Pathophysiology Unit 3

Tumor markers

Substance (antigens) that is detectable on the surface of a tumor cell

Tumor markers

Released from normal cells in response to presence of a tumor

Tumor markers

Some of the most useful __________ have been HcG, PSA, and Calcitonin

Tumor markers

Have limited values in screening tests because of differing levels in benign and early cancer states

Tumor markers

Widely used in clients with wide spread cancer to gauge the course of disease

Tumor markers

Levels are increased with rampant disease and decreased with abatement (control)

Tumor markers

Also known as cell surface antigens

Tumor markers

diagnosis of cancer is made by the presence of antigens expressed on the surface of tumor cells or substances released by normal cells in response to the presence of a tumor

HcG

Human chronic gonadotropin/useful tumor marker

PSA

Prostate specific antigen/useful tumor marker

Calcitonin

Used in identification of thyroid tumors/ useful tumor marker

Neoplasia

New growth that is uncoordinated

Neoplasia

A disorder of cell proliferation and differentiation

Neoplasia

Cells that grow without waiting for signals from the body that new tissue is needed

Neoplasia

Cells that ignore signals to stop dividing

Neoplasia

Cells that often do not mature normally (differentiate) to do the "job" the tissue is supposed to do

Neoplasia

Cells that do not die off (apoptosis) to keep the number of cells constant

Normal Cell division

The number of cells produced equals the number of cells that die (homeostasis)

Normal Cell division

The total number of cells in the body remains constant

Normal Cell division

Each cell follows a normal pattern of growth and reproduction controlled by the cells DNA

Normal Cell division

If the DNA is altered in the parent cell it will pass the mutation to the daughter cell.

Changes in cellular DNA

_______________can cause dysfunction, alter the cell structure, and lead to early cell death

Changes in cellular DNA

_____________can be caused by exposure to chemicals, viruses, environmental hazards, or radiation

Changes in cellular DNA

It is also possible for DNA to spontaneously mutate and cause _______________

Cellular proliferation and differentiation

Is necessary for tissue growth and repair

Proliferation

Tissues that are able to gain new or replacement cell by cell division is experiencing ___________

Proliferation

An example of __________ is, bleeding stimulates cell formation in bone marrow.

Differentiation

Proliferating cells transformed into different and more specialized cells are undergoing _________________

Differentiation

Cells can no longer perform cell division after it has gone completely through _______________

Differentiation

The process of specialization. Where new cells acquire the structure and function of the cells they replace.

Differentiation

The process by which cells are transformed into different more specialized cell types as they proliferate.

Characteristics of cancer cells

Cells have poor cellular differentiation which increases the growth rate

Characteristics of cancer cells

Cells have membrane changes such as decreased contact inhibition and decreased cohesiveness

Characteristics of cancer cells

Cell surface has antigens (tumor markers)

Decreased contact inhibition

Cells do not stop dividing when they come in contact with each other

Decreased cohesiveness

Malignant cells have __________. This is why they spread so easy. (they are able to break away from each other and get into the blood stream).

Growth factors

___________ attach to receptor proteins- which often work by affecting G proteinswhich turn on enzymes (proteins) which make second messengers which go down inside the cell and make it divide.

Growth factors

Cells divide only when they are told to do so by __________

Growth factors

Cause stable cells to enter the cell cycle and divide

Cell(s)

All ______ create proteins based on its genes... such as growth factor receptors

Cell(s)

Any ____ can mutate

Growth factor receptors

Ready the cell to respond to growth factors from another cell

Growth factor receptors

Growth factors bind to __________ and simulate cell division

M Phase

Mitotic Phase

Mitotic Phase

Includes Prophase, Metaphase, Anaphase, Telephase

G1 Phase

First growth phase

G1 Phase

Phase includes growth and normal metabolic roles

S Phase

Synthesis Phase

S Phase

Includes interphase

S Phase

Phase where DNA is replicated

G2 Phase

Second growth phase

G2 Phase

Phase includes growth and preparation for mitosis

Benign tumors

When differentiated, "working" cells mutate, they form differentiated "working" tumors, known as
_______ _______.

