Chapter 10 - Biology of Cancer Flashcards
(191 cards)
1
Q
How is cancer a form of Darwinian evolution?
A
tumour development has cells with a heritable change that have a survival advantage, so outcompete their neighbours
2
Q
What is the leading cause of suffering and death worldwide?
A
cancer
3
Q
Cancer is a collection of more than ___ diseases
A
100
4
Q
Is cancer age related?
A
yes, the longer we live, the greater chance DNA replication has a mutation
5
Q
Is cancer genetic or epigenetic?
A
it can be both
6
Q
Epigenetic
A
how behaviours and environment cause changes that affect gene function
7
Q
What 3 factors influence risk and development of cancer?
A
environment, heredity, behaviour
8
Q
Cancer is derived from the Greek work Karinoma meaning ____. Why?
A
crab; describes the projections of the tumour into near tissues
9
Q
Original Tumour Definition
A
any swelling caused by inflammation
10
Q
Current Tumour Definition
A
new growth or neoplasm (abnormal growth)
11
Q
Are all tumours cancer?
A
no
12
Q
Benign Tumour
A
non-cancerous
13
Q
Malignant Tumour
A
cancerous
14
Q
Well-differentiated Cells
A
normal tissues that grow and spread slowly
15
Q
Undifferentiated Cells
A
made of abnormal cells that grow and spread quickly
16
Q
What kind of cells do benign tumours have?
A
well-differentiated cells and connective tissue
17
Q
Do benign tumour invade beyond its capsule?
A
no, they maintain a normal structure
18
Q
Are benign tumours dangerous?
A
they can be
19
Q
Benign Meningioma
A
tumour at the base of the skull that can compress the brain
20
Q
Malignant tumour progress to ____
A
cancer
21
Q
Malignant tumours grow ______ and have ______ organization
A
rapidly; abnormal
22
Q
Anaplasia
A
loss of cellular differentiation
23
Q
What type of cells do malignant tumours have?
A
undifferentiated
24
Q
Pleomorphic
A
variability in size and shape
25
Stroma
supporting structure
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Metastasis
ability to spread far beyond tissue of origin
27
What is the most deadly characteristic of malignant tumours?
metastasis
28
Carcinomas
cancers arising from epithelial tissue
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Adenocarcinomas
cancers arising from ductal or glandular structures
30
Do benign tumours metastasize?
no
31
Benign tumours have a ____ mitotic index, malignant tumours have a _____ mitotic index
low; high
32
What is a carcinoma in situ (CIS)?
a pre-invasive epithelial tumour of glandular or squamous cell origin
33
What does "pre-invasive" mean?
the cancer develops incrementally as it accumulates specific genetic mutations
34
Are CIS considered malignant?
No, they have not broken the basement membrane or invaded surrounding stroma
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Situ
in natural or original place
36
CIS remain _____ for a long time
stable
37
Can CIS progress?
yes they can progress into invasive or metastatic cancers
38
Can CIS disappear?
yes they may regress
39
CIS either...
remains, progresses, disappears
40
How to classify CIS?
vary from low-grade to high-grade
41
Which class of CIS are more likely to become an invasive carcinoma?
high-grade
42
Cancer is predominantly a disease of ______
aging
43
Mutation
cancer cells acquire characteristics that provide them an advantage over other cells
44
What is the advantage of cancer cells mutating?
increased growth rate and/or decreased apoptosis
45
Do cancer cells need growth factors to multiply?
no
46
Cancer cells lack contact inhibition meaning...
