#5 Oncogenesis Flashcards

(74 cards)

1
Q

Oncoviruses are necessary but NOT _____for cancer devo.

A

sufficient

Many/most people infected with a given virus do not devo the cancer that the virus can cause

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2
Q

Viral cancers appear in context of ________infections. Occur many years to decades after acute infection

A

persitant/chronic

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3
Q

Immune system can play a _____ or a prote______ctive role in virally induced oncogenesis

A

deleterious

protective

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4
Q

see human visus associated cancers in association with

A

immunosuppresion/chronic inflammation

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5
Q

How viruses causes indirect cancer

A

Chronic infection causes cirrhosis, inflammation, tissue damage, high levels of cell division to increase chance of mutation to derail growth control

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6
Q

How do viruses directly cause cancer

A

stimulate cells to enter S phase and make viral proteins to contineu to direct cell to ovvride normal controls on growth

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7
Q

How can we tell if a cancer we’re seeing epidemiologically is viral related

A

we’ll see it in an immunosuppresed population

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8
Q

aggressive skin cancer in elderly/immunocompormised

A

Merkel Cell carcinoma

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9
Q

Mech of merkel cell carcinoma

A

common deletion renders virus unable to complete replication cycle; persistnat infecction

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10
Q

common deletion renders virus unable to complete replication cycle; persistnat infecction

A

Merkel cell carcinoma

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11
Q

Papillomaviurs is member of:
genome:
infectects:

A

papovavirus
dsDNA
mucosal/epithelial~ hands/feet/genital

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12
Q

this has ~100 sub types with 1/3 infecting genital strand

A

papillomavirus

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13
Q

E1 and E2 of HPV mediate:

A

E1 and E2 mediate replication and transcription of viral DNA

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14
Q

E4 of HPV will:

A

E4 distrupts cytokeratins to facilitate virus egress~ helps virus out of the tissue

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15
Q

L1 and L2 of HPV

A

compose the capid

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16
Q

distrupts cytokeratins to facilitate virus egress~ helps virus out of the tissue

A

E4

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17
Q

mediate replication and transcription of viral DNA

A

E1 and E2

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18
Q

E5, 6, and 7 of HPV

A

intersect with key elements of cellular growth control, are associated with oncogenesis

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19
Q

E5 in HPV

A

stimulates constituitive GF replicating signal thus the cell no longer needs the GF receptor to signal replication

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20
Q

stimulates constituitive GF replicating signal thus the cell no longer needs the GF receptor to signal replication

A

E5

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21
Q

E6 and E7 in HPV

A

neutralize major ‘brakes’ that regulate cell cyle—p53 and Rb—thus uncouple cell division from key regulatory controls

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22
Q

neutralize major ‘brakes’ that regulate cell cyle—p53 and Rb—thus uncouple cell division from key regulatory controls

A

E6 and E7

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23
Q

Cousre of HPV

A

Inocculation of epitherlium→ hand/foot/throat or cervix→ Local multiplication→ wart
–resulotion(latency) OR –cell transformation

