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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


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


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


step 1 of tumor cell transformation
cells exposed to carcinogen
DNA receives irreversible damage


2nd step of tumor cell transformation
growth becomes unregulated


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


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


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 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


tissue removal for testing for cancer
needle biopsy: palpable tumors & identified by x-ray
endoscopy: in lumen
excisional biopsy: removes whole tumor


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


used for diagnosis, staging,tumor removal, and palliation
cures local cancer and be preventative


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


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

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