Pathophysiology Unit 2: Cancer

How Cancer is Classified

(1) the type of tissue in which the cancer originates (histological type). (2) the primary site or location in the body where the cancer first developed.

Types of Skin Cancer

- Basal Cell Carcinoma (most common) - Squamous Cell Carcinoma (second most common) - Melanoma (most serious) - Cutaneous T-cell lymphoma - Dermatofibrosarcoma protuberans (DFSP) - Merkel cell carcinoma - Sebaceous carcinoma

Normal cells most likely to be damaged by chemotherapy

- Blood-forming cells in the bone marrow. - Hair follicles. - Cells in the mouth, digestive tract, and reproductive system. *cells in the heart, kidneys, bladder, lungs, and nervous system with some chemo drugs.

Major Categories of Histological Type Cancers

- Carcinoma - Sarcoma - Myeloma - Leukemia - Lymphoma - Mixed Types

Foods that Increase Cancer Risk

- Fat (especially large amounts of omega-6 fatty acids). - high-glycemic-index carbs. - food with high amounts of preservatives. - alcohol. - grilled, blackened foods. - fried foods. - high levels of calcium (over 2000mg). - refined grain products.

Distant Metastasis (M) Classification

- MX: metastasis cannot be measured. - M0: cancer has not spread to other parts of the body. - M1: cancer has spread to other parts of the body.

Types of Leukemia

- Myelogenous or granulocytic leukemia (myeloid and granulocytic white blood cells). - Lymphatic, Lymphocytic, or Lymphoblastic leukemia (lymphoid and lymphocytic blood cells). - Polycythemia vera or Erythremia (various blood cell products, predominantly red blood cells).

Regional Lymph Nodes (N) Classification

- NX: cancer in nearby lymph nodes cannot be measured. - N0: there is no cancer in nearby lymph nodes. - N1, N2, N3: refers to the number and location of lymph nodes that contain cancer. The higher the number after the N, the more lymph nodes that contain cancer.

Primary Tumor (T) Classification

- TX: main tumor cannot be measured. - T0: main tumor cannot be found. - T1, T2, T3, T4: refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further divided to provide more detail, such as T3a and T3b.

Sunlight/ionizing radiation (cancer risk)

- UV radiation causes early aging of the skin that can lead to skin cancer. - cells are damaged or altered and lead to cancer. - can cause cancers of the skin, blood, thyroid, breast, lung, and stomach. - Radon: a radioactive gas that you cannot see, smell, or taste; forms in soil and rocks.

Oncogenes

- a "bad" gene that can become permanently turned on or activated when it is not supposed to be. - causes the cell grows out of control, which can lead to cancer. - formed when a proto-oncogene mutates or there are too many copies of it.

Tumor-suppressor genes

- a gene that inhibits cell division, preventing uncontrolled cell growth that contributes to cancer. - tells cells to stop dividing. - like the brakes of a car. - when they lose function, cells multiply out of control.

9. Genomic instability.

- a high frequency of mutations within the genome of a cellular lineage. - accelerates the accumulation of genetic changes that are responsible for cancer cell evolution. - can include changes in nucleic acid sequences, chromosomal rearrangements, or aneuploidy. - has an essential role in tumorigenesis.

Tumor

- a mass or group of abnormal cells that form in the body. - produces swelling of a part of the body, generally without inflammation. - do not perform a function that supports the organism (like a parasite). - develop from the proliferation of a single abnormal cell. - can be benign or malignant (not cancerous or cancerous).

Targeted Cancer Therapy

- a type of cancer treatment that uses drugs designed to target cancer cells without affecting normal cells. - gene mutations cause cancer cells to behave differently than normal cells. - some cancers have certain types of proteins or enzymes that tell it to grow and copy itself. - the drugs can target these proteins or enzymes and block the messages being sent. - keeps cancer cells from dividing. - mostly leaves normal, healthy cells alone. - so far, it can only treat a few types of cancer. - is paired with other treatments.

