Week 1 Flashcards
1
Q
What is cancer?
A
A group of diseases characterised by unregulated cell growth and invasion and spread of cells from the site of origin to other sites in the body.
2
Q
What factors can help distinguish characteristics of a cancer?
A
The tissue of origin
3
Q
Name some ways to prevent cancer (lifestyle).
A
- Don’t smoke
- Keep a healthy weight
- Be safe in the sun
- Avoid certain substances at work
o (Asbestos) - Protect against infections
o (HPV and H.pylori) - Drink less alcohol
- Eat a high fibre diet
- Avoid un-necessary radiation
o (Including radon gas and x-rays) - Cut down on processed meats
- Avoid air pollution
- Breastfeed if possible
- Be more active
- Minimise hormone replacement therapy use
4
Q
What does a person’s risk of developing cancer depend on?
A
Age, genetics, exposure to risk factors etc.
5
Q
What is the largest cause of cancer in the UK?
A
Smoking
6
Q
Why has cancer overtaken heart disease as the main killing disease?
A
Cancer is a disease of the elderly and life expectancy has increased in recent years.
7
Q
What influences incidences and trends of cancer in recent years?
A
Risk factors and prevalence in past years.
8
Q
Describe how the number of cases and mortalities due to Melanoma have altered in recent years and explain why.
A
Cases of Melanoma have increased due to lifestyle changes such as sunbeds use etc.
However, mortality rates of Melanoma have decreased due to success with immune check-point inhibitors!!! These are extremely successful and often cause remission in stage 4 Melanoma.
9
Q
What kind of medications are often successful in treating Melanoma?
A
Check point inhibitors
10
Q
How have the chances of surviving cancer changed in recent years and why?
A
• In addition to better treatment options, diagnosis at an earlier stage of a cancer’s development is associated with improved outcomes and increased survival chances.
11
Q
How can early diganosis of cancer be improved?
A
Early diagnosis can be improved through reducing cancer waiting times, such as the time waited to see a specialist after an urgent referral from a GP, or the time waited for diagnostic tests.
It can also be improved through public health interventions, such as screening programmes and education campaigns.
12
Q
What are the different categories of risk factors for canceR?
A
Biomedical
Lifestyle
Environmental
13
Q
Name some biomedical risk factors for cancer and suggest which type of cancer they may cause.
A
- Genetic Susceptibility (cancer of the breasts, ovaries and bowels).
- Hormonal factors in females (cancers of the breast, ovary and endometrium).
14
Q
Name some lifestyle risk factors for cancer and suggest which types of cancer they may cause
A
- Smoking (lung, stomach, liver, cervix)
- Alcohol consumption (oral cavity, pharynx, larynx, bowel, liver etc).
- Physical inactivity and obesity (kidney, colon, oesophagus).
- Chronic infections (cervix and liver).
- Diet (bowel, breast, prostate).
15
Q
Name some environmental risk factors for cancer and suggest which types of cancer they may cause.
A
- Sunlight (melanoma of the skin and non-melanomal skin cancer).
- Radiation (leukaemia, cancers of the breast and thyroid)
- Occupational exposure (mesothelloma and cancer of the naval cavity).
- Poluution (skin, lung, bladder).
16
Q
Name some of the risk factors for stomach cancer.
A
- Age (60-80)
- Helicobactor vylori
- Tobacco
- Being overweight
- Smoked/ salted food
- Family history
17
Q
In terms of the TNM staging system, what does the letter T describe and what are the divisions of this category?
A
T refers to the size of the cancer and how far it has spread to nearby tissue.
It can be 1,2,3 or 4. 1 being small and 4 being large.
18
Q
In terms of the TNM staging system, what does the letter N describe and what are the divisions of this category?
A
N refers to whether the cancer has spread to the lymph nodes. It can be between 0 (no lymph nodes containing cancer cells) and 3 (lots of lymph nodes containing cancer cells).
19
Q
In terms of the TNM staging system, what does the letter M describe and what are the divisions of this category?
