Unit 3 Flashcards
(67 cards)
1
Q
What does organizes the cells into tissues do?
A
allows for more complex structures
2
Q
What are the functions of the ECM?
A
- adhesive substances
- provides structure
- presents growth factors to their receptors
- sequesters and stores growth factors
- senses and transduces mechanical signals
3
Q
What does the ecm functioning as an adhesive substance do?
A
- proteins embeded in 1 membrane have a protrusion to invade neighbor
- tracks to direct migratory cells
- concentration gradients
4
Q
What does the ecm functioning as provides structure do?
A
- defines boundaries
- provides integrity and elasticity to developing organs
- can enzymatically degrade debri and clean up microenvironment
5
Q
What does the ecm functioning to present gf to their receptors do?
A
- controls spatial distribution of ECM bound surface molecules
- facilitates cross talk between gf receptors and ecm receptors
6
Q
What does the ecm functioning to sequestor and store gf do?
A
- allows spatio temporal regulation of factor releases
- organizes morphogen gradients
- mediates release of factors in presence of correct forces
7
Q
What does the ecm functioning to sense and transduce mechanical signals do?
A
- defines mechanical properties for cell differentiation
- activates intracellular signaling through cell surface receptors
- engages cytoskeletal machinery and synergizes gf signaling
- responds to pressure
8
Q
Do all cells have cell adhesion molecules?
A
no
9
Q
What do integrins do?
A
- bind surfece of epitheleal cell with antibodies
- think IG
10
Q
What happens if there is a lack of cadherins?
A
- can’t tell structure of anything/ unorganized
- cell still mitose
- no cohesive shape or adherence
11
Q
What are the type of cell adhesion proteins?
A
- integrins
- selectins
- cadherins
12
Q
What are adhesive junctions?
A
- will attach cell to cell or cell to ecm
- always space btwn cells (25nm)
- allows for chemical transduction by exposing receptors, paracellular path
- protein filaments
13
Q
What are the tight junctions?
A
- no measureable space between cells
- stomach, bladder
- bladder has junctions for stretching (along with desmosomes)
14
Q
What organs contain desmosomes?
A
uterus, lungs, skin, bladder
15
Q
Where are gap junctions found?
A
- heart so it can contract as a unit
- has ions and electrical signals so each cell doesn’t need its own signal
16
Q
What are elastin proteins?
A
- helps allow for stretching
- break down as you age
- then forms crosslinks for less stretchability
- made by covalent bonds by lysine
- more crosslinks = less stretchy
17
Q
What is fibronectin?
A
- adhesive proteins
- many cancer cells can’t produce (gene turned off or mutated) to allow for easier metastasis
18
Q
What are the steps to breaking through the ECM?
A
- mutation and uncontrolled growth
- loss of cell adhesion
- increased motility (no anchor)
- entry and survival in circulation (seed and soil)
- exit into new tissue
- eventual colonization of new site
19
Q
What are the requirements for metastasis?
A
- aggressive phenotype
- prereqs
- microenvironment
- intravasation
- life in transit
- distant accomplices
- homing
- extravasation
- micrometastasis
- co-opted stroma
- full colonization
20
Q
What is an agressive phenotype?
A
oncogenic mutations, epigenic instability
21
Q
What is are the metasis prereqs?
A
self-renewal
invasiveness
motility
detachment
survival
22
Q
What is the metasis microenvironment?
A
- angiogenesis
- inflammation
- cancerized stroma
23
Q
What is intravasion requirements?
A
epitheleal mesenchymal transitions
24
Q
What is life in transit?
A
- platelet association
- embolism
- vascular adhesion
25
What are distance accomplices?
- vascular progenitors
- metastatic precursors
26
What is homing?
- attachment and attraction to survival signals
27
What does extravasation require?
- motility
- vascular remodeling
28
What is micro-metastasis?
- survival in dormancy
29
What is required for a co-opted stroma?
- angiogenesis
- inflammation
- cancerized stroma
30
What is required for full colonization?
- organ specific metastasis factors and functions
31
What are the pressures driving metastasis?
- hypoxia
- increased ROS (reductive oxidative species)
- decrease PH
- decreased LOX
32
How does hypoxia increase metastasis?
- HIF1 increase increases glycolysis and lactate transport
- could also increase acidity to degrade ECM proteins
33
How does increased reactive oxidative species increase metastasis?
would interfere with glycolysis through NADH
34
How does decreased LOX increase metastasis?
- H1F1 target
- decreased lox will decreae collagen fibrils in number and strength which will then decrease cell adhesion
- lox and h1f1 are directly proportional
- lox accelerates gross links makes it more rigid
35
Does LOX increase or decrease in cancer cells?
- in some tumors its increased in some its decreased
- can be increased and decreased cyclicly within the same cell
36
What guides cell motility?