Stage 0 Cancer

- abnormal cells are present but have not spread to nearby tissue. - also called "in situ".

Risk Factors for Cancer

- aging. - family history. - smoking. - alcohol - sunlight/ionizing radiation. - organic/inorganic chemicals. - viruses & bacteria. - hormone therapy. - diet & obesity. - air & water pollution.

Neoplasm (neoplasia)

- an abnormal and excessive growth of cells. - occurs when a genetic mutation causes an abnormal proliferation of cells. - cells divide at a faster rate, not coordinated with the surrounding tissue. - the cells do not die when they should, continue growing, and cannot be controlled like normal cells can. - forms a tumor.

10. Chronic inflammation.

- an important factor in the development of cancer. - body continues sending inflammatory cells even when there is no outside danger.

2. Insensitivity to anti-growth signals.

- antigrowth signals govern cell division during the cell cycle via checkpoints. - cells ignore anti-growth signals that usually prevent them from dividing when they shouldn't. - mutations in the proteins that detect DNA damage cause checkpoint mechanisms to fail, causing them to be unable to stop the cell from dividing.

Cancer

- any malignant growth or tumor caused by abnormal and uncontrolled cell division. - somatic cells which contain multiple abnormalities of both number and structure. - 93% caused by environmental factors. - 7% are hereditary.

Ways to Prevent Cancer

- avoid carcinogenic exposures. - modifying lifestyle practices. - staying physically active. - early detection of cancerous lesions.

Umbilical Cord Blood

- blood of newborn babies has large numbers of stem cells. - blood that's left behind in the placenta and umbilical cord can be taken and stored for later use in a stem cell transplant. - the blood can be frozen until needed. - the baby is not harmed in any way.

3. Evade apoptosis.

- cancer cells are able to evade cell death. - mutations (inactivation) of tumor-suppressor genes allows unregulated cell growth. - mutations in the RB and p53 genes.

Stage II Cancer

- cancer is present. - local invasion of tissues.

Stage I Cancer

- cancer is present. - no metastasis.

Stage III Cancer

- cancer is present. - spread to regional structures.

Stage IV Cancer

- cancer present. - distant metastasis to other organs of the body.

Adenocarcinoma

- cancer that develops in an organ or gland. - generally occurs in mucus membranes. - first seen as a thickened plaque-like white mucosa. - often spread easily through soft tissue. - affect organs or glands capable of secretion (breasts, lungs, colon, prostate, bladder).

Squamous Cell Carcinoma

- cancer that originates in the squamous epithelium. - occur in many areas of the body.

Metastatic Cancer

- cancer that spreads from where it started to a distant part of the body via metastasis. - also called Stage 4 Cancer.

Organic/Inorganic Chemicals (cancer risk)

- carcinogens: chemical substances that are dangerous to our health in high concentration over time. - 275 elements out of the 30,000 analyzed. - cancer causing. - jobs such as painting, construction, pesticide, and petroleum workers have an increased risk of cancer. - found in cosmetic products: dioxane, petrolatum, formaldehyde, synthetic fragrance, talc, parabens and phthalates.

Viruses & Bacteria (cancer risk)

- causes 18% of all cancers. - occurs more in developing nations. - includes HPV, Hepatitis B and C, HTLV-1, HIV, EBV, HHV8, Helicobacter pylori, Salmonella typhi, and Streptococcus bovis.

Alcohol (cancer risk)

- causes 3.6% of all human cancers. - more than two drinks per day for many years will increase chances of cancer. - classified as a group-1 carcinogen. - the liver can process 7g of ethyl alcohol each hour. - acetaldehyde (carcinogenic) is produced by the liver when it processes alcohol. - exposure to acetaldehyde can lead to cancer.

Cycles of a Cell

- cells are continually doing three things. - resting, dividing, and dying. - tissues must maintain their size by matching the rate at which cells are dying with those that are dividing.

