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