61. Neoplasia part 2

Question 1

Describe carcinoma in situ

Answer 1

very severe dysplasia, potential to become malignant and invasive, has not yet breached basement membrane

Question 2

what is an environmental factor that causes cancer

Answer 2

carcinogen

Question 3

how is carcinogenesis identified

Answer 3

epidemiological studies, occupational risk, direct evidence (eg chornobyl), and experimental testing

Question 4

Carcinogenic risk cannot be determined by …….. alone

Answer 4

structural formula

Question 5

what is the difference between Direct and Indirect carcinogens

Answer 5

direct is a carcinogen entering your body as it is (e.g. smoking)
indirect is Procarcinogens undergoing metabolic conversion into active carcinogens (nitrate into nitrosamine)

Question 6

name some carcinogen requirements

Answer 6

resisting cell death
insensitivity to growth inhibitors
sustained angiogenesis
metastasize
invasion

Question 7

how are neoplastic cells immortal (3 reasons)

Answer 7

Autocrine growth simulation
reduced apoptosis
telomerase activity

Question 8

describe Autocrine growth simulation

Answer 8

abnormal expression of oncogenes and inactivation of tumor suppressors

Question 9

describe reduced apoptosis

Answer 9

abnormal gene expression leads to inhibition of apoptosis

Question 10

describe telomerase activity

Answer 10

in normal cells the telomeres shorten with each division. this means a cell only divides a certain amount. Telomerase prevents this

Question 11

which gene encodes a protein that regulating apoptosis so when its inhibited reduced apoptosis happens

Answer 11

BCL-2 is a gene that encodes a protein playing a crucial role in regulating apoptosis

Question 12

what gene inhibits neoplastic growth

Answer 12

Tp53 that encodes for p53

Question 13

p53 is known as what type of gene

Answer 13

tumor suppressor gene

Question 14

what do caretaker genes do

Answer 14

repair dna

Question 15

what do gatekeeper genes do

Answer 15

stop damaged cells dividing (inhibit proliferation or induce apoptosis)

Question 16

describe p53

Answer 16

has gatekeeper and caretaker function
“guardian of the genome”
most frequent mutated gene in cancer

Question 17

what mutations can p53 go through

Answer 17

missense and nonsense

Question 18

what does p53 binding to oncoproteins (encoded by DNA viruses) lead to

Answer 18

HPV

Question 19

what are oncogenes

Answer 19

genes which drive neoplastic behavior in cells

Question 20

what do oncogenes produce

Answer 20

oncoproteins

Question 21

what are the 5 groups of onco(genes/protiens)

Answer 21

1. growth factors
2. receptors for growth factors
3. DNA binding transcription factors
4. signaling mediator with tyrosine Kinase activity
5. signaling mediator with nucleotide binding activity

Question 22

what are the 2 signaling mediators involved as oncogenes

Answer 22

signaling mediator with tyrosine Kinase activity
signaling mediator with nucleotide binding activity

Question 23

Diploid

Answer 23

normal amount of DNA (2N)

Question 24

Polyploidy

Answer 24

Exact multiples of diploid state (4N or 8N)

Question 25

Aneuploidy

Answer 25

Inexact multiples

Question 26

low risk HPV forms.....

Answer 26

warts

Question 27

high risk HPV forms...?

Answer 27

squamous cell carcinoma

Question 28

where can HPV happen

Answer 28

head and neck region anogenital

Question 29

What are transformation zones and what does this mean

Answer 29

Areas of transition from one epithelial type to another (ie transformation zone) most prone to instability

Question 30

where is the p53 in terms of checkpoint

Answer 30

G2-M

Question 31

what gene is at checkpoint G1-S

Answer 31

pRB - retinoblastoma protein

Question 32

what viral HPV oncoprotein acts on TP53

Answer 32

E6

Question 33

E6 viral oncoprotein acts on what

Answer 33

TP53

Question 34

what does TP53 make

Answer 34

p53

Question 35

what does p53 do

Answer 35

Activates DNA repair proteins, holding cell cycle to allow repair, initiating apoptosis of badly damaged cells Is at G2-M checkpoint

