Block 3 Micro Exam -- Viral Mechanisms Of Cancer (#11)

Front 1

Oval cells

Back 1

Hepatic stem cells

These proliferate in response to Hep B infection
These are more prone to transformation

Front 2

ORF X

Back 2

Can function as a transcription factor
May be involved in signaling via MAP kinase

Expression causes HCC in mice

Front 3

Insertion that occurs in majority of HCC tumor cells

Back 3

Viral insertion close to proto-oncogene N-MYC

Up-regulates N-MYC expression

Front 4

% risk of carrier state in Hep B infection

Back 4

5%

Front 5

% of chronic Hep B pts. that develop HCC?

Back 5

25%

Front 6

Other risk factors for HCC

Back 6

Alcohol
Aflatoxin exposure
Hepatitis B/C

Front 7

Aflatoxin

Back 7

Toxin made by apserpgillus

Contaminates some foods (ie peanuts)

Front 8

Treatments used in Hep B carrier state

Back 8

Interferon
Nucleoside analog

Front 9

Strains of HPV associated with cancer

Back 9

16, 18, 31, 33

Front 10

Cancer type that HPV is classically associated with

Back 10

Cervical cancer

Front 11

% of HPV+ pts. that go on to get cancer

Back 11

< 10%

Front 12

Other risk factors for cervical cancer

Back 12

Sexual promiscuity
Smoking
Loss of genomic sequences on chrom. 3 & 11
Immune suppression

Front 13

Other sites (beyond cervix)
where HPV can cause cancer

Back 13

Anogenital area
Head
Neck

Front 14

p21

Back 14

Actual suppressor that arrests cell cycle in response to DNA damage

p21 levels are dependent upon p53 levels
Degraded p53 cannot signal this protein to arrest the cycle

Front 15

Cellular protein that E6 effects

Back 15

p53

NOTE: E6-AP actually binds directly to p53
Complex is made: E6/E6-AP/p53

Front 16

Cellular protein that binds to E7

Back 16

Rb

Front 17

Effect of E7-Rb binding

Back 17

Rb binding to E2F is disrupted
Rb is released and activated

Active Rb activates cell cycle progression

Front 18

Area of cervix most vulnerable to infection

Back 18

Transformation zone

Front 19

Celular layers in which HPV replication occurs

Back 19

Only the UPPER layers

Note: basal layers DO contain HPV, just not growing

Front 20

What is the first sign of cervical cancer?

Back 20

Cervical dysplasia

Note: a.k.a. Cervical Intraepithelial Neoplasia (CIN)

Front 21

Hallmark of HPV infection

Back 21

Koilocyte

Front 22

% of CIN+ smears that go onto invasive cervical cancer

Back 22

5 - 10%

Front 23

HPV protein being used in vaccine

Back 23

L1 capsid protein

Front 24

Etiological agent in Burkitt's lymphoma

Back 24

EBV

Front 25

EBV Protein LMP1

Back 25

Latency protein

Can cause immortilization (via abrogation of contact inhibition)

Front 26

What cells is EBV tropic for?

Back 26

B cells

Front 27

Common translocation in Burkitt's lymphoma

Back 27

t(8;14)

myc proto-oncogene

Front 28

How quickly can a Burkitt's tumor double in size?

Back 28

In 24 hours

Front 29

Characteristics of Endemic Burkitt's

Back 29

95% EBV+
Found in equatorial Africa

UPSTREAM activation of myc
Tumors mostly in jaw

Front 30

Characteristics of NON-endemic Burkitt's

Back 30

15% EBV+
NO geographical restriction

Activation WITHIN myc
Tumors mostly in abdomen

Front 31

Lineage of Reed-Sternberg cell

Back 31

B cell

Front 32

Effect of LMP1 in Hodgkin's Lymphoma

Back 32

Resembles a TNF protein
Associated w/ upregulation of bcl-2 and IL-10

Front 33

Poor prognostic factors in Hodgkin's

Back 33

Lymphocyte-poor type
"B" symptoms -- itch, fever
Bulky disease
Distant disease

Front 34

Tumors assoc. w/ EBV

Back 34

Hodgkin's
Burkitt's lymphoma
Peripheral B cell lymphoma
Leiomyosarcoma
Nasopharyngeal Carcinoma

Front 35

X-linked lymphoproliferative disease

Back 35

Disease marked by fulminant infectious mono
Mediated by EBV+ B cells and activated T cells

Leads rapidly to death (most pts. dead before 10 y.o.)

Mortality w/ fulminant mono is >90%

Front 36

Post-transplant Lymphoproliferative Disorder

Back 36

EBV infected B cells gain a growth advantage
May manifest as acute mono picture

Risk factors include:
Pediatric pts.; Previously EBV negative
T cell depletion; T cell immunosuppression

Treatment focuses on reduction of immunosuppression

Front 37

EBV Ag w/ most oncogenic activity

Back 37

LMP-1

Can confer ligand effect on CD40
Thus, can activate B cells

Front 38

KSHV genes that lead to immortalization

Back 38

LNA - latency gene
Viral cyclin
v-FLIP - anti-apoptosis homolog

Front 39

Other diseases that can be caused by KSHV

Back 39

Primary Effusion Lymphoma
Castleman's Disease

Front 40

KSHV is highly associated w/ what other virus?

Back 40

HTLV-1

Front 41

% of homosexual men that KSHV shows up in

Back 41

20%

Front 42

Primary Effusion Lymphoma pts. are often co-infected w/ what virus?

Back 42

EBV

Front 43

What cells does HTLV-1 target?

Back 43

CD4 cells
(NOT cytopathic to these)

Front 44

What disease does HTLV-1 cause?

Back 44

Adult T cell leukemia

Front 45

Geographical clustering of ATL

Back 45

Japan
Brazil
Caribbean

Front 46

Chief etiological agent of HTLV-1

Back 46

Tax1

Front 47

Effects of Tax1

Back 47

Transforming gene all by itself
Can act as transcription factor in vitro
Represses p53 and p16
Activates NF-kappaB

Front 48

Cells targeted by HTLV-2

Back 48

CD8 cells

Front 49

Cells targeted by HTLV-3 (HIV)

Back 49

CytoPATHIC for CD4 cells

Association w/ cancer is likely secondary
Due to repression of immune surveillance

Front 50

AIDS related malignancies

Back 50

Non-Hodgkin's Lymphoma
Castleman's Disease
Primary Effusion Lymphoma
Kaposi's Sarcoma
Leimyosarcoma

Front 51

Successful therapy for SCID involved what?

Back 51

Supply of gamma chain of T cell receptor

Front 52

Latency period of how long is typical w/ Hep C?

Back 52

20 - 30 years

Front 53

Liver disease that accompanies almost all HCC that's assoc. w/ Hep C?

Back 53

Cirrhosis of the liver

Front 54

Which one integrates into the host genome?

Hep B OR Hep C

Back 54

Hepatitis B

Front 55

HCV core protein has been shown to have what oncogenic activities?

Back 55

Diminishing p53 levels
Subsequently diminishing p21 levels