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171 Cards in this Set

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Cancer arises when you get a mutation in what group of genes?
Social Control Genes
What are Social Control Genes involved in?
1. Regulate growth, division and differentiation
2. DNA repair
3. Cell mortality
4. Apoptosis
What is meant by cell mortality?
the life span of the cell is determined by the number of times they are allowed to divide
List the 4 basic phases of the spread of cancer.
1. Transformation
2. The transformed cells grow
3. Metastisis
4.
Describe the transformation phase of the spread of cancer.
Normal host cell is turned into a cancer cell
-Happens at the genetic level
-requires a mutation in the socal control gene
Do all cellular mutations bring about cancer?
No, only the ones that favor abnormal growth
What is formed in the growth stage of the spread of cancer?
A tumor
Define a tumor.
A collection of cancerous cells
What does a tumor require in order to grow larger?
A blood supply
What is direct extension?
As the tumor gets bigger it begins to metastize neihboring organs
When a tumor colonizes tissue away from the original manifestation, what form of metastisis has occurred?
Distant Metastsis
What two methods can a tumor travel the achieve distant metasis?
Through the circulatory system or the lymphatic system
In the metastsis phase, what are the two types of tumors that result?
Primary and Secondary
Which type of cancers can form metastisis without using the circulatory or lymphatic system?
Ovarian cancer
How does ovarian cancer metastisize?
The tumor sheds its cells in the endometrium and can land anywhere throughout the pelvic or peritoneal cavity
What is sceeding?
the sheding of metastisized cells of ovarian cancer throughout the pelvic cavity
What determines the clinical behavior of a cancer cell?
The cell type and origin
What is monoclonal tissue?
A single cell type that has the coapacity to change
What are the 2 phases of the cell cycle?
Interphase and Mitosis
List the stages of mitosis in order.
1. Prophase
2. Metaphase
3. Anaphase
4. Telophase
5. Cytokinesis
Describe the events of G1 phase.
Have and increase in enzyme activity (the ones necessary for DNA replication
-Preparing to make copies of its DNA
-Most cells spend the majority of their time in G1
What is occurring in S phase?
the cell is making copies of its DNA
Which phase has replication of RNA to prepare to split the cell ing half?
G2
Which cells are trapped in G0?
The limbo state of non-replicating cells such as cardiac or neuronal cells
How often do you see cardiac and neuronal cells with cancer?
Never because they are non-dividing cells
What are the Master Breaks?
the proteins that prevent the progression of the cell cycle
What are some possible areas for mutation to occur?
In the genes that code for the stimulation of cell growth or the ones that inhibit cell growth
In ____ of mitosis, the loose strands of DNA start to condese into organized chromosome
Prophase
In prophase, the _____ appears to disappear and the ______ starts to form?
nuclear membrane, mitotic spindle
What is the mitotic spindle?
intracellular proteins that are needed for movement, to align the chromosomes
-formed out of the cytoskeleton
In what phase do the chromosomes align down the center of the cell with the help of the mitotic spindle
Metaphase
Which 2 phases of mitosis are easiest to visualize on a slide>
Metaphase and anaphase
Which phase of mitosis marks the completion of NUCLEAR division?
Telophase
What is the term for the separation of the cytoplasm?
Cytokinesis
What is a totipotent cell?
The one cell of the zygote that can be any tissue
The mutlipotent cell is created from what process?
primary differentiation of the totipotent
What occurs with each differentiation step?
the cell's fate becomes more and more narrow
What are the 2 features of the terminally differentiated cell?
1. It can no longer divide
2. It is functionally mature
What is cancer's effect on differentiation?
Cancer often resists differentiation
Why does cancer resist differentiation?
It is advantageous for the cancer cells because it allows them to retain the ability to divide
What is the relationship between level of differentiation and malignancy?
The less differentiated the cancer cell, the more malignant
What is another way to describe the malignancy of a cancer cell?
The aggresiveness, how fast it grows and how invasive the cell is
How does differentiation go wrong?
When more than 50% of stem cells remain as stem cells
-or there is a mutation that allows them to differentiate but maintain their abililty to divide
What cell functionl problems are associated with leukemia?
You have a high number of undifferentiated WBCs that do not contribute to immunity, and therefore you are immunosuppressed
What is the gene that promote cancerous cell growth called?
oncogene
What will a cancerous mutation do to a gene who's normal function is to inhibit growth>?
the mutation will turn off the gene
If a normal gene acts to stimulate growth, what type of effect will a cancerous mutation have on this gene?
The mutation will overstimulate this gene causing overgrowth
What is the relationship with differentiation and cancer?
Cancerous cells act on receptors that bind to differentiation inducers and prevents the attachment. This allows the cell to ignore cues to differentiate and thus maintain its ability to multiply.
What chemical in an inhibitory pathway can bring about differentiation?
Differentiation Inducer
What type of genes are BRCA 1 and 2?
Tumor suppressor genes
What is the major function of BRCA 1 and 2?
They function to repaire damaged DNA
What does a mutation in BRCA 1 and 2 make the individual vulnerable to? Consider even the molecular level.
At the molecular level the individual has loss the ability to repair damaged DNA and thus increase the risk of cancer