A
M refers to whether the cancer has spread to other parts
0 = the cancer hasn’t spread
1 = the cancer has spread
20
Q
Describe stage 0 of cancer.
A
Carcino in situ - early form.
21
Q
Describe stage 1 of cancer.
A
usually means that a cancer is small and contained within the organ it started in
- Localized
22
Q
Describe stage 2 of cancer.
A
usually means that the tumour is larger than in stage 1 but the cancer hasn’t started to spread into the surrounding tissues. Sometimes stage 2 means that cancer cells have spread into lymph nodes close to the tumour. This depends on the particular type of cancer
23
Q
Describe stage 3 of cancer
A
usually means the cancer is larger. It may have started to spread into surrounding tissues and there are cancer cells in the lymph nodes nearby.
24
Q
Describe stage 4 of cancer
A
means the cancer has spread from where it started to another body organ. For example to the liver or lung. This is also called secondary or metastatic cancer
- Metastasized
25
What is secondary cancer?
When cancer has metastasized from its original origin and has moved to other areas of the body.
26
Why is it unlikley to find a cure for cancer?
There are different classifications and types of cancer originating in different tissues with different characteristics and mechanisms. Too difficult to target with one drug.
27
What are the 6 major categories of cancer?
```
Carcinoma
Sarcoma
Myeloma
Leukemia
Lymphoma
Mixed Types
```
28
Name the ways in which cancer is classified.
2 ways:
1. Type of tissue in which the cancer originates (histological type)
2. Primary site, or the location in the body where the cancer first developed
29
Define carcinoma
A malignant neoplasm of epithelial origin or cancer of the internal or external lining of the body.
30
What are the 2 major subtypes of carcinoma?
Adenocarcinoma
| Squamous cell carcinoma
31
Where does an adenocarcinoma generally occur and develop?
Usually occur in the mucus membranes and develop in an organ or gland.
32
What do adenocarcinomas first look like?
Seen as thickened plaque-like white mucosa.
33
Where do adenocarcinomas spread to?
Spread easily through soft tissues of the body.
34
Where do squamous cell carcinomas originate?
In the squamous epithelium.
35
Where do most carcinomas affect?
Organs or glands capable of secretion.
36
Where is epithelial tissue found?
Epithelial tissue is found throughout the body. It is present in the skin, as well as covering the lining of organs and internal passageways, such as the GI tract
37
Why are cancers likely to be frequently found in epithelial tissues ?
Epithelial cells are constantly replicating and dividing so are ideal sites for tumour growth.
38
What is a sarcoma?
A cancer that originates in supportive and connective tissues such as bones, tendons, cartilage, muscle and fat.
39
In what type of people are sarcomas most common?
Young adults
40
Describe the appearance of Sarcomas.
Usually resemble the tissue in which they grow.
41
What is myeloma?
Cancer that originates in the plasma of cells of the bone marrow.
42
What is Leukaemia ?
Cancer of the bone marrow.
43
Describe changes in the blood composition of patients with Leukaemia and what consequences are caused?
Often associated with the overproduction of immature white blood cells. These immature white blood cells do not perform well and mean that patients are prone to infection.
Red blood cells are affected and often results in poor blood clotting and fatigue due to anaemia.
44
What is the technical name for the group of 'liquid cancers'?
Leukaemia
45
Where do lymphomas develop?
Lymphomas develop in the glands or nodes of the lymphatic system, a network of vessels, nodes, and organs (specifically the spleen, tonsils, and thymus) that purify bodily fluids and produce infection-fighting white blood cells, or lymphocytes.
46
Are lymphomas solid or liquid?
Solid
47
Are leukaemias solid or liquid?
Liquid
48
What are the 2 sub categories of lymphoma?
Hodgkin lymphoma and non-hodgkin lymphoma
49
Why may cancers named by their primary site not be accurate?
Cancers named by primary site are not accurate because they do not state the type of tissue involved. Simply indicates where the cancer is located.