Benign tumors

Contains cells that look like normal tissue cells

Benign tumors

May perform the normal function of the tissue (like secreting hormones, however, could lead to over secretion)

Benign tumors

Usually encapsulated (has boundaries)

Benign tumors

Growth rate is generally slow

Benign tumors

Dose not metastasize

Benign tumors

Produces death to host by encroachment of vital organs/tissues

Benign tumors

Usually does not invade neighboring tissues

Benign tumors

When being named, they usually end in OMA

Benign tumors

Cause more local symptoms, non-cancerous

Benign tumors

Well differentiated

Benign tumors

Capable of causing damage to nearby organs by compressing them

Malignant tumors

When undifferentiated, rapidly dividing cells mutate, they form rapidly dividing tumors known as, _________ ________.

Malignant tumors

Contains cells that do not look like normal adult cells

Malignant tumors

These cells divide rapidly, so tumors grow quickly, cells also mutate faster and change type

Malignant tumors

The tumor does not have clear boundaries and sends "legs" out into surrounding tissue

Malignant tumors

Do not perform the normal functions of the organ/tissue cells

Malignant tumors

May secrete hormones associated with other tissues

Malignant tumors

Can compress and/or destroy the surrounding tissue

Malignant tumors

Cause more wide spread systemic symptoms and can cause death

Malignant tumors

When named usually end in carcinoma

Malignant tumors

Tumor has poor differentiation

Malignant tumors

Infiltrates tissues, tumor has no boundaries

Malignant tumors

Growth is usually rapid

Malignant tumors

Tumor eventually metastasizes

Malignant tumors

Tumor produces death to the host by producing vital organ dysfunction (necrosis and ischemia) or death by organ failure

Cancer

Means "crab" due to _______ cells having crablike legs

Cancer

Distribution of disease is across a life span (at all ages) but is responsible for more deaths in the 3-15 year old range than any other disease.

Cancer

Survival rates are improving

Cancer

__________ is not a single disease, but can appear in almost any organ

Cancer

A cure for _________ is dependent on type of cancer and the extent of the disease at diagnosis

Cancer

________ Cells are uncontrolled and poorly differentiated

Cancer

2nd leading cause of mortality in the US

Oncogenesis

The genetic mechanism where normal cells are transformed into cancer cells. (Beginning of cancer) Malignant tumors

Tumor cell transformation

Cell goes through three phases. Initiation, promotion and progression

Initiation

During cell transformation the initial mutation occurs

Promotion

During cell transformation the mutated cells are simulated to divide

Progression

During cell transformation tumor cells compete with each other and develop more mutations which make them more aggressive.

Types of oncogenes

Viral oncogenes, cellular oncogenes, and proto-oncogenes

Viral oncogenes

A virus that can produce cancer by entering a host cell and becoming part of the cell's DNA structure

Viral oncogenes

Types of ______________are HPV, EBV, HBV, and HTLV-1

Viral oncogenes

15% of all cancers

HPV

Human papilloma virus

EBV

Epstein-barr virus

HBV

Hepatitis B virus

HTLV-1

Human T-cell leukemia virus

Cellular Oncogene

A normal gene that, when mutated can cause cancer to develop

Proto-Oncogene

A normal protein that codes for normal proteins used in cell division

Proto-Oncogene

Codes for growth factors, and growth factor receptors

Proto-Oncogene

Codes for G proteins, and enzymes that produce 2nd messengers

Proto-Oncogene

Codes for genes that turns the production of coded proteins on and off

Contact inhibition

Is the cessation of growth after a cell comes in contact with another cell, blocking its synthesis of DNA, RNA, and proteins

Cohesiveness

Normal cell walls help support each other when they come in contact with each other by sticking together.

Mutated Proto-oncogenes

Still code for proteins needed for cell division, however the proteins may not work properly and may be produced in excess.

Mutated Proto-oncogenes

____________ are capable of producing too much of a protein, or an abnormal protein

Mutated Proto-oncogenes

___________are capable of producing proteins that turns on all by themselves

Mutated Proto-oncogenes

___________ are capable of producing proteins that are made when not needed

Mutated Proto-oncogenes

_____________are capable of producing a protein that cannot turn cell division off

Mutated Proto-oncogenes

______________are capable of producing a protein that should have been made by a different cell

Cancer risk factors

Genetic predisposition combined with environmental hazards and life style may promote the development of some cancers.

