231 - Abnormal Cell - Ch. 16 Cancer Management

Front 1

alopecia

Back 1

hair loss

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anaplasia

Back 2

cells that lack normal cellular characteristics and differ in shpae and organization with respect to their cells of origin; usually, anaplastic cells are malignant

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apoptosis

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programmed cell death

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biologic response modifier (BRM) therapy

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use of agents or treatment methods that can alter the immunologic relationship between the tumor and the host to provide a therapeutic benefit

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biopsy

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a diagnostic procedure to remove a small sample of tissue to be examined microscopically to detect malignant cells

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brachytherapy

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delivery of radiation therapy through internal implants

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cancer

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a disease process wherby cells proliferate abnormally, ignoring growth-regulating signals in the environment surrounding the cells

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carcinogenesis

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process of transforming normal cells into malignant cells

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chemotherapy

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use of medications to kill tumor cells by interfering with cellular functions and reproduction

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control

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containment of the growth of cancer cells

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cure

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prolonged survival and disappearance of all evidence of disease so that the patient has the same life expectancy as anyone else in his or her age group

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cytokines

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substances produced by cells of the immune system to enhance production and functioning of components of the immune system

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dysplasia

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bizarre cell growth resulting in cells that differ in size, shape, or arrangement from other cells of the same type of tissue

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extravasation

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leakage of medication from the veins into the subcutaneous tissues

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grading

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identification of the type of tissue from which the tumor originated and the degree to which the tumor cells retain the functional and structural characteristics of the tissue of origin

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graft-versus-host disease
(GVHD)

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an immune response initiated by T lymphocytes of donor tissue against the recipient's tissues (skin, GI tract, liver); an undesirable response

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graft-versus-disease effect

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the donor cell response against the malignancy; a desirable response

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hyperplasia

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increase in the number of cells of a tissue; most often associated with periods of rapid body growth

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malignant

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having cells or processes that are characteristic of cancer

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metaplasia

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conversion of one type of mature cell into another type of cell

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metastasis

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spread of cancer cells from the primary tumor to distant sites

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myelosuppression

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suppression of the blood cell-producing function of the bone marrow

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nadir

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lowest point of WBC depression after therapy that has toxic effects on the bone marrow

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neoplasia

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uncontrolled cell growth that follows no physiologic demand

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neutropenia

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abnormally low absolute neutrophil count

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oncology

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field or study of cancer

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palliation

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relief of symptoms associated with cancer

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radiation therapy

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use of ionizing radiation to interrupt the growth of malignant cells

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stomatitis

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inflammation of the oral tissues, often associated with some chemotherapeutic agents

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staging

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process of determining the size and spread, or metastasis, of a tumor

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targeted therapies

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cancer treatments that seek to minimize the negative effects on healthy tissues by disrupting specific cancer cell functions such as malignant transformation, communication pathways, processes from growth and metastasis, and genetic coding

Front 32

thrombocytopenia

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decrease in the number of circulating platelets; associated with the potential for bleeding

Front 33

tumor-specific antigen (TSA)

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protein on the membrane of cancer cells that distinguishes the malignant cell from a benign cell of the same tissue type

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vesicant

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substance that can cause tissue necrosis and damage, particularly when extravasated

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xerostomia

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dry oral cavity resulting from decreased function of salivary glands

Front 36

epidemiology of cancer

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most in 65 yo
men > women
> industrialized sectors and nation

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leading causes of death in US

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1. cardiovascular disease
2. cancer

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leading causes of cancer death in US men/women

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1. lung/lung
2. prostate/breast
3. colorectal/colorectal

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cancer is a disease process that begins when ...

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an abnormal cell is transformed by the genetic mutation of the cellular DNA. this abnormal cell forms a clone and begins to proliferate abnormally, ignoring growth-regulating signals int he environment surrounding the cell. the cells acquire invasive characteritics, and changes occur in surrounding tissues. the cells infiltrate these tissues and gain access to lymph and blood vessels which carry the cells to other areas of the body. (metastasis)

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The malignant potential is ultimately determined by...

