Carcinogenesis Flashcards
what are the 3 most common types of cancer
lung breast and colorectal
what is non neoplastic growth
a normal reaction to some stimulus
what are 2 types of non neoplastic growth
hypertrophy and hyperplasia
What is hyperplasia
overgrowth, the enlargement of an organ or tissue caused by an increase in the reproduction rate of its cells, often as an initial stage in the development of cancer.
how can you cause regression of the lesion with non neoplastic growth
remove the stimulus
what is neoplasm
a new and abnormal growth of tissue in some part of the body
what 3 things characterize cancer
proliferation, anaplastic and metastasize
what is proliferation
rapid growth
what is anaplastic
less specialized cells (lost their mature or specialized features)
What is metastasize
when the cells spread throughout to new sites
what is neoplasia
new growth, refers to the process of abnormal cell proliferation which results in a structure known as neoplasm (the formation or presence of a new, abnormal growth of tissue)
what is a neoplasm
a tumor, a new and abnormal growth of tissue in some part of the body, especially as a characteristic of cancer
what is a main difference with neoplastic and non-neoplastic growth
Neoplastic cells tend to be monoclonal, Non-neoplastic proliferations have cells that are polyclonal in origin.
what is monoclonality
tumor derived from a single cell
what is polyclonal tumor
multiple diff cells can produce tumor cells
what can cause a polyclonal tumor
like a bad chemical hits multiple cells and they get mutated and lead to the same outcome (doesn’t have to be the same mutation, just abnormal growth
how fast do bening tumors grow
slow
what do benign tumors do and not do
displace rather than destroy
where do benign tumors go
no where, they just stay in one place
can benign tumors kill you
no
what can happen to a bening tumor
it can promote vessel growth to become vascularized
what can happen once a tumor gets vascularized
it can detach, invade circulation and lymph
what can happen once a tumor detaches, invades circulation and lymph
it can take over and expand quickly
when do you call a tumor cancer
once its can detach and start spreading
do malignant tumors kill
yes
what are 2 ways malignant tumors spread
direct invasion (neighbor) metastasis
what kind of differentiation do benign tumors have
well differentiated, looks more like the tissue of origin
what kind of differentiation do malignant tumors have
less differentiated, anaplastic
what rate of growth in benign tumors have
slow
what rate of growth in malignant tumors have
faster usually
what local invasion do benign tumors have
none! dont leave capsule or site of origin
what local invasion do malignant tumors have
invasive and early on
do malignant tumors metastasize
yes
do benign tumors metastasize
never
do benign tumors necrosis
uncommon
do malignant tumors necrosis + why
common because outgrowth of blood supply, but much blood in the middle of the cell clumps
what is the cytology of malignant tumors
- pleomorphic
- hyperchromatic nucleui
- high nuc/cyt ratio
- abnormal mitosis
what does pleomorphic mean
they vary in size and shape
do neoplastic cells have differentiation
no it is lost, they are no longer specialized
what is a hallmark of transformation with cancer
anaplasia where there is primitive disordered cell morphology
are benign tumors differentiated
yes, well
are malignant tumors differentiated
they range from well to undifferentiated
what is 1 work to describe neoplasm
tumor
what is 1 work to describe malignant neoplasm
cancer
what is 1 work to describe tumor
neoplasm
what is 1 work to describe cancer
malignant neoplasm
what are 2 steps between normal cells and cancer cells
hyperplasia(new cells growing) and dysplasia (function and morphology change)
what is the diff with genotoxic and nongenotoxic cancer
genotoxic: a chemical capable of producing cancer by directly altering the genetic material of target cells
non-genotoxic: chemical capable of producing cancer by some secondary mechanism not related to direct gene damage
what is genotoxic
a chemical capable of producing cancer by directly altering the genetic material of target cells
what is non genotoxic
chemical capable of producing cancer by some secondary mechanism not related to direct gene damage
what are the 3 main cancer stages *
Initiation
Promotion
Progression
what happens in Initiation
- DNA mod, mutation, genotoxic
- one dividion can lock in mutation to make it non reversible mutation
- modification not enough to produce cancer
what happens in Promotion
- non direct DNA mod or mutation, non genotoxic
- multiple cell divisions necessary, clonoal expansion
- reversible, apoptosis, threshold
- lots of treatments needed to stop the growth
- proliferation
what happens in Progression
- DNA mod, genotoxic event, mutation, chromosome disarrangement
- irreversible, goes from neoplasia to malignant
- # of treatments unknown
is initiation reversible
no
is promotion reversible
yes
is progression reversible
no
what are the 2 main umbrella terms for what can cause cancer
gene or enviro
what are the 3 largest causes of cancer
diet, tobacco, infections
what are 2 main groups of genotoxic carcinogens
direct acting and indirect acting
what are 2 main gene changes that can happen
DNA damage (direct) or epigenetic
what are 5 examples of DNA damage
ss break, ds break, insertion, deletion, interstrand cross link
what are 5 examples of damaging agents to DNA
x rays, UV light, ROS, replication errors, xenobiotics (alkylatinf agents, hydrocarbons, polycyclic aromatics, anti-tumor drugs)
what are 4 consequences of DNA damage
cell cycle arrest, apoptosis, cancer and aging
what is an example of epigenetic changes that could effect cancer