50
What are the hallmarks of cancer?
Sustaining proliferative signalling.
Evading growth suppressors.
Activating invasion and metastasis.
Enabling replicative immortality.
Inducing angiogenesis.
Resisting cell death.
51
What is meant by the term 'hallmarks of cancer'?
The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors.
52
Describe what is meat by growth signal autonomy and how mutations mean this process is affected within mutations.
Normal cells need external signals from growth factors to divide. But acquired mutations in cancer cells circumvent this and this leads to uncontrolled growth.
Many cancers also develop the ability to produce growth factors.
53
What are oncogenes?
Genes that promote autonomous cell growth in cancer.
54
How are oncogenes derived and what do they do?
Oncogenes are derived by mutations in proto-oncogenes and are characterised by the ability to promote cell growth in the absence of normal growth-promoting signals.
55
What are the products of oncogenes and how are they different from the normal products of proto-oncogenes?
Oncoproteins resemble normal products of proto-oncogenes except that oncoproteins are devoid of important regulatory elements and their production in transformed cells does not depend on growth factors or other external signals.
56
How is growth signalling altered within cancer cells?
Normally growth factors are made by one type of cell in order to act on another type of cell. Cancer cells can acquire the ability to create and secrete their own growth factors which stimulates a feedback loop in which more cancer cells can divide and so on.
57
How many growth factor reception be altered in cancer cells?
Cancer cells can have mutations in growth factor receptors. A larger number of receptors are present on the surface of cancer cells. Cancer cells become hyper-responsive to ambient levels of growth factor. Cells are constantly signalled to grow and divide.
58
By what mechanisms is growth in cancer cells different than normal cells?
Cancer cells can alter the level of growth signal produced. Produce excessive growth signal via a positive feedback loop.
Over-expression of growth factor receptors.
Structural alteration of growth factor receptors.
59
How may structural alteration of growth factor receptors lead to tumour formation?
The growth factor receptors could be structurally altered, lacking regulatory regions which result in them being permanently 'turned on'. Constantly signalling for cells to grow and divide.
60
What is the most common gene in human cancer?
Mutant Ras
61
Describe how cancer cells evade growth inhibitory signals and describe the effects this has
Most normal cells respond to inhibitory signals to maintain homeostasis, placing cells in G0.
Some cells permanently exit the cell cycle, moving to a post-mitotic state and will not divide again.
In most cells antigrowth factors block cell growth by cellular quiescence through G0 or by using the post-mitotic state. H
However, acquired mutations in cancer cells can remove this block to allow cell growth to continue.
62
What are the 2 methods that antigrowth factors use to block cell growth in healthy cells?
Cellular quiescence though G0
Using the post-mitotic state
63
What causes cyclins to be produced?
Growth factors
64
What is the main function of cyclins?
Once cyclins are produced in response to growth factors, they bind and activate CDKs. CDKs then release transcription factors.
65
How does retinoblastoma work and what is it?
Retinoblastoma is a tumour supressor protein.
During the G1/S checkpoint, cells monitor their microenvironment to choose whether to continue in the cell cycle and enter G0 or enter a post-mitotic state.
Any antigrowth signals that may be used at this stage are funnelled through the Retinoblastoma protein.
66
What influences activation of the retinoblastoma protein?
Antigrowth signals from the surrounding microenvironment.
67
In terms of cancer, how may the tumour suppressor function of retinoblastoma be evaded?
Mutations of mutations in cancer cells may bypass the antigrowth signals from the surrounding microenvironment. This means the retinoblastoma pathway will be disrupted and E2F transcription factor will be liberate. This promotes cell division and therefore tumour growth.
68
Describe what phosphorylation of Rb means in terms of E2F transcription factor.
Unphosphorylated Rb binds E2F meaning E2F cannot bind the DNA and transcription is blocked.
Whereas phosphorylated Rb releases E2F which binds DNA and turns on gene expression, advancing the cell cycle and further cellular growth.
