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Neoplasia Flashcards

Ch. 6 PBVD and Ch. 7 R&C (63 cards)

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1
Q

Which tumors metastasize through lymphatics?

A

Carcinomas

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2
Q

Which tumors metastasize through blood?

A

Sarcomas, to liver/lungs

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3
Q

Molecules that cause cachexia?

A

TNF alpha (cachectin)
IL-1
IL-6
Prostaglandins

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4
Q

What is cell cycle arrest initiated by?

A

p53

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5
Q

What molecule do senescent cells produce?

A

beta-galactosidase

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6
Q

Morphologic hallmarks of apoptosis

A

Margination of chromatin
Condensation and fragmentation of nucleus
Condensation of cell with preservation of organelles

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7
Q

Major cellular inhibitor of autophagy

A

mTOR kinase

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8
Q

Steps of neoplastic transformation

A

Initiation- mutagen causes irreversible genetic change
Promotion- proliferation, reversible, benign tumor of initiated cells
Progression- genetic and epigenetic changes that results in malignancy

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9
Q

Two angiogenic factors produced by tumors

A

VEGF and FGFs

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10
Q

What do vessels produce that stimulate tumor cell proliferation?

A

IL-1 and PDGF

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11
Q

What do NK cells release to kill tumor cells? Stimulates by?

A

Perforin, which mediates entry of granzymes
Granzymes (serine proteases), which stimulate apoptosis
Stimulated by IL-2 and binding of stress-induced ligand to NK receptor

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12
Q

How to macrophages kill tumor cells? Stimulated by?

A

Stimulated by IFN gamma, direct contact and release of ROS, enzymes, NO, and TNF (MHC independent)

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13
Q

How do CD4+ T cells contribute to tumor immunity?

A

Secrete IL-2 and IFNgamma, which stimulate NK cells, macrophages, and CD8+ T lymphocytes

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14
Q

What immune cell enhances tumor cell survival

A

Treg cells

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15
Q

How do B cells contribute to tumor cell death?

A

Produce antibodies, which bind to tumor cells and activate complement and MAC
Also via NK cell or macrophage Antibody dependent cell-mediated cytotoxicity (ADCC) via FC receptors

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16
Q

How do tumors suppress immune system?

A

Produce TGF-beta
Produce Fas ligand, stimulate T lymphocyte apoptosis
Tregs and tumor associated macrophages

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17
Q

Humoral hypercalcemia of malignancy is caused by (3, in order); mechanism?

A

AGASACA, lymphoma, multiple myeloma; produces PTHrp

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18
Q

What is associated with space-occupying thoracic lesions?

A

Hypertrophic osteopathy

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19
Q

What syndrome is observed with mediastinal tumors (ie thymoma); in cats?

A

Myasthenia gravis; alopecia

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20
Q

What tumor is associated with nodular dermatofibrosis in GSDs?

A

Bilateral renal cystadenocarcinoma

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21
Q

Methylation profile in cancer

A

CpG islands are hypermethylated (silenced), body sites are unmethylated (activated); heritable

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22
Q

Prototypical oncogene

A

RAS (overactivation)

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23
Q

Prototypical tumor suppressor gene; two hit hypothesis?

A

Guardian of genome- p53 (loss), initiates cell cycle arrest via p21, and induces apoptosis if repair unsuccessful; both alleles must be mutated
Also RB- Governor of proliferation

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24
Q

Prototypical apoptosis regulating genes (3)

A

p53 mutation
Overexpression of MDM2- degrades p53, so can’t upregulate PUMA (pro-apoptotic), so can’t overwhelm BCL2
BCL2 overexpression- antiapoptotic (stabilizes mitochondrial membrane so cytochrome c can’t leave)
IAP upregulated (inhibits caspase 9)

