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Pathophysiology Chapter 7

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cancer
2nd leading cause of death in US
leading cause of death of ages 3-15
64% 5 year survival rate
certain cancers more likely to cure or be deadly
some organs more likely to produce cancer
neoplasm
new growth or tumor
cells in neoplasms proliferate & change
can be benign or malignant
naming benign tumors
add "oma" to tissue of origin
benign glandular: adenoma
benign blood vessel: hemagioma
naming malignant tumors
malignant epithelial tissues: carcinomas
malignant mesenchymal: sarcoma
malignant glandular: adenocarcinoma
malignant vessel tumor: hemangiosarcoma
benign tumors
well differentiated cells
slow growth
well defined edges
no mets, death unlikely
can compress vital things like brain
malignant tumors
grow fast
attract blood vessels, spread widely, kills
solid tumors
begin in 1 organ
spread thru blood & lymph
hematological tumors
begin in blood/lymph
spread through body right away
tumor cell characteristics
lack of differentiation makes cells look abnormal
graded on degree of anaplasia from 1-4
genetic instability - chromosome abnormalities
cancer growth properties
cells divide rapidly, live long, & crowd
maintain telomeres to live forever
proliferate w/o proper signals
loss of density inhibition
cells pile up
loss of cohesion
cells no longer stick together
loss of anchorage dependence
cells can live detached
TSA's
abnormal surface antigens expressed by cancer cells
target mets to particular tissues
useful for markers & treatments
tumor growth
cancers avoid apoptosis, avoid G0
malignant tumors: high # of cells in cycle
short time for tumor to double
tumor spread
invade nearby tissues or seed when dropped body cavity
proteases breach basement membrane
must evade immune system
angiogenesis - attract blood vessels to grow
metastatic spread
spread thru lymph & blood to distant tissues
can be mapped through sentinel node mapping
genetic & molecular basis of cancer
tumor suppressor genes inactivated
proto-oncogenes constitutively active
DNA repair/apoptosis genes inactivated
oncogene formation
point mutations, insertions, deletions alter gene function
translocations make proteins active always
amplification lead to gene over-expression
loss of tumor suppressor activity
inherited mutation +1 hit or 2 hits
p53 gene abnormal to fix or end cell cycle when mutation present
Retinoblastoma gene inactivated
methylation silences tumor suppressor gene
cellular pathways in cancer
gf binds to gf receptor
this activates a cascade that activates MAP kinase
kinase phosphorylates a transcription factor, which leads to transcription of gene
=cell division
initiation
step 1 of tumor cell transformation
cells exposed to carcinogen
DNA receives irreversible damage
Promotion
2nd step of tumor cell transformation
growth becomes unregulated
progression
3rd step of tumor cell transformation
even more DNA damage accumulates
tumor cells are full malignant
heredity as cancer factor
BRCA 1&2 oncogene mutations
40% of retinoblastoma by Rb gene mutation
Familial adenomatous polyposis also autosomal dominant
hormones as cancer factor
may drive breast, ovary, endometrium, & prostrate cancer
obesity as cancer factor
adipose produces androgens & estrogens - increase breast cancer
increase insulin & IGF1 stimulates cell division
immune mechanisms as cancer factor
natural kills cells kill general cancer
macrophages take up TSAs & activate helper T cells
B cells release antibodies to attack cancer
Cytotoxic T cells kill cancer directly
Immune suppression leads to cancer
chemical carcinogens
cause up to 30% of cancers
cause cancer directly or chemically alter body
Ethanol from drinking and polycyclic from tobacco & charbroiled meat
radiation
impact depends on dose, age, & sex
long time after exposure to see leukemia, thyroid, and skin cancer
long exposure to sun in childhood & irradiation also risks
oncogenic viruses
HPV causes cervical cancer
Epstein Barr virus - lymphomas & nasopharyngeal
Hep B - liver
direct tissue effects of cancer
erodes/compresses blood vessels, nerves, & lymph vessels
destroys bone & blood marrow
obstructs lumens
causes effusions & extreme pain later on
indirect effects of cancer
anorexia, weight loss, & tissue wasting
effect prognosis w/ increased toxicity & effects of chemo
cytokines may play role in weight loss
also sleep disorders & fatigue
anemia
from blood loss, destroyed blood vessels, & impaired hematogenesis
comes from treatment & disease
decrease tolerance of treatment - not good for outcomes/q.o.l.
paraneoplastic syndromes
cancer produces hormones, coagulation factors, & antigens for auto-immune response (muscle weakness)
ADH - hyponatremia
ACTH - Cushing's syndrome
PTH - hypercalcemia
GH - acromegaly
secondary disease prevention
screening thru:
observation
palpation
X-rays
observation of epithelial tests
pap test of epithelial cells for cervical cancer
tumor markers
antigens produced/overproduced by tumors
used for diagnosis
not high early in disease
biopsy
tissue removal for testing for cancer
needle biopsy: palpable tumors & identified by x-ray
endoscopy: in lumen
excisional biopsy: removes whole tumor
immunohistochemistry
antibodies used to find cancer cells
microarray technologies
screen genome for cancer risk alleles
tumor testing as well
gleason score
level of anaplasia in prostate biopsy
sum of 2 most prominent tissues found in biopsy
poorly differentiated =8
staging tumors
assess spread of tumor
grading tumors
assesses degree of anaplasia
TNM system
Tumor: indicates elements of stage & grade
Nodes: indicated if lymph nodes increase
Metastasis: indicates presence of mets
surgery
used for diagnosis, staging,tumor removal, and palliation
cures local cancer and be preventative
radiation
primary Rx for some cancers
decrease size of other cancers palliatively
pre or post op, causes DNA damage & apoptosis at cell division
affects some cancers more than others
modes of delivery of radiation
external beam, brachytherapy, or injected unsealed source
adverse effects of radiation
injures/kills normal cells
N/V & diarrhea
suppresses bone marrow
skin burns & hair loss
chemotherapy
reaches tumors & mets anywhere
fixed fraction of cells die w/ each does
kills @ cell division - good for high growth fraction tumors
chemo drug stages
S - methotrexate blocks DNA synethesis
Non-specific - alykalating agents damage resting DNA
different drug classes can work together
adverse reactions of chemo
nadir - time point of maximum toxicity
-let person rest, tho tumor regrows a bit
supresses bone marrow
nausea, vomiting, diarrhea, fatigue, hair loss
carcinogenic & teratogenic
hormonal therapy
when tumors express hormone receptors
remove gonads in sex hormone responsive cancers
aromatase inhibitors block androgen & estrogen to stop breast cancer
tamoxifin = hormone receptor blockers
immune therapy
active - give antigen to develop antibodies
passive - give monoclonal antibody/other immune activators
adoptive - take out immune cells and activate them
targeted therapy
monoclonal antibodies against antigens
inhibit angiogenesis
Gleevec fits into ATP pocket to prevent ATP fitting and activating substrate that causes chronic myelegenous leukemia
childhood cancers
genetic abnormalities increase cancer risk
childhood cancers have good prognosis but may cause chronic health problems
-also increased risk for 2nd malignancy