Topic 9 - Cancer Flashcards
1
Q
What does cancer immunotherapy refer to? microbes have an affect?
A
- that cancers cells will produce specific antigens that they present on their surface
- these antigens are targeted by the immune system, particularly antibodies
- a recent study examined how specific members of the gut microbiota influence the efficacy of this type of immunotherapy
2
Q
What percentage of deaths are due to cancer? heart disease?
A
- 29.9% deaths due to cancer (the most)
- 19.7% deaths due to cancer
3
Q
Examining a spread of cancer deaths throughout the Canadian provinces/ territories, what is the trend
A
- higher rates of cancer deaths in the territories compared to the 10 provinces
- population gap however* OR the effect of light on breast cancer
4
Q
What effect does Light at Night have on the risks of Breast Cancer?
A
- too much light at night decreases the melatonin levels in the body
- this lack of melatonin now fails to suppress ESTROGEN which is linked to increases in Breast Cancer risk
- particularly shift workers affected
5
Q
What is the correlation between Cancer Risk and Age/Gender? ASIR?
A
- increased risk of cancer with an increase in age
- Age-standardized incidence rates
- across the board, females have a lower risk of cancer? - due to higher inclination of seeing a doctor
6
Q
What does Canada’s future look like regarding population within 10 years
A
- there will be a growth between 55-65
- while any age below that will only grow due to increase in population size naturally
7
Q
What does Canada’s future look like in regards to NEW CANCER CASES within 10 years?
A
- a significant increase in cancer cases begining at age 45-49, maxing at 65-750, tapering off beyond 85+
- Notably significantly more Male cancer cases compared to females
8
Q
What are particular cancer prevalences that will increase significantly in the next 10 years? (4)
A
- Colorectal
- Lung
- Prostate
- Breast
- 4 major cancers
9
Q
What is the trend like for cancer deaths AVOIDED? 1. All Cancers 2. Lung Cancer
3. Breast Cancer
A
- will have projected decreased rates cancer deaths – due in part to improvements in Cancer treatments
10
Q
Explain the Relative Survival Rates (RSR) of the 4 cancers: prostate, breast, colorectal, lung - 1, 3, 5, 10 years
A
this point examines the survival rate after having treatment to the cancer
- high chances of survival from BREAST and COLORECTAL cancer, PROSTATE
- less RSR from treatment for LUNG cancers after treatment
11
Q
What can we infer from tumour cell population doublings and identifying breast cancer?
A
- after 25 tumour cell population doublings, it will first be visible on an Xray (10^8 cells)
- after 28 tumour cell population doublings, the tumour is first palpable (10^9 cells)
- after >35 tumour cell population doublings, the patient will die (10^12 cells)
12
Q
Explain the relative trends of Cancer events for Females from 1930 onwards.
A
- consistent cancers: pancreas, ovary, breast
- consistent decrease in cancers: colon & rectum, uterus, stomach
- Increase in CANCER cases: lung cancer 1965 (not as significant as male lung cancer)
13
Q
Explain the relative trends of Cancer events for Males from 1930 onwards.
A
- consistent cancers: leukemia, liver, pancreas, colon rectum, prostate
- consistent decrease in cancers: stomach
- increase in CANCER cases: lung cancer (significantly more than females)
14
Q
Explain the Global Events that lead to the increase in lung cancers among the population?
A
- global consumption of cancer skyrockets - 1920-1980s
- global lung cancer deaths caused by smoking (estimate) skyrockets 1950-present
- small portion of lung cancer UNRELATED to tobacco
15
Q
What was the Heliobacter Pylori Experiment
A
- Barry Marshall and Robin Warren, working on a treatment for H. pylori infections
- stomach cancer was that to arise from ulcers in the stomach
- Marshall produced an antibiotic for H. pylori, consumed it got sick and treated himself with the antibiotics
16
Q
Explain the Cancer Screening story, should we all be screened?
A
- Paper published 2 million people develop preventable cancers each year which are caused by viruses, bacteria, and infectious agents
- it is not politically exciting to save lives this way… saving the lives could not justify the EXTREME cost of such screen
- over-treatment (common in breast and prostate cancer - increase in antibiotic resistance)
- screen for all cancers?
17
Q
Where are PAP tests used?
A
- for the papilomavirus - HPV vaccines
18
Q
Carcinomas
A
- cancers of the epithelial cells, ex. the skin or lining of internal organs
19
Q
Sarcomas
A
- cancers of connective tissues or NON-epithelial tissues, ex. muscles
20
Q
Leukemia & Lymphomas
A
- cancers of White Blood Cells and Lymphocytes (lymph nodes)
- malignant progressive disease where bone marrow and blood-forming organs produce immature/abnormal blood cells
21
Q
Carcinogenesis
A
- the initiation of cancer forming chemical compounds are linked to mutagenesis (causing mutation in DNA which will produce mutant cells which can take ahold in tissues)
- can be chemical or radiation, ex the sun which cause the thymine dimers
22
Q
What is the Thymine Dimer?
