Oncology Foundations Flashcards
0
Q
Endoplasmic reticulum
A
Produces CYP metabolic enzymes
1
Q
Circadian regulation
A
Clock/bmall per/cry regulate each other
Gravity can trigger rather than light
2
Q
Methylation
A
Gene in off position
Decreased transcription
3
Q
Chromosome
A
Gene: functional unit of heredity
Allele: alternative form of a gene
4
Q
PXR
A
CYP 3A4 transcription factor
5
Q
Gene imprinting
A
Silenced
Methylation
Can result in Prader-Willi Syndrome
6
Q
Down syndrome
A
Trisomy 21
Type of aneuploidy
7
Q
Genetically dominant
A
One allele determines phenotype over another allele
8
Q
Translocation
A
Chronic leukemia
Philadelphia chromosome
9
Q
Ring
A
Infertility
10
Q
Recessive trait phenotype
A
Every other generation
11
Q
Dominant trait
A
50% inheritance
12
Q
Genomics
A
Structure/function character of the genome
Genome(genetic complement of an organism)
13
Q
Most genomic medicine based on..
A
A Conformation
14
Q
Pharmacogenes
A
2% of all genes
Genome maintenance
Signal transduction
Biochemical balance
15
Q
Mitochondrial DNA
A
Circular
From mother
Can tolerate more damage
Contains all genetic information like chromosomes
16
Q
Multiplicity of RNA
A
Alternative promoters on DNA
Alternative splicing of mRNA introns
17
Q
General transcription complex (GTC)
A
Recognizes promoter TATA box
Promoter controls whether a gene should be transcribed
18
Q
Expression differentiation
A
Transcription factor determines if gene is transcribed or not
19
Q
4 types of transcription factors HHLZ
Proteins of different conformations that regulate gene transcription and expression
A
Helix loop helix :myo D muscle differentiation
Helix turn helix: pdx1
Leucine zipper
Zinc finger: PXR, estrogen receptor
20
Q
Transcription factories
A
Transcription locations with Shared RNA polymerase
Genes with similar functions
21
Q
Gene expression silencing RNA polymerase
A
Endo-siRNA
microRNA
Break down and modify mRNA after processed by si/microRNA
Silencing
22
Q
mRNA production RNA polymerase
A
Heterogenous nuclear RNA
23
Q
Protein translation RNA polymerase
A
pre-rRNA
rRNA
tRNA
24
Translation
AUG methionine start codon
RCCAUG starting sequence
25
Post translational modifications
Proteolytic processing generates protein diversity
Protein folding for degradation stability
Acetylation - activate
Methylation - silence
Phosphorylation- signal transduction
26
P53 tumor suppressor
Phosphorylate to activate and suppress tumor
Stress, UV radiation can activate kinase/acetyltransferase and p53 activation
27
Argonaute complex
Recognize and modify mRNA after processing small RNA(siRNA, microRNA)
Increase RNA degradation
Repress translation
Decrease transcription
Circular RNA counteract microRNA activity
28
4 Rules of genetic based diseases
1) genetic diseases are difficult to treat
2) most genetic alterations cause no phenotype changes
3) somatic DNA alterations (after birth) are the ultimate causes for cancer
4) DNA alterations may occur in promoter, coding region, and intron
29
Silence substitution
Substituted base that results in the same amino acid codon
30
Missense substitution
Substitution Forms a different amino acid
31
Frameshift
Insertion, deletion
Severe, changes multiple codons and downstream amino acids
32
Nonsense substitution
Forms a stop codon
33
Germline genetics
From parents, before birth
All cells in organism
Inheritable
Polynorphisms
34
Somatic genetics
After birth
Affected by environment
Small number of cells
Cancer
35
Most frequently used for sequencing
HiSeq
Cheapest, fastest 98% accurate though
Opposite Sanger: slowest, expensive
36
Sequencing analysis
DNA: genome
mRNA: expression
ChIP: protein-DNA interaction, global mRNA expression
37
EcoRI
Recognizes and cleaves DNA sequence
Endonuclease
Restriction fragment length polymorphism
38
Primer
Determines which gene is amplified in PCR
Short complementary DNA strand
The more PCR cycles needed, the lower the expression
39
PCR differentiation
Can detect insertion, deletion
Can differentiate by Endonuclease restriction digest
40
FISH
Fluorescent in situ hybridization
Probe for disease gene
41
Prenatal testing for trisomy 21
Mothers over 35
Increased prevalence with age
Amniotic fluid, placenta villi, ultrasound
42
Sickle cell disease
Single gene disease
43
Viral vector
Efficient
Costly
More dangerous/concerning
44
Reverse genetics
Determine a phenotype associated with a gene
45
Forward genetics
Determine a gene responsible for a phenotype
46
In vivo gene therapy
Nano particle, IV IM, plasmid, virus
insert corrected copy of gene
47
Ex vivo
Take cells out, introduce DNA sequence, see if working properly, inject back into patient
48
Carboxylesterases (CES)
Hydrolyze esters for activity
Tamiflu
Irinotecan to SN38 activation CES2
Plavix aspirin deactivation
Regulated by pharmacogenes
49
Assay that detects proteins
Western blotting uses antibody reveal protein of interest
Inmunocytochemistry-uses antibody to visualize the specific protein location of expression
50
Assay that detects activity
HPLC - chromatography
LC-MS mass spectrometry
51
