Exam 1: Ch 7 Flashcards
2nd leading cause of death in US
all cancers lumped together
leading cause of death for children 3-15 YOA
cancer
what is the 5-year survival rate of cancer
64%
prevalence vs incidence
prevalence: how many have the disease
incidence: how many new cases (stable overall now)
is cancer a single disease?
no
some organs are much more likely to produce cancer
some cancers are much more deadly
cancers that are readily cured
Hodgkin’s disease
`
testicular
acute lymphoblastic leukemia
cancers with low 5-year survival rates
small cell lung cancer
pancreatic
high incidence, low death rates
prostate, breast
lower incidence, high death rates
lung and bronchus
pancreatic
neoplasm
new growth, synonymous with tumor
benign or malignant
benign have well differentiated cells, malignant less so
tumor name identifies….
tissue of origin
benign tumor add ___ to the end
oma
fibroma, adenoma, hemagioma, papilloma
fibroma: benign fibrous tumor
adenoma: benign glandular
hemagioma: benign blood vessel tumor
papilloma: benign projections from any surface
carcinoma, sarcoma, adenocarcinoma, hemangiosarcoma,
carcinoma: malignant epithelial tumor
sarcoma: malignant mesenchymal
adenocarcinoma: malignant glandular
hemangiosarcoma: malignant blood vessel tumor
polyp
growth projecting from mucosa
cancer in situ
localized malignant tumor that hasn’t broken through the basement membrane
benign tumor characteristics
well differentiated cells
slow growth, no mets
well defined edges
unlikely to be lethal
may compress vital structures –brain
malignant tumor characteristsics
grow fast
anaplasia – undifferentiated
attract blood vessels
spread widely
lethal
2 major types of malignant tumor
solid: start in 1 organ, spread through blood/lymph
hematological: cancers of blood-forming cells, begin disseminated
lack of differentiation makes cancer cells look _____
abnormal
cells and nuclei of various shape
nuclei contain extra DNA and stain very dark
cancer cells are graded on the basis of…
degree of anaplasia
the more abnormal, the more dangerous
grade 1: fairly well differentiated
grade 4: high degree of anaplasia
genetic instability
large scale chromosome abnormalities
important to know genetic makeup of individual and the cancer
cancer cells divide ____, live ____, and ____ together
rapidly, long, crowd
how to cancer cells escape apoptosis
they have their own telomerase so they’re immortal
proliferate without proper signals
3 things cancer cells have a loss of
density inhibition: cells can pile up
cohesion: cells no longer stick together
anchorage dependence: can live detached
tumor specific antigens (TSAs)
cancer cells express abnormal surface antigens
can target mets to particular tissues
may be useful as markers in treatment
some cancers express…
hormones and clotting factors
paraneoplastic syndrome
determinants of tissue growth rate
of cells going through cell cycle
duration of cell cycle
of cells dying
why do cancer cells grow fast
avoid apoptosis
almost all tumor cells are cycling (no G0)
malignant tumors have a high.. and a short…
high growth fraction (fraction of total cells in cell cycle)
short doubling time (time for a tumor to double in size)
if a tumor has no blood supply..
they don’t get very big
epithelial tissue is avascular
invasion of nearby tissue
bordering tissues or seeding of a body cavity
requires secretion of proteases to break through basement membrane
seeding can occur during surgery
metastasis
development of secondary tumors at distant sites
through lymph or blood
lymphatic metastasis
sentinel node mapping checks nodes that drain area of the tumor
mets through blood
metalloprotease enzymes break down collagen
brain receives high blood flow and lots of mets
lungs receive entire CO, common site of mets
tumors from the abd cavity spread to ___ via blood
liver
some tumors bind to sites in specific ___
tissues
prostate cancer –> bone
how do cancer cells evade the immune system
stop secreting TSAs
aggregate as emboli
kill immune cells
angiogenesis
tumor cells attract blood vessels
allows tumors to grow
proto oncogene
normal
stimulate cell division normally
turn into oncogene (cause cancer)
examples of tumor suppressor gene inactivation
RB – retinoblastoma
BRCA 1
p53
examples of oncogenes
RAS
RAF
HER-2 (breast)
oncogene formation
point mutations, insertions, deletions
translocations can create fusion proteins that are always active
amplification can lead to over expression of genes
loss of tumor suppressor activity
requires either an inherited mutation plus 1 hit OR
2 hits
p53 gene product
monitors cells for genetic mutations
arrests cell cycle with mutation present so repair or apoptosis can occur
abnormal in 50% of all cancers
epigenetic mechanisms
methylation of promotor region can silence tumor suppressor genes
3 steps of tumor cell transformation
initiation: cell exposed to carcinogen –> irreversible changes (multiple small doses cause damage)
promotion: growth becomes unregulated
progression: tumor cells become fully malignant
cancer cells can be familial
BRCA 1 & 2 are TS genes… mutation increases breast cancer risk
