Chapter 10 Flashcards
1
Q
What is the leading cause of suffering and death in the developed world?
A
Cancer
2
Q
What is cancer?
A
Collection of more than 100 different diseases, each caused by a specific
and often age-related accumulation of genetic and epigenetic alterations.
3
Q
What 3 things interact to modify the risk of developing cancer?
A
- Environment
- Heredity
- Behaviour
4
Q
What does Epignetic mean?
A
Study of how behaviors and environment cause changes that affect gene function
5
Q
Are all tumours or neoplasms cancer?
A
No, they can be benign or malignant
6
Q
What cells do benign tumours have?
A
Well-differentiated cells and is encapsulated
7
Q
What do benign tumours have that is well-organised?
A
Stroma
e.g Connective tissue
8
Q
What kind of tissue structure do benign tumours retain?
A
Normal tissue structure
9
Q
Where don’t benign tumours invade beyond?
A
The capsule
10
Q
Are benign tumours dangerous?
A
Yes
e.g Benign meningioma at base of skull can compress local brain tissue
11
Q
What are well-differentiated tumours?
A
Cells and tissue structures that are like normal tissues and tend to grow and spread slowly
12
Q
What are poorly differentiated/undifferentiated tumours?
A
Made up of cells that look very abnormal and often grow and spread quickly
13
Q
What do malignant tumours progress to?
A
Cancer
14
Q
What kind of organisation do malignant tumours have?
A
Abnormal
15
Q
Malignant tumours growth rates?
A
Rapid growth rates
16
Q
What is the hallmark of cancer?
A
Anaplasia
17
Q
What is anaplasia?
A
Loss of cellular differentiation, undifferentiated cells
18
Q
What do malignant tumours exhibit?
A
Pleomorphism
19
Q
What does it mean if a tumour is pleomorphic?
A
Variability in size and shape
20
Q
What kind of stroma do malignant tumours have?
A
Large stroma that is disorganised with an abnormal structure
21
Q
What is the most deadly characteristic that malignant tumours have?
A
Metastasis
22
Q
What is Metastasis?
A
Ability to spread far beyond tissue of origin
23
Q
What are some types of malignant tumours?
A
Carcinomas
Adenocarcinomas
24
Q
What are carcinomas?
A
Cancers arising from epithelial tissue
25
What are adenocarcinomas?
Cancers arising from ductal or glandular structures
26
Are malignant tumours encapsulated?
NO
27
What does Situ mean?
In natural or original place
28
What are Carcinoma in situ CIS?
Preinvasive epithelial tumours of glandular or squamous cells origin
29
How do carcinoma in situ cancers develop?
Incrementally as they accumulate specific genie lesions (mutations)
30
Why are CIS not considered malignant?
CIS have not broken through basement membrane or invaded surrounding stroma
31
What are the three fates of CIS?
1. Remain stable for a long time
2. Progress to invasive/metastatic cancers
3. Regress and disappear
32
What cancer predominantly a disease of?
Aging
33
What is required before cancer can develop?
Multiple mutations
34
What is a mutation?
Cell acquires characteristics that provide advantage over neighboring cells
35
What are some common advantages gained from mutations?
Increased growth rate and/or decreased apoptosis
36
What is the result of common advantages caused by mutations?
- Decreased need for growth factors to
multiply
- Lack contact inhibition
- Anchorage independence to disseminate through body (metastasis)
- Immortality: no apoptosis
37
What are the two fundamental cancer concepts?
1. Cancer is a genetic disease arising from multiple mutations
2. Tumour microenvironment is a mixture of cells (cancerous and benign) as well as their secretions.
38
What are the 3 stages of Cancer?
1. Tumour initiation
2. Tumour promotion
3. Tumour progression
39
What is tumour initiation stage?
-Producing initial cancer cell
-First stage of cancer development
-Dependent on specific mutations
40
What is tumour promotion stage?
-Population of cancer cells expands with diversity of phenotypes
-Additional mutations
41
What is tumour progression stage?
-Spread of tumour to adjacent (invasion) and distal sites (metastasis)
-Governed by more mutations and changing microenvironments
42
What are the 2 divisions of mutations?
Small-scale changes
Large-scale changes
43
What are small-scale changes called?
Point mutations
44
What are large-scale changes called?
Translocations
45
What are point mutations?
Alteration of one or a few nucleotide base pairs
-can have profound effects on activity of resultant proteins.
46
What are the types of point mutations?
Substitution
Insertion
Deletion
47
What are driver mutations?
Mutations that drive the progression of cancer
48
What are passenger mutations?
Mutations that don’t contribute to malignant phenotype. Some are just random events and referred to as “passenger mutations”
49
What are the 2 kinds of large scale mutations?
