1
Q
human development index
A
- HDI: Composite measure of a nations longevity, education, income
- It was created to emphasize that people and their capabilities should be the ultimate criteria for assessing the development of a country not economic growth alone
2
Q
cancer in ancient times
A
- Cancer has always affected humans
- In 1900 the mortality rate from cancer was 3.3%
- Increase in cancer rates could be a recent biological event
- Being old could cause cancer, in the past century life expectancy went from 40-50 to 70-80
- There is a scarcity of cancers in the thousands of ancient human mummies
- Soft tissue cancers wont be able to be seen in ancient remains because they have no tissue so its hard to know the incidence of some cancers historically
3
Q
Cells as a unit of selection
A
- Evolution: organisms are the units of selection and differential reproductive success
- Cancer: the cells are the units of selection
- An individual cell may accumulate mutations that provide it with the capacity to override normal growth inhibition and determine clonal expansion
o Lineage expansion at the expense of other cell lineages
o Cancerous cells are positively selected for their advantages
o Cancerous cells lose the advantage of mutualistic relationship with human body
4
Q
2 main selective pressures on cancerous cells and cancer workarounds
A
- Predation: from the immune system/medical therapy
- Resource availability: distance from vasculature (blood supply)
Workarounds:
- Within a tumor cells can develop new traits that allow them to overcome these selective pressures
- Metastases often have specific genetic profiles and adaptations
5
Q
Cancer as an Atavism
A
- Atavism: traits that have disappeared now reappear
- We used to be unicellular but now multicellular, but cancer is a unicellular organism
- Cancer: reawakens the “selfishness” of cells of ancient genetic programs seen in our single celled ancestors
- More recent genes that regulate growth in multicellular cooperation are damaged or lost
6
Q
volvox
A
- Volvox was the first organism to transition from unicellular to multicellular organism
- Volvox: genus of species of freshwater algae, which form spherical hollow colonies that contain hundreds-thousands cells embedded in a gelatinous wall
- Volvox are the first step in the evolution of multicellular organisms as they have 2 cell types – have somatic and reproductive cells
- Primordial unicellular volvox had a specific gene responsible for the regulation of life history decision to survive or reproduce
- transition to a multicellular volvox was allowed by the evolution of such gene into a cell differentiation switch of reproductive or somatic
- further evolution allowed organism to have spatial temporal control of proliferation
7
Q
Unicellular – Multicellular Transition
A
- transition to multicellular organisms required cells to develop mechanisms that control proliferation, differentiation, cell turnover and apoptosis
- multicellular organisms involve cooperativity where the survival of the whole is important (favor whole organism over singular cells) as opposed to unicellular organisms that are selfish (favor singular cells over whole organism)
- cancer cells readopt this archaic behavior (selfishness) that can ultimately kill the organism and the cancer genotype
8
Q
cancerous cells have increased fitness
A
- in evolutionary terms cancerous cells have greater fitness because they can proliferate regardless of surrounding cells/tissues/organs
- as the cancer clone expands more mutations occur and sub clones develop which furthers the evolution of the cancerous cells in the body
- mutations in specific genes may be particularly valuable for cancer cells as they would enable the accumulation of additional mutations
1. increases genomic instability
2. inhibited apoptosis
3. increased proliferation
9
Q
cancerous cells and mutations (general)
A
- Origin of cancer is a single cell that acquires mutations in genes responsible for regulating cell cycle, proliferation, apoptosis
- Healthy cells have mechanisms that check for mutations and repair them but none in cancer cells
- If the mutation isn’t corrected it can cause great damage especially if it alters the function of regulatory genes