40% of retinoblastoma is autosomal dom. Rb gene mutation
familial adenomatous polyposis autosomal dom
hormones may drive cancers of the …
breast, ovary, endometrium, and prostate
obesity contribution to cancer
adipose produces androgens and estrogens, which increases breast cancer risk
higher insulin and IGF1 stimulates cell division
NK cell
general cancer killer
macrophages
take up TSA’s and activate T helper cells, which activate B cells to release antibodies that attack cancer cells
cytotoxic t cells
kill cancer cells directly
immune system kills most ___ cells
cancer
failure results in cancer to succeed
immune suppression leads to cancer, aids and Kaposi’s sarcoma
chemical carcinogens may cause up to ___% of cancers
30
many associated w/ lifestyle choices
direct vs indirect chemical carcinogen
direct: cause cancer without chemical change in the body
indirect: require chemical alteration in the body
polycyclic hydrocarbons
produced with tobacco burns and meat is charbroiled
EtOH causes what kinds of cancer
oral and esophageal
radiation causing cancer
impact depends on dose, age, sex
long latency period for leukemia, thyroid and skin cancer
intense sun exposure in childhood most dangerous
therapeutic radiation also a risk
oncogene viruses
HPV permanently changes genes of cervix
Epstein-Barr virus –> lymphomas and nasopharyn cancer
Hep B –> liver cancer
cancer disrupts tissues
local/regional or direct effects (extreme pain)
erodes or compresses blood vessels, nerves, lymph vessels
destroys bone and marrow
obstructs lumens
causes effusions
cancer cachexia and anorexia
many cancers cause anorexia (loss of appetite) and cachexia (wasting away)
weight loss could be an early symptom
makes prognoses more negative by increasing toxicity and side effects of chemo
cytokines may play a role in
TNF, IL-1 & 6
impact satiety center to decrease appetite
cause fever to increase calorie use
anemia
result from treatment as well as disease
poor quality of life and poor outcome
from blood loss, hemolysis, or impaired hematogenesis
decreases tolerance of treatment
paraneoplastic syndrome
cancer cells can produce hormones
ADH (hyponatremia)
ACTH (Cushing’s syndrome)
PTH (hypercalcemia)
GH (acromegaly)
coagulation factors
cancer cells can produce
cancer cells can produce ___ that trigger an _____ response
antigens, autoimmune
causes muscle weakness
eaton-lambert syndrome
small cell lung cancer
autoimmune production of antibodies to motor end plate structures
type of paraneoplastic syndrome
cancer screening
observation
palpation (breast, thyroid, prostate, lymph nodes)
xrays: mammography
observation of epithelial cells
pap smear: examination of epithelial cells of cervix on a microscope slide
tumor markers
antigens may be produced/overproduced by tumors, but not in early stages
PSA: prostate cancer
CA125: ovarian cancer
alpha-fetal protein (AFP): liver cancer
carinoembryonic antigen (CEA): colorectal/GI cancer
biopsy and types
tissue removal for testing
needle: palpable tumors and those IDed by xray
endoscopy: lumen
excisional: remove entire tumor
immunohistochemistry
antibodies used to find cancer cells
microarray technologies
screen genome for cancer risk alleles
allows for tumor testing
gleason score
level of anaplasia in prostate biopsy
staging
assess spread of tumor
TNM system
TNM system
T: elements of stage & grade
N: are lymph nodes positive?
M: presence of metastasis
radiation therapy
primary treatment for some cancers
palliative, decreases size of cancers
pre or post op
some cancers more sensitive to radiation than others
radiation mechanism and modes of delivery
DNA damage causes apoptosis
external beam: linear accelerator
brachytherapy: inserted sealed source
injected: I-131 for thyroid cancer
adverse effects of radiation therapy
injures or kills normal cells
GI effects: diarrhea N/V
bone marrow suppression
skin burns and hair loss
chemotherapy
can potentially reach all tumors and mets
cancer cells killed exponentially (fixed fraction die with each dose)
more effective against high growth factor tumors
can be a primary form of treatment
chemo drugs can be classified by ____
stage
S-phase specific: methotrexate blocks DNA synthesis
phase non-specific chemo
alkylating agents damage resting DNA
adverse rxns to chemo
bone marrow suppression
vomiting and diarrhea
fatigue and hair loss
drugs themselves are carcinogenic and teratogenic
nadir
time point of max toxicity
hormonal therapy
useful when tumors express hormone receptors
removal of gonads in sex hormone responsive cancers
aromatase inhibitors block androgen (estrogen in peripheral tissue – breast cancer)
hormone receptor blocker tamoxifin
immune therapy
active: give antigen
passive: give monoclonal antibody or other immune activators
adoptive: give activated immune cells
targeted therapy
monoclonal antibodies against cancer antigens
angiogenesis inhibitors
specific drugs to block action of chimeric cancer proteins (Gleevec for CML)
Downs may inc risk for which cancer
acute lymphoblastic leukemia
childhood cancers
many have good prognosis
survivors may have chronic health problems from radiation/chemo
increased risk for 2nd malignancy
