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Lecture 6

BIOL 2160 Lecture Notes - Lecture 6: Hpv Vaccines, Ovarian Cancer, Cervical Cancer


Department
Biological Sciences
Course Code
BIOL 2160
Professor
Cross- Eyed
Lecture
6

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CHAPTER 6
CANCER
2nd leading cause of death in U.S. (kills > 500,000 people / year).
Causes ~20% of deaths in U.S. each year.
Due to failure of cellular mechanisms that normally control cell division.
This is a result of genetic damage, that is often due to tumor-promoting chemicals,
hormones, and sometimes viruses.
o Genetic Damage:
Can result from a mutation in 1 of 3 types of genes: proto-oncogenes,
tumor-suppressor genes, and caretaker genes.
Proto-oncogenes: normally promote cell division, but are changed into
oncogenes by mutations that make the gene excessively active.
Tumor-suppressor genes: normally restrain growth. Mutations cause
inactivation of these genes, allowing excessive cell division to occur.
Caretaker genes: also, linked to cancer. Normally protect genome.
When caretaker genes are inactivated, mutations in the genome
accumulate.
Genes in these 3 classes encode proteins that help regulate cell birth, cell
death (apoptosis), and DNA damage repair.
o Carcinogens
Environmental substances that induce cancer-causing mutations in cells.
Includes:
UV radiation (excessive sunlight)
Tobacco
Asbestos
Alcohol
Benzene
Lead
Nickel
Countless other chemicals…
o Viruses that cause cancer
HPV-Human papilloma virus- Causes warts on the skin, mouth, genitals,
and larynx. Spread through physical contact with infected areas. (cont
below)
Hepatitis (B) and (C) viruses - cause liver infections that can develop into
liver cancer. In the U.S., over 30% of liver cancers are related to Hep. B
or C. Higher in other countries.
Spread through un-protected sexual contact, or exchange of blood.
HPV
o 3 / 4 sexually-active people already have HPV. Clears up naturally in 1 or 2
years in 90% of cases.
o 80% of women will get HPV in their lifetime.
o 60% of female students will get HPV during their 4 years in college.
o In about 10% of women, HPV remains in the cells of the cervix and increases the
chances of cervical cancer, though most women with HPV infections will not
develop cervical cancer.
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o HPV causes 90-98% of ALL cervical cancers.
o Factors that increase an individual’s risk of contracting cervical cancer: increasing
age, smoking, and lowered immunity.
o Cervical cancer is the 3rd most common type of cancer in women, behind lung and
breast cancer.
o Can be detected by regular pap smears, which have reduced the death rate by
70%.
o Sexually-transmitted DNA virus.
o A viral protein E5, only 44 amino acids long, spans the plasma membrane and
forms a dimer or trimer.
o Each E5 polypeptide can form a stable complex with one endogenous receptor for
PDGF.
o Platelet-derived growth factor is a protein that plays a key role in angiogenesis.
o So E5 can aggregate 2 or more PDGF receptors together at the cell membrane.
o This receptor-dimerization is the exact same process that occurs when PDGF
normally activates its receptor at the plasma membrane.
o This causes sustained receptor activation and promotion of cell division.
o Vaccine?
Gardasil-given in 3 injections over 6 months.
Targets the types of HPV that contribute to cervical cancer and genital
warts. About 30% of cervical cancers will not be prevented by the vaccine.
Only effective if you have not been exposed to disease-causing HPV. It’s
a vaccine, not a treatment.
o HPV also encodes E6 that inhibits p53 activity.
o And E7 that inhibits Rb, retinoblastoma protein, which controls cell cycle. First
tumor-suppressor gene to be discovered. Inactivated Rb protein is present in
almost all cancer cells.
o The current HPV vaccine is composed of a capsid protein called L1, and is
designed to trigger an immune response. It contains no virus, alive or dead.
o It protects against 4 strains of HPV: 6, 11, 16, and 18.
MUTATIONS
o Occur mostly in somatic cells (non-germ-line cells). Usually aren’t passed on to
offspring.
o However, some mutations occur in germ-line cells and can be passed on to
offspring.
o Many years may be required to accumulate the multiple mutations that are
necessary for tumor formation, which is why most cancers develop later in life.
OVARIAN CANCER
o 8th most common form of cancer in women.
o 5th leading cause of cancer death in women.
o Ovulation: process in which an ovarian follicle ruptures, and discharges an ovum
(egg), that bursts through the wall of the ovary.
o Upon release of the mature ovum (ovulation), cells on the surface of the ovary
must divide to repair the hole caused by the bursting ovum.
o If these cells contain mutations in genes that encode vital cell-cycle-control
proteins, then cell division will be excessive. Tumors will result.
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“THE PILL”
o The most commonly-used oral contraceptive, but is also taken to regulate monthly
menstrual cycles by stabilizing the endometrium.
o Usually a combination of varying levels of progestin and estrogen, hormones that
prevent follicular development and inhibit ovulation, not menstruation.
o Without ovulation, no ovum is released, and damage to ovarian walls is
prevented, eliminating the need for cell division.
o Harvard and Oxford studies have shown that women who take the pill for 10
years or more reduces their risk of contracting ovarian cancer by as much as 50%.
o The longer the pill was taken, the lower the risk of developing the disease.
o Furthermore, protection against ovarian cancer remained in women for up to 20
years AFTER they stopped taking the pill.
o Natural Process??
Natural doesn’t always equal healthy.
Ovulation serves NO biological purpose whatsoever if pregnancy is not
desired.
There is ZERO evidence showing that women who ovulate are any
healthier than women who don’t. There is actually strong evidence to the
contrary.
READ JOHN ROCK’S ERROR
ONCOGENESIS
o The cancer-forming process.
o Result of an interplay between genetics and the environment.
o Most cancers are a result of genes being mutated by carcinogens, or by errors in
the copying and repairing of DNA.
o When healthy cells become cancerous
o Result of genetics and environment
Error that was made when DNA was copied/repaired (any time cells
divide, there is a chance for a mistake)
TUMOR
o A rapidly proliferating cell type that escapes normal growth restraints and
stimulates the growth of vasculature to obtain oxygen.
o Cells that proliferate quickly, and are in abundant supply, are the most dangerous.
i.e. skin cells, ovarian cells
o Rapidly proliferating = very quickly and very often
o Escapes normal growth constraints = there are natural processes that prevent your
cells from over-producing, but cancer cells can escape this
o Vasculature to obtain oxygen = they get a blood flow
o METASTASIS
A case in which cells from the primary tumor migrate to new sites where
they can form secondary tumors.
Complex process, and invasion of new tissues is non-random, depending
on the nature of both the metastasizing cell and the invaded tissue.
Most cancer deaths are due to invasive, fast-growing metastasized tumors.
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