Chapter 10 - Biology Of Cancer Flashcards
(138 cards)
1
Q
What interacts together to modify risk of developing cancer and response to treatment
A
Environment, heredity and behaviour
2
Q
What is the leading cause of suffering and death in developed world
A
Cancer
3
Q
Cancer is derived from what Greek word?
A
Karinoma (crab)
4
Q
Karkinoma
A
Used “crab” to describe projections extending from tumours into adjacent tissue
5
Q
Tumour
A
Describes a new growth or neoplasm
6
Q
Not all tumours or neoplasms are
A
Cancer
7
Q
well differentiated and undifferentiated are
A
Both tumours
8
Q
Well differentiated
A
Are called and tissue structures that are like normal tissues and tend to grow and spread slowly
9
Q
Poorly differentiated or undifferentiated tumours
A
Are made up of cells that look very abnormal and often grow and spread quickly
10
Q
Benign tumours
A
-encapsulated
-well differentiated with organized stroma
-retain normal tissue and don’t invade beyond capsule
11
Q
What’s an example of how benign tumours can still be dangerous
A
Benign meningioma at base of skull can compress local brain tissue
12
Q
Malignant tumours progress to
A
Cancer
13
Q
Malignant tumours
A
-rapid growth rate
-abnormal organization
-large stroma
14
Q
What does it mean that malignant tumours are anaplasia
A
Loss of cellular differentiation
15
Q
Malignant tumour: pleomorphic
A
Variability in size and shape
16
Q
Malignant: metastasis
A
Ability to spread far beyond tissue of origin
-most deadly characteristic
17
Q
Cellular differentiation
A
Process in which a stem cell alters from one type to a differentiated one
18
Q
Carcinomas
A
Cancers arising from epithelial tissue
19
Q
Adenocarcinomas
A
Cancers arising from ducal or glandular structures
20
Q
Benign or malignant: grows slowly
A
Benign
21
Q
Benign or malignant: not encapsulated
A
Malignant
22
Q
Benign or malignant: invasive
A
Malignant
23
Q
Benign or malignant: poorly differentiated
A
Malignant
24
Q
Benign or malignant: low mitotic index
A
Benign
25
Benign or malignant: do not metastasize
Benign
26
Situ
In natural or original place
27
Carcinoma in situ
Preinvasive epithelial tumours of glandular or squamous cells origin
28
CIS have not
Broken through basement membrane or invaded surrounding stroma
-not considered malignant
29
CIS three fates
1.remain stable for a long time
2.progress to invasive/metastic
3.regress and disappear (immune system)
30
CIs vary
From low grade to high grade
-high grade lesions have highest likelihood of becoming invasive carcinoma
31
Cancer is predominantly a disease of
Aging
32
Multiple _____ required before cancer can develop
Mutations
33
Cancer mutations
Acquire characteristics that provide advantage over neighbouring cells
34
Common advantages of cancer cells
Increased growth rate and or decreased apoptosis
35
Result of mutations in cancer cells
1. Decreased need for growth factors to multiply
2. Lack contact inhibition
3. Anchorage independence to travel through body
4. Immortality/no apoptosis
36
Contact inhibition
37
Ten features of cancer
1.resisting cell death
2. Deregulating cellular energetic
3. Sustained proliferative signaling
4. Evading immune destruction
5. Evading growth suppressors
6. Enabling replicative immortality
7. Tumour promoting inflammation
8. Activating invasion and metastasis
9. Genomic instability
10. Inducing apoptosis
38
Cancer is a ___ disease arising from multiple ___
Genetic, mutations
39
Tumour microenvrioment is a ___ of cells both ___ and ___ as well as their secretions
Mixture, cancerous, benign
40
Stage one of cancer
Tumour initiation
-producing initial cancer cell
-dependant on specific mutations
41
Second stage of cancer
Tumour promotion
-population of cancers cells expands with diversity of phenotypes
-additional mutations
42
Stage three of cancer
Tumour progression
-spread of tumour to adjacent and distal items
-more mutations and changing micro environments
43
Mutations include
-small scale : point mutations
-large scale : translocations
44
Small scale : point mutations
Alteration of one or a few nucleotide base pairs
-can have profound effect on activity of resultant proteins
45
Driver mutations
Mutations that “drive” progression of cancer
46
Passenger mutations
Mutations that don’t contribute to malignant phenotype
-random events and referred to as passenger mutations
47
Large scale : chromosome translocations
-large changes in chromosome structure
-section of one chromosome is translocated to another chromosome
48
Large scale : gene amplification
Instead of normal two copies of gene, tens or even hundreds of copies are present