10
Q
Accumulation of mutations
A
- Cancer develops when a cell acquires mutations on key genes responsible for regulating cell cycle, proliferation, apoptosis mechanisms
- Several mutations on key genes need to be present for cancer to develop
- Passenger mutation: don’t promote cancer but are in background
- Driver mutation: promote proliferation and lower apoptosis
- Late onset = from environmental factors
- Early onset = mostly due to genetics
11
Q
Cancer is mostly caused by mutations on 2 specific genes
A
- Proto-oncogenes: stimulates proliferation (cell growth, division, survival)
- Cancer mutation on Proto oncogenes = enhanced function = increased proliferation - Tumor suppressor genes: normally repress proliferation (prevent unrestrained cellular growth and promote DNA) or induce apoptosis
- Cancer mutation on onco suppressors = inhibited suppression of proliferation = increased proliferation
12
Q
Oncogene example
-treatment
A
- HER 2: human epidermal growth factor receptor 2
- Gene that codes for an epidermal growth factor receptor present on the surface of several cell types including epithelial breast cells
- function: Amplifications or over expression of this oncogene contributes to progression of certain aggressive types of breast cancer
- It’s a marker for 30% of breast cancer patients
- treatment: Herceptin is a drug that binds the receptor blocking the proliferative stimuli
13
Q
Onco suppressors example
A
- P53 is a tumor suppressor: monitors cellular stress and genomic integrity and stops proliferation or initiates DNA repair
- P53 is described as “the guardian of the genome” because of its role in conserving stability by preventing genome mutations
- P53 is mutated in 50% of cancer patients
- Loss of function of p53 = abnormal cell growth (increased)
- Normally p53: can arrest growth by holding the cell cycle at the G1/S phase or it can initiate apoptosis if it detects a mutation in the cells
14
Q
9 hallmarks of cancer
A
- Ability to proliferate without the need for external growth stimuli
- evade growth suppression
- Resistance to apoptosis
- An unlimited ability to replicate
- Sustained angiogenesis
- An uncontrolled capacity for invasion and metastasis
- Altered metabolism
- Evasion of immune mediated attacks
- Genome instability (drives all 8 others)
15
Q
1 Hallmark: Ability to proliferate without the need for external growth stimuli
A
- Noncancer cells: require growth factors to proliferate
- Cancer cells: have own stimuli to drive proliferation
- Ex: mutations on HER 2
- Oncogene mutations because involved with signaling cascades for growth factors
16
Q
2 Hallmark: ability to evade growth suppression
A
- Non cancer cells: respond to growth suppression stimuli (contact inhibition)
- Cancer cells: can override growth suppression signals and proliferate
- Cancer cells can grow regardless of the space permitted and will start growing on top of each other
17
Q
3 Hallmark: resistance to apoptosis
A
- Non cancer cells: have checkpoints that monitor cell state and promote apoptosis if needed
- Cancer cells have defective apoptosis mechanisms, so the cancer cells don’t die
- Ex: mutations on p53 that prevent apoptosis
18
Q
4 Hallmark: unlimited ability to replicate
A
- Noncancer cells: cease to proliferate after certain number of divisions
- Cancer cells: are able to proliferate indefinitely
- Example: activation of telomerases that promote telomeres elongation because when there is no telomere left proliferation stops
19
Q
5 Hallmark: sustained angiogenesis
A
- Noncancer cells: have regulated and physiological angiogenic potential
- Cancer cells: can promote angiogenesis to support cancerous growth by supplying nutrients through the new blood vessels
- Example: HIF 1 hypoxia inducible factor 1 stimulates VEGF (vascular endothelial growth factor) which promotes growth of new blood vessels to supply nutrients to cancer cells
20
Q
6 Hallmark: and uncontrolled capacity for invasion and metastasis
A
- Noncancer cells: respond to cell to cell signaling that regulates cell expansion and movement
- Cancer cells: are able to invade tissues and metastasize to distant sites