69
What evokes phosphorylation of Rb?
Cell growth.
70
What do normal cells do if they detect they have damaged DNA
They activate apoptosis to remove themselves from the population of cells.
71
What is the purpose of protein P53?
It is responsible for detecting DNA damage, chromosome abnormalities and arresting the cell cycle to initiate repair. If repair cannot occur, apoptosis is initiated.
72
What increases apoptosis induced by P53?
The presence of BAX pro-apoptotic protein.
73
Outline the changes/ differences caused to P53 by cancer cells and what effects this has.
Cancer cells may have damaged or missing P53 which compromises P53 activity by increasing the inhibitors of P53 or silencing the activators of P53. This means apoptosis is greatly reduced in cancer cells.
74
What is the hayflick limit?
The number of successive cell growth and division cycles that the body cells can undergo.
75
What is a telomere?
A region of repetitive nucleotide sequences associated with specializes proteins at the ends of linear chromosomes.
76
What is the main purpose of a telomere?
They protect the terminal regions of chromosomal DNA from progressive deletion due to the end replication problem.
77
How is production of telomerase altered in cancer cells?
90% increased production.
78
Via what do cancer cells spread by metastasis?
Lymph system or blood stream.
79
What is a metastatic tumour or cancer?
One that has spread from the primary origin or site where it started, to different areas of the body.
80
Name the steps to tumour metastases and give brief details.
1. Tumour grows (proliferation) and infiltrates the surrounding connective tissues.
a. Overcome hallmarks such as ability growth signal autonomy and evasion of growth inhibitory signals (this process uses antigrowth factors to block cell growth via cellular quiescence).
2. Tumour breaks through the basement membrane.
a. MMPs used to help this. They breakdown the basement membrane to help invade.
b. Intravasion occurs.
3. Overcome inhibitor substances to the enzymes it produces to break down the connective tissue proteins.
4. Attach to endothelium and enter lymphatic channels to evade immune cells in the blood
5. Lodge in the capillaries at destination and attach to and travel through the endothelium
a. Attachment and intravasion.
6. Proliferate and produce tumour.
a. Uses the process Angiogenesis.
b. Preparation of the metastatic niche must occur for the tumours to spread.
81
What is Angiogenesis?
The physical process through which new blood vessels form from pre-existing vessels formed in earlier stages of vasculogenesis.
82
How do tumours gain a sufficient blood supply?
Tumours can cause a blood supply to form by giving off chemicals that stimulate angiogenesis.
83
How do tumours avoid immune destruction?
Tumours engineer micro-environments to evade immune surveillance and attack by modulating certain immune check point pathways.
84
What are immune checkpoints?
The built-in control mechanisms of the immune system that maintain self-tolerance and help avoid collateral damage during a physiological immune response.
85
What is the Warburg effect?
The rate of glucose uptake dramatically increases and lactate is produced, even in the presence of oxygen and fully functioning mitochondria.
86
How do cancer cells use the Warburg effect to their advantage?
Cancer cells initially produce ATP directly via glycolysis rather than using oxidative phosphorylation. This is counter intuitive. However, this process increases biosynthesis which increases the rate of proliferation and so is advantageous to cancer cells.
87
How is using glycolysis more advantageous to cancer cells than using oxidative phosphorylation to produce ATP?
Increased glycolysis allows diversion of glycolytic intermediates into biosynthetic pathways enabling nucleoside and amino acid synthesis.
88
What indicators suggest that inflammation is linked to cancer?
White blood cells being present in tumours.
89
How does telomerase aid tumour growth / production?
Shortening of telomeres leads to genome instability which can aid cancer in accruing mutations. Telomerase activity maintains telomere length providing cells with extended proliferative capabilities which is another hallmark of cancer.
90
Which molecule is responsible for the extreme inflammatory response in tumour production and what type of molcule is it?
NFkB (Nuclear factor -kB) which is a transcription factor.
