Chapter 10 - Biology of Cancer Flashcards
1
Q
what is cancer?
A
leading cause of suffering and death in developed word.
2
Q
what caused cancer?
A
specific and often age-related accumulation of genetic and epigenetic alterations
3
Q
___, ___, and ____ interact to modify risk of developing cancer and response to treatment
A
environment, heredity and behavior
4
Q
what is the study of how behaviors and environment causes changes that affect gene function
A
epigenetic
5
Q
what does karinoma mean?
A
crab
6
Q
what is tumuor?
A
new growth or neoplasm (new/abnormal growth)
7
Q
cells and tissues structures that are like normal tissues and tend to grow and spread slowly?
A
well-differentiated
8
Q
made up of cells that look very abnormal and often grow and spread quickly
A
poorly differentiated or undiffrentiated
9
Q
True or False: well-differentiated and undifferentiated are both tumuors
A
True
10
Q
which type of tumour progresses to cancer?
A
malignant
11
Q
loss of cellular differentiation; aka hallmark of cancer
A
anaplasia
12
Q
what is pleomorphic? which type of tumour is this associated?
A
variability in size and shape; malignant
13
Q
the most deadly characteristic of malignant tumuors
A
metastasis
14
Q
what is metastasis?
A
ability to spread far beyond tissue of origin
15
Q
these are cancers arising from epithelial tissue
A
carcinomas
16
Q
cancers arising from ductal or glandular structures
A
adenocarcinomas
17
Q
T or F: CIS is not considered malignant.
A
True
18
Q
what is CIS?
A
preinvasive epithelial tumours of glandular or squamous cells origin
19
Q
three fates of CIS?
A
remains stable for long time (1)
progress to invasive/metastatic cancers (2)
regress and disappear (3)
20
Q
CIS vary from ___ grade to ____ grade dysplasia
A
low; high
21
Q
which grade lesions having highest likelihood of becoming invasive carcinoma
A
high grade
22
Q
Cancer is a predominantly a disease of ____
A
aging
23
Q
T or F: Single mutations required before cancer can develop/
A
false; multiple mutations
24
Q
result of multiple mutations?
A
decreased need for growth factors to multiply (1)
lack of contact inhibition (2)
anchorage independence to disseminate through body (metastasis) (3)
immortality - no apoptosis (4)
25
2 fundamental concepts of cancer:
cancer is a ___ (1) disease arising from ____ (2) mutations.
tumour environment is a ____ (3) of cells (cancerous and benign) as well as their secretions
genetic (1); multiple (2); mixture (3)
26
the three stages of cancer:
(1). tumour ___
(2). tumour ___
(3). tumour ___
initiation; promotion; progression
27
what is tumour initiation?
- first stage of cancer dev
- dependent on specific mutations
- producing initial cancer cell
28
what is tumour promotion?
- pop of cancer cell expands with diversity of phenotypes
- additional mutations
29
what is tumour progression?
- metastasis
- more mutations and changing microenvironments
30
small-scale changes: ___ mutations
large-scale changes: ___
point; translocations
31
two types of small-scale:
driver mutations (1)
passenger mutations (2)
32
what is point mutations?
alteration of one or few nucleotide base pairs
33
what is driver mutations?
mutations that drive progression of cancer.
34
what is passenger mutations?
random events; mutations that don't contribute to malignant phenotype.
35
two types of large-scale mutation?
chromosome translocation & gene amplification
36
what is chromosome translocations?
- large change in chromosome structure
- section of one chromosome is translocated to another chromosome
37
what is gene amplification?
instead of normal 2 copies of gene, tens or even hundreds of copies are present.
E.g., gene expression of HER2 proteins
38
selective advantage cancer cell has over neighboring cells
clonal proliferation model (CPM)
39
In CPM, cancer cells can replicate ___ than nonmutant neighbors
faster
40
increasingly __ cell division and ____ DNA repair mechanisms of cancer cells. This continues the accumulation of ___ throughout progression to most aggressive metastatic lesion.