-Specifically Breast and Ovarian cancer
What is the lifetime risk of breast cancer for individuals with BRCA 1 mutations?
60%
Other than mutations, what is another source for oncogenes?
Viral
What is the most common viral induced viral induced oncogene?
HPV
What infection has been found to be involved in 70% of all cervical cancer types/
HPV
What aspects of cell function could be targets of oncogenes?
1. Cell cycle control
2. Signal transduction
3. DNA repair
4. Cell growth
5. Cell differentiation
6 Transcriptional regulation
7. Apoptosis
8. Senescene
What is senescene?
Describes the limit to how many times a cell can make copies of itself
Why does a cell practice senescene?
There is a limit to the number of copies because with every copy that a cell makes of its DNA it becomes more vulnerable to mutation.
What happens to a cell that has a mutation in its senescene?
The cell becomes immortalized.
Nearly half of all tumor cells have what mutation?
a p53 mutation
What are 2 common proteins that are common for mutation?
-BRCA 1 and 2
-p53
-RB
What is RB?
Retinoblastoma

-The RB protein is a master break for the cell cycle
-strong tonic inhibition of the cell cycle
-many forms of cancer will have an RB gene mutation.
When is a p53 protein normally expressed?
When functional, it is expressed when a cell accumulates multiple sites of damaged along its DNA.

-Major initiator of apoptosis
What protein is a major initiator of apoptosis of a cell due to massive DNA damage?
p53
What are the 5 basic properties/behaviors of cancer cells?
1. proliferate despite lack of growth-initating signals from the environment

2. They escape signals to die and achieve a kind of immortality in that they are capable of unlimited replication

3. lose differentiated features and contribute poorly or not at all to the function of their tissue

4. Are genetically unstable and evolve by accumulating new mutations at a much faster rate than normal cells.

5. Invade their local tissue and overrun their neighbors
What does autonomy mean in terms of cancer cells?
They are independent of social cues
Define anaplastic in terms of cancer cells?
Loss of differentiation

-want to maintain their ability to multiply
Name the theory argues that some cells have developed the ability to produce and release growth factor onto themselves?
Autocrine stimulation theory
What are the 2 main mechanisms used by the oncogene to achieve autonomy and anaplasia?
1. Autocrine stimulation theory
2. Receptor changes
What type of changes can occur at the receptor level that lead to autonomy or anaplasia?
1. Growth mediated or production of constituently active receptors
2. down regulation of the receptors (differentiation inducers)
3. can modify signal transduction pathway
4. remove the element that brings about an inhibitory pathway, causing unrestrained growth
What is the average number of divisions that can occur before senescence?
50-60
What is the CRISIS once a cell has divided between 65-70 times.
The cell has reached it maximum division and the cells start to die off in mass.

-they hit crisis because the cells are genetically unstable, many DNA errors
If a healthy cell hits the crisis level, what protein is being activated?
p53
What are the cells that escape crisis considered?
CANCER CELLS

immortalized
What anatomical structure on the chromosome controls the number of replication the chromosome can undergo?
Telomere
What are telomeres?
Located on the end of the chromosome and they get shorter with each division until the cells stop dividing.
What is telomerase? what can occur when a mutation takes place with telomerase?
It is the enzyme responsible for fixing the telomere after each replication but it actually decreases with the number of replication

-A mutation here that leads to cancer is a switch on of telomerase allowing the cancer cells to continue to divide without control.
WHat occurs in the cytoskeleton of cancer cells?
It is completely disassembled which allows for nuclear replication
What effect does cancer cells have on the adhesiveness of the cell (fibronectin)?
The cancer cell will either not express adhesion proteins or will express dysfunctional fibrontectin allowing the cells to easilty shed off the tumor and spread to another area.

-Loss of adhesion proteins make the cell able to move about.
Other than the ability to anchor, what other function do adhesion proteins have for the cell?
They allow the cell to be aware of how many neighbors it has. Higher density = less growth in healthy cells

-In cancer cells that have turned off adhesion proteins, they grow on top of each other
What is density dependent growth? What is it aka?
Healthy cells will only grow in an area they can fit and with enough nutrients to maintain it. Too many neighbors = no more growth

Also known as Contact inhibition.
How do cancer cells react to density dependent growth?
They completely ignore it because they have turned off the expression of adhesion proteins.

