Cancer Biology Flashcards
Nail it dude. (98 cards)
1
Q
What is hypertrophy?
A
Increase in cell size with a normal organisation.
2
Q
What is neoplasia?
A
Disorganised growth with a net increase in the number of dividing cells.
3
Q
What is dysplasia?
A
Disorganized growth.
4
Q
What is hyperplasia?
A
Increase in cell number with a normal organisation.
5
Q
What are the hallmarks of cancer?
A
1) Self-sufficiency in growth signals.
2) Insensitivity to anti-growth signals.
3) Evasion of apoptosis.
4) Limitless replicative potential.
5) Sustained angiogenesis.
6) Tissue invasion and metastasis.
6
Q
What is the method of angiogenesis?
A
The tumour expresses vascular epithelial growth factors.
7
Q
How do tumours evade apoptosis?
A
Cancer cells often activate a gene to produce telomerase, which caps DNA to prevent apoptosis. Mutations in the p53 gene.
8
Q
Why are tumours insensitive to anti-growth signals?
A
Tumour suppressor genes are mutated in tumour DNA, preventing them from halting reproduction.
9
Q
What causes tumour cells’ limitless reproductive potential?
A
Typically, cells must be stimulated to divide by a growth factor. Cancer cells growth factor receptors may be locked onto active mode, causing incessant reproduction.
10
Q
What are two types of DNA damage?
A
CC to TT mutation of DNA in p53 tumour suppressor gene. Gene amplification where multiple copies of a gene are created.
11
Q
What happens in BRCA 1 and BRCA 2
A
BRCA 1 and 2 are genes producing proteins which fix double-stranded breaks by homologous recombination. These repaired breaks are likely to either promote an oncogene or remove a tumour-suppressor.
12
Q
What is an Oncogene?
A
Genes whose presence can contribute to uncontrolled cell proliferation.
13
Q
What is a Tumour Suppressor Gene?
A
Genes whose absence can contribute to uncontrolled cell proliferation.
14
Q
What is vasculogenesis?
A
During embryonic development, undifferentiated cells are converted into endothelial cells that organize themselves into a network of channels representing the major blood vessels.
15
Q
How is transcription in bacteria and eukaryotes differ?
A
In eukaryotes, transcription and translation are separated (occur in the nucleus and cytoplasm respectively). Bacterial mRNA encodes more than one protein and eukaryotic mRNA encodes one protein. Promoters in eukaryotic DNA are also more complex.
16
Q
Why do tumour cells perform angiogenesis?
A
To grow big and strong!
17
Q
What triggers angiogenesis?
A
VEGF = vascular endothelial growth factor
18
Q
What is a gene and what does it do?
A
A gene is a sequence of nucleotides in DNA or RNA that codes for a molecule that has a function
19
Q
What is the central dogma of cell biology?
A
A cell builds the proteins it needs from instructions encoded in its genome. The flow of information in the cell is from DNA to mRNA (through transcription) and then to proteins (by translation).
20
Q
How are eukaryotic genes different from prokaryotic genes?
A
Eukaryotic genes have introns (non-coding genes) and exons(coding)
21
Q
What are the three types of mutation? Explain each one.
A
Point mutation - single base pair change that can result from errors in DNA replication
Missense mutation - point mutation causing a change in the amino acid sequence of a protein
Silent mutation - mutations not causing change in amino acid sequence
22
Q
How is transcription in bacteria and eukaryotes differ?
A
In eukaryotes, transcription and translation are separated (occur in the nucleus and cytoplasm respectively). Bacterial mRNA is is polycistronic (encodes more than one protein) whereas eukaryotic mRNA is monocistronic (encodes for one protein). Promoters in Eukaryotic RNA are more complex and diverse. Bacterial cells require RNA polymerase and eukaryotes have several DNA polymerases (I, II, and III)
23
Q
How does cancer metastasize?
A
Cells penetrate the walls of the lymphatic vessels and go to lymph nodes. Here they can lodge and grow. Lymph nodes are also connected to blood vessels so cells can proliferate through the body.
24
Q
What is Sensitivity in cancer screening?
A
what percentage of people with a given type of cancer will have their cancer detected when a screening test is used. If a test is not sensitive, there will be many false negatives.
25
What is Specificity in cancer screening?
what percentage of people that do not have cancer are correctly identified as being disease free. If a test is not specific, there will be many false positives leading to potentially costly follow-ups and anxiety.
26
What are Koch’s Postulates and what are they for?
1) pathogen must be detected in diseased tissue
2) pathogen must be isolated from the host and grown in the lab
3) lab grown pathogen must cause the disease when administered to a healthy organism*
4) pathogen isolated from the newly infected host must be the same as the original pathogen*
Prove that given disease results from a specific pathogen
27
What causes Burkitt's Lymphoma?