-gene expression of HER2 proteins
49
Clonal proliferation model
Selective advantage cancer cell has over neighbouring cells
-replicate faster than non mutant neighbours
50
What leads to accumulation of mutations
Rapid cell division and impaired DNA repair
51
Inactivation of APC
Cell seems normal but is predisposed to proliferate excessively
52
Mutation activation of K-ras
Cell begins to proliferate too much but is otherwise normal
53
Loss of DCC + over expression of COX-2
Cell proliferates more rapidly
-undergoes structural changes
54
Loss of TP53 + activation of telomerase
Cell grows uncontrollably and looks obviously abnormal
55
Transformation
Process by which a normal cell becomes a cancer cell
56
Transformation is directed by
Progressive accumulating of genetic changes that alter basic nature of cell
-drives it to malignancy
57
Each cancer may develop its own set of
Mutations
58
Cancer that does not accumulate critical set of mutations
Lose to competition and dies
59
Initial pro inflammatory response
-triggers typical prinflammatory response by itself and non malignant cells
60
Mediators that are recruited by initial pro inflammatory response
-inflammatory immune cells : T, B and macrophages
-tissue repair : fibroblasts, adipocytes, mesenchymal, endothelial
61
Extensive paracrine signals affects
Both stroma and cancer cell populations
62
Stroma
-Surrounds and infiltrates tumour
-make up 90% of tumour mass
63
Stroma not just affected by rapid cancer cell proliferation but
Various cell additions stroma
64
Cancer cells ___ proliferation and become
Increase
-more heterogenous
65
Cancer becoming more heterogenous and diverse =
Higher rate of cancer cell death
-surviving cells more aggressive
-metastatic phenotype
66
How does the cancer cell: sustain proliferation signals
-pro-oncogene control
-blocking body’s mechanism to stop uncontrolled growth
67
First hallmark of cancer
Uncontrolled cellular proliferation
68
Normal cells only enter proliferative phases in response to
Growth factor
-which bind to specific receptors on cell surface, activating pathways—> activate DNA synthesis and cellular growth
69
Proto-oncogenes
Normal genes that direct protein synthesis and cellular growth
70
Oncogenes
Mutated proto-oncotgene cells
-independant
-uncontrolled growth
-produce their own growth factors
71
Growth receptors: RAS, P13K, MYC, D-cyclins are activated by
Cancer oncogenes
72
Translocations can cause
Excessive production of oncogenes
73
Burkitt lymphoma produces
Abnormal B lymphocytes
74
How does the cancer cell: evading growth suppressor
-two mutations required
-inactivation of tumour suppressor genes
75
Evading growth suppressors —> mutation of
Tumour suppressor genes
76
Normal tumour suppressor gene function
-inhibit proliferation
-stop cell division when cells are damaged
-prevent mutations
77
Tumour suppressor genes must be
Inactivated for cancer proliferation to occur
78
Classic tumour suppressor gene
Tumour protein P53
-guardian of the genome
79
P53
-monitors cellular stress and activates caretaker genes to repair genetic damage
-control apotposis
80
Inactivation of P53 requires at least
Two mutations
-inc cancer risk in offspring
81
How does the cancer cell: limited cellular division
Activates telomerase to provide unlimited tickets to divide
82
Hayflick limti
Most body cells are not immortal and can only divide a limited number of times
83
Telomeres
Protective caps on each chromosome
84
What happens to telomere during proliferation
The caps shorten with each division
85
When telomeres run out
The cell can no longer divide, and it die
86
Telomerase
Enzyme that maintains telomeres
-don’t decrease in number with cell division
87
Telomerase is usually only active in
Ovaries and testes, and stem cells
88
Cancer cells activate telomerase =
Unlimited telomeres
89
Unlimited proliferation =
Immortality
90
How does the cancer cell: get its own blood supply for movement
-angiogenesis
-irregular development of vessels
-risk of hemorrhages
-access to systemic blood system
91
Angiogenesis
Cancer cells can activate production of new blood vessels
92
Advanced cancers secrete ____ factors
Angiogenic
93
Vessels formed within tumours
Perform irregular branching from existing capillaries
-less tight, more porous=hemorrhage
-allow passage of tumour cells=metastasize
94
How does the cancer cell: program energy metabolism
-Warburg effect/lactic acid
-inc risk of hemorrhage
-rapid cellular growth
95
Energy metabolism in normal cells
-oxygen=aerobic metabolism
-limited oxygen=glycolysis=lactic acid