Cancer risk factors

Heredity, hormonal factors and immunologic mechanisms have been linked to cancer.

Genetic predispositions

Heredity, hormones and immunologic mechanisms

Environmental hazards

Chemical carcinogens, radiation, oncogenic viruses

Chemical carcinogens

Air pollution and occupational hazards

Radiation

Includes both Ionizing and non-ionizing ___________

Radiation

Risk is determined on intensity and length of exposure

Lifestyle risks

Include diet, tobacco use, and sexual behaviors

Diet

A person can predispose themself to develop cancer with a __________ high in fat and low in fiber. Also, if nitrate consumption is increased.

Diet

Types of cancers caused by ____________ are stomach cancer and colon cancer

Diet

1/3 of cancer causes are related to ___________

Tobacco

A person can predispose themselves to develop cancer with the use of ________________. (primary and secondary and oral use is a risk factor).

Tobacco

Types of cancers caused by _____________ are lung cancer and oral cancer

Tobacco

1/3 of all cancer cases

Sexual behaviors

A person can predispose themselves to develop cancer with their _________________, by engaging in coitus prior to 18 yrs. Old, by having more than 2 sexual partners in a life time, or by having a partner with multiple partners.

Sexual behaviors

Types of cancers caused with poor _______________ are cervical cancers and testicular cancers.

Immunosuppression

Allows tumor cells to go undetected until they are established and difficult to eliminate

Immunosuppression

allows for successful spreading of tumors because the tumor is able to escape the hosts immune defenses

Grow up

Normally after a cell has divided, it becomes either a permanent or a stable cell. These cells stop reproducing and get to work for the body.

Grow up

Cells are called differentiated because they look different form one another, you can tell a spleen cell from a skin cell.

Tumor immunobiology

Includes both tumor surveillance hypothesis and immune surveillance escape mechanisms

Tumor surveillance hypothesis

The ability of the immune system to recognize and react to antigens produced by cancerous tumors as it would any other foreign antigen

Immune surveillance escape mechanisms

The ability of cancer cells to avoid or resist the host's immune response

Mechanisms of cancer spread

Lack of a well-defined border makes complete excision difficult if not impossible

Mechanisms of cancer spread

Methods of spread are direct extension, seeding, and metastasis

Direct extension

Cancer spreads to tissues adjacent to primary tumor

Direct extension

Malignant tumors grow rampantly by filtration and invasion of surrounding tissues.

Seeding

Tumor cells are shed from primary tumor and develop into more tumors

Seeding

Erosion of cancer cells into body cavities

Metastasis

Tumor cells travel through the blood and or lymph vessels and develop in a site distant form the primary tumor.

Metastasis

Metastatic cells have enzymatic qualities that enable them to breakdown a cells matrix and invade surrounding tissues through the blood stream

Tumor growth

Depends on how many cells that are actively engaged in proliferation, the duration of cell cycle, and number of cells lost vs. number of cells produced

Process of tumor spread

Attachment, dissolution and locomotion

Attachment

The tumor cell attaches to the basement membrane of the tissue affected

Dissolution

The tumor cell secretes substances to break down the cell membrane

Locomotion

The tumor cell moves (using pseudopods) into the tissue

Grading

Is according to histological (cellular) characteristics

Grading

diagnosis is made by the ____________ being governed by the histologic or cellular characteristics.

Grading

For an example, the surgeon would rather remove and the histologist would determine the level of differentiation of the cells.