rapid; impaired; mutations
41
a process by which a normal cell becomes a cancer cell
transformation
42
___ ____ that do not accumulate a critical set of mutations lose to competition and die
cancer cells
43
T or F: each cancer develop its own set of mutations
true
44
Transformation is directed by ___ accumulation of ____ ____ that ____ basic nature of cell and drive it to ____
progressive; genetic changes; alter; malignancy
45
Cancer development is similar to ____ _____
wound healing
46
initial cancer cell proliferation triggers a typical ______ response by itself and ____ nonmalignant cells
proinflammatory; adjacent
47
wound healing, mediators recruit:
- inflammatory or ____ cells (e.g., T cells, B cells and macrophages)
- cells associated with ___ repair like (f____, adipocytes, m____ stem cells and e____ cells
immune; tissue; fibroblasts, mesenchymal, endothelial
48
stroma cells make up ___% of tumour mass
90%
49
extensive _____ signaling among stromal and cancer cells affect both population:
(1) ____, & (2) _____
paracrine; secretory cell (1); adjacent target cell (2)
50
In Ab wound healing, recruited cells form a _____ (tumour microenvrionment
stroma
51
In ab wound healing, effect:
cancer cells ____ proliferation
becomes more ____ (diverse)
increase; heterogenous
52
In ab wound healing, process,
- great deal of cancer cell ___
- surviving cells are more ____
- many take on _____ phenotype
death; aggressive; metastatic
53
what is the first hallmark of cancer?
uncontrolled cellular proliferation
54
Normal cells generally only enter proliferative phases in response to ____ factors
growth
55
what is proto-oncogenes?
normal genes that direct protein synthesis and cellular growth
56
what are oncogenes?
mutated proto-oncogenes cells
57
_____ produce oncogenes, which allows uncontrolled growth
mutations
58
oncogenes are ____ of normal regulatory mechanisms
independent
59
____ can cause excessive and inappropriate production of oncogenes
translocations
60
translocation changes normal chromosomes into _____ lymphoma
Burkitt
61
what does Burkitt lymphoma produces?
Abnormal B lymphocytes
62
how do cancer cells evade growth suppressors?
mutation of tumour suppressor genes
63
what does normal tumour suppression genes do?
- inhibit proliferation
- stop cell division when cells are damaged
- prevent mutations
64
Tumour suppressor genes (which are called ____-_____) must be _____ for cancer proliferation to occur.
anti-oncogenes; inactivated
65
What is the classic tumour-suppressor gene?
tumour-protein P53
66
another name for tumour protein P53
guardian of the genome
67
what does P53 do?
- monitor cellular stress and activates caretaker genes to repair genetic damage
- also controls cellular apoptosis
68
Inactivation of P53 requires at least ___ mutations
two
69
what is Hayflick Limit?
the limit on cell replication imposed by shortening of telomeres in each division.
70
What are the protective caps on each chromosome?
telomeres.
71
when most cells proliferate, ______ caps ____ with each cell division
telomeres; shorten
72
T or F: When telomeres run out, cell can no longer divide, thus cells dies.
True
73
what is the enzyme that maintains telomeres, which don't decrease in number with cell division
telomerase
74
Telomerase -- usually active only in _____ and ____ (germ cells) and ____ cells
ovaries; testes; stem
75
T or F: cancer cells deactivate telomerase = unlimited telomeres
False; activate telomeres
76
what is the result of cancer cells activating telomerase?
unlimited proliferation which = to immortality.
77
what is angiogenesis?
production of new blood vessels -- activated by cancer cells
78
what happens if angiogenesis occurs?
vessels are more porous = prone to hemorrhage
irregular branching from existing capillaries
allow passage of tumour cells int vascular system = metastasize
79
advanced cancers secrete ____ factors
angiogenic
80
normal cells use ____ metabolism with O2
aerobic
81
with limited O2, normal cells use ____ and produce ____ acid
glycolysis; lactic
82
cancer cells use only ______ even in presence of O2. What effect is this called?
glycolysis; Warburg
83
Warburg effect = _____ glycolysis
aerobic
84
what is the cancer benefit of Warburg effect?
shift to glycolysis which allows continual production of lactate
85
what pathway is relatively dormant until death receptor is activated. What death receptor is needed?
extrinsic; BAK
86
T or F: The activation of both extrinsic and intrinsic pathways = T cells and NK cells induce apoptosis
true
87
Apoptotic pathways are ______ in cancers
dysregulated
88
T or F: Cancer cells do not undergo programmed apoptosis
True
89
Metastasis is the defining characteristic of cancer and the major cause of _____ from cancer.