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the degree of anaplasia

Front 41

Common cellular characteristics of all cancer cells - cell membranes

Back 41

altered, which affects fluid movement in an out of cell
2. of malignant cells - contains proteins called tumor-specific antigens (CEA and PSA)
3. malignant membranes - contain less fibronectin (a cellular cement), so are less cohesive and do not adher to adjacent cells readily

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tumor-specific antigens

Back 42

CEA - carcinoembryonic antigen
PSA - prostate-specific antigen

-develop as they become less differentiated (mature) over time
-proteins in the cell wall of malignant cells that distinguish them from benign cells
-useful in measruing the extent of disease and in tracking the course of illness during treatment or relapse

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common cellular characteristics of cancer cells

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-nuclei are large and irregularly shaped (pleomorphism)
-nucleoli (house RNA) are larger and more numerous in malignant cells, perhaps because of increased RNA synthesis
-chromosomal abnormalities and fragility of chromosomes are common
-mitosis occurs more frequently in maliignant cells
-

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as malignant cells grow and divide, more....

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more glucose and oxygen are needed. if glucose and oxygen are unavailable, malignant cells use anaerobic metabolic channels to produce energy, which makes them cells less dependent on the availability of a constant oxygen supply

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invasion

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growth of the primary tumor into the surrounding host tissues

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ways of invasion

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-mechanical pressure - exerted by rapidly proliferating neoplasms forcing fingerlike projections of tumor cells into surrounding tissue and intersititial spaces
-malignant cells are less adhernt and may break off from the primary tumor and invade adjacent structures
-malignant cells possess or produce destructive enzymes that destroy surrounding tissue, also facilitating invasion

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mechanisms of metastasis (3)

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1. lymphatic spread
2. hematogenous spread
3. angiogenesis

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lymphatic spread

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-the most common mechanism of metastasis
-tumor emboli enter the lymph channels by way of the interstitial fluid or by penetrateing lymphatic vessels by invastion
-then either lodge in the lymph nodes or pass between the lymphatic and venous circulations
-ex breast tumors frequently metastasize this way

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hematogenous spread

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-the dissemination of maignant cells via the bloodstream
-directly reated to the ascularity of the tumor
-few malignant cells can survive the turbulence of arterial circulation, insufficient oxygenation, or destruction by the immune system, and structure of most arteries and arterioles is far too secure to permit malignant invasion.
-those that do survive - attach to endothelium and seal themselves from the immune system. secrete enzymes, become implanted

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angiogenesis

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the growth of new capillaries from the host tissue by the release of growth factors and enzymes such as vascular endothelial growth factor (VEGF)

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3 steps of carcinogenesis

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1. initiation
2. promotion
3. progression

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initiation of carcinogenesis

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-carcinogens (initiators) escape normal enzymatic mechanisms and alter the genetic structure of the cellular DNA. they escape normal protective mechanisms and permanent cellular mutation occur. these are usually not significant until the 2nd step of carcinogenesis

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normally, alterations to DNA...

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are reversed by DNA repair mechanisms, or the changes initiate apoptosis

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promotion of carcinogenesis

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-repeated exposure to cocarcinogens (promoting agents) causes the expression of abnormal or mutant genetics information even after long latency periods

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promoting agents are aka..

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cocarcinogens

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cellular oncogenes

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responsible for growth and differentiation

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cellular proto-oncogenes

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"on switch" for cellular growth
-influenced by multiple growth factors that stimulate cell proliferation, such as EGF (epidermal growth factor) and transforming growth factor alpha
-also,KRAS2 oncogene on chromosome 12 plays an important role in cancer development

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cancer suppressor genes

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-turn off or regulate unneeded cellular proliferation
-when they become mutated, rearranged, or lose regulatory capabilities, malignant cells are allowed to reproduce
-ex p53 (TP53)

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p53 (TP53)

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cancer suppressor gene frequently mutated in many human cancers
-alteration may decrease apoptotic signals
-mutant TP53 is associated with a poor prognosis and may be associated with determining response to treatment

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progression of carcinogenesis

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cellular changes formed during initiation and promotion exhibit increased malignant behavior

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categories of etiology in carcinogenesis

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viruses and bacteria
physical agents
chemical agents
genetic or familial factors
dietary factors
hormonal agents

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Epstein Barr virus is highly suspect as a cause in ..