Proto-oncogenes

- cellular genes responsible for normal cell growth and division. - tell cells to divide. - like the gas pedal of a car. - alterations in the expression of these cells result in oncogenes. - the gas pedal gets stuck and cells divide out of control.

Cell Cycle Checkpoints

- checkpoints that regulate the cell cycle. - cells must go through a series of checkpoints before they are allowed to divide. - ensures a cell does not pass through if the cell DNA is damaged. - G1 checkpoint: between G1 and S phase. - G2 checkpoint: between S phase and G2. - M checkpoint: before mitosis (cell division).

Goals of Chemotherapy

- cure - control - palliation

Goals of Radiation Cancer Therapy

- cure or shrink early-stage cancer. - stop cancer from coming back (treat areas where the cancer most often spreads). - treat symptoms caused by advanced cancer. - treat cancer that has returned.

Chemotherapy

- cytotoxic drugs used for cancer treatment. - considered a systemic treatment. - the drugs travel throughout the body, and can kill cancer cells that have metastasized to parts of the body far away from the primary tumor. - the drugs target fast-growing cells at different phases of the cell cycle, but can't tell the difference between healthy cells and cancer cells. - commonly given in scheduled intervals (cycles) in order to find a balance between killing the cancer cells and sparing the normal cells. - most normal cells recover over time. - cancer cells are mutated and usually don't recover.

Hormone Therapy (cancer risk)

- estrogen and progestin therapy may increase the risk of breast and uterus cancers. - tamoxifen and aromatase inhibitors reduce estrogen production, which ceases cellular proliferation. - steroid hormones can induce gene expression in the nucleus of cancer cells which lead to reduced hormonal production and subsequent cellular growth arrest.

Unavoidable Risk Factors for Cancer

- family history. - aging.

Foods that Decrease Cancer Risk

- fruits. - vegetables. - fiber. - foods containing vitamin A, B6, C, D, E, and folate. - whole grains. - lycopene. - legumes/nuts.

Family History (cancer risk)

- genetic mutations can increase the risk of cancer. - passed from parent to child. - does not guarantee cancer will develop. - increased chance of developing cancer.

Leukemia

- histological cancer type. - cancer of the bone marrow. - "liquid cancers" or "blood cancers". - means "white blood" in greek. - overproduction of immature white blood cells. - also affects red blood cells.

Lymphoma

- histological cancer type. - cancer that originates in the glands or nodes of the lymphatic system. - "solid cancers". - may also occur in the stomach, breast, or brain (extranodal lymphomas). - two categories: Hodgkin Lymphoma and Non-Hodgkin Lymphoma. - Reed-Sternberg cells are present in Hodgkin Lymphoma.

Myeloma

- histological cancer type. - cancer that originates in the plasma cells of bone marrow. - plasma cells produce some of the proteins found in blood.

Mixed Cancer Types

- histological cancer type. - cancer with components within different categories. - includes adenosquamous carcinoma, mixed mesodermal tumor, carcinosarcoma, teratocarcinoma.

Carcinoma

- histological cancer type. - malignant tumor that originates in epithelial cells. - skin and the lining of organs and internal passageways (GI tract). - account for 80-90% of all cancer cases. - divided into two subtypes: adenocarcinoma and squamous cell carcinoma.

Sarcoma

- histological cancer type. - malignant tumor that originates in supportive and connective tissues. - bones, tendons, cartilage, muscle, and fat. - generally occur in young adults. - usually resemble the tissue in which they grow.

Growth Factor

- hormones in the form of proteins. - released by cells as a way of signaling to nearby cells that it's okay for them to divide. - controls normal cell division. - binds to receptors on cells and activates the intracellular cascade that leads to cell division.

Chemotherapy Side Effects

- includes Fatigue, Hair loss, Easy bruising and bleeding, Infection, Anemia, Nausea and vomiting, Appetite changes, Constipation, Diarrhea, Mouth, tongue, and throat problems, Peripheral neuropathy, Skin and nail changes, Urine and bladder changes and kidney problems, Weight changes, Chemo brain, Mood changes, Changes in libido and sexual function, Fertility problems. - Every person doesn't get every side effect. - Some people get few, if any. - Severity varies greatly from person to person. - Medicines can help prevent certain side effects. - Some chemo drugs cause long-term side effects. - Many people have no long-term problems.