Grading

The tumor cells would be categorized as grade 1-4, with the most poorly differentiated cells grade 4

Grading

This method is used to determine tumor size and lymph node involvement

Staging

Is the definition of the extent of the disease by category

Staging

In _____________ T= primary tumor

Staging

In _____________ N = Node involvement

Staging

diagnosis is made by the classification of cancers by ____________ them according to the clinical spread of the disease

Staging

In ____________ M = Metastatic spread

Staging

For an example, the surgeon would classify a tumor as a "ToNoMo" if there was no evidence of a tumor (To), no node involvement (No), and no metastasis (Mo)

Diagnostic methods

PAP test, biopsy, staging, grading and by the presence of tumor markers

PAP test

diagnosis is made through microscopic cytology

Biopsy

diagnosis is made by removal of tissue for microscopic study

Successful spread of a tumor is dependent on

The tissue invaded is compatible to the tumor cell type

Successful spread of a tumor is dependent on

The tumor being able to escape the hosts immune system

Successful spread of a tumor is dependent on

The tumor being able to access a blood supply (via angiogenesis)

Clinical manifestations of cancer

Tissue integrity, pain, cachexia, paraneoplastic syndroms, blood dyscrasias, and infection

Tissue integrity

Tissues involved with cancer are friable (easily broken) and hemorrhagic.

Tissue integrity

Cancer disrupts _______________by creating obstruction, pain from tissue erosion and compression, ulceration, and necrosis

Pain

Is caused by pressure/stretching, obstruction, and invasion of tissues by tumor

Pain

There is usually little or no ____________ in early stages, but is manifested in late stages.

Pain

_____________ management is of major concern in cancer treatment

Cancer Cachexia

wasting" syndrome related to malnutrition and increased BMR from growing tumor(s)

Cancer Cachexia

Is identified with wasting of body fat and muscle tissue

Cancer Cachexia

Can become exacerbated (made worse) by cancer therapies

Blood dyscrasias

include Anemia, Leukopenia, and Thrombocytopenia

Anemia

is caused from bleeding, malnutrition, and cancer treatments (especially radiation therapy)

Anemia

is a condition in which the body does not have enough healthy red blood cells (red blood cells provide oxygen to the body tissues)

Leukopenia

is caused from bone cancers or cancer treatments

Leukopenia

is a condition where there is a decrease in WBC, which causes a decrease in disease fighting cells that are circulation in the blood stream

Thromnocytopenia

is caused from bone cancers or cancer treatment

Thromnocytopenia

is a condition is which your blood has a lower than normal number of blood cells called fragments called platelets.

Platelets

are also called thrombocytes.

Platelets

travel through you blood vessels and stick together (clot) to stop bleeding that may happen if a blood vessel is damaged.

Infection

most significant cause of mortality

Infection

risk of __________ is increased due to malnutrition and blood dyscrasias

Paraneoplastic syndrome

is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells.

Paraneoplastic syndrome

These phenomena are mediated by humoral factors (by hormones or cytokines) excreted by tumor cells or by an immune response against the tumor.

Paraneoplastic syndrome

an example, some cancers heighten the body's ability for hypercoaguability and venous thrombosis

dyscrasias

means disease or disorder

cancer treatment goals

Curative, adjuvant (or control), and palliative

Curative

the goal is to have the cancer eliminated from the body

Adjuvant (or control)

the goal is that treatment will prolong the individuals life by slowing the growth and or prevent the spread of cancer.

Palliative

the goal is that treatment will provide comfort to the individual with terminal (life expectancy < 6 months) cancer

Cancer treatment types

chemotherapy, radiation, surgery, immunotherapy, and BRM's (biologic response modifiers)

Chemotherapy

has evolved as one of the major systemic treatment modalities.

Chemotherapy

enables drugs to reach the site of the tumor

Chemotherapy

there are different classifications of ___________________ based on the drugs mechanism of action

Chemotherapy

in _____________ multiple drugs may be used or may be used with other therapies

Chemotherapy

_______________ has adverse reactions such as nausea, vomiting, diarrhea, bone marrow suppression, and secondary malignancies

Radiation

Primary method of treatment (postoprative and preoprative)

Radiation

may be used with chemo or chemo-surgery treatment

Radiation

when coupled with palliative treatments it reduces symptoms for a person with advanced cancer

Radiation

ionizing ____________ may be used externally or internally ( implants)

Radiation

most effective treatment for rapidly growing, poorly differentiated tumor cells

Radiation

_____________has adverse reactions such skin problems, mucous membranes, bone marrow suppression, and alopecia

Surgery

is used for diagnosis, staging of cancer, and tumor removal

Surgery

is a component of adjuvant therapy with chemo or radiation therapy

Surgery

May be used curative, adjuvant or palliative care

Surgery

May assist with "TNM" identification

Immunotherapy

immune system identifies and destroys cancer cells without damaging normal cells with the use of biological response modifiers

Immunotherapy

also known as biotherapy

Colony stimulation factors

stimulates bone marrow to increase cell production to restore what is lost through cancer therapy

Colony stimulation factors

They do not directly affect tumors but through their role in stimulating blood cells they can be helpful as support of the person's immune system during cancer treatment.