- collagen alignment and the ECM
- ecm remodels and collagen increases in number and rigidity
- contains mutated fibroblasts
- forms pathway for cells to get to blood vessels
37
What do MMPs do in metastasis?
- facilitate breakdown of ECM
- requires ZN2+ or Ca2+ to work
- key regulator of tumor growth at primary and metastatic sites
- could exhbit pro or anti=apoptotic signals
- once tumor cell enters the blood stream, mmps can help break down epitheleal cells of blood vessels
38
How are MMPS regulators of tumor growth?
- tumor must break through ECM to go anywhere
39
How do MMPS facilitate the breakdown of the ECM?
- guides re-organization
40
Why are MMPS pro-metastatic and anti-metastatic ?
- pro apoptotic when it has somewhere to go
- anti-metastatic when primary site has plenty of room for growth or if there are no nearby blood vessels
41
How do MMPs help metastasis with blood vessels
helps start the process of angiogenesis if they detect there are no nearby blood vessels
42
How can MMPs be used as a cancer cure?
- cancer marker for detection
- drug target
43
What is an example of mmps in cancer?
1. contact with omentum increases mmp transcription, protein expression, activation, secretion in ovarion
2. proteins break down epithelial cells
3. pieces of broken protein fibers allows for an increase of adhesion using integrins
44
What did hippocrates do?
- thought we had disease because of black bile
(400)
45
What did vesalius do?
- no black bile in dead bodies, must be in lymphatic system
- 1540
46
What did virchow do?
- thought irritation promoted cancer
- any kind of chaffing, fast heart beat
- no data to back up
-1800
47
What did rous do?
- viruses caused cancer
- 1911
- found in chickens originally, then rabbits
- WW2 prevented us from continuing this research
48
What did dennis burkitt do?
- burkitts lynphoma
- 1950s
- found in malaria belt of africa
- cancer of B cells
- cancer viruses now accepted because it was found in humans
- even postulated it was transmitted by mosquitos
- evidence: coorelation between amount of malaria and BL, epidemeology studies, how many people with bl had malaria
- found EBC lead to lynphoma, checked if viral DNA was in genome
- infects Myc oncogene
49
What did bishop and varmus do?
- cellular origins
- 1970
- studied Rous sarcoma virus that had 20% bigger genome and attached to SRC genome
- proved having virus does 't equal cancer but tirggers proto-oncogene mutation
50
What are the big cancer advancements in the 1970s and 1990s?
- discovered P53 while studying viral antigens
- discovered RB
- use of knockout mice to discover oncogenes and tumor suppressor genes
- large amount of discovery because of no research laws
51
What is human retrovirus?
- human t-cell lukemia virus
- long latency period
- discovred by Gallo and staal
- staal cloned HIV and determined its function but got no credit because she was female
52
What did percy julian do?
chemist in 1920s
- developed lots of drugs and cortesone
53
What did daly do?
- studied effects on blood sugar and cholesterol on heart
54
What did almeida do?
discovered all the corona viruses
55
What are factors affecting research?
- funding
- bias (need peer review to avoid)
- politics (bias of politicians, what is going on in world, most politicians are men so they will fund more men based research
- culture (religion has power, different cultures could resist research and change, hot topics at the time)
56
What are the steps to a clinical trial?
1. in vitro (tube)
2. cell culture
3. Animal studies
4. human
57
What is phase 0?
- not every drug undergoes
- does the drug do what you expect
- 10-15 patients in hospital
- where you live effects opportunities
- pts won't benefit but researchers will
58
What is phase 1?
- is it safe
- 30/40 people
- could up dose
- where you live effects chances
59
What is phase 2?
- up to 100 pts
- everyone gets same dose
- no placebo
- still being run in hospitals
- can be phased out to other doctors and hospitals
- could last years
60
What is phase 3?
- more communities get it
- is it better than current options
- kaplan myer looking for space between graph
- double blind
- could go on for decades
- can submit for FDA approval
61
Why are double blind studies necessary?
- avoids confirmation bias
- keeps people in study
- prevents interference by dr
- keeps people from making lifestyle changes
62
What is phase 4?
- now approved by FDA
- gives info on rare side effects, long term effects
- marketing can happen (can either give info on what drug does and list side effects or just leave ambiguous)
- drug is out there and don't have to be in study to get
- FDA could conditionally approve
63
What must drugs be to pass all clinical trials?
- safe
- effective
- cost effective
64
Vesalius
disproved theory on black bile causes cancer, believed it was the lymphatic system instead.
65
Virchow
irritation promoted cancer
66
EBV
Epstien-Barr virus leads to lymphoma. Infects Mac oncogene, involved with Burkitt's lymphoma
67