47
Anchorage independence
48
Do cancer cells undergo apoptosis?
no, they are immortal
49
How many mutations are required for cancer cells to form?
multiple
50
Tumour Microenvironment
mixture of cells (cancerous and not) and their secretions
51
Stage 1 of Cancer: Tumour Initiation
production of initial cancer cells, first stage of development
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What does tumour initiation depend on?
specific mutations
53
Stage 2 of Cancer: Tumour Promotion
population of cancer cells expands with diverse phenotypes, the cells undergo additional mutations
54
Stage 3 of Cancer: Tumour Progression
tumour spreads to near (invasion) and far (metastasis), more mutations occur
55
Point Mutations
small-scale genetic changes, alteration of one or a few base pairs
56
Translocations
large-scale genetic changes
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Driver Mutations (small-scale)
drive the progression of cancer forward
58
Passenger Mutations (small-scale)
don't contribute to malignant phenotypes, just random events
59
Chromosome Translocations (large-scale)
large changes in chromosome structure
60
During chromosome translocation...
a section of one chromosome is translocated to another
61
Gene Amplification (large-scale)
rather than 2 normal gene copies, tens or hundreds are made
62
HER2 Proteins
too many receptors signalling cells to grow and divide too quickly
63
Clonal Proliferation Model
advantage of cancer cells that causes them to replicate faster than neighbours
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What drives the accumulation of mutations?
rapid cell division and impaired DNA repair mechanisms
65
What does inactivation of the antigen presenting cell cause?
the cell seems normal but proliferates excessively
66
What does the mutation that activates K-ras cause?
normal cell that proliferates too much
67
What does a loss of DCC and an over-expression of COX-2 cause?
rapidly proliferating cell undergoing structural changes
68
What does a loss of TP53 and the activation of telomerase cause?
uncontrollable abnormal cell growth
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Transformation
process by which a normal cell becomes a cancer cell
70
What directs transformation?
accumulation of genetic changes that drive it to malignancy
71
Do all cancer cells have the same mutations?
not necessarily, some have their own set of mutations
72
What is the result of transformation?
heterogenous mixture of cells that accumulate more and more mutations
73
Heterogenous
diverse in character
74
Which cancer cell triggers the initial pro-inflammatory response?
the initial cancer cells
75
Who is affected by the initial pro-inflammatory response?
the cancer cells that triggered it and the neighbouring nonmalignant cells
76
What is recruited during the pro-inflammatory response?
-Inflammatory and immune cells (macrophages, T and B cells)
-tissue repair cells (fibroblasts, adipocytes, mesenchymal stem cells, endothelial cells)
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What do these recruited cells form?
a stroma/ tumour microenvironment
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What does the stroma do?
surround and infiltrates the tumour
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What % of the tumour mass may the stroma contribute to?
90%
80
What directs stroma growth?
-cancer cell proliferation
-cell additions
81
How does abnormal wound healing affect cancer cells?
increase proliferation and increases the diversity of said cells
82
Many cancer cells die but the surviving cells are more _______
aggressive and take on a metastatic phenotype
83
How do cancer cells gain the ability of uncontrolled growth?
sustained proliferation signals
84
What is pro-oncogene?
mutations that control sustained proliferation signals
85
What does pro-oncogene do?
blocks the body's mechanism of stopping uncontrolled growth
86
What is the 1st hallmark of cancer?
uncontrolled cellular proliferation
87
When do normal cells enter proliferative phases?
in response to growth factos
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What do growth factors do?
bind to receptors on the cell surface and activate signalling pathways to stimulate DNA synthesis and growth
89
Proto-oncogenes
normal genes that direct protein synthesis and growth
90
Oncogenes
mutated proto-oncogenes cells
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Oncogenes are _______ of normal regulatory mechanisms
independent
92
How do stroma contribute to uncontrolled growth?
by producing their own growth factors
93
Which growth receptors are activated by cancerous oncogenes?
RAS, P13K, D-cyclins
94
What do translocations cause?
excessive and inappropriate oncogene production
95
What does Burkitt Lymphoma produce? How?
abnormal B-lymphocytes by translocation changing normal chromosomes
96
How do cancer cells stop tumour suppressor genes?
evading growth suppression by 2 mutations to inactivate tumour suppressor genes
97
What do normal tumour-suppressor genes do?
inhibit proliferation, stop cell division of damaged cells, prevent mutations
98
Anti-oncogenes
tumour suppressor genes
99
What must be inactivated for cancer to continue?
tumour suppressor genes
100
Tumour-Protein P53 is a...
classic tumour-suppressor gene
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P53 aka '_______ of the genome'
guardian
102
What does P53 do?
monitor cellular stress and activates 'caretaker genes'
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What do caretaker genes do?
repair genetic damage and control apoptosis
104
How many mutations are required to inactivate P53?
