Transcript Ovarian Cancer Case Study - Mrs. Felker`s Science Site

But I’m Too Young!
A Case Study of Ovarian Cancer
by
Nancy A. Rice, Department of Biology, Western
Kentucky University, and
Bruno Borsari, Biology Department, Winona State
University
1
Abby is Sick:
Review of the Story So Far…
• Abby has been having abdominal pain.
• She has gone to see Dr. Allen.
• An ultrasound has indicated a mass on
her right ovary.
• She is preparing to have the mass and
ovary removed surgically.
2
Group Discussion
• If you were Abby, what questions would
you have?
• Should Abby be worried about cancer?
The doctor said it was a cyst!
3
CQ1: Do you know someone
personally that has had cancer?
A: Yes
B: No
4
Overall
Cancer
Incidence
and
Mortality
Trends in
U.S.
5
A
snapshot
of ovarian
cancer
From: A Snapshot of Ovarian
Cancer, National Cancer
Institute, updated 2007.
6
CQ2: Abby wondered: what is the
difference between cancer and
tumor? What do you think?
A: The two terms can be used interchangeably as
they are synonymous.
B: Cancer is a disease that eventually disrupts body
functions whereas a tumor is a mass of cells with
no apparent function in the body.
C: Cancer is a disease which affects men whereas a
tumor may affect both men and women.
E: Cancer is a disease of the digestive tract whereas
a tumor may develop anywhere in the body.
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What is Cancer?
• Simplest definition
From the American Cancer Society
“ cancer is a group of diseases characterized by
uncontrolled growth and spread of abnormal cells. If
the spread is not controlled, it can result in death.”
• Tumor
– Two types:
• Benign (non-cancerous) – this is not cancer!
– Does not spread; it can eventually become malignant in
some cases.
• Malignant (cancerous) – this is cancer!
– Has the potential to spread to other parts of body.
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Role of Cell Division in Cancer
Top = normal cell division
Bottom = unregulated cell
division and tumor formation
Malignant
If tumor invades
surrounding tissue
(cancerous)
Benign
If tumor has no effect on
surrounding tissue
(non-cancerous)
Metastatic
If individual cells break
away and start a new
tumor elsewhere
(cancerous)
Image from the National Cancer Institute
9
CQ3: Normal CA-125 levels are indicated
by values of 35 U/ml or less. Abby’s CA125 levels taken at two different times are
indicated below. Is Abby likely to have a
cyst or cancer?
700
600
A. Cyst
B. Cancer
500
400
300
CA-125 level
200
100
0
Normal
patient
Abby
Abby-2
weeks
later
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Preparing for Surgery
Before the surgery, Dr. Allen came in to talk to Abby about
her test results.
“I am really sorry, but your CA125 level is high and it looks
like your ovary actually does not have a cyst, but instead
has a tumor. It is best now to go ahead and remove both of
your ovaries.”
Dr. Allen explained she had consulted with a pathologist to
verify the diagnosis. She pulled out a brochure titled
Ovarian Cancer and opened it to show Abby three
photographs. One showed normal ovarian tissue; the other
two showed benign and malignant ovarian tissue.
11
Normal
ovarian
epithelium
Ovary
cystoadenoma
(benign)
Ovarian
adenocarcinoma
(malignant)
12
The genetics of ovarian cancer
Abby had already learned a lot about ovarian cancer so she followed Dr.
Allen’s explanation.
“I’m only 20 years old. How did I get ovarian cancer? Isn’t this a disease of
older women?
“Typically ovarian cancer does affect older women. However, you may have
a genetic predisposition for it. Cancer cells have mutations in specific genes
that regulate cell division. When they are mutated, cell division becomes
uncontrollable,” the doctor explained.
“I learned about those genes on the Internet! Is it true that some ovarian
cancers are associated with mutated copies of genes called BRCA1 or
BRCA2?” asked Abby.
“Yes,” said Dr. Allen. “You likely were born with one a mutated copy of
these genes already. A mutation of the second copy could have occurred
more recently, triggering the development of your tumor.”
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CQ4: Why does cancer primarily
affect older people rather than young
people?
A:Because the immune system of older people is
not as effective in distinguishing normal cells from
cancer cells.
B: Because older people have been exposed to
more carcinogens.
C: Because cancer develops after multiple
mutations have occurred which takes years to
happen.
D: None of the above.
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Cancer is a genetic disease
• Cancer arises from the accumulation of
genetic changes (mutations).
• Most cancers have a minimum of 6-9 different
genes mutated.
