Midterm Flashcards
(178 cards)
1
Q
What are the four Rights of personalized medicine?
A
right patient
right drug
right time
right dose
2
Q
What are the pros of personalized medicine?
A
more accurate diagnosis, safer, faster, lower s/e, increase efficacy
3
Q
What are some challenges of personalized medicine?
A
patient engagement, privacy, cost, data ownership
4
Q
Explain personalized medicine of tamoxifen?
A
used for breast cancer but needs CYP 2D6 to be active. some people are deficient in this
5
Q
What are the cell cycle stages?
A
G1: grows and prepares
S: DNA replication
G2: grow
M: Mitosis
G0: Leaves cell cycle
6
Q
What are the 2 checkpoints in cell cycle?
A
G1:before DNA Synth
G2: Prep for mitosis
7
Q
When is the restriction point in the cycle?
A
commits to division
happens before S stage
8
Q
How many chromosomes?
A
23 pair
9
Q
What histones in chromosomes?
A
2 of H2A, H2B, H3 and H4 and H1 which clips it
10
Q
What is transcription?
A
gene-> RNA
11
Q
What is translation?
A
RNA->protein
12
Q
What are Promoters?
A
promote expression, upstream
13
Q
How can we suppress promoters?
A
methylation
14
Q
What is encoding for genomes?
A
annotation of the pairs to make reading easier= AATTCCGGG to AAT TCC GGG
15
Q
What are SNP’s?
A
single change
16
Q
Most common genetic variation?
A
SNP
17
Q
What are Copy number variations? What causes them?
A
variations in the number of copies of a gene
caused by recombination
18
Q
What are insertions and deletions?
A
deletion of one or more or insertion of one or more
19
Q
What are large scale variations?
A
LARGE portion repeated or gone
20
Q
What is a hot spot of structural variations?
A
short arm of chromosome 1
21
Q
What is bioinformatics?
A
merge biology and computers
22
Q
Genetics vs genomics
A
look at one gene vs look at all genes
23
Q
What is transcriptomics?
A
study of RNA and their functions
24
Q
What is an exon vs intron?
A
exon- encodes
intron- does not encode/ spliced out
25
What is constitutive splicing?
exons retained in order
26
What is proteomics
study of proteins and their functions
27
What is top down vs bottom up?
top down= analyze without being broken down
bottom up= digest them into peptides first
28
What is metabolomics?
study of metabolites and their function
29
What is glycomics?
structure and function of glycans
30
What is a biomarker?
sign of normal OR abnormal
31
What is conventional medicine?
empirical therapy with universal drugs
32
What is PCR? steps?
quick method to make lots of copies of DNA
1. denature
2. anneal
3. synthesize
33
What is different about qPCR?
add fluorescent reporter- taqMan probe
34
What test uses PCR?
Abbott HIV-1 targeting 2 spots
35
Which is more money whole genome or whole exons?
whole genome
36
How do you sequence RNA?
make cDNA and then shatter it
37
What is the biggest gene?
duchene muscular dystrophy-X linked
38
What is a biochip? Which molecule cant be used?
array of biomolecules immobilized on surface
No RNA because unstable
39
What is a microarray?
uses DNA chip to sequence and analyze ********
40
What does 23 and me use for biochip?
gene profiling array (DNA chip) affymetrix
41
What does AmpliChip CYP450 do?
biochip to see deletions and insertions of ALL CYP 450
42
What is a bio-Rad
protein chip
43
What is SELDI?
probe to immobilize then lazer to ionize
44
What is a kinome array?
when kinase rxn occurs with binding
45
What is an issue with protein chips?
more cost cause less stable
46
What is microfluidics?
use small amounts for biochips
47
What is FISH?
fluorescent prob
48
What biomolecules are you looking at for gene expression profiling?
RNA and protein
49
What are some gene expression tech?
DEG, SEG, SAGE, biopsy, rna splicing
50
What is a PET scan?
positron, use fluorodeoxyglucose as tracer
51
What is a drug?
substance with physiological effect
52
what is an aptamer?
chemical antibody
53
What makes a good drug?
potent and specific
54
What are the steps of drug development?
target selection-find stuff that binds to target- good ones are put through
then preclinical: Phase 1-2--3, approval, post marketing
55
How long to make a drug and how much money?
15 years, 1.5 billion
56
What is the most expensive part of discovery?
clinical
57
What is the data mining approach to identification?
identify important proteins in disease- look at databases
58
What is the genetic approach to identification?
identify genes that cause by comparing
59
What is the in vitro approach to identification?
identify targets
60
What is target validation?
does knock out of target give right effect
61
What is difference between knock out and knock down?
down= decreased, reversible
out= all and permanent
62
What is a choke point?
no other alternative pathways
63
Two methods to chemogenomic screen?