1. Chromosome translocation
2. Gene amplification
50
What is chromosome translocation?
-Large changes in chromosome structure.
-Section of one chromosome is translocated to another chromosome.
51
What is Gene amplification?
Instead of normal two copies of gene, tens or even hundreds of copies are present.
-Example: gene expression of HER2 proteins
52
What is the clonal proliferation model?
selective advantage cancer cell has over neighboring cells
-it can replicate faster than nonmutant neighbors.
53
What mechanisms of cancer cells continue the accumulation mutations?
Increasingly rapid cell division and impaired DNA repair
54
The continuing accumulation of mutations progress to?
To most aggressive metastatic lesion
55
What is transformation (mutations)?
Process by which a normal cell becomes a cancer cell
56
What directs transformation?
Progressive accumulation of genetic changes that alter basic nature of cell and drive it to be malignant
57
What can each cancer cell develop?
Its own set of mutations
58
What is the result of cancer cells developing mutations?
Genomically heterogeneous mixture of cells
59
What increases the cell's malignant potential?
Subsets accumulating more and more mutations
60
What happens to cancer cells that do not accumulate a set of mutations?
Lose to competition and die.
61
What is cancer development similar to?
Wound healing
62
What about cancer development and would healing are similar?
The initial pro inflammatory response
63
What does initial cancer cell proliferation trigger?
A typical pro inflammatory response by itself and adjacent nonmalignant cells
64
What do mediators recruit during the initial pro inflammatory response?
-Inflammatory or immune cells
-Cells associated with tissue repair
65
What kind of inflammatory or immune cells do mediators recruit?
T cells
B cells
Macrophages
66
What cells associated with tissue repair do mediators recruit?
Fibrolasts
Adipocytes
Mesenchymal stem cells
Endothelial cells
67
What do recruited cells form during abnormal wound healing?
A stroma (tumour microenvironment)
68
What does the Stroma do during abnormal wound healing?
Surrounds and infiltrates tumour
69
What percentage of tumour mass is made up of stroma cells?
90%
70
What is stroma growth affected by?
a. Rapid cancer cell proliferation
b. Various cell additions
71
What affects both stroll and cancer cell populations?
Paracrine signalling
72
What is the effect of paracrine signalling on cancer cells during abnormal wound healing?
Cancer cells increase proliferation
Become more heterogenous/diverse
73
During the process of abnormal wound healing what happens to most cancer cells?
They die
74
What happens to the surviving cancer cells during abnormal wound healing?
They are more aggressive and take on a metastatic phenotype
75
What mechanism is used to give cancer cells the ability of uncontrolled growth?
Sustained proliferation signals
76
What controls sustained proliferation signals?
Pro-oncogene
77
What is the result of oncogenes on the sustained proliferation signalling mechanism?
Body's mechanism to stop uncontrolled growth is blocked
78
What is the first hall mark of cancer?
Uncontrolled cellular proliferation
79
How do normal cells enter proliferative phases?
In response to growth factors
80
How do growth factors control cellular growth?
Generally bind to specific receptors on cell surface and activate intracellular signalling pathways affecting DNA synthesis and cellular growth
81
What are Proto-oncogenes?
normal genes that direct protein synthesis and cellular growth
82
What are Oncogenes?
Mutated proto-oncogenes cells
83
What are oncogenes independent from?
Normal regulatory mechanisms
84
What do mutations produce?
Oncogenes
85
What do oncogenes allow?
Uncontrolled growth
86
In addition to oncogenes, what else contributes to uncontrolled growth?
Stroma cells that produce their own growth factors
87
What growth receptors are activated by cancer oncogenes?
RAS, P13K, MYC, and D-cyclins
88
What kind of mutations can cause excessive production of oncogenes?
Translocations
89
What is an example of translocation changing normal chromosomes to cancer?
Burkitt Lymphoma
-Abnormal B lymphocytes
90
What mechanism allows cancer cells to stop tumour suppressor genes?
Evading growth suppressor
91
What is required for the evading growth suppressor mechanism to function?
Two mutations
92
What is the result of the evading growth suppressor?
Tumour suppressor genes are inactivated
93
How does the evading growth suppressor inactivate the tumour suppressor genes?
Via mutations
94
What do NORMAL tumour-suppressor genes do?
1. Inhibit ptoliferation
2. Stop cell division of damaged cells
3. Prevent mutations
95
What is the other name for tumour-suppressor genes?
Anti-oncogenes
96
What must be inactivated for cancer proliferation to occur?
Tumour suppressing genes
97
What is the classic tumour suppressor gene?
Tumour-protein P53
98
What is P53 referred to as?
Guardian of the Genome
99
What is the function of P53?