The cancer cells will grow and grow no matter how many cells are near them.
What are the nuclear changes that take place in cancer cells?
They have disorganized cell nucleus constantly in cell division.

-Can often see metaphase and anaphase
What type of change in enzyme production takes place in cancer cells? How does this cell benefit the cancer cell?
-The cancer cell aquires the ability to release lysosomal enzymes into the environment

-These enzymes can degrade the area to allowing for further growth of the cancer cells
What is CEA in cancer cells? What do they do for the immune system of the host?
Carcinoembryonic antigen:

Proteins that appear as spikes on the cancer cell and serve and cancer specific antigens

-They are often tumor specific

-They are the way for the immune system to potentially recognize the cells and destroy them by NK or cytotoxic T cells
What are the 4 major difference between a normal cell and a cancer cell?
1. Cancer cells are jumbled from a broke cytoskeleton.
2. Cancer cells are missing adhesion proteins
3. Cancer cells have CEA
4. Cancer cells have AFP
Describe the Gene-environment interaction route of mutagenesis?
Not very understood

-gene expression affected by environmental factors
-caused by carcinogenic or mutagenic substances.

-ex. cigarettes, industrial cleaners, combustion of fossil fuels

-The rate of the risk depends on the closeness and the time of exposure
Where does the mutation occur for inherited oncogenes?
ON the germ line genes
WHat are some examples of inherited oncogenes?
BRCA 1 and 2
THe majority of inherited oncogenes are which type of genes?
Tumor Suppressor genes
What are the 4 routes of mutagenesis?
1. Gene-environment interaction
2. Inherited Cancer genes
3. Oncogenic Viruses
4. Oncogenic Bacteria
What are the two categories for mutagenesis for oncogenic viruses?
Direct and indirect mutagenesis
What is direct mutagenesis?
AKA insertional mutagenesis

-The virus inserts and oncogene into the host cell and the host cell replicates the oncogene that transforms the cell
Describe indirect mutagenesis?
Is about the consequence of infection.

-Increase in chronic inflammation increases cell turnover and increases the likelihood of mutation.
What is initiation and the initiation theory?
Initiation: the mutation itself. the transformation of the cell into a cancer cell.

This theory says transformation is not enough because cells transform all the time
What are the 3 stages of transformation by altered genetic changes?
1. Initiation
2. Promotion
3. Progression
What is promotion?
The occurrence of an outside condition that works on a transformed cell to allow it to proliferate
What theory explains why cancer has a long latent period?
The promotion period of transformation
Which period of transformation is conditional?
Progression period
What are the 2 grades of cancer?
HIgh grade and low grade
What does high grade cancer mean?
YOu have cells that have a high turnover rate.

-have a high rate of accumulation of cells

-rate of division is higher than the rate of death
What cancer cells have the highest grade?
the ones that are least differentiated
How do you describe cancer stage?
It is the degree of spread

-goes from 1-4
What is the stage of cancer dependent on?
How far the cancer has spread and how far it has progressed
Why is cancer staging difficult?
Hard because different cancer types spread in different patterns
How does a benign tumor spread by local invasion?
It is encapsulated and it begins to bulge, displacing healthy tissue
Describe local invasion with a malignant tumor?
Malignant tumor does not displace cells in local invasion, it eats its way through neighboring tissue. It can get to local blood supply and then metastasize through the blood stream
What are the 3 ways cancers spread?
1. Local invasion
2. Metastasis through blood stream
3.Implantation
4. Shedding
Once a cancer cell has spread through the blood stream, what is its next method of metastasis?
Implantation
What are some common organs that are attacked by cancer through implantation?
Ones that get a lot of blood

-lungs, liver and kidneys
What type of cancer is known for metastisizing through shedding?
Ovarian cancer

to the pelvic and abdominal cavity
The ability of malignant tumors to induce formation of blood vessels is called?
Tumor-induced angiogenesis
What is FGF? WHat is it involved in?
Fibroblast growth factor.

Involved in tumor induced angiogenesis
Is angiogenesis always pathological?
No, it occurs when our tissues grow in a normal way

ex. puberty: the lean muscle mass goes up in men.
What cancers originate from epithelial cells?
carcinomas
When a cancer cell occurs in connective tissue, what is it categorized as?
Sarcoma
Lymphoma and Leukemia refer to cancer of which cells?
Tumors derived from blood and bone marrow cells
What is a mesothelioma?
Cancer cell that originates in cells that line the peritoneum and the pleura
What is the name of a cancer cell originating from brain cells?
Glioma astrocytoma
WHat are germ cell tumors?
malignant tumor derived from germ cells normally found in the testicles and ovary
What is a tumor of the melanocytes called?
Melanoma
What is an adenocarcinoma?
form of carcinoma that originates from glandular tissue
What is the best predictor of the clinical behavior of a cancer?
The cell type of origin
What type of cancer is breast cancer?
adenocarcinoma
What type of treatment would be used for cancer cells in hormone sensitive tissue?
Hormone deprivation
What are the most common forms of skin cancer?
Basal cell and squamous cell carcinoma
Which type of skin cancer is most invasive and has a mortality rate of 15-20%?
Melanomas
What is the primary treatment for melanomas?
surgery and chemotherapy
What characterizes small cel lung cancer?
Known as oat cell carcinoma because it looks like oats
What are the 2 types of possible lung cancer cells?
carcinomas or adenocarcinomas
What are the aggressive lung cancers?
high grade oat cell carcinomas