A
- a simple mutation caused by the Carcinogen UV-light that will form a dimer between two thymine subunits
23
Q
Explain the 3 cases of balancing proliferation and apoptosis.
A
- Homeostasis: normal cell division and normal apoptosis
- Tumour: increased cell division and normal apoptosis
- Tumour: normal cell division and decreased apoptosis
24
Q
What makes Cancer so dangerous?
A
- reproduce without the normal constraints on growth and division
- invade and colonize other tissues
25
Define a Benign Tumour
- cell growth that is not invasive, localized
| - the tumour has not invaded other tissue yet since it has not broken through the basal lamina
26
Define a Malignant Tumour
- tumour has broken through the basal lamina and has started spreading to other tissues
27
Define Tumour Metastasis
- in a normal epithelium cell a mutation occurs which cause a benign tumour to grow
- cells become invasive and enter a capillary where they travel through the blood and attempt to adhere to blood vessels walls and break through this membrane
- micrometastasis will occur where the cells take up shop as a secondary growth
NOTE: one in a million cells will actually establish itself in a new tissue environment - majority of cells will not be able to take up a new site
28
Define the barriers to metastasis
- DIFFICULT: to escape from parent tissue (which would cause entry into new vessels)
- EASY: traveling through circulation (survival in circulation, arrest in a capilary, exit into remote tissue/organ)
- DIFFICULT: Colonization of remote sites (survival of cells in foreign tissue, initial growth of these cells, persistence of growth)
29
Explain how the cell hierarchy affects tumour growth
- upon cell differentiation from Stem cells, in normal tissue this process is slow and rare where daughter cells consist of stem cells & differentiatiating specialized cells
- compared in cancer tissues, a cancer stem cell is rare, and cells will need to overcome limited renewal capacity
30
What are two hurdles cancer cells must overcome?
- limited self renewal capacity
| - rare stem cells become cancerous so differentiation of a cancer cell to perform a different action in a cell is rare
31
What is the origin of a mutation, is a single mutation enough, and a tumour only has one cell type?
- it will originate from a signal cell which had a mutation persist through a number of replication cycles which extends to daughter cells
- requires multiple mutations of a number of cellular functions (a gradual accumulation of mutations) -- at least 5 different genes will need to mutate to lead to TUMOUR PROGRESSION - consider the tumour graph
- a tumour consists of many cells (cancer cells are genetically unstable)
32
In the cancer founder cell, what 3 heritable changes may lead to cancer arising?
point mutation
- a mutation in the promoter OR coding region OR difference in the sequence will cause this mutation to persist during cell division if not fixed -- leads to gene inactivation
- an epigenetic mutation causes gene inactivation; different regulation of the gene, ex. heterochromatins form around the packed DNA meaning the gene is inactive and cannot be expressed
- an accident causes DNA methylation itself and inactivation of the sequence itself
33
Are epigenetic changes also heritable over generations?
YES; epigenetic inheritance may allow an organism to continually adjust its gene expression to fit its environment - without changing its DNA code.
- however in case of mutation this will be detrimental to the cell
34
What results from the accumulation of somatic mutations?
- this accumulation results when a mutation is able to persist within the cell, "survival of the fittest" - where the cell is now better adapted to out grow the other cells
35
Define a "Driver Mutation"
- mutation within a gene that confers a selective growth advantage (thus promoting cancer development)
- cancer critical genes which will compromise cellular function
36
Define a "Passenger Mutation"
- mutations that don't contribute to the development of cancer but have occurred during the growth of the cancer
37
Two factors that may lead to cancer development?
- lifestyle and environmental factors
- constitutional mutations (genetic inheritance)
- interesting point: with a change in lifestyle up to 50% of cancer can be avoided
38
Name a few examples of Carcinogens.
- vinyl chloride
- Benzene
- Aresenic
- Asbestos
- Radium
39
Explain the Ames Test and its limitations
- The Ames Test is used to test the potential mutagenic factor of a test compound
- ex. potential mutagen is mixed with a culture of histidine-dependent salmonella and homogenized liver extract
- mixed and cultured on a plate
- the addition of the liver extract helps i trying to get a mutation to survive
40
Why is the liver extract aded in the Ames test?
- contains cytochrome P450 enzyme which is able to break down molecules or convert mutagenic molecules to make them into a harmful chemical
- if the mutagen is strong enough it will be able to breakdown the p450 and cause the mutation
41
Given an example in detecting cancer?
ex. the Philadelphia chromosomes in chronic myloid leukemia (CML)
- a rearrangement between two chromosomes 22 and chromosome 9 occur
- chromosome becomes longer, while chromosome 22 shorter
- this rearrangement/random duplication occurs all over the place
42
What is the difference between INTERchromosomal rearrangement and INTRAchromosomal rearrangement
- rearrangement between two chromosomes: typically between the homologous maternal and paternal chromosomes
- rearrangment within a single chromsome
43
Where would a GOF occur and what effect would it have?