Assay that detects mRNA
Northern blotting
RT-qPCR
ChIP
52
Gel electrophoresis
Separate based on charge and molecular weight
Protein expression
53
Histone acetyltransferase (HAT)
Increased transcription by acetylation
Co-activator with ligand
54
HDAC histone deacetylase
Remove acetyl to decrease transcription
Co-repressor
55
CAR transcription factor
Phenobarbital CYP2B activator
Overlaps with PXR to compensate if necessary
56
PXR
Rifampicin CYP3A4 activator
Largest binding domain
Flexible, lipophilic
57
Transcription factor (nuclear receptor) mutants
Contributes to individual variation of certain enzymes and transporter gene expression
58
Genetics
Individual gene-based
59
Genomics
Genome wide based variation and environment interaction
60
Histone methyltransferase
Leads to decreased transcription
61
Aryl hydrocarbon receptor (AhR)
Dioxin CYP 1A coactivator via AhR
62
PPAR peroxisome proliferator activated receptor
Clofibrate CYP4A coactivator
63
Poor 2C19 metabolism polymorphism
20% Asian
64
Aspirin resistance pharmacogenomics
Increased hydrolysis via increased CES2
Excessive COX expression
Aspirin irreversible COX inhibition
65
Plavix pharmacogenomics
Clopidogrel oxidized by CYP for activity
Lower activity if higher CES1 hydrolysis to metabolite
Resistance with decreased oxidation, increased hydrolysis, and ADP P2Y12 receptor mutations
Hyper responder decreased hydrolysis, increased CYP induction, low CYP competitive inhibition , high risk for bleeding
66
Senescence
Prevent further cell proliferation
Area for cancer research
67
Blastocyst
Embryo with stem cells inside for possible extraction
68
Induced pluripotent stem cells (iPS)
Adult cells able to undergo viral transduction to stem cells
Mature cells can be reprogrammed to become pluripotent stem cells
69
Trandifferentiation
Pancreas to liver cell
Specialized to specialized
70
Regenerative medicine
Replacing, regenerating human cells, tissues, organs to restore/establish normal function
71
Fetal liver stem cell enrichment with..
EpCAM epithelial cell adhesion molecule
72
Somatic cell cloning
Embryo developed from somatic cell genome
73
Molecular cloning
Common isolation of single gene sequence
74
Embryonic cloning
Blastocysts from one fertilized egg are developed into multiple embryos
75
Proliferation
Increase in cell number
76
Hyperplasia
Increase in cell number
77
Dysplasia
```
Increase cell number
Abnormal morphology (pathological)
```
78
Carcinoma in situ
Cancer without spreading
79
Metastatic cancer
Carcinoma plus spreading
80
Five truths about cancer PRICD
```
Preventable
Refractory
Informative
Curable
Diagnosable
```
81
Malignant cancer suffixes
Carcinoma
Sarcoma
Hodgkin lymphoma
82
Features of neoplasm (benign and malignant)
Excessive growth
Apoptosis evasion
Limitless replication
83
Malignant features distinct
Sustained angiogenesis (ability to grow a blood vessel)
Invasion and metastasis
Abatable growth, migration, soft agar growth
84
Cancer progression
Initiated by DNA damage
Damaged cell proliferation
Progressive invasion and spreading
Metastasis is point of no return
85
Cancer stem cells
Induce cancer
Want to target CSC in addition to chemotherapy
86
Carcinogens
Full - no activation needed
Radiation, solid gel materials
Microorganisms bacteria, virus, parasite
H. Pylori stomach cancer chronic inflammation
HepB/C liver cancer, transfer of oncogenes that transform normal cells
87
Carcinogenesis
```
P53 tumor suppressor weakened
More free radical damage
Aging of telomeres
Increased inflammation
Immune cell apoptosis
```
88
Oncogene function/oncogenesis
```
Growth factor
Cytokines
Kinase
Signal transducer
Transcription factors
```
```
Immortalization
Growth signal
Enhanced survival via DEC1
Invasion
Angiogenesis
```
Enhanced when tumor-suppressor genes are dysfunctional, silenced by epigenetic mechanisms: methylation, deacetylation, microRNA
Activated by mutation, overexpression, amplification, and translocation MOAT
89
Antioncogene function
| Tumor suppressor genes
Antiproliferation Rb
Antimetastasis
Cell suicide
DNA repair BRCA
P53 does all 4!
90
Irinotecan
SN38 anti cancer activity by inhibition of topoisomerase
Want to promote CES hydrolysis to SN38
And ABC efflux into the blood from hepatocyte
Cancer cell resistant if able to efflux SN38
91
Perfect irinotecan candidate
Effective uptake in liver
Hydrolysis
Efflux SN38 from the liver
Nontoxic systemic levels
Effective uptake of SN38 and irinotecan
Hydrolysis
Minimal efflux of SN38
Topoisomerase dependence
92
Effective cancer therapy
Assessable oncogenes signaling in cancer
Known systemic and cancer exposure/perfusion
Fast therapeutic outcomes
93
Liquid biopsy
Circulating tumor cells/ CT DNA in blood
Sequence analysis for sensitivity/resistance
94
Xlinked dominance
Affects all female offspring from dominant father
95
X linked recessive
Primarily affects male offspring from recessive mother
96
Y linked
Affects male offspring
97
Karyotype
Number, gender, description of affected
98
Polyploid
Extra set
| Lethal
99
Autopsy
Multi sampling
Non-designed
Tissue quality