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25
Prototypical DNA repair gene
26
How are p53 and RB related?
p53 inhibits progression through cell cycle by producing p16 and p21, which inhibit CDKs, so RB is hypophosphorylated, and E2F is bound and can't bind DNA to transcribe
27
Carcinogens vs mutagens
Mutagens cause DNA damage, not always cause cancer Carcinogens are anything that cause cancer, often are mutagens
28
Worst UV radiation; mechanism?
UVB; mutagenic and carcinogenic, causes pyrimidine dimers in DNA (covalent cross-linking of pyrimidine bases), distorts DNA
29
Ionizing radiation- electromagnetic vs particulate; mechanism?
X-rays, gamma rays vs alpha, beta particles, protons, neutrons; chromosome breakage, translocations
30
Viruses that utilize host-derived oncogenes
feLV
31
Viruses that utilize their own oncogenes; examples
Papillomavirus; E6, which inhibits p53 and stimulates TERT (telomerase expression) E7, which inhibits pRB and p21 E5 activates PDGF beta receptor- fibroblast growth and loss of contact inhibition
32
What is insertional mutagenesis; example
Virus inserts itself in a host cell oncogene promoter region; avian leukosis virus
33
What is the hit and run mechanism? example?
Transient infection of cells initiates carcinogenesis; bovine papillomavirus
34
What indirect mechanisms can viruses use to induce oncogenesis? Examples
Suppress immune system, stimulate target cell proliferation Marek's disease- t cell lymphoma because can't eliminate transformed cells Rabbit poxvirus- encodes EGF gene
35
Oncoprotein inhibition- What applies brakes to RAS activation? What inhibits PI3K pathway?
GAP; PTEN
36
What is the warburg effect?
Shift from oxidative phosphorylation to aerobic glycolysis
37
How does cellular metabolism change in growth (in response to GF activating RTK)
Glucose transporters (GLUT1) upregulated via PI3K-Akt, so increased glucose uptake Glutamine utilization increased via MYC Glycolysis
38
What drives Warburg effect?
Hypoxia-->HIF1alpha not hydroxylated, not broken down by VHL, so target genes turned on RAS activation
39
Most important apoptotic pathway in cancer cells
Intrinsic
40
What prevents replicative immortality?
RB and p53
41
What allows for replicative immortality?
Telomerase (via TERT)
42
Transcription factors that control epithelial to mesenchymal transition; change in markers in EMT
SNAIL and TWIST; downregulation of e-cadherin and upregulation of vimentin and SMA
43
Which enzyme breaks down type IV collagen in BM?
MMP9
44
What stimulates motility of neoplastic cells when invading?
Hepatocyte growth factor (HGF) aka scatter factor from stroma binds RTK MET on tumor cells
45
Two enabling characteristics for tumors
Genomic instability Tumor promoting inflammation
46
How do tumor associated macrophages help tumor cells? What type of macs are they?
Prevent anoikis; M2
47
Order of cell cycle
Gknot-->G1-->G1/S checkpoint-->S-->G2-->G2/M checkpoint-->M
48
What causes checkpoints to occur?
p53
49
What causes G1 to S transition
Cyclin D/CDK 4 and 6 Cyclin E/CDK 2
50
What causes S to G2 transition
Cyclin A/CDK 1 and 2
51
What causes G2 to M transition
Cyclin B/CDK 1
52
What inhibits G1 to S transition; how?
p16, p15, p18, p19 aka CDKN2A,B,C,D; inhibits Cyclin D/CDK 4 and 6
53
What inhibits the cycle broadly?
p21, p27, p57 aka CDKN1A,B,C
54
What's another name for p16
INK4a
55
Six effects of transcription factor p53
Growth arrest p21 and p16 DNA damage repair via GADD45 MDM2 production (negative feedback on p53) Activates BAX and PUMA-->apoptosis Senescence
56
TGF beta effect on cell cycle
Increases production of CDKIs through serine-threonine kinase receptor-->phosphorylation of SMADs-->enter nucleus, bind SMAD4-->CDKI gene transcription (p21 and p15)
57
Most important transcription factor in cancer; effects (5)
MYC D cyclin production Protein synthesis Warburg effect Telomerase activity Stem cell transition
58
What stimulates MYC production?
RAS, Notch, Wnt, hedgehog
59
Important factor for canine neoplasia
NFkappaB (see article)
60
What does CDKN2A encode?
p16- inhibits CDK complex p14- inhibits MDM2
61
How do tumor cells inhibit T-cell activation?
Upregulate CTLA-4 on T cells, which removes B7 ligands from APCs (preventing binding of CD28 for second signal) Upregulate PD-L1 and L2, which activate programmed death-1 receptor on T cells
62
What T cell type does BCL-6 suppress?
TFH
63

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