Back 62

-Burkitt lymphoma
-nasopharyngeal cancers
-some types of non-Hodgkin lymphoma and Hodgkin disease

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Herpes simplex type II, CMV, and HPV types 16,18, 31, and 33 are associated with

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dysplasia and cancer of the cervix

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hepatitis B and hepatitis C viruses are associated with

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cancer of the liver

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human T-cell lymphotropic virus is associated with..

Back 65

some lymphocytic leukemias and lymphomas

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HIV is associated with

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Kaposi's sarcoma

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bacterium Helicobacter pylori is associated with

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-gastric malignancy, perhaps secondary to inflammation and injury to gastric cells

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physical agents that act as carcinogens

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-UV rays
-ionizing radiation (x-rays, radiation therapy, radioactive materials, background radon gas radiation)
-tobacco use

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chemical agents that act as carcinogens

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-tobacco smoke, chewing tobacco, chemical substances found in the workplace

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____ of all cancers are thought to be related to the environment

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75%

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tobacco smoke is the singe most lethal chemical carcinogen and accounts for at least ____of cancer deaths

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30% of cancer deaths

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body sites most commonly affected by chemical exposure

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liver, lungs, and kidneys, probably because of their roles in detoxifying chemicals

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proactive (protective) dietary substances

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high fiber foods (fruits, vegetables, whole grain cereals)
cruciferous vegetables (cabbage, broccoli, cauliflower, Brussels sprouts, kohlrabi)

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dietary factors that increase the risk of cancer

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fats
alcohols
salt-cured or smoked meats
nitrate- and nitrite-containing foods
high caloric intake
obesity

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obesity is associated with

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endometrial cancer and postmenopausal breast cancers

Front 76

DES - diethylstilbestrol

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-a cause of vaginal carcinomas

Front 77

oral contraceptives and prolonged estrogen replacement therapy as carcinogens

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-increased incidence of hepatocellular, endometrial, and breats cancers
-decrease risk of ovarian cancer
-estrogen plus progesterone appears safer (decreases risk of endometrial cancer)
-

Front 78

WHI studies support what with hormonal therapy with estrogens and progestins

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discontinuing this type of therapy because if the increased risk of breast cancer, coronary heart disease, stroke and blood clots

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hormonal changes with increased pregnancies cause...

Back 79

a decreased incidence of breast, endometrial, and ovarian cancers

Front 80

role of the immune system

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some evidence indicates that the immune system can detect the development of malignant cells and destroy them before cell growth becomes uncontrolled. when the immune system fails to id and stop the growth of malignant cells, clinical cancer develops

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findings associated with neurofibramatosis type 1

Back 81

mutiple cafe au lait spots
axillary freckling
two or more neurofibromas

Front 82

findings associated with a polyposis syndrome

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multiple colon polyps

Front 83

findings associated with Cowden syndrome

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-facial trichilemmomas
-mucosal papillomatosis
-multinodular thyroid goiter
-thyroid adenomas
-macrocephyaly
-fibrocystic breast
-other fibromas or lipomas

Front 84

What cells are responsible for recognizing tumor-associated antigens?

Back 84

T lymphocytes and macrophages

Front 85

When T lymphocytes recognize tumor antigens, what happens next?

Back 85

other T lymphocytes that are toxic to the tumor cells are stimulated. these proliferate and are released into the circulation (a cytotoxic property)
-also, they can stimulate toher components of the immune system to rid the body of malignant cells

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lymphokines

Back 86

-produced by lymphocytes
-certain ones are capable of killing or damaging various types of malignant cells
-others can mobilize other cells, such as macrophages, that disrupt cancer cells

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interferon

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-produced by the body in response to viral infection
-possesses some antitumor properties

Front 88

antibodies produced by B lymphocytes

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-associated witht he humoral immune response
-also have some antitumor properties

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natural killer (NK) cells

Back 89

major component of the body's defense against cancer
-a subpopulation of lymphocytes that act by directly destroying cancer cells or by producing lymphokines and enzymes that assist in cell destruction

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What are the ways in which the immune system can fail?