2
105
What does only a single mutation of P53 result in?
increased cancer risk in offspring
106
How do cancer cells stop limits on their division?
telomere activation to provide unlimited "tickets" to divide
107
Hayflick Limit
limited number of divisions imposed on most body cells
108
What are telomeres?
protective caps on each chromosome
109
What happens to telomere caps as cells divide?
they shorten with each division
110
What happens when telomeres run out?
the cell can no longer divide so the cell dies (apoptosis)
111
What is telomerase?
an enzyme that maintains telomeres with cell division
112
Under normal conditions, where is telomerase active?
ovaries, testes, stem cells
113
What is the result of cancer cells activating telomerase?
unlimited telomeres (= unlimited division)
114
How do cancer cells gain their own blood supply to move around the body?
by angiogenesis -- the irregular development of vessels
115
What does angiogenesis by cancer cells increase the risk of?
hemorrhage
116
Angiogenesis means cancer has access to...
the systemic blood system
117
What do advanced cancers secrete?
angiogenic factors to promote growth
118
What are the angiogenic growth factors produced?
vascular endothelial GF, platelet-derived GF, basic fibroblast GF
119
Are tumour vessels the same as healthy blood vessels?
no
120
Do tumour vessels branch the same as healthy blood vessels?
no, they branch irregularly from existing capillaries
121
Why are tumour vessels more prone to hemorrhage?
the cells are less tight together and are hence more porous so can leak
122
How do tumour vessels promote metastasize?
they allow the passage of tumour cells in the vascular system so it can spread
123
How do cancer cells gain the building blocks to gain more cells?
they program energy metabolism to increase cellular growth
124
Normal cells use ______ metabolism
aerobic (mitochondria ETC)
125
When normal cells have limited oxygen they undergo glycolysis and produce ____ _______.
lactic acid
126
Warburg Effect
Aerobic glycolysis: cancer cells, even in adequate oxygen presence, use only glycolysis
127
What does the Warburg effect allow cancer cells to do?
continually produce lactate
128
What is lactate used for?
lipid, nucleoside, amino acid, molecular building block production needed for growth
129
How do cancer cells resist apoptosis?
utilizing the intrinsic/extrinsic pathway to activate BAK and block apoptosis
130
Apoptosis: What does the intrinsic pathway do?
monitors cellular stress
131
What does the intrinsic pathway activate if a cell can recover?
BAX
132
What does the intrinsic pathway activate if a cell must be destroyed?
BAK
133
What do BAX and BAK regulate?
mitochondrial release of pro-apoptotic molecules (cytochrome C)
134
When is the extrinsic pathway activated from dormancy?
when BAK, the death receptor is activated
135
What does activation of both the intrinsic and extrinsic pathways result in?
Apoptosis induced by cytotoxic T-cells and natural killer T-cells
136
The dysregulation of apoptotic pathways in cancer cells means they do not...
undergo apoptosis
137
What is the major cause of death from cancer?
metastasis
138
Can cancer that has not metastasized be cured?
Often yes by surgery, chemotherapy, radiation
139
Are surgery, chemotherapy, and radiation effective against metastasized cancer?
not usually
140
How do cancer cells develop the ability to metastasize?