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24
Q

Life cycle of papillomavirus is tied to the differenation state of

A

keratinocytes

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25
Stage of HPV virions fucking you up
a. Early gene expression in the basal layer of E1, E2, E6 and E7 b. Late gene expression and viral genome amplication: in the spinous layer c. Virion assembly and release in the cornified layer
26
a. Early gene expression in the_____ layer of E1, E2, E6 and E7
basal
27
Late gene expression and viral genome amplication: in the ____ layer
spinous
28
Virion assembly and release in the _____layer
cornified
29
HPV stimulation of cell cycle causes cell in _______ to replicate
stratum spinosum | the spinosum is spitting out hpv
30
Where are cells supposed to regulate?
the stratum basal | BASICALLy, the basal layer
31
is the engine of the cell cycle: move the clel cycle ahead by phosphorylating key substrates
CDKs
32
CDK regulation
by enZ synthsis, degredation of cyclins, phosphorylation events, inhibtiors
33
key brake that blocks progression to S phase
Rb
34
Rb-P is in its'
inactive state... lets cell go G1--> S
35
how do we P Rb?
accumulate Cdk/cylcins and phosphorylate it
36
____ protein of papillomavirus binds to Rb—targets it for proteosomal degradation
E7 | ---E7 like syltherin... sneaky snake bastard
37
guaduain of genome to prevent proguression to S phase by making cyclins or inducing apoptosis
p53
38
the killer of p53 by targeting upiquitin to it!
E6 | 666 like the devil and now the cell is immoral! aghh!
39
two naughty function of E6
blocks p53 and increase telomerae
40
More then 99% of cervical cancers specimens show evidence of infection with ‘high risk’ strains of HPV strains
HPV 16 (50-60%) HPV 18 (10-20%), HPV6 HPV 11
41
See correlation btwn high risk strains and activity of_______proteins in vitro assays of cell transformation
E6 and E7
42
a. high risk; E6 + E7 can immortalize
keratinocytes
43
Early stage of acute and persistent HPV infection, viral DNA is maintained as
episome | -stays as a little extra chromo on its own then gets integrated into host DNA
44
Devo of carcinoma associated with integration of DNA into the host as what is retained?
E6 and E7 (always retained in cancer cells)
45
Integration disrupts expression of ________, which is transcriptional repressor, allow increased levles of E6 and E7
E2 gene | *Replication of integrated DNA triggers DNA amplications and chromosomal abnormalities
46
Our transcriptional repressor that is disrupted during integration of HPV into genome
E2
47
______ _______ key step towards oncogeneis in HPV
Genome integration
48
LSIL is
low grade squamous intraepitheilal lesion
49
HSIL
HIgh grade squamous intraepithelilal lesion
50
CIN
cervical intraepithelial neoplasia
51
productive infection we see ______ | with low E7 and low viral DNA
LSIL; productive infection
52
Cellular Gene Deregulation: | we see increased:
E7 and viral DNA
53
Cervical cancer: DNA integration we see a break in ______ | with high levels of
basal membrane | E7
54
Normal cervix→ to HPV invected cervix: seen in 370 million and often
cleared
55
HPV infected cervix→ to Low grade SIL: in about 70 million and can______ or move to ______
regress | HG-SIL
56
causes that precipitate moving from LSIL to HG-SIL
(especially if they smoke, OC use, viralload, coinfections)
57
HG-SIL (in 10 million) can regress or move on to
cervicle cancer: | in .5 million cases and can’t go back
58
How do we progress from HG-SIL to cervical cancer
occurs in viral integration methylation
59
* **E6/E7 mRNA is present as we______ | * **___ will disappear as we move to cancer
progress | L1
60
cytological evidence of displasia or neoplasia; detect koilocytotic cells (vacuolated cytoplasm) which are rounded and appear in clumps
Pap smear
61
Pap smear that show evidence of displasia or neoplasia looks like:
detect koilocytotic cells~~~ round and clumpy
62
Step 1: Release nucleic acid: clincial specimes are combined with a base solution which release target
DNA
63
Step 2. Hybridize RNA probe with Target DNA: target DNA combines with specific RNA probes creating
RNA:DNA hybrids
64
3. Capture Hybrids: multiple RNA:DNA hybrids captured onto solid phase coated with universal capsure _____ specific for RNA:DNA hybrids
antiBs
65
4. Label for detection: captured hybrids dectected with multiple antiBs conjugated to ______. Signal then amplified 3000 fold
alkaline phosphatase
66
5. Detect, read and interpret results: bound alkaline phosphates detected with ________ substrate. Upon cleavage by alkaline phosphatase, substartes produce light measure on luminometer in ______
chemiluminsent | Relative Light Units (RLUs)
67
Vaccine issues
a. need mucosal infection d/t route of infection b. need to recognize multiple high risk strains c. admin of vaccine that includes oncogenes not possible d. societal issues: is this a vaccine to prevent cancer or STD
68
Capsid protein L1 will induce:
humoral innuminty
69
recombinant L1 can be made in culture | b.L1 self-assembles into_____ that resemble virions and induce appropriate immunological response
“VLPs”
70
Vaccine contains purifed VLPs | induces protective, humoral immunity
antiBs present at mucosal surfacee prevent incoming HPV from establishing infection
71
Guardasil | 1. prevents precancerous lesion and warts: HPV
6, 11, 16, and 18
72
Gardasil admin age
2. can be administerd as young as 9 and as old as 26
73
Type of vaccine Gardasil is? | when and why do you use it?
HPV is leading cause of cervicle cancer should be given before onset of sexual activity but either way get vaccinated this is a tetravelant vaccine
74
Cervical cancer stats FYI
1. 15,000/year in US infected with cervcle cancer and 4,100 die per year d/t this 2. 500,000 new cases /yr worldwide and see 250,000 deaths 3. second or thrid most common cancer among women 4. Vaccines for pre-adolescent girls with VPL vaccine and vaccine for men to deplete high risk HPV from popuation 5. HPV is associated with penile cancers, vulvar cancers and anal cancer~ %25 of oroparnyeal cancers