Precancerous Tumor

- masses that are not yet cancerous but have the potential to do so if left untreated.

Anti-growth Signals

- mechanisms of the cell cycle checkpoints. - detect damaged or mutated cells and activate proteins that stop the cell at a particular checkpoint. - function to stop mutated cells from dividing and growing into tumors. - tumor suppressor genes code for the "stop" proteins.

Aging (cancer risk)

- most important risk factor. - most cancers occur in people over 55. - accumulating damage to the stem and progenitor cells.

Smoking (cancer risk)

- most preventable cause of death. - causes 85% of all lung cancers. - causes 30% of all deaths. - second hand smoke increases risks by 5%. - more likely to develop different types of cancers. - 400 out of 4,000 chemicals found in tobacco are harmful to humans. - 40 of the 400 chemicals are carcinogenic.

4. Limitless replicative potential.

- normal cells have a finite replicative potential (60-70). - telomere maintenance is usually accomplished by activating the gene encoding telomerase. - cancer cells maintain the telomere length and structure above a critical threshold by the reverse transcriptase telomerase and a multiprotein telomere complex called shelterin. - cancer cells are able to divide indefinitely.

1. Self-sufficiency in growth signals.

- normal cells require growth signals before they start dividing. - a mutation in the cell DNA causes the production of a faulty growth factor receptor. - the new receptor can activate itself without the growth factor. - the receptor activates the intracellular cascade that leads to cell division. - the cell is now able to divide when it shouldn't. - the faulty receptor DNA is passed on to the daughter cells. - results in uncontrolled growth.

Radiation Cancer Therapy

- one of the most common treatments for cancer. - uses high-energy particles or waves, such as x-rays, gamma rays, electron beams, or protons, to destroy or damage cancer cells. - works by making small breaks in the DNA inside cells, which keep cancer cells from growing and dividing and cause them to die. - nearby normal cells can also be affected, but most recover and go back to working the way they should. - typically a local treatment. - doesn't reach all parts of the body, which means they're not helpful in treating cancer that has spread to many places within the body.

Diet & Obesity (cancer risk)

- poor diet with reduced physical activity may increase the risk of several diseases - coronary heart disease, stroke, high blood pressure, diabetes, and cancers. - some artificial food additives have been associated with cancer and other human diseases. - antioxidants help to prevent cancer by preventing oxidative DNA damage. - physical activity causes muscle cells to use more oxygen, leaving less for cancer cells to access. - physical activity decreases insulin, insulin-like growth factors, obesity, inflammation, free radicals. - physical activity increases gut motility.

6. Tissue invasion and metastasis.

- primary tumors spawn pioneer cells that move out, invade adjacent tissues, and travel to distant sites. - enables cancer cells to colonize in parts of the body where they can find additional space and nutrients. - the cause of 90% of human cancer deaths.

Cancer Staging

- refers to the extent of your cancer, such as how large the tumor is, and if it has spread. - helps with understanding how serious the cancer is. - a cancer is always referred to by the stage it was given at diagnosis, even if it gets worse or spreads. - new information is added on to the original stage. - includes information about tumor location and size, whether the cancer has spread to lymph nodes or other parts of the body, and tumor grade (how abnormal the cells look). - different systems are used for different cancers.

Biopsy

- removing a small piece of tissue (called a sample) for diagnostic examination. - one way to help diagnose cancer. - how to know if a person has cancer and what kind of cancer it is.

Preventative Surgery

- surgery done to remove body tissue that's likely to become cancer - even though there are no signs of cancer at the time of the surgery. - women with a strong family history of breast cancer, etc.