1. have a chemical what does it effect
2. I have a target what binds
64
What are the most successful targets?
enzymes and GPCRs
65
All targets are druggable?
NO
66
What makes a protein druggable?
binding site size
67
How can you predict druggability?
sequence based
structure based(pockets)
does it bind endogenous
high affinity drug(ligand based)
established target (precedence based)
68
Why has antibiotic research fallen off?
cant put high price on them
liability for side effects
rapid resistance
69
What is the pasteur act?
pay the company the value it is rather than the amount prescribed
70
What are the properties of targets in bacteria?
essential to survival, and only in bacteria
71
Explain CCR5 and HIV?
if you get the delta 32 version it is shorter so then the HIV cell cannot kill T cell
72
What is the K value paradox?
complexity does not correlate with number of chromosomes
73
What is the c value paradox?
complexity is not correlated with genome size
74
What is the n value paradox?
complexity is not correlated with gene number
75
Why are mice good models?
share a lot of same genes
76
What are common variations in CYP?
CYP2D6
CYP 2C9-warfarin
CYP 4F2- lowers vitamin K
77
What does VKORC1 do?
recycles Vit K
78
What is the function of CFTR and what does variation cause?
chloride channel in lung
variation= no transport or not enough, this will cause cystic fibrosis
79
How does Ataluren work?
overcome nonsense mutation(premature stop codon), so it reads through
80
What is the G551D mutation of CFTR? What drug fixes?
channels dont open correcly
kalydeco
81
What medication fixed CFTR mutations that lower the amount and helps them open correctly?
TRIKAFTA
82
What is an antisense oligonucleotide?
single stranded NA that hybridize with mRNA= inhibit expression
83
What name shows its an ASO?
rsen
fomivirsen
84
What are the mutations in the DMD gene (muscle dystrophy)?
large deletions and SNPs
85
Which gender does DMD affect?
male b/c x linked
86
If woman are carriers, how do they present?
some muscle weakness
87
How can Eteplirsen help with DMD?
skip exon 51(nonsense mutation)
88
What other med can help with DMD?
Ataluren-supressor tRNA that makes it place an AA instead of stopping
89
How does SMA happen?
neurodegenerative disease of spinal neurons due to SMN1 and SMN2
90
Which one has more function, SMN1 or 2? why?
SMNI has more cause more stable
91
What drug helps with SMA?
nusinersen that helps SMN2 the copy of SMN1
92
WHat does SMN2 lack?
exon 7
93
What are molecular glues? What are the uses?
encourage 2 proteins to come together
used if no druggable active site and need less levels
94
What is PROTAC?
glue that forces target to be ubiquitinylated and degraded in proteasome
95
What are the characteristics of cancer cells?
Proliferative
evade growth suppress
evade cell death
angiogenesis
immortal
metastasis
96
Benefits of small molecules
easier to cross membranes
act in or outside cells
97
What is the first drug for tyrosine kinase?
imatinib
98
How many small molecules interact with TK?
LOTS
99
What makes BCR ABL gene and what does this do?
translocation of piece of Chromosome 22 and 9
makes always on TK
100
How does imatinib work?
blocks ATP from donating to enzyme
101
What is BCR ABl mutations that are dependent and independent resisitance?
dependent= change imatinib binding site= p loop and T3151
Independent= change transport that imports drug = stops import
102
What is the only effective TRK inhibitor that can bypass BBB?
entrectinib
103
What is the front end of an antibody? What is back?
front=binds targets
Back= bind other immune cells
104
What are bispecific antibodies?
bind two usually bind to bad then bind to CD3 of t cell
105
Mechanism of antibody drugs.
can flag it for NK destruction
or deliver toxin to the cell
106
What drug is used for Her2?
trastuzumab= flags for killing
107
What role does pertuzumab have?
also blocks dimerization
108
What happens if EGFR1 inhibitor is used with a tumour with KRAS?
NO effect
109
How does bevacizumab work?
stops angiogenesis
110
What do MMP's do for tumour?
dissolve ECM and build vessels
111
What happens if a tumour is very turgid?
reisstant to drugs
112
What does VEGF do?
vessel survive, increase permeability and angiogenesis
113
What CYP is a major player in metabolism and has alot of genetic variability?
CYP 2D6
114
What is the concept of tumour heterogenicity?
surface make up of cells are not constant neither in time as well
115
How can tumour heterogenicity effect personalized medicine?
make take sample from part of the tumour that doesnt have the target. The drug will not kill it all
116
How does antigen shedding work?
shedding the antigen can dodge the drug, by modulating.