Question 36

what viral HPV oncoprotein acts on RB

Answer 36

E7

Question 37

E7 acts on what

Answer 37

RB

Question 38

what is RB

Answer 38

retinoblastoma protein that inhibits cell cycle progression until cell is ready to divide

Question 39

RB or TP53 first

Answer 39

RB

Question 40

what virus is associated with some lymphomas and carcinoma (HINT- EBV)

Answer 40

Epstein Barr Virus (EBV) is a type of herpesvirus (“glandular fever”) About 90% of the population end up with some kind of (usually transient) EBV infection

Question 41

What can EBV cause

Answer 41

EBV driven lymphoproliferative disorder

Question 42

what are EBVs associated with

Answer 42

Burkitt Lymphoma Hodgekin Lymphomas primary effusion lymphoma

Question 43

what promotes nasopharyngeal carcinoma

Answer 43

smoking. inactivation of p16/CDKN2A and TGFBR2

Question 44

major cause of radiation skin cancer

Answer 44

UV (ultraviolet)

Question 45

which UV is most common for skin cancer

Answer 45

UVB

Question 46

what cancers are UV most associated

Answer 46

malignant melanoma basal cell carcinoma

Question 47

melanoma is cancer of which cells

Answer 47

melanocytes (produce melanin pigment)

Question 48

what is the scale of UV damage and melanin

Answer 48

fitzpatrick scale - Pale people are more susceptible to UV damage

Question 49

what increases risk of UV damage

Answer 49

tanning beds, sunburns

Question 50

what is ionising radiation (give examples)

Answer 50

radiation which detaches electrons from atoms or molecules. Gamma rays, x rays and nuclear radiation

Question 51

what is radiation which detaches electrons from atoms or molecules

Answer 51

Ionising Radiation

Question 52

which tissues are sensitive to carcinogenic effects of ionising radiation

Answer 52

thyroid, bone, breast, haematopoetic tissue

Question 53

name a bacteria carcinogen

Answer 53

Helicobacter Pylori

Question 54

what is Helicobacter Pylori linked with

Answer 54

Gastric adenocarcinomas and some lymphomas They releases toxins which activate oncoproteins such as CagA at SHP2 binding site

Question 55

what Hormones are carcinogens

Answer 55

excess oestrogen (linked to excess adipose tissue) anabolic steroids growth hormones IGF1

Question 56

Is age a factor in tumour development?

Answer 56

Older you are the more likely you are to get cancer

Question 58

does diet impact as a carcinogen. If yes elaborate.

Answer 58

Yes. Obesity - excess adipose tissue means higher levels of growth hormones Processed meats - Nitrate ->Nitrosameine (chemical carcinogen) Alcohol - acetaldehyde cause cell damage esp. when paired with smoking

Question 59

Some people have inherited mutations which predispose them to certain types of cancer. which ones.

Answer 59

BRCA1, BRCA 2, MEN syndromes (endocrine)

Question 60

what makes cancer cells 'behave' badly

Answer 60

- Invasiveness determined by the neoplastic cell - Decreased cellular adhesion (become unstuck from eachother) - Secretion of proteolytic enzymes(damage surrounding tissue) - increased cellular motility (they move around)

Question 61

What is metastasis?

Answer 61

The process by which tumour cells get from their site of origin (primary) to another part of the body (secondary)

Question 62

how many steps of metastasis

Answer 62

6

Question 63

what are the 6 steps of metastasis

Answer 63

1. detachment 2.Invasion of surrounding tissue 3. Intravasation into vessels 4. Evasion of host cell defenses 5. Adherence to endothelium else where 6. Extravasation of cells from vessel into surrounding tissue

Question 64

what are some of the routes of metastasis

Answer 64

Haematogenous (by blood) Lymphatic Transcoelomic across a body cavity (ie peritoneum)