7. Reprogramming energy metabolism.

- the ability of cancer cells to alter their metabolism. - supports the increased energy request due to continuous growth and rapid proliferation. - activated by oncogenes and mutated tumor suppressors. - cancer cells extract nutrient from the blood. - are able to divide even in hypoxic or acidic states. - use products of aerobic glycolysis for rapid cell growth. - convert glucose to lactate even when oxygen is present.

8. Evade the immune system.

- the immune system likely encounters and eliminates cancer cells on a daily basis. - some cancer cells possess mechanisms that allow them to escape the immune responses. - cancer cells deliver signals that cause immune cells to become ineffective. - a major stumbling block in designing effective anticancer therapeutic strategies.

TNM Staging System

- the most widely used cancer staging system. - the T refers to the size and extent of the primary tumor. - the N refers to number of nearby lymph nodes that have cancer. - the M refers to whether the cancer has metastasized. - there will be numbers after each letter that give more details about the cancer.

Metastasis

- the process by which cancer cells break away from the original tumor (primary tumor), travel through the body, and begin to grow in other tissues and organs. - cancer cells move into nearby blood vessels and lymph vessels and travel throughout the body. - some cancer cells die while traveling. - other cancer cells survive and stick to vessel walls, then move through the vessel wall into another body tissue. - causes death by damaging important organs (brain, lungs, liver, etc.)

Cell Cycle

- the process the cell needs to go through in order to divide. - growth stage (G1). - DNA replication stage (S stage). - second growth stage (G2). - mitosis (M) - resting phase (G0): performing normal function and don't enter the cell cycle and divide.

Air & Water Pollution (cancer risk)

- the results of biological, biochemical and atmospheric particles which cause damages to our living environment. - air pollution is a significant risk factor for respiratory infections, cardiac disease and lung cancer. - water pollution is caused by microorganisms, wastes, acids, salts, toxic metals, water-soluble nitrates and phosphates, and organic compounds which cause various human diseases, including cancer.

Immunotherapy for Cancer

- treatment that uses certain parts of a person's immune system to fight diseases such as cancer. - immune system like substances are made in a lab and given to the patient. - stimulates or boosts the immune system to work harder and smarter to attack cancer cells. - works better for some types of cancer than for others. - used by itself or with other treatments.

Malignant Tumor

- tumors that can grow slowly or fast. - cells are poorly differentiated and do not look like the tissue of origin (anaplasia). - usually cancerous. - carry the risk of spreading and destroying multiple tissues and organs. - fatal if left untreated. - can arise in bodily structures such as breasts, skin, lymph nodes, GI tract, and others.

Benign Tumor

- tumors that grow slowly and do not transfer to cancer. - cells are well differentiated and look like the tissue of origin. - do not have the capacity to spread to other tissues. - not life threatening. - includes uterine fibrosis, skin moles, and lipomas. - suffix -oma.

Metastatic Tumors

- tumors that have developed after the primary tumor metastasizes. - example: if colon cancer metastasizes to the liver, it is still colon cancer, not liver cancer.

Stem Cell Transplant for Cancer

- used to give back stem cells when the bone marrow has been destroyed by disease, chemotherapy (chemo), or radiation. - also called a bone marrow transplant, peripheral blood stem cell transplant, or cord blood transplant, depending on where the stem cells come from.

Restorative Surgery

- used to improve the way a person looks after major cancer surgery. - also used to restore the function of an organ or body part after surgery. - breast reconstruction, bone grafts, prosthetics, etc.

Debulking Surgery

- used to remove some, but not all, of the cancer. - done when taking out the entire tumor would cause too much damage to nearby organs or tissues. - designed to take out as much of the tumor as possible and then treat what's left.

Palliative Surgery

- used to treat problems caused by advanced cancer. - used with other treatments to correct a problem that's causing discomfort or disability. - done to help ease problems not to treat or cure the cancer. - the cancer is usually in an advanced stage.

Curative Surgery

- usually done when cancer is found in only one part of the body and it's likely that all of the cancer can be removed. - the purpose of the surgery is to remove all of the cancer completely.