-Monitors cellular stress and activates caretaker genes to repair genetic damage
-Controls apoptosis
100
The inactivation of P53 requires what?
2 mutations
101
If P53 undergoes a single mutation what happens?
Increased cancer risk in OFFSPRING
102
What does cancer activate to allow it to divide as many times as it wants?
Activates telomeres
103
Are most body cells immortal?
No, most can only divide a limited number of times
aka Hayflick Limit
104
What are telomeres?
Protective caps on each chromosome
105
What happens to telomeres when most cells proliferate?
Telomere caps shorten with each cell division and become smaller and smaller
106
What happens when the telomeres run out?
The cell can't divide anymore and dies via apoptosis
107
What enzyme is maintains telomeres?
Telomerase
108
What does telomerase prevent?
Prevents telomeres from decreasing in number with cell division
109
Where is telomerase usually active?
Only in ovaries, testes (germ cells) and stem cells
110
What do cancer cells activate to be immortal?
Activate telomerase (for unlimited telomeres ---> causes unlimited proliferation)
111
How do cancer cells create their own blood supply?
Angiogenesis
112
What does Angiogenesis increase the risk of?
Haemorrhage
113
What is angiogenesis?
Production of new blood vessels
114
What is the result of cancer cells activating angiogenesis?
Cancer has access to systemic blood system
115
What do advaced cancers secrete?
Angiogenic factors
116
What growth factors are involved in Angiogenesis?
Vascular endothelial GF
Platelet-derived GF
Basic Fibroblast GF
117
Are vessels formed within tumours the same as healthy vessels?
No they are different
118
How are tumour vessels different from healthy vessels?
Tumour vessels perform irregular branching from existing capillaries
Healthy vessels perform regular branching
119
Why are tumour vessels more prone to haemorrhage?
They are more porous because cell contact between endothelial cells is less tight
120
How do tumour vessels contribute to metastasis?
The vessels allow passage of tumour cells into the vascular system
121
How do cancer cells get more building blocks to build more cells?
Programming Energy Metabolism
122
What risk is associated with programming energy metabolism?
Increased risk of hemorrhage
123
What is the result of programming energy metabolism?
Rapid cellular growth
124
What method of metabolism do cancer cells use?
Even in adequate oxygen only use Glycolysis
-Aerobic glycolysis
125
What is the name of the effect of cancer cells only using glycolysis?
Warburg effect
126
How do cancer cells benefit from the Warburg effect?
Allows continual production of lactate
127
What is the purpose of lactate?
Produces building blocks needed or rapid cell growth
128
Production of what uses lactate?
-Lipids
-Nucleosides
-Amino acids
plus other molecular building blocks
129
What do cancer cells resist?
Apoptosis
130
What are the 2 pathways that control apoptosis?
1. Intrinsic
2. Extrinsic
131
What does the Intrinsic pathway monitor?
Cellular stress
132
What 2 groups can the intrinsic pathway activate?
BAX and BAK group
133
What activates BAX?
If the cell can recover
134
What activates BAK?
If the cell must be destroyed
135
What do BAX and BAK groups regulate?
The mitochondrial release of pro-apoptotic molecules
136
What is the pro-apoptotic molecule?
Cytochrome c
137
What triggers the extrinsic pathway?
Death or BAK receptor is activated
138
What happens when both pathways are activated?
Cytotoxic T-cells and Natural Killer cells induce apoptosis
139
How do Cancer cells resist apoptosis?
The apoptotic pathways are dysregulated and cancer cells do not undergo programmed apoptosis
140
How do cancer cells develop the ability to metastasise?
EMT
141
What is EMT?
epithelial-mesenchymal transition
142
What is Metastasis?
Spread of cancer cells from site of original tumour to distant tissues and organs through body.
143
What is the major cause of death from cancer?
Metastasis
144
Example of Metastasis affecting the survival rate of cancer?
-localized low-stage breast cancer 5-year survival rate =
greater than 90%
-metastasized breast cancer survival rate = 30% after 5 years
145
Can non-metastasised cancer be cured?
Often can be cured with surgery, chemo and radiation
146
Can metastasised cancer be cured?
It is less curable, often the therapies that work on not metastasised cancer are ineffective against metastasised cancer
147
Where do Carcinomas originate from?
Highly differentiated epithelial cells
148
What must cancer cells dissociate from to metastasise?
Dissociate from extra cellular matrix ECM
149
What prevents dissociation from the ECM in initial carcinomas?
They still retain epithelial-like characteristics
150
How do carcinomas dissociate from the ECM?
With a programmed transition from a partially epithelial-like carcinoma to a more undifferentiated mesenchymal-like carcinoma aka initiation of EMT
151
Where does EMT normally occur?
Embryonic development
Wound healing
152
What happens to normal cells when dissociated from their ECM?