117
How does antigen modulation work?
endocytosis the antigen back inside cell
118
IN relation to general cancer what is cancer stem cells?
more resistant
more metastasis
infinite proliferative
119
WHat are the issue with cancer vaccine development?
suppress immune system
look normal
large or advanced
each tumour is unique
people who are sick already have weakened immune system
120
What cancers have vaccines?
viral ones- HPV, HBV,
121
How does BCG vaccine work?
uses weakened bacteria to help boost bladder cancer
122
How does Sipuleucel-T vaccine work?
patients own dendritic cells that are stimulated to boost immune response to prostate cancer
123
What does MCH-1 tell us?
I am infected
124
What bacteria is involved in BCG vaccine?
mycobacterium bovis- TB
125
What does MCH-2 tell us?
i am immune cell
126
What is overproduced in prostate cancer?
PAP and PSA
127
How can we boost cytotoxic t cells?
modify to release perforins and granzyme to break down
CAR-T
128
What is CAR-T for usually?
liquid cancer
129
Side effects of CAR-T?
CRS= massive release of cytokines that results in fever and drop in BP
Mass die off of B cells= aplasia
130
Issues with CAR-T?
expensive, time consuming
tumour heterogeneity is bad
131
What happens if PD-L1 or PD-L2 bind to PD-1?
T cell apoptosis, downregulation, suppress anti tumour response
132
What is an example of PD-1 blockers?
nivolumab or pembrolizumab
133
How does CTLA-4 work and what drug blocks it?
CTLA inhibits T cell activation
drug- iplimumab
134
What are the 4 types of biomarkers?
Molecular
Radiographic
histological
Physiological
135
What are radiographic biomarkers?
from medical images so like CT scan or x ray
136
What is a histological biomarkers?
reflects molecular changes such as cancer grading
137
What is a physiological biomarker?
measures body processes such as BP
138
How long to develop biomarker?
3-4 years
139
Which stage of biomarker development is the most expensive?
clinical validation
140
What is multiomics?
combo of genomics etc
141
What is a susceptibility biomarker?
indicates potential of disease
ex BRCA gene
142
What is a diagnostic biomarker?
detect or confirm disease
Ex GFR, B amyloid
143
What type of biomarker is GFR?
diagnostic for CKD
144
What is a monitoring biomarker?
assess status of disease
145
What is an example of a monitoring biomarker?
level of CA-125 or PSA
146
What is a prognostic biomarker?
likelihood of health outcome
147
True or False: Prognostic biomarker predicts response to treatment
FALSE
148
What is a predictive biomarker? Ex?
identify those likely to respond
ex- HER2 gene= use HER2 therapy
149
Where does trastuzumab and pertuzumab work?
4
2
150
What is a pharmacodynamic/response biomarker?
drug interacts with target
ex BP
151
What is a safety biomarker?
presence of toxicity
ex albumin or S cr from nephrotoxic drug
152
What is a pharmacogenomic biomarker?
genetic differences
ex CYP P450
153
What is proteomics?
total set of [proteins and how they function and interact
154
What is primary protein structure?
AA sequence
155
What is secondary structure?
how it folds
156
Why study proteomics?
change in gene or RNA does not always translate into protein, post translational mods
157
What is functional, expression and structural proteomics?
F= how it functions
E= expression
S= structure
158
Why use electrophoresis?
separate based on charge and size
159
Pros of using X ray crystallography and cons?
pros- high resolution, see structure
Cons- time consuming, expensive
160
What does a protein microarray do?
purify, function and quanitfy
161
What is P4?
predictive
personalized
preventive
participatory
162
What is benefits of P4 mentality?
cost effective, lower rates of illness,
163
True or false P4 is curative
False- more preventative
164
What is systems medicine?
uses studys of the levels of life to integrate good care
165
What does omics mean?
interactions and functions of biomolecules
166
What does pharmacoproteomics?
deals with the changes of proteins due to drugs
167
Why is it better to look at proteins than DNA?
1 gene makes multiple proteins and Post TM
168
What is purpose of electrophoresis?
isolate crude identification and quantification
169
What is purpose of chromatography?
isolate crude identification and quantification
170
What do you need to do before mass spectrometry?
chromatography
171
What is purpose of immunoassay and mass spectrometry?
identify and quantify
172
What is a western blot?
gel put on paper to visualize
173
What moves slower in chromatography?
whatever is close to what stationary phase is
174
What is mass spectrometry?
see gas ions and sort based on charge and size
175
What is toxicoproteomics?
how chemical exposure modifies protein or expression
176
The Philadelphia chromosome is formed between chromosome 9 and chromosome 22 due to:
Translocation
177
In general, how many coding SNPs are present in a gene?
5
178