highly undifferentiated and have poor prognosis.
WHat are the risk factors and Tx for lung cancer?
Smoking, exposure to carcinogens such as radon gas, asbestos, infections

Tx: surgery, chemo and radiation
Colon cancer is often originates from which cells?
Most often adenocarcinoma but some are carcinomas
Where does colon cancer often spread?
Through the blood and lymph to the liver and lungs
What are the risk factors for Colon cancer?
-age (usually beyond age 50)
-the discovery of polyps (benign growths)
-a history of any type of cancer
-smoking, diet (high consumption of red meat)
-physical inactivity
-inflammatory bowel disease
-high alcohol consumption
Why can breast cancer spread easily?
It is surrounded by lymph tissue.
95% of cervical cancers are characterized as ________?
adenocarcinomas
70% of cervical cancer is caused by?
HPV
How does cervical cancer usually grow?
Through local invasion
What is the only organ that cervical cancer tends to spread to>
The liver
What are the risk factors of cervical cancer?
-smoking
-HIV
-HPV
-STI's
-OCs
-Family history
-
What is a common diagnostic method for cervical cancer?
Vinegar sprays
90% of endometrial cancers are what category?
Adenocarcinomas
How does uterine cancer grow?
Usually stays within the uterus. Grow centrally into the uterine cavity

-some cancers can grow and invade the myometrium, but rarely grow out of the uterus
What are some common risk factors for endometrial cancer? What are the Txs?
-Occurs mostly in post-menopausal women
-vaginal bleeding in a woman who has not had a period for at least 12 months

-Tx: surgery, hysterectomy
All prostate cancer are what type of cells?
adenocarcinomas: glandular
Which age group has the highest rate of colon cancer?
Over 50
How does prostate cancer grow?
Initially grows through local invasion and first metastasize seminal vesicles and then blood and lymph for distance.
What are the Tx options for prostate cancer?
Surgery, radiation, hormone deprivation, chemo and cancer vaccines
What is PSA testing?
Prostate specific antigen testing. This is present in both normal and cancerous cells, but increases in numbers for cancer cells.
Ovarian cancer is formed from what cells?
epithelial cells
How does ovarian cancer spread?
Through shedding

-goes to the pelvic and abdominal cavity
HOw often does ovarian cancer derive from germ-line cells?
Very rarely
Why is ovarian cancer very insidious?
Because the only sign is abdominal bloating
What stage is ovarian cancer usually at when it is diagnosed>
Stage 2-4
What are the risk factors for Ovarian cancer?
1. Women over 40
2. Hx of cancer
3. BRCA 1 and 2 (especially 1)
4. Hx of endometriosis
5. Having never been pregnant
6. Post-menopausal estrogen replacement
Where does liposarcoma occur?
Fat cells of deep tissue

Not often subcutaneous fat
Are metastasis common in liposarcoma?
yes, very!

can travel from blood and lymph attach to lung and liver
What is the most common forms of brain tumor?
astrocytoma
How do brain tumors spread?
entirely through local invasion

-rarely leave the brain
What are the first signs and symptoms of brain tumors a result of?
Increase in intracranial pressure that causes seizures
What are the Tx options for brain tumors?
Surgery, chemo and radiation
Can the brain be a site for secondary cancers?
Yes, it is common.
What is DES? Exposure to it has been found to increase the risk for what?
Diethystilvestrol: drug given in the 1940s-1960s to women who had had miscarriages to reduce their risk of another.

Has been found to increase the risk for breast cancer
What is the relationship between race and breast cancer?
Caucasion women are more likely to be diagnosed with breast cancer, but African American women are more likely to dies of breast cancer

AA women also get breast cancer before age 55 usually
What type of breast tissue has a higher risk for developing breast cancer?
Dense tissue: high glandular % as opposed to fat
What type of benign growths in breasts increase the risk for breast cancer?
proliferative lesions
How does menstruation relate to a risk for breast cancer?
If you have early onset or late menopause.
What has been found to reduce the risk of breast cancer?
Breast feeding and exercise
What are the treatments for breast cancer?
Hormone blocking, chemo, radiation, surgery