EMT - epithelial-mesenchymal transition
141
Where do carcinomas originate?
highly differentiated epithelial cells in sheets stabilized be adhesions to neighbouring cells
142
What prevents carcinomas from dissociating from the extra cellular matrix (ECM)?
their epithelial like characteristics
143
What must happen for cancer cells to metastasize?
dissociation from the extra-cellular matrix
144
Metastasis is achieved by a programmed transition from a partially epithelial-like carcinoma to a more ____________ mesenchymal-like carcinoma?
undifferentiated
145
When does epithelial-mesenchymal transition occur normally?
embryonic development and wound healing
146
Anoikis
apoptosis that occurs when normal cells are separated from their ECM
147
Intravasation: How do tumour cells enter circulation?
via leaky angiogenesis vessels created by the cancer
148
Where do tumour cells spread?
through vascular and lymphatic pathways
149
Extravasation: Where do tumour cells go after they exit circulation?
host tissue
150
What allows tumour cells to survive in circulation?
cancer clot: platelets that coat the tumour to provide protection
151
Tumour-Initiating Cells aka cancer stem cells
the few cancer cells required to form a tumour in a new location
152
Does metastasis guarantee proliferation?
No
153
Dormancy
stable, non-proliferating state
154
Is dormancy reversible?
Yes
155
2/3 of breast cancer deaths occur after a __ year disease-free interval
5
156
What are some viruses associated with cancer?
Human Papillomavirus (HPV), Epstein-Barr Virus (EBV), Hepatitis B and C
157
Oncolytic Viruses
a new cancer therapy that uses these virus to attack cancer cells
158
3 Ways Cancer cells avoid the immune response:
1. don't produce tumour antigen
2. MHC gene mutation needed for antigen presentation
3. immunosuppressive protein production or expressing inhibitory cell surface proteins
159
______ immune system protects against cancer
normal
160
__________ fosters cancer
immunosuppression (ie. non-hodgkin's lymphoma, Kaposi sarcoma)
161
What does the release of immunosuppressive factors into the tumour microenvironment increase?
resistance to chemotherapy and radiation
162
They phenotype of a macrophage depends on the tumour m____e_______
microenvironment
163
What stage do 'Classic Macrophages' (M1) respond to?
inflammatory stage
164
What do classic (M1) macrophages do?
phagocytosis
165
What stage do M2 macrophages respond to?
healing
166
What do M2 macrophages do?
produce anti-inflammatory mediators to suppress inflammation
167
Do tumour-associated macrophages (TAM) perform like M1 or M2?
M2
168
What do TAMs do?
block T-cells and NK cells, produce cytokines that are advantageous to tumour growth and spread
169
What is analyzed microscopically to determine cancer staging?
present of metastasis
170
Stage I
no metastasis
171
Stage II
local invasion
172
Stage III
spread to regional structures
173
Stage IV
distant metastasis
174
Cancer Treatment: Surgery
-prevention
-biopsy for diagnosis and staging
-lymph node sampling
-palliative surgery
175
Palliative Surgery
used for pain relief rather than dealing with the cause of the condition
176
What does ionizing radiation do?
damage cancer cell's DNA
177
Cancer Treatment: What is the goal of radiation?
eradicate cancer without excessive toxicity and damage to normal structures
178
What does chemotherapy target in cancer cells?
specific vulnerabilities
179
Cancer Treatment: Why is chemotherapy given in combinations?
it can be designed to attack many different weaknesses of the cancer at the same time
180
Paraneoplastic Syndromes
a group of rare disorders triggered by an abnormal immune response to a cancerous tumour
181
What causes paraneoplastic syndromes?
biological substances released by the tumour
182
What is usually the earliest symptom of unknown cancer?
paraneoplastic syndromes
183
Is pain a symptom of early malignancy stages?
usually no, if so it is influenced by fear, anxiety, sleep loss, physical deterioration
184
Cachexia Syndrome
weakness and wasting of body due to severe chronic illness
185
What is the most severe form of malnutrition?
cachexia syndrome
186
Cachexia Syndrome Symptoms
anorexia, early satiety, weight loss, anemia, asthenia, taste alterations, altered lipid, protein, carbohydrate metabolism
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Asthenia
weakness, lack of energy and strength
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What does direct tumour invasion of bone marrow cause?
leukopenia and thrombocytopenia
189
Leukopenia
reduced WBC count in blood
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Thrombocytopenia
low platelet count in blood
191
What increases the risk of infection?
when neutrophil and lymphocyte counts fall