91
How is NFkB transcription factor activated and how does it remain inactive when necessary
It does not require any proteins to be activated.
| It is held in an active state by IkBa protein which binds NFkB and prevents it from moving into the nucleus of the cell.
92
How is NFkB activated? What can it do once activated?
IkB kinase adds a phopshate group to IkBa, tagging it for degradation. This means it can no longer hold NFkB in an inactive state. NFkB is then free to move into the nucleus of the cell and activate a wide range of genes that promote cell growth, survival, migration and formation.
93
Descrie the action of NFkB in the context of cancer and inflammation
The activation of NFkB in immune cells induces the production of molecules that activate NFkB in cancer cells. These then induce molecules that attract more immune cells into the tumour. This is a feed-forward loop that results in uncontrolled growth, with the immune cells actively enhancing the hallmark capabilities of the cancer cells. NFkB binds to genes which trigger genes involved in chronic inflammation. This triggers systemic inflammation and allows metastasis to occur from the initial site of the tumour. This is done using is signalling cascade.
94
How does NFkB enhance the hallmark capabilities of cancer cells?
NFkB binds to genes which trigger genes involved in chronic inflammation. This triggers systemic inflammation and allows metastasis to occur from the initial site of the tumour. This is done using is signalling cascade.
95
What are TAMs?
Tumour Associated Macrophages
96
How do TAMs act as a hallmark of cancer
TAMs support a growing tumour by assisting the cancer cells to bypass some of the anti-cancer defence mechanisms that are represented by the hallmarks.
97
What are the 4 mechanisms by which TAMs can help a tumour to develop and grow.
- TAMs provide the growth factors required by a tumour.
- TAMs secrete VEGF and PDGF to ensure a good blood supply is available via angiogenesis.
- TAMS secrete matrix degrading enzymes which aid metastasis of cancer.
- TAMs can suppress the adaptive immune system.
98
Explain how TAMs aid the growth of cancers.
TAMs provide growth factors such as epidermal growth factor, fibroblast growth factor, cytokines etc which all aid tumour growth.
99
Explain how TAMs help provide sufficient blood supply for a tumour.
And explain how this becomes a cycle.
A blood supply is established via Angiogenesis. This process is regulated via vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF).
TAMs secretes both of these growth factors.
The TAMs also accumulate in regions of oxygen starvation which are characteristic of advanced tumours. In these areas TAMs activate angiogenesis through the hypoxia response pathway.
VEGF attracts TAMs to tumours to demonstrate a feed-forward loop where TAMs surrounding a tumour secrete VEGF which in turn attracts more TAMs to the tumour.
100
How do TAMs aid cancer metastasis.
3. Cancer cells spread from the primary site with the use of degradation of the extra cellular matrix.
Matrix-degrading enzymes (secreted by matrix metalloproteases and TAMs) aid invasion and spread of cancer cells to distant body sites.
101
Explain how TAMs suppress the adaptive immune system.
They produce immunosuppressive molecules, allowing the tumour to evade the immune system. They also release cytokines that attract other immune cells that have no cell-killing activity.
102
What does acquiring the hallmarks of cancer usually depend on?
Genomic alterations and faulty DNA repair mechanisms.
103
What are the advantages and disadvantages of using the TNM system in cancer ?
Ad:
- Universal code that can be recognised between different types of medical staff in different areas.
- Little room for discrepancies.
- Useful point of reference for categorisation.
Dis:
- Objective
- Vague
- Not all cancers have the same risk based upon their staging. Very dependent on the cancer that is being studied.
104
How can 'Ras' mutations allow cancer to acquire sustained proliferative signalling?
- If ‘Ras’ protein becomes mutated, this growth factor will become permanently switched on. This causes a positive feedback loop in which more cancer cells are caused to divide and so the tumour constantly grows. Ras Binds GTP and causes signalling via a number of different pathways (such as the mTOR pathway which causes cell growth. So if Ras is constantly on the mTOR pathway will be in overdrive and lead to excessive cell growth).