Individuals are Immuno-compromised by malaria, and the Epstein-Barr virus may proceed to cause lymphoma. Also the first oncogenic virus in humans!
28
What is a telomere? What is its function?
A telomere is a region of non-coding base pairs at the end of linear chromosomes. When the replication fork reaches the end of a linear chromosome, there is no way to replace the RNA primer from the lagging strand with DNA. This single-stranded, if not modified, will be degraded. Telomeres will be degraded without causing damage to cell function allowing for many replications.
29
What are the steps of transcription?
Initiation
Elongation
Termination
30
How is gene expression regulated?
Transcription factors regulate gene expression (basal or general transcription factors and gene-specific
31
What virus causes the most human cancers?
HPV
32
How do infections cause cancer?
1) agents can increase cancer risk indirectly by compromising immune function
2) agents can create tissue destruction and chronic inflammation
3) agents can directly stimulate cell proliferation
33
What are the stop and start codons?
Stop codons - UAA, UAG, UGA
| Start codon - AUG
34
What is RNA splicing? Why is it necessary?
Transcription generates a primary RNA transcript containing exons and introns. Splicing removes introns before translation.
35
What are the building blocks of proteins? Describe their structure.
Amino acids are the building blocks of proteins. They are composed of a carboxylic acid and amino group attached to a central carbon. The central carbon is attached to a unique functional group.
36
Briefly describe the four structures of proteins.
Primary - linear, unique sequence of amino acids
Secondary - results from hydrogen bonding between carbonyl oxygen of one amino acid residue and the amino hydrogen of another. (Alpha and beta structures)
Tertiary - results from interactions between R groups and the peptide backbone of the same polypeptide
Quaternary - produced by the bonding of two or more polypeptide subunits
37
What is the function of enzymes?
They act as biological catalysts to increase the rate of reaction as compared to the rate without any enzymes present. Most biological chemical reactions only occur at meaningful rates in the presence of an enzyme.
38
What are the steps in transcription?
Initiation
Elongation
Termination
39
What are proto-oncogenes?
Proto-oncogenes are normal genes that make essential contributions to the regulation of cell proliferation and survival.
40
What are some emotional upon diagnosis of cancer?
Shock, fear, anger, sadness and guilt. Based on an individuals perception of the threat.
41
What are some emotional upon diagnosis of cancer?
shock, fear, anger, sadness and guilt
42
What is the outcome of increased cancer survival rates?
More considerations for the psychological difficulties that can occur with living with cancer as a chronic disease, or living as a survivor.
43
How do oncogenes arise?
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Point Mutations
Gene Amplification
Chromosomal Translocations
Local DNA Arrangements
Insertional Mutagenesis
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44
What are some psychological difficulties people with cancer are at risk of?
anxiety and depression, sexual dysfunction, trauma related problems, body image issues, insomnia, etc
45
What are invasive species?
Typically something we perceive as negative to us, or the "native" species.
46
What are the concepts leading to invasion?
Species-poor habitats, disturbed habitats, and islands
47
What are the reasons for using a stage-based approach?
Some populations succeed and become 'invasive' while others do not; focus on population phenomena
Life history or environmental characters may influence whether a species is 'invasive' or not; focus on stage-specific factors is easier and more informative
We can assess (human) interactions (positive or negative) at each stage of the process.
48
What is the invasion phase of cancer from an ecological perspective?
The invasion phase is the initiation. During this phase, there must be the right cell, at the right place, in the right time for an invasion to occur.
49
What is an evolutionary stable strategy? How does it differ from an evolutionary stable state?
The evolutionary stable strategy is a lofe strategy whereby, if every member of a population adopts it, no mutant strategy can invade. An evolutionary stable state is a subcategory of the stable strategy. It is an evolutionary state where the genetic composition of a population is maintained, even after a disturbance (pending a larger disturbance)
50
How is aging related to the ESS (evolutionary stable state)?
Age is the leading factor contributing to cancer development. From an ecological perspective, aging acts as an environmental disturbance that facilitates cancer invasion.
51
What are the resources defining niche space in the human body?
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Some examples:
blood flow - O2, glucose, iron, phosphorus, lipids
pH
extracellular space
immune response
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52
What is the establishment phase?
Once an invasive species enters a host, it must establish itself in that environment. Establishment can be thought of as "Can it survive its environment?"
53
How is glycolytic metabolism linked to the establishment phase in an ecological perspective on cancer?