- Gain of Function mutation (typically in oncogenes)
- results in an overactivity mutation
- one mutation in one of the alleles that activate the mutation which promotes cell transformation
- dominant
44
Where would a LOF occur and what effect would it have?
- Loss of Function mutation (typically in tumour suppressors)
- a mutation event results in an inactivation of one allele of a tumour suppressor, which is still active due to a functional gene copy
- a second mutation in the second allele of the tumour suppressor results in the elimination of the tumour suppressor gene completely
- recessive
45
How does a proto-oncogene go to an oncogene?
- a point mutation in the coding sequence: produces a hyperactive protein in a signalling pathway
- regulatory mutation: over expression of a normal protein (hypersensitivity)
- gene amplification: normal protein is over expressed, ex. signal protein or a receptor causing hyper-phosphorylation or hyperactivity
- Chromosome rearrangment: (2) a nearby regulatory DNA sequence causes a normal proteins over production OR fusion of a actively transcribed gene produces hyperactive proteins
46
How do you identify an oncogene? definition? example?
- gene that has the potential to cause cancer, that when mutated becomes an oncogene
- oncogene may result in the "loss of contact inhibition by cancer cells
- meaning normal cells will only grow in a monolayer attached to a plate, while cancer cells will grow on top of each other
- Ras as an oncogene: functions in signal transduction pathway of MAP kinase kinase kinase
47
How do you identify Cancer Cells?
- Cancer cells will switch from cellular respiration (oxidative phosphorylation and Oxygen with high energy ATP) instead using GLYCOLYSIS to produce ATP via NADPH
- this is known as the Warburg Effect
48
Examine hereditary cancers of the retinoblastoma genes (3 cases)
1. a normal healthy cell with two health chromosomes - a mutation may inactivate on of the Rb genes but it does not persist - so NO TUMOUR formation
2. in NON-hereditary Rb, where an occasional cell mutates an Rb gene, the second copy is still RARELY inactivated; BUT excessive proliferation if both mutate - excessive proliferation leads to the rare Rb tumour in ONE eye
3. hereditary Rb where one gene is mutant; occassionally only one mutant with one good copy of the Rb gene -- excessive cel proliferation of a double mutant now results in tumours in BOTH eyes
49
Name the 6 ways a normal Rb gene can be lost?
- chromosome loss
- chromosome loss followed by chromosome duplication
- mitotic recombination event
- gene conversion during mitotic event
- deletion
- point mutation
50
Compare a genetic change and an epigenetic change?
- genetic mutation will be required in both genes to lead to cancer
- epigenetic change also required in both genes to lead to cancer
- or a combination of the two will lead to cancer
51
Name two methods of identifying Cancer Genes? as old techniques.
- Microarrays
- Sequencing; amplify and sequence the coding exons, then sequencing the cancer genome (whole gene families and coding exons), then sequencing of transcription
52
What is a sequencing technique we complete now a days?
- sequence RNA and compare the healthy RNA vs tumour RNA
53
What is the purpose of Cancer Genome Sequencing? - where are tumour suppressors most active?
- to identify new oncogenes or tumour suppressor genes
- ex. IDH1 in the Kreb cycle or FOXL2: tissue-specific TF
- many tumour suppressors are involved in chromatin modification and remodelling
54
What is a future ambition for Cancer genome sequencing?
- to sequence the individuals cancer genome and healthy genome
55
Expain IMATINIB and CML
- CML: chronic myeloid lymphoma
- a hyperactive oncogeneic kinase (ATP bound) will phosphorylate a phosphatase which leads to: signal for cell proliferation and survival
- GLEEVEC will instead bind to the oncogenic kinase at the same site as ATP thus inactivating the oncogenic kinases activity
56
Why are multi-drug treatment important in cancer?
- single treatment on a tumour, may have a rare mutant emerge to drug A which breaks off forming a tumour B -- drug B also becomes resisted against by a rare mutation where these mutants are now UNCONTROLLABLY CANCER RESISTANT TO BOTH DRUGS
- simultaneously treat cancer with both drugs prevent any resistance to the drugs & cures cancer
57
Immunological Therapy will examine what?
- Antibodies designed for specific antigens on the target cancer cells will bind to them and inject poisons
- this will attack the immunosuppressive environment where cells can prevent interactions between immune cell receptors and the cancer cells antigens
58
Is Ras an oncogene? and Rb a tumour suppressor gene?
- Ras is a monomeric GTPase responsible for functions in signal transduction pathway of MAP kinase kinase kinase which activates gene transcription
- Rb functions as a tumour suppressor since it will inhibit the activation of E2F (this protein when free will active cell cycle advances and promote DNA synthesis and proliferation)