- Example: alteration of proteins that regulate migration and adhesion of cancer cells so that they can grow outside normal bounds and break off into blood vessels to metastasize another area
21
Q
7 Hallmark: altered metabolism
A
- Non cancer cells: require adequate nutrition to survive
- Cancer cells: adapt to hypoxic and nutrient poor conditions
- Example: switching to anaerobic metabolism because they cant get enough oxygen but this is less efficient so treatment could be to starve self with limited nutrients so it starves the anaerobic cancer cells of nutrients too but not the aerobic cells in body acting regularly
22
Q
8 Hallmark: Evasion of immune mediated attacks
A
- Non cancer cells: tissues are constantly scanned for presence of infected or damaged cells, the immune system usually destroys such cells
- tumor cells secrete anti-inflammatory cytokines that suppress the immune response so the cancerous cells avoid destruction by immune system
23
Q
9 Hallmark: genomic instability
A
- most important hallmark because it drives/causes all of the other 8 hallmarks which allows the cancer to have many mechanisms to evade destruction and continue proliferation
- noncancer cells: regulate DNA repair mechanisms
- cancer cells: unable to correct mutations and accumulate them which makes the genome unstable
24
Q
TNM Staging system
A
- T describes the primary tumor = level of invasion into other layers/tissues
o TX: cant be measures (inconclusive results or haven’t tested yet)
o T0: cannot be found = “cancer free”
o Tis: in situ = localized to a single tissue
o T1-T4: size and level of invasion into other areas - N describes whether the cancer has invaded lymph nodes
o N0: no lymph node infection
o N1-3: size and location of lymph nodes involved - M describes the presence of metastases
o MX: metastases cant be evaluated
o M0: no distant metastases
o M1: presence of distant metastases = stage 4 cancer regardless of other tags
25
stages of cancer
Stage 1: T1 or T2, N0, M0
Stage 2: T3 or T4, N0, M0
Stage 3: any T, N1, M0
Stage 4: any T, any N, M1
26
Sunlight exposure and cancer
- UV radiation = carcinogen
- Over 419,000 cases of skin cancer in the US a year are linked to indoor tanning
- More people develop skin cancer from tanning than lung cancer from smoking
- UV light contributes to formation of free radicals
27
Types of UV rays
- UVA: are mutagens that promote cancerous growths because they reach deep into your skin
- UVB rays: higher energy level and are mainly responsible for sunburns and cancers
- UVC rays: have the highest energy level but are blocked by the ozone layer thus aren’t normally the cause of skin cancer
28
melanin
- Melanin: a group of natural pigments produced by melanocytes to absorb and dissipate light
- Over 99% of light absorbed though UV radiation can be dissipated by melanin
- Melanogenesis occurs after exposure to UV radiation which is how you tan but it requires the oxidation and polymerization of tyrosine to do so
- Melanin protects skin cells from UV radiation damage = reduce risk of cancer
- Lower incidence for skin cancer = individuals with more concentrated melanin = because they can dissipate UV rays better
29
Skin Cancer and Mismatched Environments
- Humans evolved melanin based on where they lived but in present day people move around the globe from their ancestral origins which can cause a mismatch between amount of melanin and UV exposure
- Mismatch example: High rates of skin cancer in light skinned people who migrate to areas with high levels of UV radiation
- Populations that migrate from tropical climates to temperate climates may have lost the ability to synthesize large amounts of melanin to maintain sufficient Vit D synthesis
- Subsequent climate change caused by migration to tropical areas may be deleterious and lead to an increased risk of cancer
30
Gel manicures
- UV nail lamps have similar properties to traditional UV tanning beds
- Mostly UVA radiation
- Diverse use of UV lamps
- Carcinogenic potential is controversial
- Many case studies of women who develop squamous cell carcinoma on the dorsal aspect of the hand could have anecdotal evidence that points to gel manicure, but they actually already could have underlying factors for skin cancer like genetic predisposition
