco Smoke
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Low-Strength Radiation
Annual Sunshine(UV radiation)
SkinCancer
Incidence
Most
Dallas
Pittsburgh
High
Detroit
LowLeast
Some atoms give off radiation, which is energy that travels through space. Prolonged or repeatedexposure to certain types of radiation can cause cancer. Cancer caused by the sun’s ultravioletradiation is most common in people who spend long hours in strong sunlight. Ultraviolet radiationfrom sunlight is a low-strength type of radiation. Effective ways to protect against ultraviolet radiationand to prevent skin cancer are to avoid going into strong, direct sunlight and to wear protectiveclothing. Sunscreen lotions reduce the risk of some forms of skin cancers.
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High-Strength Radiation
Most
High
LowLeast
LeukemiaIncidence
X-ray Dose(atomic radiation)
Increased rates of cancer also have been detected in people exposed to high-strength forms of radiation such asX-rays or radiation emitted from unstable atoms called radioisotopes. Because these two types of radiation arestronger than ultraviolet radiation, they can penetrate through clothing and skin into the body. Therefore, high-strength radiation can cause cancers of internal body tissues. Examples include cancer caused by nuclear falloutfrom atomic explosions and cancers caused by excessive exposure to radioactive chemicals.
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Lag Time
4000
3000
2000
1000
20-Year Lag Time BetweenSmoking and Lung Cancer
CigarettesSmoked
per Personper Year
Lung CancerDeaths (per100,000 people)
Year
Lungcancer(men)
Cigaretteconsumption(men)
1900 1920 1940 1960 1980
150
100
50
Chemicals and radiation that are capable of triggering the development of cancer are called “carcinogens.” Carcinogens act through amultistep process that initiates a series of genetic alterations (“mutations”) and stimulates cells to proliferate. A prolonged period of time isusually required for these multiple steps. There can be a delay of several decades between exposure to a carcinogen and the onset ofcancer. For example, young people exposed to carcinogens from smoking cigarettes generally do not develop cancer for 20 to 30 years.This period between exposure and onset of disease is the lag time.
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Viruses
Virus insertsand changesgenes forcell growth
Cancer-linked virus
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Examples of Human Cancer Viruses
Some Viruses Associated with Human Cancers
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Bacteria and Stomach Cancer
H. pyloriPatient’stissue
sample
The bacterium Helicobacter pylori, which can cause stomach ulcers, has been associated with thedevelopment of cancer, so people infected with H. pylori are at increased risk for stomach cancer.Research is under way to define the genetic interactions between this infectious agent and its hosttissues that may explain why cancer develops.
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Heredity and Cancer
Inherited factor(s)
All Breast Cancer Patients
Other factor(s)
Cancer is not considered an inherited illness because most cases of cancer, perhaps 80 to 90 percent, occur in peoplewith no family history of the disease. However, a person’s chances of developing cancer can be influenced by theinheritance of certain kinds of genetic alterations. These alterations tend to increase an individual’s susceptibility todeveloping cancer in the future. For example, about 5 percent of breast cancers are thought to be due to inheritance ofparticular form(s) of a “breast cancer susceptibility gene.”
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Heredity Can Affect Many Types of Cancer
Inherited Conditions That Increase Risk for Cancer
Inherited mutations can influence a person’s risk of developing many types of cancer inaddition to breast cancer. For example, certain inherited mutations have been describedthat increase a person’s risk of developing colon, kidney, bone, skin or other specific formsof cancer. But these hereditary conditions are thought to be involved in only 10 percent orfewer of all cancer cases.
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Cancer is a group of related diseases which arecharacterized by uncontrolled cellular growth
and division
Cells divide when they should not divide and theylack the normal control systems to shut off unwanted
cell division
How does cancer affect the human condition ?
CARCINOMA !!!
CANCER
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"He who cures a disease maybe the skill fullest, but he that
prevents it is the safestphysician”
Thomas Fuller