105
By what types of mutations may cancer cells acquire sustained proliferative signalling?
Ras mutations.
Increased affinity for ligands occuring in receptor tyrosine kinases.
Mutated PTEN
106
What may occur within receptor tyrosine kinases to caused increased proliferative signalling in cancer cells? And how does this process work?
Increase receptor affinity for ligands causing increased receptor signalling and so increased proliferation.
107
Explain how PTEN mutations may cause cancer cells to have sustained proliferative signalling.
What is the specific hallmark in this scenario?
PTEN is a tumour suppressor which inhibits the mTOR pathway using P13K. If PTEN is mutated, the mTOR pathway will be in overdrive and there will be a strong drive for proliferation.
Hallmark - evades inhibitor signals.
108
What are the signalling and cellular effects of a loss of function mutation in p21 and explain how and why this occurs.
If loss of function mutation in p21 occurs, Rb (a tumour suppressor protein) will not be phosphorylated via use of the activator Cdk2 cyclin complexes. Unphosphorylated Rb usually binds transcription factor E2F which binds to DNA. If E2F cannot bind the DNA, the retinoblastoma pathway will be liberated and E2F will promote cell division to increase tumour growth and enhance the cell cycle.
Cdk2 phosphorylation of Rb occurs even in the presence of DNA damage and all cells enter the S phase of the cell cycle.
109
How could a loss of function of P53 help tumour cells escape apoptosis?
P53 is usually responsible for detecting DNA damage and arresting th cell cycle to initiate repair. If P53 is not functioning, repair will not be induced and so apoptosis will occur.
110
How does P53 induce apoptosis?
It increase the production of BAX pro-apoptotic protein.
111
How do cancer cells affect P53 activity and what effect does this have?
P53 activity is compromised by cancer cells due to increased inhibitors of P53 silencing the activators of P53. This means that apoptosis is greatly reduced in cancer cells.
P53 is responsible for BH3 expression. - In the absence of non-functioning BH3, BH3 protein expression will not okay. Pro-survival proteins such as Bcl-2 will not be expressed. Bcl-2 usually prevents apoptosis.
Bcl-2 will signal apoptosis as it is a pro-apoptotic protein.
112
What is mutagenesis?
The produce of genetic mutations.
113
What is carcinogenesis?
The initiation of cancer formation.
114
Name some endogenous ways by which cells in somatic tissues may accumulate mutations.
Spontaneous
Steady deamination of cytosines
115
Name some external ways in which cells in somatic tissues may accumulate mutations.
UV light
Carcinogens found in tobacco.
116
Outline what the classical model of carcinogenesis is.
The classical model states that cancer is a family of diseases driven by somatic point mutations as well as other genetic and epigenetic alterations. Environmental agents are also known to be carcinogenic hazards to humans.
117
How do non-mutagenic carcinogens increase the risk of cancer?
In healthy tissues, competing clones probably grow close together in a steady state. If the tissue is exposed to a chemical that causes many cells to undergo apoptosis, certain cells with pre-existing mutations may clonally expand in the presence of this new selective constraint.
118
Name a non-mutagenic carcinogen that could increase the risk of cancer.
Changes to tissue environment and immune filtrate may also cause new selective constraints.
119
In what type of cells do sarcomas originate?
Mesoderm cells
120
Sarcomas are cancers of the ...?
Bones or muscles
121
Adenocarcinomas are cancers of the ....?
Glandular tissues
122
Define autonomous
Carried out without control.
123
What is mean by the hallmarks of cancer ?
The hallmarks of cancer are essential for carcinogenesis.
124
Explain the hallmark to cancer 'autonomous cell growth signals'.
o Normal cells need external signals from growth factors to divide. However, cancer cells are not dependent on normal growth factor signalling. Cancer cells use acquired mutations to short-circuit growth factor pathways. This leads to unregulated growth.