• Not a hereditary disease – we do not pass on
cancer to offspring.
• We can inherit dispositions (susceptibility) to
cancer.
• Many genes that are mutated in cancer are
involved in regulating the cell cycle.
15
Review: The cell cycle has four
phases and controls cell division
• Two gap or
growth
phases (G1
and G2)
• S phase DNA
synthesis
• M phase Mitosis
Interphase
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Checkpoint control system
• 3 major checkpoints:
– G1
• Can DNA synthesis begin?
– G2
• Has DNA synthesis been
completed correctly?
• Commitment to mitosis
–M
• Are all chromosomes attached
to spindle?
• Can sister chromatids separate
correctly?
Cell Cycle Checkpoints
• Three checkpoints in cell cycle
– G1-S transition
– G2-M transition
– Exit M phase transition
• Checkpoints are where the cell
assesses whether conditions are
favorable for cell division.
• When the environment is not
favorable (for example, when the
cell’s DNA is damaged), a
protein called p53 can stop the
cell cycle and cause the cell to
die.
• When the proteins that regulate
the cell cycle are mutated or
absent, cells can divide
uncontrollably, leading to cancer.
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Major Checkpoints – G1
1. G1 checkpoint (Most important!)
–
–
–
Controlled by cell size, growth factors, environment
“Go”  completes whole cell cycle
“Stop”  cell enters nondividing state (G0 Phase)
2. G2 checkpoint
• Controlled by DNA replication completion, DNA
mutations, cell size
3. M-spindle (Metaphase) checkpoint
–
Check spindle fiber (microtubule) attachment to
chromosomes at kinetochores (anchor sites)
G0 phase
• G0 phase
– non-dividing, differentiated state
– many human cells in G0 phase
 liver cells
M
Mitosis
G2
Gap 2
S
Synthesis
 in G0, but can be “called
G1
Gap 1
back” to cell cycle by
external cues
 nerve & muscle cells
G0
 highly specialized
Resting
 stopped in G0 & can
never divide
Cell Cycle Control System
• Checkpoint = control point where stop/go signals
regulate the cell cycle
“Go-ahead” signals
• Protein molecules that promote cell
growth & division
Where is
the P
attached?
– internal signals
• “promoting factors”
– external signals
• “growth factors”
External Regulatory Factors
External Regulatory Factors
 Growth Factor: proteins released by other cells
to stimulate cell division
 Density-Dependent Inhibition: crowded cells
normally stop dividing; cell-surface protein binds
to adjoining cell to inhibit growth
 Anchorage Dependence: cells must be attached
to another cell or ECM to divide
Internal Regulatory Molecules
MPF = maturation-promoting factor
•
specific cyclin-Cdk complex which allows cells
to pass G2 and go to M phase
Cancer & Cell Growth
• Cancer is essentially a failure
of cell division control
– unrestrained, uncontrolled cell growth
• What control is lost?
– gene p53 plays a key role in G1 restriction point
• p53 protein halts cell division if it detects damaged DNA
p53 is the
Cell Cycle
Enforcer
– options:
» stimulates repair enzymes to fix DNA
» forces cell into G0 resting stage
» keeps cell in G1 arrest
» causes apoptosis of damaged cell
• ALL cancers have to shut down p53 activity
p53 — master regulator gene
NORMAL p53
p53 allows cells
with repaired
DNA to divide.
p53
protein
DNA repair enzyme
p53
protein
Step 1
Step 2
Step 3
DNA damage is caused
by heat, radiation, or
chemicals.
Cell division stops, and
p53 triggers enzymes to
repair damaged region.
p53 triggers the destruction
of cells damaged beyond repair.
ABNORMAL p53
abnormal
p53 protein
Step 1
Step 2
DNA damage is
caused by heat,
radiation, or
chemicals.
The p53 protein fails to stop
cell division and repair DNA.
Cell divides without repair to
damaged DNA.
cancer
cell
Step 3
Damaged cells continue to divide.
If other damage accumulates, the
cell can turn cancerous.
CQ5: What would you expect cells to
be like if they did not have properly
functioning p53?
A: The absence of p53 inside cells would cause
them to divide more rapidly.
B: The absence of p53 could cause cells to replicate
with damaged DNA that could ultimately lead to
cancer.
C: The absence of p53 could cause cells to skip
mitosis (M phase) and stay in S phase of the cell
cycle.
D: The absence of p53 would have no effect on the
cells.
