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CHAPTER NINE: MITOSIS NOTES PT. 3The Cellular Basis of Inheritance

What Happens When Mitosis Goes Wrong?? ¨ Cancer

¤ Caused by uncontrolled cell reproduction (mitosis) and severe disruption of the mechanisms that control mitosis

¤ Cancer can spread or grow geometrically (2- 4- 8)

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Tumors

¨ The uncontrolled cells form a mass called a tumor¨ Two types of tumors

1. Benign: Non-Cancerous2. Malignant: Cancerous

Tumor Types

¨ Abnormal mass of normal cells

¨ Non-Anaplastic¨ Non-Invasive¨ Encapsulated¨ Slow Growing – no

metastasis¨ Highly Differentiated¨ Mitosis Rare

¨ Abnormal mass of cancer cells¤ Malignant tumor displaces the normal

tissue as it grows¤ If it is not removed, the cells can break

off and spread to other areas of the body via blood or lymph

¤ The spread of cancer cells beyond their original site is called metastasis

¨ Anaplastic - cancer cells that divide rapidly and bear little or no resemblance to normal cells

¨ Non-Encapsulated¨ Invasive¨ Tendency toward de-differentiation¨ Mitosis relatively common¨ Usually rapid growth

Benign Tumor Malignant Tumor:

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Oncology

¨ The study of cancer and cancerous tumors is oncology.

¨ Oncologist – Doctor who studies cancer. ¨ Epidemiologist – Doctor who studies the etiology of

disease. ¨ Etiology – The way a particular disease works.

History of Cancer

¨ Cancer dates back to prehistoric times

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Carcinogens

¨ Carcinogens – substances known to cause or promote cancer¤ Two types:

n Man-made; i.e., cigarette smoke n Naturally occurring; i.e., UV Radiation from Sun, Oncogenes

¨ After exposure, 5-40 years to develop, so to ID carcinogen is difficult

¨ Number of exposures and length of time are keys

Carcinogens

Known Man Made Carcinogens Affects

Arsenic Lungs

Asbestos Lungs

Benzene (Plastic Manufacture, Exhaust, Cigarette Smoke)

Bladder

Tobacco Lungs, Esophagus, Mouth

Alcohol Pancreas, Head, Neck Liver

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Carcinogens

¨ Naturally Occurring Cancers¤ Oncogenic: genes

n Oncogenes – genes that initiate cells to transform from normal to malignant BRCA 1 – Breast

n Oncogene Viruses = Virus that initiates/causes cancer n 40 discovered HIV, HPV (Human ~Papilloma Virus), Herpes Virus,

Hepatitis B and C, Retroviruses

¤ Normally, the immune system recognizes cancer cells and gets rid of them, however an overwhelmed immune system may not do this. This may be a link between cancer and HIV.

Types and Symptoms of Cancer

Type of Cancer Symptoms

Uterine or Ovarian Unusual Discharge

Breast or Testicular Lump that does not go away

Mouth Sore that does not heal in 2 weeks

Lung Unusual Hoarseness or Cough

Esophagus, Head, or NeckIndigestion or Difficulty Swallowing

Skin Change in wart or mole

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Early Causes: Chemical Exposure

¨ Small, wiry boys were selected as chimney sweeps, because they could go places an adult could not.

¨ Working to remove soot from chimneys, they got covered with grime.

¨ Hygiene standards were low, so soot remained on their skin, particularly in obscure places.

Early Causes: Chemical Exposure

¨ Percivall Pott 1775, London.

¨ Traced relationship between exposure to soot (collecting under scrotum) and increased incidence of scrotal cancer in chimney sweeps.

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Early Causes: Asbestos

¨ What is Asbestos?¤ Family of naturally occurring fibrous

minerals.¤ Made of magnesium, silicon, or other

elements.¤ “Mined” from soil and rocks throughout

the world.¤ Used as an insulating material, in

manufacture of paper and clothing since ancient times.

¤ People are exposed to asbestos mainly though inhalation of fibers in the air they breathe.

Early Causes: Asbestos

¨ The connection between asbestos exposure and lung cancer was noted as early as 1925 and confirmed by many epidemiological studies of asbestos-exposure over the next 70 years.