125
How do cancer cells evade growth inhibitory signals and what consequence does this have?
o Cancer cells do not respond to growth inhibitory signals which normally maintain homeostasis. This is because they have acquired mutations which interfere with or silence genes which interfere with the growth inhibitory pathways.
126
What gives cancer cells their unlimited replicative potential and how does this differ from healthy cells?
o Normal cells have an autonomous counting device (shortening of the telomere) to define the finite number of cell divisions after which they become senescent.
o Cancer cells retain the length of their telomere and this results in unlimited replicative potential.
127
What gives cancer cells their unlimited replicative potential and how does this differ from healthy cells?
o Normal cells have an autonomous counting device (shortening of the telomere) to define the finite number of cell divisions after which they become senescent.
o Cancer cells retain the length of their telomere and this results in unlimited replicative potential.
128
What is angiogenesis?
The formation of new blood vessels
129
Explain why angiogenesis is a hallmark of cancer.
o Cancer cells induce the formation of new blood vessels which aids tumour survival and expansion.
o Altering the balance between angiogenic inducers and inhibitors can activate the angiogenic switch.
130
What are the 2 enabling characteristics of the hallmarks of cancer?
Genome instability and tumour promoting inflammation
131
What are the 2 emerging hallmarks of cancer and why are they not established yet?
Reprogramming energy metabolism and avoiding immune destruction.
Their relationship to the established 6 main hallmarks needs further research.
132
Explain how reprogramming energy metabolism could be a hallmark of cancer.
Uncontrolled cell division required increased fuel and in biosynthetic precursors that is obtained by adjusting energy metabolism.
Cancer cells carry out glycolysis, even in the presence of oxygen. Glycolysis intermediates can then be used in biosynthetic pathways.
133
In genera, why are malignant tumours life threatening?
They are physical obstructions. As they enter organs they compromise function. They also compete with healthy tissues for nutrients and oxygen.
134
Describe what a benign tumour is and if they are life threatening or not.
Benign tumours do not metastasise and remain capsulated but they can be life threatening depending on their site of origin.
135
How can cancer cells be distinguished from healthy cells in cell culture conditions?
Normally cells grow in a single monolayer in a petri dish due to contact inhibition (contact with a neighbouring cell inhibits growth). However, cancer cells fail to have contact inhibition so grow as piles of cells, known as foci, against a monolayer of normal cells.
Cancer cells can also grow in conditions of low serum and they adopt a round morphology rather than the expected flat, extended morphology. Unlike healthy cells, cancer cells can also grow without attaching to the substrate (Petri dish) and so exhibit anchorage independence.
135
How can cancer cells be distinguished from healthy cells in cell culture conditions?
Normally cells grow in a single monolayer in a petri dish due to contact inhibition (contact with a neighbouring cell inhibits growth). However, cancer cells fail to have contact inhibition so grow as piles of cells, known as foci, against a monolayer of normal cells.
Cancer cells can also grow in conditions of low serum and they adopt a round morphology rather than the expected flat, extended morphology. Unlike healthy cells, cancer cells can also grow without attaching to the substrate (Petri dish) and so exhibit anchorage independence.
136
How can cancer cells be distinguished from healthy cells in cell culture conditions?
Normally cells grow in a single monolayer in a petri dish due to contact inhibition (contact with a neighbouring cell inhibits growth). However, cancer cells fail to have contact inhibition so grow as piles of cells, known as foci, against a monolayer of normal cells.
Cancer cells can also grow in conditions of low serum and they adopt a round morphology rather than the expected flat, extended morphology. Unlike healthy cells, cancer cells can also grow without attaching to the substrate (Petri dish) and so exhibit anchorage independence.
137
Explain why there is an increased risk of cancer with age.
Mutations within cells accumulate over time which represents the multi-step process that underlies carcinogenesis and shows by there is an increased risk of cancer with age.
137
Explain why there is an increased risk of cancer with age.
Mutations within cells accumulate over time which represents the multi-step process that underlies carcinogenesis and shows by there is an increased risk of cancer with age.
138
What are somatic cells?