death
90
T or F: Cancer that has not mestastized can often be cured by a combination of surgery, chemotherapy and radiation
true
91
T or F: Same therapies are frequently effective againts metastasized cancer
False; ineffective against metastasized
92
How do cancer cells develop ability to metastasize?
epithelial-mesenchymal trasition (EMT)
93
To metastasize, cancer cells must dissociate from _____
ECM
94
Carcinomas originate from highly _____ _____ cells that form structured sheets stabilized by multiple adhesions to neighboring cells.
differentiated epithelial
95
EMT -- achieved with a programmed transition from a ____ epithelial- like carcinoma to a more _______ mesenchymal-like carcinoma.
This step is initiation of _____-mesenchymal transition process
partially; undifferentiated; epithelial
96
EMT occurs normally in ____ development and wound ____ healing
embryonic; wound
97
what happens to normal cells when separated from their ECM?
normal cells undergo Anoikis -- induction of apoptosis in cell's loss of ECM
98
T or F: Cancer cells avoid anoikis by entering circulation and spread
True
99
what are the three steps of EMT?
(1) Intravasation - entry of tumor cells into circulation
(2) extravasation -- exit of tumor cells from circulation to host tissue
(3) survival in circulation -- platelets coat tumor = provide protection
100
what does platelets coat tumor do? and what stage of EMT you can find them?
provide protection; aka cancer clot. Stage 3 of EMT: survival in circulation
101
In terms of survival in new loc, only a ____ cancer cells required to establish a tumour in new loc.
few
102
what do you call to cancer cells establish in new location?
tumour initiating cells (TIC) or cancer stem cells
103
T or F: metastasis does guarantee proliferation.
FALSE; it doesnt guarantee.
104
what is dormancy?
a stable non-proliferating state that is reversible.
105
how many of the breast cancer deaths occur after a 5 year disease-free interval?
2/3
106
T or F: studies of deceased individuals with no history of cancer have dormant cancer cells.
True
107
what are the viruses associated with cancer?
HPV, EBV, & Hepatitis B and C
108
what is a new cancer therapy?
dev of oncolytic viruses that specifically attack cancer cells
109
cancer cells avoid immune detection and destruction using 3 mechanisms:
failure to produce tumor antigen (1), mutation in MHC genes (2) & production of immunosuppressive proteins or expression of inhibitory cell surface proteins
110
T or F: normal immune system protects against cancer
true
111
T or F: immunosuppression fosters cancer
True
112
Ways on how immunosuppression fosters cancer?
(1) Non-hodgkin's lymphoma (10x)
(2) Kaposi sarcoma (1000X)
(3) Release of immunosuppressive factors into tumour microenvironment increases resistance of tumour to chemo and radiotherapy
113
What are the different phenotypes of macrophages?
M1, M2 & TAM
114
What is M1?
classic macrophage (M1) responds to inflammatory stage to perform phagocytosis
115
during healing, what does M2 produces? And what does it do?
anti-inflammatory mediators, which suppress inflammation
116
what does TAM (tumour-associated macrophages) do?
perform like M2; TAM block T cells and NK cells and produce cytokines advantageous to tumour growth and spread
117
what are the 4 stages based on presence of metastasis?
Stage 1: no metastasis
Stage 2: local invasion
Stage 3: spread to regional structures
Stage 4: distant metastasis
118
what are some cancer treatment?
surgery, radiation & chemotherapy
119
what is paraneoplastic syndromes?
group of rare disroders that are triggered by an ab immune system response to a cancerous tumour.
120
____ or ____ pain is associated with early stages of malignancy
little; no
121
weakness and wasting of body due to severe chronic illness
cachexia syndrome
122
what is cachexia syndrome?
most severe form of malnutrition (1)
includes anorexia, early satiety, weight loss, anemia, asthenia, taste alteration, altered protein, lipid and carbo metabolism
123
what is asthenia?
weakness; lack of energy and strength
124
What causes when there is a direct tumour invasion of bone marrow?
leukopenia and thrombocytopenia
125
what is leukopenia?
reduced WBC in blood
126
what is thrombocytopenia?
blood platelet count too low
127
its a risk that increases when absolute neutrophil and lymphocyte counts fall
infection
128