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Development of Cancer
• Cancer develops only after a cell experiences ~6 key
mutations (“hits”)
– unlimited growth
• turn on growth promoter genes
– ignore checkpoints
• turn off tumor suppressor genes (p53)
– escape apoptosis
• turn off suicide genes
– immortality = unlimited divisions
• turn on chromosome maintenance genes
– promotes blood vessel growth
• turn on blood vessel growth genes
– overcome anchor & density dependence
• turn off touch-sensor gene
It’s like an
out of control
car!
What causes these “hits”?
• Mutations in cells can be triggered by




UV radiation
chemical exposure
radiation exposure
heat




cigarette smoke
pollution
age
genetics
Cancer Prevention
Anyone can get cancer but there are ways to
minimize risk:
• Don’t smoke, legal or illegal (includes
hookahs, chew, 2nd-hand smoke)
• Use sun protection
• Exercise and keep weight at ideal level
• Eat 5-7 servings of fruit and veggies a day
• Use screening/preventative measuresbreast/testicle/mole checks
• Practice abstinence or use condoms
• Vaccines (eg. HPV)
Tumor suppressors and
oncogenes
• Mutations in oncogenes and tumor
suppressor genes can lead to cancer.
• http://science.education.nih.gov/supple
ments/nih1/cancer/activities/activity2_an
imations.htm
(Animation #5)
32
CQ6: The BRCA1 and BRAC2 genes
that may be mutated in Abby’s cells
would be considered?
A: An oncogene
B: A tumor suppressor
gene
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From Benign to Malignant
• Cancer cells divide too quickly and can leave
the original site and enter the blood, lymph,
or tissues.
• Most cells divide a set number (60-70) of
times, then they stop dividing.
• This usually limits benign tumors to small
sizes.
• Cancer cells can divide indefinitely.
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Tumors
• Mass of abnormal cells
– Benign tumor
• abnormal cells remain at original site as a lump
– p53 has halted cell divisions
• most do not cause serious problems &
can be removed by surgery
– Malignant tumors
• cells leave original site
– lose attachment to nearby cells
– carried by blood & lymph system to other tissues
– start more tumors = metastasis
• impair functions of organs throughout body
CQ7: How do cancer cells travel
through the human body?
A: Cancer travels through the body by way of sexual
intercourse between a healthy person and one
affected by the disease.
B: The circulatory system only is responsible for
relocating cancer cells.
C: The lymphatic system collects fluids from capillaries
and with it cancer cells, which are then delivered by
the circulatory system.
D: They are moved around on neurons throughout the
body.
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The vessels of the circulatory and lymphatic systems
provide a pipeline for cancer cells to move to other
locations in the body through a process called metastasis.
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Abby’s treatment options
Dr. Allen came to see Abby after her surgery.
“Everything went really well. Now we need to think
about preventing this from ever coming back.
Typically we use a combination of various types of
therapy, which includes radiation and
chemotherapy.”
– Radiation - Uses high-energy rays to kill cancer cells. A
large machine directs radiation at the body.
– Chemotherapy - Uses anticancer drugs to kill cancer
cells.
39
Traditional treatments for cancers
• Treatments target rapidly dividing cells
– high-energy radiation
• kills rapidly dividing cells
– chemotherapy
• stop DNA replication
• stop mitosis & cytokinesis
• stop blood vessel growth
Typical Ovarian Cancer Treatments
One common chemotherapy for
ovarian cancer is Taxol, which
was first isolated from Yew bark
in 1962 by the National Cancer
Institutes (NCI).
Taxol blocks a cell's ability to
break down the mitotic spindle
during mitosis. With the spindle
still in place, the cell can't divide
into daughter cells and therefore
the cancer can’t grow.
Taxus Brevifolia
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Cancer Detection
and Treatment
C hange in bowel or bladder
habits
A sore that does not heal
• Earlier detection and
treatment of cancer
greatly increase the
odds of survival.
• Therefore, knowing
the warning signs of
cancer is important
to health.
U nusual bleeding or
discharge
T thickening or lump
I ndigestion or difficulty
swallowing
O bvious change in wart or
mole
N agging cough or
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hoarseness
CQ8: Can surgery successfully cure
a cancer that has metastasized?
A. No, all body cells are dividing uncontrollably
B. Yes, it could remove all cells with defective
cell-cycle regulation
C. No, cancer cells are no longer localized in
one spot
D. Yes, if the tumor is benign
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Abby’s ovarian cancer has been in remission for 10 years.
She graduated from college with a BA in Anthropology.
Three years later she married, and today she is living
happily with her husband Charles and their four-year-old
adopted daughter.
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