Back 90

-if the body fails to recognizee the maignant cell as different from "self"
-when tumors do not possess tumor-associated antigens
-tumor antigen-antibody complexes may from that suppress further production of antibodies
-tumors can also change their appearance or produce substances that impair usual immune responses
-abnormal levels of host suppressor T-cells that diminish immune responses

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As a result of prolonged contact with a tumor antigen, the body may be depleted of the specific lymphocytes and no longer...

Back 91

be able to mount an appropriate immune response to this tumor and infection from other various pathogenic organisms

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primary prevention

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concerned with reducing the risks of cancer in healthy people

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secondary prevention

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involves detecting and screening to achieve early diagnosis and prompt intervention to halt the cancer process

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primary prevention knowledge

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-avoid carcinogens
-dietary and lifestyle changes
-medications that can reduce risk (ex. tamoxifen for breast cancer)

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tamoxifen

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can reduce the incidence of breast cancer by 49% in post-menopausal women identified as being at high risk for breast cancer

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which vitamins reduce cancer risk

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vitamins A and C

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TNM system for staging

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T-extent of the primary Tumor
N-lymph Node involvement
M-extent of Metastasis

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grading

Back 98

the classification of the tumor cells
-seek to define the type of tissue from which the tumor originated and the degree to which the tumor cells retain the functional and histologic characteristics of the tissue of origin
-obtain a sample of cells
-graded I to IV

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grade I tumors...

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well-differentiated tumors - closely resemble the tissue of origin in structure and function

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grade IV tumors...

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poorly differentiated or undifferentiated - tumors that do not clearly resemble the tissue of origin in structure of function
-more aggressive and less responsive to treatment than grade I

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range of possible treatment goals

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cure - eradication
control - prolonged survival and containment of cells
palliation - relief of symptoms

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modalities commonly used in cancer treatment...

Back 102

surgery
radiation therapy
chemotherapy
targeted therapy

Front 103

What is the ideal and most frequently used cancer treatment method?

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surgery

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What is the definitive method of identifying the cellular characteristics that influence all treatment decisions?

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diagnostic surgery, such as biopsy

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sentinel nodes

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lymph nodes that process lymphatic drainage for the involved area. sometimes biopsy these as well

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3 most common biopsy methods

Back 106

excisional
incisional
needle methods

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excisional biopsy

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-most frequently used for easily accessible tumors os the skin, breast, upper and lower GI tract, and upper respiratory tract
-can remove the entire tumor and surrounding marginal tissues as well to decrease the possibility that residual microscopic disease cells may lead to a recurrence of the tumor and decreases the chances of seeding the tumor

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"seeding" the tumor

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disseminating cancer cells through surrounding tissues

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incisional biopsy

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-performed if the tumor mass is too large to be removed
-a wedge of tissue from the tumor is removed for analysis
-cells must be representative of the tumor mass

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excisional and incisional approaches are often performed through...

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endoscopy. however surgical incision may be required to determine the anatomic extent or stage of the tumor

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needle biopsy

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-performed to sample suspicious masses that are easily accessible, such as some growths in the breast, thyroid lung, liver, and kidneys
-fast, inexpensive, usually local anesthesia
-decreases likelihood of seeding

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Tx

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primary tumor cannot be assessed

Front 113

T0

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no evidence of primary tumor

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Tis

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carcinoma in situ

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T1-T4

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increasing size and/or local extent of the primary tumor

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NX

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regional lymph nodes cannot be assessed

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N0

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no regional lymph node metastasis

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N1-N3

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increasing involvement of regional lymph nodes

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MX

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distant metastasis cannot be assessed

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M0

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No distant metastasis