Carcinogenesis Flashcards
1
Q
what are the 3 most common types of cancer
A
lung breast and colorectal
2
Q
what is non neoplastic growth
A
a normal reaction to some stimulus
3
Q
what are 2 types of non neoplastic growth
A
hypertrophy and hyperplasia
4
Q
What is hyperplasia
A
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.
5
Q
how can you cause regression of the lesion with non neoplastic growth
A
remove the stimulus
6
Q
what is neoplasm
A
a new and abnormal growth of tissue in some part of the body
7
Q
what 3 things characterize cancer
A
proliferation, anaplastic and metastasize
8
Q
what is proliferation
A
rapid growth
9
Q
what is anaplastic
A
less specialized cells (lost their mature or specialized features)
10
Q
What is metastasize
A
when the cells spread throughout to new sites
11
Q
what is neoplasia
A
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)
12
Q
what is a neoplasm
A
a tumor, a new and abnormal growth of tissue in some part of the body, especially as a characteristic of cancer
13
Q
what is a main difference with neoplastic and non-neoplastic growth
A
Neoplastic cells tend to be monoclonal, Non-neoplastic proliferations have cells that are polyclonal in origin.
14
Q
what is monoclonality
A
tumor derived from a single cell
15
Q
what is polyclonal tumor
A
multiple diff cells can produce tumor cells
16
Q
what can cause a polyclonal tumor
A
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
17
Q
how fast do bening tumors grow
A
slow
18
Q
what do benign tumors do and not do
A
displace rather than destroy
19
Q
where do benign tumors go
A
no where, they just stay in one place
20
Q
can benign tumors kill you
A
no
21
Q
what can happen to a bening tumor
A
it can promote vessel growth to become vascularized
22
Q
what can happen once a tumor gets vascularized
A
it can detach, invade circulation and lymph
23
Q
what can happen once a tumor detaches, invades circulation and lymph
A
it can take over and expand quickly
24
Q
when do you call a tumor cancer
A
once its can detach and start spreading
25
do malignant tumors kill
yes
26
what are 2 ways malignant tumors spread
```
direct invasion (neighbor)
metastasis
```
27
what kind of differentiation do benign tumors have
well differentiated, looks more like the tissue of origin
28
what kind of differentiation do malignant tumors have
less differentiated, anaplastic
29
what rate of growth in benign tumors have
slow
30
what rate of growth in malignant tumors have
faster usually
31
what local invasion do benign tumors have
none! dont leave capsule or site of origin
32
what local invasion do malignant tumors have
invasive and early on
33
do malignant tumors metastasize
yes
34
do benign tumors metastasize
never
35
do benign tumors necrosis
uncommon
36
do malignant tumors necrosis + why
common because outgrowth of blood supply, but much blood in the middle of the cell clumps
37
what is the cytology of malignant tumors
- pleomorphic
- hyperchromatic nucleui
- high nuc/cyt ratio
- abnormal mitosis
38
what does pleomorphic mean
they vary in size and shape
39
do neoplastic cells have differentiation
no it is lost, they are no longer specialized
40
what is a hallmark of transformation with cancer
anaplasia where there is primitive disordered cell morphology
41
are benign tumors differentiated
yes, well
42
are malignant tumors differentiated
they range from well to undifferentiated
43
what is 1 work to describe neoplasm
tumor
44
what is 1 work to describe malignant neoplasm
cancer
45
what is 1 work to describe tumor
neoplasm
46
what is 1 work to describe cancer
malignant neoplasm
47
what are 2 steps between normal cells and cancer cells
hyperplasia(new cells growing) and dysplasia (function and morphology change)
48
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
49
what is genotoxic
a chemical capable of producing cancer by directly altering the genetic material of target cells
50
what is non genotoxic
chemical capable of producing cancer by some secondary mechanism not related to direct gene damage
51
what are the 3 main cancer stages *
Initiation
Promotion
Progression
52
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
53
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
54
what happens in Progression
- DNA mod, genotoxic event, mutation, chromosome disarrangement
- irreversible, goes from neoplasia to malignant
- # of treatments unknown
55
is initiation reversible
no
56
is promotion reversible
yes
57
is progression reversible
no
58
what are the 2 main umbrella terms for what can cause cancer
gene or enviro
59
what are the 3 largest causes of cancer
diet, tobacco, infections
60
what are 2 main groups of genotoxic carcinogens
direct acting and indirect acting
61
what are 2 main gene changes that can happen
DNA damage (direct) or epigenetic
62
what are 5 examples of DNA damage
ss break, ds break, insertion, deletion, interstrand cross link
63
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)
64