¨ 1964 Selikoff, Churg and Hammond published conclusive link between exposure to asbestos and subsequent development of mesothelioma (255 dead of 632 workers working 20+ years in asbestos.

¨ Rates of increase of lung cancer in asbestos workers were documented in studies published in1935, 1947, 1949, 1951.

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Early Causes: Asbestos

¨ Graphs?

Early Causes: Tobacco

¨ Tobacco has been known and used in the new world since the time of Columbus.

¨ The story of tobacco’s link to cancer is complicated by its many uses.

¨ Types of uses1. Snuff2. Pipe/Cigar smoking3. Cigarette smoking

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Tobacco and Cancer of the Nose Lips and Mouth

¨ John Hill of London was the first to recognize the dangers of tobacco.

¨ In 1761, only a few decades after tobacco became popular in London, in his book he wrote of the association between “cancer of the nose” and “the immoderate use of snuff.”

¨ Samuel Thomas von Sommeringreported a high incidence of lip cancer “where men indulge in pipe smoking.”

Tobacco and Lung Cancer

¨ Lung cancer was uncommon until the 20th Century.¨ Many observed the rise in lung cancer rates and

rise in popularity of cigarette smoking.¨ Finally came experiments showing that tobacco

smoke caused cancer in laboratory animals.¨ Epidemiologic studies followed

¤ Found that lung cancer death rate is dose dependent (directly related to the total number of cigarettes smoked).

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Tumor-initiating Agents in the Particulate Phase of Tobacco Smoke

Confirmed Carcinogenic Agents in the Gas Phase of Cigarette Smoke

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Not only lungs are involved

¨ Cigarettes also increase the risks of cancer of ¤ The upper respiratory tract¤ Esophagus¤ Bladder¤ Pancreas¤ Stomach¤ Liver¤ Kidney

¨ Cigarettes are implicated in chronic myelocyticleukemia (cancer of the blood and bone)

¨ Inhalation of other people’s cigarette smoke is less dangerous but it is not benign

Modern Day Understanding of Cancer

¨ Observations, epidemiological studies and experiments created a chain of evidence linking many substances to cancer.

¨ Today we recognize and avoid many specific substances that cause cancer.

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Modern Day Understanding of Cancer

¨ Known chemical carcinogens include: ¤ Coal Tar ¤ Hydrocarbons¤ Aniline Dyes ¤ Asbestos¤ Estrogen ¤ Chemicals in Tobacco

¨ Radiation (including UV)

Modern Day Understanding of Cancer

¨ Most recently viruses have been linked to cancer: ¤ Hepatitis Virus

n Liver Cancer

¤ Herpes Virus n Non-Hodgkin’s Lymphoma & Nasopharyngeal Cancer

¤ HIV n Kaposi’s Sarcoma

¤ Human Papilloma Virus n Genital Cancers

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Five Groups of Cancer

1. Carcinoma¤ Tumor originates in epithelial system (surface tissue of

body organs)¤ Primary Starting place is unknown¤ Most common – 80-90% of all cancer cases

Five Groups of Cancer

2. Sarcoma¤ Malignant tumors of bone, cartilage, or muscle ¤ Tumors also of fibrous connective tissue or fatty tissue¤ 3 Types of Sarcoma

1. Soft Tissue Sarcoma - Develops in muscle, fat, blood vessels, nerves, synovial tissue (joints)

2. Kaposi’s Sarcoma - Tissues under skin or mucous membranes that line mouth, nose and anus n Red or purple lesions on skin that spread

3. Ewing’s Sarcoma - Bone; usually pelvis, thigh, upper arm, ribsn Teenagers mostly

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Five Groups of Cancer: Sarcoma

Soft Tissue Sarcoma Kaposi’s Sarcoma Ewing’s Sarcoma

Five Groups of Cancer

3. Myeloma¤ Uncontrolled growth of plasma cells in bone marrow.

n Plasma cells are made in bone marrow and move to bloodstream

¤ Usually Monoclonal – 1 defective cell is origin

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Five Groups of Cancer

3. Myeloma¤ Causes of Myeloma

n Plasma cells are normally present in the bone marrow (making up less than 5% of the bone marrow) and are responsible for the production of antibodies when the body is dealing with infection.

n Cancerous plasma cells (myeloma cells) build up in the bone marrow, interfering with normal immune response and bone marrow production of normal blood cells.

n These myeloma cells invade and damage the bone, causing tumors (myelomas) to form. Myeloma cells then travel to other sites in the body, causing further tumors (hence the name "multiple myeloma").