Any non-sex cells
139
What type of mutations are most of the mutations within a tumour?
Somatic mutations
140
Describe the inheritance of somatic mutations.
These mutations are not passed on to offspring and cannot be inherited. But they are passed on to daughter cells after division.
141
What lesser known factors also prove that cancer is a group of diseases caused by destruction of the genome at a cellular level?
Modifications of the genome and chromatin structure also play a role in carcinogenesis
142
Why is cancer not just a cell autonomous process?
It is also dependent on interactions between tumour cells and their own microenvironment and with long-distance systemic signalling.
143
Why is the development of cancer described as clonal?
All cells in a primary tumour arise from a single cell that contains an accumulation of initiating mutations. So the initiation in the development of cancer is clonal.
The clonal evolution of cells explains the heterogenous nature of cells within a tumour – primary tumours become composed of subclones.
144
What are the 3 processes that contribute to the cell count in an individual?
Cell proliferation
Elimination of cells by programmed cell death
Differentiation
145
How does differentiation affect the overall cell count of an individual?
During differentiation some cells can enter an inactive phase of cell growth. If these genes are mutated or the balance
145
How does differentiation affect the overall cell count of an individual?
During differentiation some cells can enter an inactive phase of cell growth. If these genes are mutated or the balance
145
How does differentiation affect the overall cell count of an individual?
During differentiation some cells can enter and inactive phase of cell growth. If these genes are mutated or the balance
145
How does differentiation affect the overall cell count of an individual?
During differentiation some cells can enter and inactive phase of cell growth. If these genes are mutated or the balance
145
How does differentiation affect the overall cell count of an individual?
During differentiation some cells can enter anq inactive phase of cell growth. If these genes are mutated or the balance
146
What is the purpose of porto-oncogenes in healthy cells?
They help cellular regulation and encode for proteins that function the signal transduction pathway of normal cellular proliferation.
147
What is an oncogene?
A gene that is a mutated form of a gene involve in normal cell growth.
148
What are the 2 major types of mutates genes which contribute to carcinogenesis?
Oncogenes
| Tumour suppressor genes
149
What are oncogenes?
Genes mutated such that their protein product is produced in higher quantities or has increase activity and therefore acts in a dominant nature to initiate tumour formation.
150
How many alleles of an oncogene need to be mutated for this to be visible in the phenotype and why?
1 - these mutations are dominant in nature.
151
Describe how oncogenes of growth factor receptors work.
An oncogene produces a growth factor receptor with increased activity because it has been altered so that it is always ‘on’ and does not require growth factor to transduce a signal into the cell
152
What are tumour suppressor genes?
They code for protein that inhibit growth and tumour formation.
153
How can mutations affect tumour suppressor genes and what does this result in?
Some mutations cause a loss of function in these genes and so loss of growth inhibitor occurs. This results in growth being permitted.
154
How many tumour suppressor alleles need to be mutated for the phenotype to be seen ?
i. Tumour suppressor mutations are mainly recessive. So usually both alleles of the gene must be mutated before the loss of function is seen phenotypically.
154
How many tumour suppressor alleles need to be mutated for the phenotype to be seen ?
i. Tumour suppressor mutations are mainly recessive. So usually both alleles of the gene must be mutated before the loss of function is seen phenotypically.
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How can oncogenes be identified by cell transformation assays?
The DNA of interested is isolated and introduced into a standard cell line (NIH/3T3) by calcium phosphate precipitation or electroporation. If the test DNA contains an oncogene, foci will form and will be easily identifiable against a monolayer of untransformed NIH/3T3 cells.
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How do stem cells relate to carcinogenesis and why?
Stem cells are undifferentiated and have the ability to renew and produce differentiated progeny.
- Both cancer cells and stem cells rely on self-renewal molecular programmes which is why stem cells may be a may be a main starting point for carcinogenesis.
- Cancer is also more likely to develop in cells which are actively proliferating as there is a greater chance of mutations accumulating. s