what are 4 consequences of DNA damage
cell cycle arrest, apoptosis, cancer and aging
65
what is an example of epigenetic changes that could effect cancer
Diff chemicals interfere with epigenetic changes, like increased or decreased cell proliferation
66
what activates the AHR receptor
dioxin
67
what happens when the AHR receptor is activated
it leads to increased CYP 1 transcription
68
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
69
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
70
what is benzeo(a)pyrene
polyaromatic hydrocarbon
71
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
72
explain: self sufficiency in growth signals
all normal cells require extrinsic factors produced by other cells, but not cancer cells
73
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
74
how do cancer cells prolonged ligand-induced signalling
decreased degradation, turn off negative regulator
75
what are 2 important genes in cancer
oncogene and tumor supressor gene
76
what is oncogene
a gene when mutated, amplified or activated, promotes unregulated cell growth gain-of-function (always "ON")
77
what is tumor suppressor gene
a gene when mutated or inactivated will release cell cycle inhibition, loss of function
78
what is an example of an oncogene
ras
79
what is an example of an tumor suppressor gene
Rb and p53
80
where are the cell cycle checkpoints
between G1 and S, and inside mitosis
81
what does RAS do normally and how
it is activated by receptors to exchange GDP to GTP
82
what happens to mutant forms of RAS
they are not inactivated (always on)
83
what % of all cancers have RAS mutation
15-20%
84
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
85
which stage are most cells in
G0
86
what inhibits further cell growth
terminal differentiation, growth inhibitory proteins
87
what can produce cell cycle arrest
oncogene expression
88
what is another name for tumor suppressor genes
antiproliferative genes
89
what are 3 examples of antiproliferative genes
retinoblastoma protein
Rb
p53
90
what does retinoblastoma protein do
normally keeps cell in G0 (suppressor)
91
what is cell cycle arrest
the cell is no longer involved in the processes surrounding duplication and division
92
what are 2 cancers that Rb mutations are common in
retinoblastomas, small cell lung cancers (80%)
93
what is the main role of Rb
antiproliferative
94
what is the main role of p53
antiproliferative
95
what is the main role of retinoblastoma protein
antiproliferative
96
what % of cancers have p53 mutation
50-75%
97
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)
98
what is necrosis role in cancer (evading apoptosis)
evidence might do more damage by recruiting tumor promoting inflammatory cells that bring growth stimulating factors
99
what are 2 examples of ways that cells do cell death
necrosis and autophagy
100
what is autophagy
Activate mechanism to remove organelles or proteins they don’t need to survive - cancer cells is activated during starvation
101
what are 2 ways that cancer cells do limitless proliferative capacity
avoid replicative senescence and avoid crisis
102
what are 2 ways that cancer cells avoid replicative senescence
- mutate p53/Rb can extend lifespan
| - rare mutations lead to immortalization
103
how do cancer cells avoid massive death and chromosomal (karyotypic) disrray
activate telomerase (adds nucleotides at the end of the chromosomes)
104
how do tumors increase blood flow + how does it work
activate VEGF--> signal endothelial cell proliferation and growth of blood vessels
105
what are the center of tumors usually like and why
necrotic because oxygen cannot reach, angiogenesis does not keep up
106
what is the warburg effect
most cancer cells produce energy by glycolysis due to lack of oxygen
107
what about cancer kills you
metastasis, not the primary tumor
108
whata re 2 things that metastatic cells must be able to do
enter and leave the bloodstream and to survive in an ectopic location
109
what is the underlying mechanism of tissue invasion and metastasis
unknown, succession of cell changes... lots of things
110
what are 2 new emerging cancer hallmarks
deregulating cellular energetics, avoiding immune destruction
111
what are 2 new enabling cancer characteristics
genome instability and mutation, tumor promoting inflammation
112
are tumors complex tissues
yes - like their own organs, with some diff cell types, microenvironments and vasculature
113
what are 3 environmental DNA damaging agents
chemicals, radiation, viruses
114
what are 2 genes that mutations in can cause cancer
genes affected DNA repair and cell growth or apoptosis
115
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
116
what 2 things lead to clone expansion
unregulated cell proliferation and decreases apoptosis
117
what 3 things make clone expansion lead to tumor progression and malignant neoplasm
additional mutations, angiogenesis, escape from immunity
118
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)