Diff chemicals interfere with epigenetic changes, like increased or decreased cell proliferation
what activates the AHR receptor
dioxin
what happens when the AHR receptor is activated
it leads to increased CYP 1 transcription
what is an example of bioactivation
AHR receptor is activated, it leads to increased CYP 1 transcription, increasing metabolism enzymes which can make compounds genotoxic
what is an example of something that becomes more toxic with metabolism
benzeo(a)pyrene, which can get extra epoxide to be resistant to hydrolation, leading to tumors
what is benzeo(a)pyrene
polyaromatic hydrocarbon
what are the 6 hallmarks of cancner cells
- self sufficiency in growth signals
- insensitivity to anti growth signals
- evading apoptosis
- limitless replicative potential
- sustained angiogenesis
- tissue invasion and metastasis
explain: self sufficiency in growth signals
all normal cells require extrinsic factors produced by other cells, but not cancer cells
how do cancer cells achieve self sufficiency in growth signals (5)
- prolonged ligand-induced signalling
- increase sensitivity
- express new receptors
- make own growth factors
- signal in absense of ligand
how do cancer cells prolonged ligand-induced signalling
decreased degradation, turn off negative regulator
what are 2 important genes in cancer
oncogene and tumor supressor gene
what is oncogene
a gene when mutated, amplified or activated, promotes unregulated cell growth gain-of-function (always “ON”)
what is tumor suppressor gene
a gene when mutated or inactivated will release cell cycle inhibition, loss of function
what is an example of an oncogene
ras
what is an example of an tumor suppressor gene
Rb and p53
where are the cell cycle checkpoints
between G1 and S, and inside mitosis
what does RAS do normally and how
it is activated by receptors to exchange GDP to GTP
what happens to mutant forms of RAS
they are not inactivated (always on)
what % of all cancers have RAS mutation
15-20%
what happens usually in normal cells (not cancer cells that insensitivity to anti growth signals)
-most cells in G0 with growth inhibitory proteins in extracellular space
which stage are most cells in
G0
what inhibits further cell growth
terminal differentiation, growth inhibitory proteins
what can produce cell cycle arrest
oncogene expression
what is another name for tumor suppressor genes
antiproliferative genes
what are 3 examples of antiproliferative genes
retinoblastoma protein
Rb
p53
what does retinoblastoma protein do
normally keeps cell in G0 (suppressor)
what is cell cycle arrest
the cell is no longer involved in the processes surrounding duplication and division
what are 2 cancers that Rb mutations are common in
retinoblastomas, small cell lung cancers (80%)
what is the main role of Rb
antiproliferative
what is the main role of p53
antiproliferative
what is the main role of retinoblastoma protein
antiproliferative
what % of cancers have p53 mutation
50-75%
what are 3 ways that cancer cells avoid apoptosis
- decoy death receptors
- mutations in intracellular proteins that monitor DNA damage(p53)
- increased expression of various anti-apoptotic proteins (bcl-2)
what is necrosis role in cancer (evading apoptosis)
evidence might do more damage by recruiting tumor promoting inflammatory cells that bring growth stimulating factors
what are 2 examples of ways that cells do cell death
necrosis and autophagy
what is autophagy
Activate mechanism to remove organelles or proteins they don’t need to survive - cancer cells is activated during starvation
what are 2 ways that cancer cells do limitless proliferative capacity
avoid replicative senescence and avoid crisis
what are 2 ways that cancer cells avoid replicative senescence
- mutate p53/Rb can extend lifespan
- rare mutations lead to immortalization
how do cancer cells avoid massive death and chromosomal (karyotypic) disrray
activate telomerase (adds nucleotides at the end of the chromosomes)
how do tumors increase blood flow + how does it work
activate VEGF–> signal endothelial cell proliferation and growth of blood vessels
what are the center of tumors usually like and why
necrotic because oxygen cannot reach, angiogenesis does not keep up
what is the warburg effect
most cancer cells produce energy by glycolysis due to lack of oxygen
what about cancer kills you
metastasis, not the primary tumor
whata re 2 things that metastatic cells must be able to do
enter and leave the bloodstream and to survive in an ectopic location
what is the underlying mechanism of tissue invasion and metastasis
unknown, succession of cell changes… lots of things
what are 2 new emerging cancer hallmarks
deregulating cellular energetics, avoiding immune destruction
what are 2 new enabling cancer characteristics
genome instability and mutation, tumor promoting inflammation
are tumors complex tissues
yes - like their own organs, with some diff cell types, microenvironments and vasculature
what are 3 environmental DNA damaging agents
chemicals, radiation, viruses
what are 2 genes that mutations in can cause cancer
genes affected DNA repair and cell growth or apoptosis
what happens once there are mutations in genome of somatic cells (3)
inactivation of growth promoting oncogenes, inactivation of tumor suppressor genes, alterations in genes that regulat apoptosis
what 2 things lead to clone expansion
unregulated cell proliferation and decreases apoptosis
what 3 things make clone expansion lead to tumor progression and malignant neoplasm
additional mutations, angiogenesis, escape from immunity
what is the total cell-cell cycle time with cancer
typically normal (cancer cells do not grow or divide faster than normal cells, lack of control of cell growth, so that they keep on growing without limit, even if slowly)