Mutated cells survive and start proliferating in the tissue, decreasing oxygen availability within the tumor. Interior cells switch to glycolosis and lactic acid fermentation creating an acidic environment that normal somatic cells are excluded from. The acidic environment also allows up-regulation of HIF-1 and hypoxia, stimulates VEGF and promotes angiogenesis. All of these contribute to the establishment of cancer.
54
What is the problem or cost/benefit of invasive species and cancer ecology?
The cost/benefit analysis is the choice between a proactive approach (prevention) versus a reactive approach (conservation or treatment). A proactive approach detects potential invaders before establishment and a reactive approach determines the impact of invaders. There is a hysteretic phenomenon in a reactive approach however - the path to cancer is not the same path back and requires more energy, work, etc.
55
What is a proximate question?
It addresses the mechanisms that produce a behaviour: the environmental stimuli that trigger a behaviour and the genetic and physiological mechanisms that make it possible. It asks how.
56
What is an ultimate question?
It addresses the evolutionary significance of a behaviour: how a behaviour increases the evolutionary fitness of the animal demonstrating it, helping it to survive and reproduce in its environment. It asks why.
57
What is evolutionary fitness?
How well a species is able to reproduce in its environment.
58
What is adaptive behviour?
Any behaviour that contributes directly or indirectly to an individual's reproductive success.
59
What does the MYC protein do?
It stimulates the transcription of genes required for cell proliferation.
60
What is the difference between insertional mutagenesis and insertion of viral oncogenes in the case of MYC proteins?
Insertional mutagenesis is where overproduction of MYC leads to excessive stimulation of cell proliferation. Insertion of viral oncogenes occurs when a virus has its own MYC oncogene, so an abnormal form of the MYC protein is produced.
61
Give an example of chromosomal translation.
Burkitt's Lymphoma - a segment of chromosome 8 containing the normal MYC gene is frequently exchanged with a segment of chromosome 14 resulting in excess MYC protein.
Another example - Philadelphia chromosome
62
Name the 4 ways DNA can rearrange. What can this cause?
Deletion, insertion, transposition, inversion. Can cause oncogenes to arise.
63
How do proteins coded by oncogenes cause cancer?
Oncogenes can cause cancer in a variety of ways including the ones listed below:
- producing growth factors
- producing receptor proteins (these can transmit signals as protein kinases that are permanently activated, regardless of growth factor presence)
- producing membrane G proteins (signals activation of Ras-MAPK regardless of growth factor presence)
- etc
64
What do Rb proteins do? How can this be altered?
Rb proteins restain cell proliferation in the absence of growth factors by binding to E2F, unless it is phosphorylated. Factors in the Ras-MAPK pathway trigger the production of cdk-cyclin which phosphorylates Rb and allows for the onset of the S phase.
65
What are the two classes of tumor suppressor genes? How to they differ?
Two classes: gatekeeper genes and caretaker genes.
Gatekeeper genes restrain cell proliferation so a loss of function opens the gates to tumor formation. Examples are RB, APC, and p53.
Caretaker genes are involved in DNA maintenance and repair so a loss of function causes increased mutation rates for all genes. Examples are ATM, BCRA1, and BCRA2.
66
What is the role of p53?
p53 responds to DNA damage. Phosphorylation stabilizes p53. When stabilized it can bind to DNA to allow for the transcription of a cdk-cyclin gene leading to cell arrest. When DNA damage cannot be repaired, p53 activates genes coding for cell death.
67
Briefly explain repair by homologous recombination.
In response to a double-stranded DNA break, enzymes, tumor suppressor genes and a complex catalyze the removal of nucleotides from one strand of the double helix at each broken end. The exposed sing-stranded DNA regions are coated and will displace one of the two strands of the intact DNA being used as a template. The single strand will move along the template until it reaches a complementary sequence, at which point the broken DNA will be repaired using the complementary sequence as a guide.
68
What is a cell survival curve?
A mathematical way of describing the relationship between radiation and the proportion of living cells (both cancerous and normal).
69
What is target theory in radiobiology?
Target theory states that certain sensitive tragets within the cell must be hit in order to inactivate the cell. The shape of a cell survival curve is determined by the number of tragets within each cell taht have been damaged and the number of times each target must be hit.
70
What are the 4 Rs of radiobiology?
Repair
Reoxygenation
Repopulation
Redistribution
71
What is the most important part of the rationale for fractionation in radiation?
Repair. The premise is that late-reacting normal cells have a greater propensity for repair than tumor cells, so if time between doses is sufficient for complete repair, sublethal damage can be repaired before the next exposure.