96
Energy metabolism in cancer cells
Adequate oxygen=use only glycolysis
97
Warburg effect
Glucose—>glycolysis—>pyruvate—>lactate
Aerobic glycolysis
98
Benefit for cancer using the Warburg effect
-shift to glycolysis allows continual production of lactate
-lactate used for production of lipids, nucleoside, aa for building blocks = rapid growth
99
How does the cancer cell: resisting apoptosis
-intrinsic/extrinsic pathway
-activate BAK
-apoptosis blocked
100
Apoptosis intrinsic pathway
Monitors cellular stress
-cell recovers = activated BAX
-cell needs to be destroyed = activated BAK
101
Both BAX and BAK regulate
Mitochondrial release of pro-apoptotic molecules
-cytochrome c
102
Apoptosis extrinsic pathway
Relatively dormant until death receptor BAK is activated
103
Activation of both intrinsic and extrinsic apoptosis pathways causes
T cells and natural killer cells to induce apoptosis
104
How does the cancer cell: EMT
The ability to metastasize
105
Cancer that has not metastasized can be
Cured, by a combination of surgery, chemotherapy and radiation
106
Cancer that has metastasized can
Find the same therapies ineffective
107
Epithelial mesenchymal transition (textbook)
108
Initial carcinomas can adequately complete local tumour expansion but still
Retain epithelial like characteristics that prevent dissociation from ECM
-must dissociate from ECM to metastasize
109
How do cancer cells dissociate from ECM
-need greater degree of de-differentiation, to produce phenotype to separate from primary tumour
-turn into undifferentiated mesenchymal like carcinoma
—> initiates epithelial mesenchymal transition process
110
EMT occurs normally in
embryonic development and wound healing
111
Normal cells when separated from ECM.. BUT cancer cells..
Undergo anoikis—>apoptosis
Avoid anoiki—>enter circulation and spread
112
Intravasation
Entry of tumour cells into circulation
-through the vessel the cancer has created
-spreads through vascular and lymphatic pathways
113
Extravasation
Exit of tumour cells from circulation to host tissue
114
Survival in circulation
Platelets coat tumour = provide protection called a cancer clot
115
Cancers survival in new location
only need a few cancer cells -> tumour initiating cells or cancer stem cells
116
Dormancy
Stable non proliferating state that is reversible
117
Viruses associated with cancer
HPV, EBV, HEP B + C
118
new cancer therapy
Development of oncolytic viruses that specifically attack cancer cells
119
Cancer cells avoid immune detection and destruction using three 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
120
Immunosuppressive fosters cancer (2)
-non Hodgkin’s lymphoma x10
-kaposi sarcoma x1000
121
Release of im o suppressive factors into tumour micro environment increases
Resistance of tumour to chemotherapy and radiotherapy
122
Classic macrophage (M1)
Responds to inflammatory stage to preform phagocytosis
123
M2 macrophage
Appears during healing, to produce anti inflammatory mediators that suppres inflammation
124
Tumour associated macrophages (TAM)
Preform similar to M2
-block T cell and NK cells and produce cytokines for tumour growth and spread
125
Cancer/metastasis stage one
No metastasis
126
Cancer/metastasis stage two
Local invasion
127
Cancer/metastasis stage three
Spread to regional structure
128
Cancer/metastasis stage four
Distant metastasis
129
Cancer treatment: surgery
-prevents
-biopsy for diagnosis and staging
-lymph node sampling
-palliative surgery
130
Cancer treatment: radiation
Ionizing radiation damages cancer cells DNA
-eradicate cancer without excessive toxicity
-avoid damage to normal structures
131
Cancer treatment: chemotherapy
Takes advantage of specific vulnerabilities in target cancer cells
-combinations designed to attack cancer from many different weakness at a same time
132
Paraneoplastic syndrome
Group of rare disorders that are triggered by abnormal immune system response to cancerous tumour
133
Paraneoplastic syndrome caused by
Biological substances released by tumour
-earliest symptom of unknown cancer
134
Cancer pain
Little or no pain is associated with early stages
-influenced by fear, anxiety, sleep loss, physical deterioration
135
cachexia syndrome
Weakness and wasting of body due to severe chronic illness
-malnurition
136
Leukopenia and thrombocytopenia
Direct tumour invasion to bone marrow
-reduced WBC
-reduced platelets in blood
(Respectively)
137
Cancer infection levels
Risk increases when absolute neutrophil and lymphocyte counts fall
138
Asthenia
Weakness lack of energy and strength
