Oncology Foundations Flashcards

0
Q

Endoplasmic reticulum

A

Produces CYP metabolic enzymes

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1
Q

Circadian regulation

A

Clock/bmall per/cry regulate each other

Gravity can trigger rather than light

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2
Q

Methylation

A

Gene in off position

Decreased transcription

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3
Q

Chromosome

A

Gene: functional unit of heredity
Allele: alternative form of a gene

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4
Q

PXR

A

CYP 3A4 transcription factor

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5
Q

Gene imprinting

A

Silenced

Methylation

Can result in Prader-Willi Syndrome

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6
Q

Down syndrome

A

Trisomy 21

Type of aneuploidy

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7
Q

Genetically dominant

A

One allele determines phenotype over another allele

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8
Q

Translocation

A

Chronic leukemia

Philadelphia chromosome

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9
Q

Ring

A

Infertility

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10
Q

Recessive trait phenotype

A

Every other generation

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11
Q

Dominant trait

A

50% inheritance

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12
Q

Genomics

A

Structure/function character of the genome

Genome(genetic complement of an organism)

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13
Q

Most genomic medicine based on..

A

A Conformation

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14
Q

Pharmacogenes

A

2% of all genes

Genome maintenance
Signal transduction
Biochemical balance

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15
Q

Mitochondrial DNA

A

Circular
From mother
Can tolerate more damage

Contains all genetic information like chromosomes

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16
Q

Multiplicity of RNA

A

Alternative promoters on DNA

Alternative splicing of mRNA introns

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17
Q

General transcription complex (GTC)

A

Recognizes promoter TATA box

Promoter controls whether a gene should be transcribed

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18
Q

Expression differentiation

A

Transcription factor determines if gene is transcribed or not

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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

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20
Q

Transcription factories

A

Transcription locations with Shared RNA polymerase

Genes with similar functions

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21
Q

Gene expression silencing RNA polymerase

A

Endo-siRNA
microRNA

Break down and modify mRNA after processed by si/microRNA

Silencing

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22
Q

mRNA production RNA polymerase

A

Heterogenous nuclear RNA

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23
Q

Protein translation RNA polymerase

A

pre-rRNA
rRNA
tRNA

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24
Q

Translation

A

AUG methionine start codon

RCCAUG starting sequence

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25
Q

Post translational modifications

A

Proteolytic processing generates protein diversity

Protein folding for degradation stability

Acetylation - activate
Methylation - silence
Phosphorylation- signal transduction

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26
Q

P53 tumor suppressor

A

Phosphorylate to activate and suppress tumor

Stress, UV radiation can activate kinase/acetyltransferase and p53 activation

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27
Q

Argonaute complex

A

Recognize and modify mRNA after processing small RNA(siRNA, microRNA)

Increase RNA degradation
Repress translation
Decrease transcription

Circular RNA counteract microRNA activity

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28
Q

4 Rules of genetic based diseases

A

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

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29
Q

Silence substitution

A

Substituted base that results in the same amino acid codon

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30
Q

Missense substitution

A

Substitution Forms a different amino acid

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31
Q

Frameshift

A

Insertion, deletion

Severe, changes multiple codons and downstream amino acids

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32
Q

Nonsense substitution

A

Forms a stop codon

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33
Q

Germline genetics

A

From parents, before birth

All cells in organism
Inheritable
Polynorphisms

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34
Q

Somatic genetics

A

After birth
Affected by environment
Small number of cells

Cancer

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35
Q

Most frequently used for sequencing

A

HiSeq

Cheapest, fastest 98% accurate though

Opposite Sanger: slowest, expensive

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36
Q

Sequencing analysis

A

DNA: genome
mRNA: expression
ChIP: protein-DNA interaction, global mRNA expression

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37
Q

EcoRI

A

Recognizes and cleaves DNA sequence

Endonuclease

Restriction fragment length polymorphism

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38
Q

Primer

A

Determines which gene is amplified in PCR

Short complementary DNA strand

The more PCR cycles needed, the lower the expression

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39
Q

PCR differentiation

A

Can detect insertion, deletion

Can differentiate by Endonuclease restriction digest

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40
Q

FISH

A

Fluorescent in situ hybridization

Probe for disease gene

41
Q

Prenatal testing for trisomy 21

A

Mothers over 35

Increased prevalence with age

Amniotic fluid, placenta villi, ultrasound

42
Q

Sickle cell disease

A

Single gene disease

43
Q

Viral vector

A

Efficient
Costly
More dangerous/concerning

44
Q

Reverse genetics

A

Determine a phenotype associated with a gene

45
Q

Forward genetics

A

Determine a gene responsible for a phenotype

46
Q

In vivo gene therapy

A

Nano particle, IV IM, plasmid, virus

insert corrected copy of gene

47
Q

Ex vivo

A

Take cells out, introduce DNA sequence, see if working properly, inject back into patient

48
Q

Carboxylesterases (CES)