72
Briefly explain each of the 4 Rs
Repair - late-reacting normal cells can reapir better, so if given sufficient time (about 24h), sublethal damage to normal cells can be repaired before the next exposure
Reoxygenation - hypoxic cells require a higher dose to treat, and are increased in number after treatment, so time should be allowed for cells to reoxygenate
Repopulation - during a course of radiotherapy, there is more repopulation of cancer cells than normal cells, so the longer the course of treatment lasts, the more difficult it is to contro, tumor repopulation
Redistribution - cells irridated during the mitotic phase are most sensitive so theretically there would be benefit if cancer could be caught in mitosis after ecah fraction
73
Provide some examples of infectious agents in human cancers.
Viruses - HPV, Hep B and C, KSHV
Bacteria - H. pyloria
Parasites - blood flukes and liver flukes
74
What are tumor suppressor genes?
Genes whose absence can contribute to uncontrolled cell proliferation.
75
What are the main stages of carcinogenesis?
1. Inititaion (mutation)
2. Promotion (cell proliferation)
3. Progression (rinse and repeat)
76
What is the difference between benign and malignant tumors?
Benign - local growth only, rarely life threatening, usually slow growth rate, and well differentiated
Malignant - spreads by invasion and metastasis, often life-threatening, may be rapidly growing, and variable state of differentiation.
77
What variable has the greatest impact on cancer?
Age!
78
What are the two models of enzymes. How do they differ?
Induced fit - when the substrate binds to the enzyme active site, the enzyme changes slightly preventing further substrate binding
Lock and key - exactly what is sounds like - unique shape fits into other unique shape
79
What are post-translational modifications?
Processing of proteins after translation before they are ready to perform functions in the cell. This can include folding, and the addition or removal of a phosphate group to activate it.
80
Describe the process of initiation in translation.
1. Ribosome binding site sequence binds to the complementary sequence in the RNA molecule in the small subunit
2. Initiator aminoacyl tRNA binds to the start codon (AUG)
3. Large subunit of ribosome binds
81
Describe the process of elongation in translation.
1. new tRNA moves into A site
2. amino acid attached to the tRNA in the P site is transferred to the tRNA in the A site
3. ribosome moves down mRNA. tRNA attached to polypeptide chain moves into P site. A site is empty
4. new tRNA moves into A site
5. polypeptide chain attached to the tRNA in the P site transferred to aminoacyl tRNA in the A site
6. ribosome moves down mRNA. tRNA attached to polypeptide moves to P site, tRNA from P site moves to E site, and A site is empty again
82
Describe the process of termination in translation.
1. translocation opens the A site and expose one of the stop codons causing a release factor to fill the A site. The release factor catalyzes hydrolysis to break the bond linking tRNA and the polypeptide
2. polypepetide is relased from the ribosome. tRNAs also released
3. ribosomal subunits dissociate and are ready to attach to the start codon of another mRNA
83
What does each site in the ribosome do?
A - holds aminoacyl tRNA
P - holds tRNA with growing polypeptide attached
E - hold tRNA that will exit
84
What is the wobble hypothesis?
Proposed by Francis Crick and states that the anticodon of tRNAs can still bind successfully to a codon whose third position requires a nonstandard base pairing.
85
What are the two structures of tRNA?
secondary structure is a cloverleaf, tertiary is a secondary but folded to produce L shape
86
What are snRNPs?
Small nuclear ribonucleoproteins. They form a spliceosome complex which catalyzes the splicing reaction
87
What is a holoenzyme? Give an example.
An enzyme made up of a core enzyme and other required proteins. An example is bacterial RNA polymerase which has a core unit able to synthesize RNA and a sigma subunit which acts as a regulatory factor.
88
What is a mutation?
Permanent change in an organism's DNA. Mutations are heretible and alter the genotype (which can alter the phenotype).
89
Describe the process of transcription.
Just know this man, I don't want to write it all
90
What enzyme protects the ends of telomeres?
Telomerase!
91
Describe the process of DNA replication in bacterial chromosomes.
I really don't want to write it all out, but you got this bud!
92
What is the primary structure of DNA?
nitrogenous base, sugar, and phosphate group
93
What is the difference between DNA and RNA?
RNA can a hydroxyl group on the 2' carbon of the sugar backbone. RNA also has uracil instead of thymine
94
How many points of origin are there in bacterial chromosome replication and eukaryotic chromosomes?
Bacterial chromosomes have 1 point of origin whereas eukaryotic DNA has many
95
What must be added to RNA before it can be transcribed?
poly(A) tail and 5' cap (7-methylguanylate)
96
What is the function of the TATA box? What fills its role in bacterial chromosomes?
TATA box is a promoter of transcription. In bacterial chromosomes, the promoters are -10 and 035 boxes (10 and 35 bases upstream from starting site)
97
What is an adaptive strategy?
A behavioral/life history strategy that increases the fitness of an individual.
98
How do the concepts of competition and predation relate to cancer biology?
Discuss.