Undergo Anoikis
153
What is Anoikis?
Induction of apoptosis when cell loses ECM attachment
154
Do cancer cells undergo Anoikis?
NO they don't. Cancer cells avoid Anoikis so they can enter circulation and spread/metastasize
155
What are the 3 steps to Epithelial-mesenchymal Transition (EMT)?
1. Intravasation
2. Extravasation
3. Survival in circulation
156
What is Intravasation?
Entry of tumour cells into circulation
157
How is Intravasation completed?
Often via leaky angiogenesis vessels cancer has created
158
What pathways spread tumour cells?
Vascular and lymphatic pathways
159
What is Extravasation?
Exit of tumour cells from circulation to host tissue
160
How do tumors survive in circulation?
Platelets coat the tumour and provide protection
-Cancer clot
161
What are cancer cells that establish a tumour in a new location called?
Tumour-initiating cells (TICs)
or Cancer stem cells
162
What is Dormancy?
A stable non-proliferating state that is reversible
163
Does metastasis guarantee proliferation?
No
164
When do 2/3 of breast cancer deaths occur?
After a 5 year disease free interval
165
What do deceased individuals with no history of cancer have?
Dormant cancer cells
166
What viruses are associated with cancer?
Human Papillomavirus HPV
Epstein-Barr virus EBV
Hepatitis B and C
167
How do Cancer cells avoid immune detection?
Using 3 mechanisms
1. Failure to produce tumour antigen
2. Mutation in MHC genes needed for antigen presenting
3. Production of immunosuppressive proteins
or expression of inhibitory cell surface proteins
168
Can a normal immune system protect against cancer?
Yes
169
Are those with immunosuppression more likely to foster cancer?
Yes
170
How many times more likely are immunosupressed people to get Non-hodgkin's lymphoma?
10x
171
How many times more likely are immunosupressed people to get Kaposi sarcoma?
1000x
172
Why does immunosuppression foster cancer?
The release of immunosuppressive factors into tumour microenvironment increases resistance of tumour to chemo and radiation
173
Depending on the tumour microenvironment, there are different what?
Phenotypes of macrophages
174
What are the types of macrophages?
M1
M2
TAM
175
What are M1?
Classic macrophages
176
What do M1 respond to?
Inflammatory stage
177
What do M1 do?
Phagocytosis
178
What are M2?
Macrophages used during healing
179
What do M2's do?
Produce anti-inflammatory mediators to suppress inflammation
180
What are TAMs?
Tumor-associated macrophages
181
What macrophage type do TAMs preform like?
M2
182
What do TAMs do?
-Block T cells and NK cells
-Produce cytokines to help tumour grow and spread
183
How are cancers staged?
Based on presence of metastasis
184
What is Stage I?
No metastasis
185
What is Stage II?
Local invasion
186
What is Stage III?
Spread to regional structures
187
What Stage IV?
Distant metastasis
188
What are some treatments for cancer?
a. Surgery
b. Radiation
c. Chemotherapy
189
What are some ways surgery is used for cancer treatment?
Prevent cancer
Biopsy
Lymphnode sampling
Palliative surgery (relieve pain)
190
How does radiation treat cancer?
Ionising radiation damages cancer cell's DNA
191
What are the goals of radiation treatment?
Eradicate cancer without excessive toxicity
Avoid damage to normal structures
192
What does chemotherapy take advantage of?
Specific vulnerabilities in target cancer cells
193
How is chemotherapy given?
In combinations designed to attack a cancer's different weaknesses at the same time
194
What are Paraneoplastic syndromes?
Group of rare disorders that are triggered by an abnormal immune system response to a cancerous tumor.
195
What causes Paraneoplastic syndromes?
Caused by biological substances released by tumour
196
What may be the earliest symptom of unknown cancer?
paraneoplastic syndromes
197
How much pain is associated with early stages of malignancy?
Little to no pain
198
What influences pain in the manifestation of cancer?
Fear, anxiety, sleep loss, fatigue and overall physical deterioration
199
What is Cachexia syndrome?
Weakness and wasting of body due to severe chronic illness
200
Cachexia is the most severe form of what?
malnutrition
201
What are signs/symtoms of Cachexia?
anorexia, early satiety, weight loss, anemia, asthenia, taste alterations, and altered protein, lipid, and carbohydrate metabolism
202
Direct tumour invasion of bone marrow causes what?
1. leukopenia
2. Thrombocytopenia
203
What is Leukopenia?
Reduces WBC in blood
204
What is Thrombocytopenia?
Blood platelet count too low
205
When does risk of infection increase?
When absolute neutrophil and lymphocyte counts fall
206
What is Asthenia?
Weakness, lack of energy and strength