Signs & Symptoms of Cancer

- varies depending on where the cancer is, how big it is, and how much it affects nearby organs or tissues. general signs & symptoms: - fatigue or extreme tiredness. - weight loss or gain for no known reason (10lbs+). - eating problems (not feeling hungry, trouble swallowing, belly pain, nausea, vomiting). - swelling or lumps in the body. - pain (new or with no reason). - skin changes (lump that bleeds, new mole, change in a mole, sore that doesn't heal, jaundice). - cough or hoarseness that doesn't go away. - unusual bleeding or bruising for no known reason. - change in bowel habits (constipation, diarrhea, change in stool appearance). - bladder changes (pain when urinating, blood in urine, urinating more or less often). - fever or night sweats. - headaches. - vision or hearing problems. - mouth changes (sores, bleeding, pain, numbness). *and significant long lasting or worsening changes in the way your body works or the way you feel.

Cachexia

- weakness and wasting of the body due to severe chronic illness. - causes extreme weight loss and muscle wasting. - a symptom of many chronic conditions such as cancer, chronic renal failure, HIV, and multiple sclerosis.

Hematopoietic Stem Cells

- young, immature white blood cells, red blood cells, and platelets (blood forming cells). - formed in bone marrow. - can mature into any type of blood cell, depending on what the body needs.

5. Sustained angiogenesis.

-a blood supply is needed for cancer cells to grow. -cancer cells stimulate the growth of blood vessels to supply nutrients to tumors. - this plays an important role in tumor growth.

Hallmarks of Cancer

1. self-sufficiency in growth signals. 2. insensitivity to anti-growth signals. 3. evade apoptosis. 4. limitless replicative potential. 5. sustained angiogenesis. 6. tissue invasion and metastasis. 7. reprogramming energy metabolism. 8. evade immune system 9. genomic instability. 10. chronic inflammation.

Peripheral Blood Stem Cells

A small number of the immature stem cells that get into the bloodstream.

Common sites where cancer spreads

Bladder: bone, liver, lung. Thyroid: bone, liver, lung. Prostate: bone, liver, lung, adrenal gland. Uterus: bone, liver, lung, peritoneum, vagina. Breast: bone, liver, lung, brain. Kidney: bone, liver, lung, brain, adrenal gland. Lung: bone, liver, other lung, brain, adrenal gland. Melanoma: bone, liver, lung, brain, skin, muscle. Colon: liver, lung, peritoneum. Ovary: liver, lung, peritoneum. Rectal: liver, lung, peritoneum. Pancreas: liver, lung peritoneum. Stomach: liver, lung, peritoneum.

Distant Cancer

Cancer has spread to distant parts of the body.

Regional Cancer

Cancer has spread to nearby lymph nodes, tissues, or organs.

Localized Cancer

Cancer is limited to the place where it started, with no sign that it has spread.

Types of Sarcoma

Histology: benign / malignant - bone: osteoma / osteosarcoma - cartilage: chondroma / chondrosarcoma - adipose tissue: lipoma / liposarcoma - fibrous tissue: fibroma / fibrosarcoma - embryonic fibrous tissue: myxoma / myxosarcoma - smooth muscle: leiomyoma / leiomyosarcoma - skeletal muscle: rhabdomyoma / rhabdomyosarcoma - blood vessels: hemangioma / hemangiosarcoma or angiosarcoma - membranous lining (mesothelium): benign mesothelioma / mesothelioma - lymph vessels: lymphangioma / lymphangiosarcoma - brain and spinal cord: benign glioma / glioma or astrocytoma - mixed connective tissue: mixed mesodermal tumor

Unknown Cancer

There is not enough information to figure out the stage.

Palliative Care

Treatment used to reduce symptoms or improve comfort.

Proliferation

rapid reproduction of a cell.

Frailty

the condition of being weak and delicate.

Tumorigenesis

the production or formation of a tumor or tumors.

Oncology

the study of tumors/neoplasia.