- It would take 10,000 sessions to increase the risk of cancer
31
smoking
- Tobacco smoke contains chemical that are harmful to smokers and nonsmokers
- 250/7,000 chemicals in tobacco smoke are harmful
o Hydrogen cyanide
o Acetaldehyde
o Benzene
o Carbon monoxide
o Ammonia
- Causes cancers of the lung, esophagus, larynx, mouth, throat, kidney, bladder, liver, pancreas, stomach, cervix, colon, rectum as well as acute myeloid leukemia
32
origins of smoking
- 5000 BC in shamanistic rituals in the Americas = which is a super short time in relation to the evolutionary lifespan
- Quickly spread globally in 16th century
- In 1940s firs research started to prove the health concerns with tobacco smoking
33
Fried and Baked Food and oils
- Heating of cooking oils emits volatile organic compounds including aldehydes (also ketones, hydrocarbons, alcohols) that exhibit mutagenicity and genetic toxicity
- Those compounds are released if the cooking temp is above the smoke point
- Should use oils with higher SP to avoid the release of carcinogens like aldehyde when cooking
- Canola oil SP: 238 C
- Extra virgin olive oil SP: 195 C
- Frying: 180 C
34
Acrylamide
- Acrylamide = carcinogen
- Its formed in starchy food from the modification of glucose and asparagine
- Formed during high temp cooking processes like frying, roasting, baking, toasting but NOT boiling
35
Evolutionary perspective of cooking
- Harnessing fire = cooking food = shorter digestive tract
- Archeological evidence of fire and cooking about 800,000 years ago
- Biological evidence shows that homo erectus arose with larger brains and smaller guts and jaws/teeth suggesting that cooking was developed around 1.8 MYA
- Harvard biologist Richard Wrangham argues that cooking was essential for humans to increase their brain size
36
humans vs apes: fiber and meat intake
- Apes: anatomy and physiology of GI tract adapted to digestion of foods that need extensive digestion like roots and leaves (fiber)
- Humans: reduced gut size showing reduced need to digest fiber rich foods and more reliance on meat
37
fiber
- Fiber rich diet promotes colon health
- The bacterium Butyrvibrio fibrisolvens ferments fiber producing short chain fatty acids such as butyrate
- Butyrate inhibits HDACs (histone deacetylase) that orchestrate epigenetic regulation of DNA expression
- Diets poor in fiber increases risk for cancer of mouth, pharynx, larynx, esophagus, colon, rectum, stomach because less fiber = more cell proliferation
38
Vitamins as antioxidants
- Vit A, C, D, E can reduce toxic reactive species
- Vit D has antiangiogenic functions and thus inhibiting cancer growth
- Vit E is fat soluble, so it is important for membrane formation
- Other substances as antioxidants:
resveratrol (anti atherogenic, anti-inflammatory, growth inhibiting) and
quercetin (antioxidant flavonoid)
39
red meat and cancer
- Its speculated that consumption of red meat increases risk for cancer through an increase in IGF 1
- IGF 1 (insulin-like growth factor 1) is a mitogen and stimulates cell proliferation
- IGF 1 is necessary for kids but increased levels may contribute to cancer
40
alcohol and cancer
- Alcohol = Group 1 carcinogen
- The international agency for research on cancer (IARC) classifies alcoholic beverage consumption as a cause of breast, colorectum, larynx, liver, esophagus, mouth, pharynx, and possibly pancreatic cancer
41
history of alcohol
- Earliest evidence of wine drinking from domesticated vines comes from a pottery jar dated 7400-7100 years before present in Iran
- Incorporation of distilled alcoholic beverages into human diet came much later 800-1300 AD
- In average US diet alcohol contributes to 1.4% of the total energy consumed
42
exercise and cancer
- Increased physical activity in intensity, duration, or frequency can reduce risk of developing colon, endometrial, and breast cancer by up to 40% relative to those who are sedentary regardless of BMI
- Aerobic and anaerobic exercise results in alterations in redox homeostasis
- Athletes develop metabolic adaptations
- Aerobic exercise creates a system that can better deal with reactive oxygen species
HBIO405 Exam #3
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