Tumor Vaccines

vaccines would be used following a cancer diagnosis to prevent recurrence, get the body to reject tumor lumps and to prevent metastasis

Tumor Vaccines

vaccines are used after someone has cancer

Immunotherapy advantages

Immunotherapy has a high specificity for antigens

Immunotherapy advantages

Immunotherapy creates immune memory cells that give long protection

BRM's (Biologic Response Modifiers)

substances that are able to trigger the immune system to indirectly affect tumors

BRM's (Biologic Response Modifiers)

These include cytokines such as interferon's and interleukins

BRM's (Biologic Response Modifiers)

This strategy involves giving larger amounts of these substances by injection or infusion in the hope of stimulating the cells of the immune system to act more effectively.

BRM's (Biologic Response Modifiers)

Mobilizes the patient's immune system to fight cancer

BRM's (Biologic Response Modifiers)

Have direct cytotoxic effects

BRM's (Biologic Response Modifiers)

Initiate/augment the hosts tumor-immune rejection

BRM's (Biologic Response Modifiers)

Increases cancers susceptibility to the immune system

BRM types

cytokines, monoclonal antibodies, and hematopoietic growth factors

Monoclonal antibodies

These antibodies can be useful in fighting diseases because they can be designed specifically to only target a certain antigen, such as one that is found on cancer cells.

Monoclonal antibodies

A major advantage of these drugs is that because they are so specific, they may have only mild side effects, unlike some other cancer treatments

hematopoietic growth factors

are a group of substances with the ability to support hematopoietic (blood cell) colony formation in vitro

hematopoietic growth factors

This group of substances includes erythropoietin, interleukin-3 and colony-stimulating factors (CSFs).

hematopoietic growth factors

used to promote bone marrow proliferation in aplastic anemia, following cytotoxic chemotherapy, or following a bone marrow transplant

cytokines

regulate the innate immune system: natural killer (NK) cells, macrophages, and neutrophils. They also regulate the adaptive immune system, the T and B cell immune responses

cytokines

messengers of the immune system

etiology

the study of causes of a disease

Pediatric cancers

are usually found by accident

Pediatric cancers

patients are usually tolerant to treatment

Pediatric cancers

patients have long term side effects

Pediatric cancers

Most tend to be diagnosed during peak growth times

Pediatric cancers

cancer is often overlooked because common childhood disease signs and symptoms are often similar to those of cancer

Pediatric cancers

cancer is less prevalent in children and is not expected on routine examinations

Pediatric cancers

most involve the hematopoietic system, connective tissue, nervous system, or nervous tissue

Pediatric cancers

Leukemia's account for 1/3 of childhood cancers

Pediatric cancers

Embryonic tumors(usually diagnosed before 5) are very rare

Pediatric cancer incidence

second leading cause of death by disease in children 1-14 years of age

Pediatric cancer incidence

80% of cancers have metastasized at time of diagnosis

Pediatric cancer incidence

1% of all cancer cases are children

Pediatric cancer incidence

Patient is usually predisposed

Pediatric cancer incidence

genetic causes are greater than environmental causes

Pediatric cancer incidence

few cancers can be prevented

long term side effects

altered sex cells

long term side effects

neurologic dysfunction

long term side effects

impaired growth

long term side effects

high risk of second malignancies

Adult cancers

99% of all cancer cases are adults

Adult cancers

environmental causes are high

Adult cancers

80% can be prevented

Adult cancers

detection of cancer is during routine/screening exams

Adult cancers

usually intolerant to treatment

Adult cancers

less responsive to treatment