A

Hydrolyze esters for activity

Tamiflu
Irinotecan to SN38 activation CES2
Plavix aspirin deactivation

Regulated by pharmacogenes

49
Q

Assay that detects proteins

A

Western blotting uses antibody reveal protein of interest

Inmunocytochemistry-uses antibody to visualize the specific protein location of expression

50
Q

Assay that detects activity

A

HPLC - chromatography

LC-MS mass spectrometry

51
Q

Assay that detects mRNA

A

Northern blotting
RT-qPCR
ChIP

52
Q

Gel electrophoresis

A

Separate based on charge and molecular weight

Protein expression

53
Q

Histone acetyltransferase (HAT)

A

Increased transcription by acetylation

Co-activator with ligand

54
Q

HDAC histone deacetylase

A

Remove acetyl to decrease transcription

Co-repressor

55
Q

CAR transcription factor

A

Phenobarbital CYP2B activator

Overlaps with PXR to compensate if necessary

56
Q

PXR

A

Rifampicin CYP3A4 activator

Largest binding domain
Flexible, lipophilic

57
Q

Transcription factor (nuclear receptor) mutants

A

Contributes to individual variation of certain enzymes and transporter gene expression

58
Q

Genetics

A

Individual gene-based

59
Q

Genomics

A

Genome wide based variation and environment interaction

60
Q

Histone methyltransferase

A

Leads to decreased transcription

61
Q

Aryl hydrocarbon receptor (AhR)

A

Dioxin CYP 1A coactivator via AhR

62
Q

PPAR peroxisome proliferator activated receptor

A

Clofibrate CYP4A coactivator

63
Q

Poor 2C19 metabolism polymorphism

A

20% Asian

64
Q

Aspirin resistance pharmacogenomics

A

Increased hydrolysis via increased CES2
Excessive COX expression

Aspirin irreversible COX inhibition

65
Q

Plavix pharmacogenomics

A

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
Q

Senescence

A

Prevent further cell proliferation

Area for cancer research

67
Q

Blastocyst

A

Embryo with stem cells inside for possible extraction

68
Q

Induced pluripotent stem cells (iPS)

A

Adult cells able to undergo viral transduction to stem cells

Mature cells can be reprogrammed to become pluripotent stem cells

69
Q

Trandifferentiation

A

Pancreas to liver cell

Specialized to specialized

70
Q

Regenerative medicine

A

Replacing, regenerating human cells, tissues, organs to restore/establish normal function

71
Q

Fetal liver stem cell enrichment with..

A

EpCAM epithelial cell adhesion molecule

72
Q

Somatic cell cloning

A

Embryo developed from somatic cell genome

73
Q

Molecular cloning

A

Common isolation of single gene sequence

74
Q

Embryonic cloning

A

Blastocysts from one fertilized egg are developed into multiple embryos

75
Q

Proliferation

A

Increase in cell number

76
Q

Hyperplasia

A

Increase in cell number

77
Q

Dysplasia

A
Increase cell number
Abnormal morphology (pathological)
78
Q

Carcinoma in situ

A

Cancer without spreading

79
Q

Metastatic cancer

A

Carcinoma plus spreading

80
Q

Five truths about cancer PRICD

A
Preventable
Refractory
Informative
Curable 
Diagnosable
81
Q

Malignant cancer suffixes

A

Carcinoma
Sarcoma
Hodgkin lymphoma

82
Q

Features of neoplasm (benign and malignant)

A

Excessive growth
Apoptosis evasion
Limitless replication

83
Q

Malignant features distinct

A

Sustained angiogenesis (ability to grow a blood vessel)

Invasion and metastasis

Abatable growth, migration, soft agar growth

84
Q

Cancer progression

A

Initiated by DNA damage
Damaged cell proliferation
Progressive invasion and spreading

Metastasis is point of no return

85
Q

Cancer stem cells

A

Induce cancer

Want to target CSC in addition to chemotherapy

86
Q

Carcinogens

A

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
Q

Carcinogenesis

A
P53 tumor suppressor weakened
More free radical damage
Aging of telomeres
Increased inflammation
Immune cell apoptosis
88
Q

Oncogene function/oncogenesis

Growth factor
Cytokines
Kinase
Signal transducer
Transcription factors
A
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
Q

Antioncogene function

Tumor suppressor genes

A

Antiproliferation Rb
Antimetastasis
Cell suicide
DNA repair BRCA

P53 does all 4!

90
Q

Irinotecan

A

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
Q

Perfect irinotecan candidate

A

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
Q

Effective cancer therapy

A

Assessable oncogenes signaling in cancer
Known systemic and cancer exposure/perfusion

Fast therapeutic outcomes

93
Q

Liquid biopsy

A

Circulating tumor cells/ CT DNA in blood

Sequence analysis for sensitivity/resistance

94
Q

Xlinked dominance

A

Affects all female offspring from dominant father

95
Q

X linked recessive

A

Primarily affects male offspring from recessive mother

96
Q

Y linked

A

Affects male offspring

97
Q

Karyotype

A

Number, gender, description of affected

98
Q

Polyploid

A

Extra set

Lethal

99
Q

Autopsy

A

Multi sampling
Non-designed
Tissue quality