Myeloma

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Myeloma

Five Groups of Cancer

4. Lymphoma¤ Lymph System

n Lymph: Colorless, watery fluid that contains white blood cells called lymphocytes

n Lymph nodes: Organs that make and store infection fighting cells

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Five Groups of Cancer

4. Lymphoma¤ Occurs when cells in lymphatic system grow out of

control. n Cells are immature and do not die like a normal celln Cells continue to divide like normal cells but can not do

their jobsn Too much tissue forms and tumors developn Lymph tissue is in many parts of body so cancer cells can

spread to liver, spleen, or bone marrow very easily.

Five Groups of Cancer

¨ 2 Types of Lymphoma1. Hodgkin’s 2. Non-Hodgkin’s

Lymphoma

¨ Symptoms of both¤ Painless swelling of

lymph nodes¤ Fever¤ Fatigue

Hodgkin’s Lymphoma

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Five Groups of Cancer

5. Leukemia¤ Malignant disorder of body’s blood forming tissue –

mainly bone marrow, lymph nodes and spleen ¤ Blood forming tissues flood the blood stream and

lymph system with immature White Blood Cellsn White Blood Cells can not fight infectionn Reduces production of Red Blood Cells and platelets

¤ Symptoms: n Infectionn Severe Anemian Bruising,n Hemorrhaging

Five Groups of Cancer

5. Leukemia¤ Two categories of

Leukemian Chronic: progresses

slowly; adultsn Acute: White Blood Cell

number progresses rapidly; children

Chronic Leukemia: A 70 year old man with a 6-year history

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Treatments

1. Hormone Therapy¤ Natural Hormones or Synthetic Hormones

n 3 Ways to Receive Hormone Therapyn Injection or Orallyn Surgical removal of hormone producing glandsn Radiation treatment to destroy hormone producing cells

Treatments

2. Radiation Therapy¤ High electron penetrating rays or subatomic particles

n Given 2-ways (sometimes both are used)n Delivers radiation to cancer inside the body n Delivers radiation on the surface of the skin

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Treatments

3. Internal Radiation¤ Radioactive substance is sealed in container like a

wire, tube, seed, capsule or needle called an implant.n Implant put directly in tumor or in body cavity

n Container remainsn Radioactive Substance remains for length of half-life

§ Ex. Half-life = 72 hours = fights effectively for 72 hours

n Permanent Implants n Unsealed Radiation in liquid form

Treatments

4. Palliation¤ To treat it partially and insofar as possible, but not

cure it completely. Palliation cloaks a disease.n Medication for pain, like bone cancer, Superior Vena

Cava syndrome, or others that may not be cured

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Treatments

5. Chemotherapy¤ Highly toxic medications are used to destroy cancer

cells by stopping cell growth or reproductionn Used to prolong life when a cure is improbable

Treatments

6. Biological Therapy/Immunotherapy¤ Uses living organisms, vaccines or bacteria to

stimulate the immune system to act against cancer cells or lessen side effects

¤ Restore the body’s natural cancer defense mechanisms

¤ Reverse process of Angiogenesis; prevent cancer cells from spreading

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Treatments

7. Surgical Therapy¤ Staging Surgery – determines extent, next step &

prevents unnecessary radical procedures (hysterectomies, prostatectomies)

¤ Definitive Surgery – removes tumor and surrounding tissues to prevent metastasis.n (If early in disease, can cure cancer.)

¤ Preventative – family history, increased risk, questionable tissue

¤ Palliative – relieves symptoms in advanced stages by interrupting nerve pathways causing pain.

Treatment Side Effects and Solutions

¨ Chemotherapy and Radiation¤ Nausea¤ Vomiting

n Solution: eat and drink slow, small amounts, eat dry food, drink clear liquids

¨ Radiation in Colon, Rectum, or Prostate¤ Diarrhea¤ Constipation

n Solution for Diarrhea: eat and drink slow, small amounts, eat dry food, drink clear liquids

n Solution for Constipation: increase fluids, increase fiber, exercise