61. Neoplasia part 2 Flashcards
Describe carcinoma in situ
very severe dysplasia, potential to become malignant and invasive, has not yet breached basement membrane
what is an environmental factor that causes cancer
carcinogen
how is carcinogenesis identified
epidemiological studies, occupational risk, direct evidence (eg chornobyl), and experimental testing
Carcinogenic risk cannot be determined by …….. alone
structural formula
what is the difference between Direct and Indirect carcinogens
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)
name some carcinogen requirements
resisting cell death
insensitivity to growth inhibitors
sustained angiogenesis
metastasize
invasion
how are neoplastic cells immortal (3 reasons)
Autocrine growth simulation
reduced apoptosis
telomerase activity
describe Autocrine growth simulation
abnormal expression of oncogenes and inactivation of tumor suppressors
describe reduced apoptosis
abnormal gene expression leads to inhibition of apoptosis
describe telomerase activity
in normal cells the telomeres shorten with each division. this means a cell only divides a certain amount. Telomerase prevents this
which gene encodes a protein that regulating apoptosis so when its inhibited reduced apoptosis happens
BCL-2 is a gene that encodes a protein playing a crucial role in regulating apoptosis
what gene inhibits neoplastic growth
Tp53 that encodes for p53
p53 is known as what type of gene
tumor suppressor gene
what do caretaker genes do
repair dna
what do gatekeeper genes do
stop damaged cells dividing (inhibit proliferation or induce apoptosis)
describe p53
has gatekeeper and caretaker function
“guardian of the genome”
most frequent mutated gene in cancer
what mutations can p53 go through
missense and nonsense
what does p53 binding to oncoproteins (encoded by DNA viruses) lead to
HPV
what are oncogenes
genes which drive neoplastic behavior in cells
what do oncogenes produce
oncoproteins
what are the 5 groups of onco(genes/protiens)
- growth factors
- receptors for growth factors
- DNA binding transcription factors
- signaling mediator with tyrosine Kinase activity
- signaling mediator with nucleotide binding activity
what are the 2 signaling mediators involved as oncogenes
signaling mediator with tyrosine Kinase activity
signaling mediator with nucleotide binding activity
Diploid
normal amount of DNA (2N)
Polyploidy
Exact multiples of diploid state (4N or 8N)
Aneuploidy
Inexact multiples
low risk HPV forms…..
warts
high risk HPV forms…?
squamous cell carcinoma
where can HPV happen
head and neck region
anogenital
What are transformation zones and what does this mean
Areas of transition from one epithelial type to another (ie transformation zone) most prone to instability
where is the p53 in terms of checkpoint
G2-M
what gene is at checkpoint G1-S
pRB - retinoblastoma protein
what viral HPV oncoprotein acts on TP53
E6
E6 viral oncoprotein acts on what
TP53
what does TP53 make
p53
what does p53 do
Activates DNA repair proteins, holding cell cycle to allow repair, initiating apoptosis of badly damaged cells
Is at G2-M checkpoint
what viral HPV oncoprotein acts on RB
E7
E7 acts on what
RB
what is RB
retinoblastoma protein that inhibits cell cycle progression until cell is ready to divide
RB or TP53 first
RB
what virus is associated with some lymphomas and carcinoma (HINT- EBV)
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
What can EBV cause
EBV driven lymphoproliferative disorder
what are EBVs associated with
Burkitt Lymphoma
Hodgekin Lymphomas
primary effusion lymphoma
what promotes nasopharyngeal carcinoma
smoking. inactivation of p16/CDKN2A and TGFBR2
major cause of radiation skin cancer
UV (ultraviolet)
which UV is most common for skin cancer
UVB
what cancers are UV most associated
malignant melanoma
basal cell carcinoma
melanoma is cancer of which cells
melanocytes (produce melanin pigment)
what is the scale of UV damage and melanin
fitzpatrick scale - Pale people are more susceptible to UV damage
what increases risk of UV damage
tanning beds, sunburns
what is ionising radiation (give examples)
radiation which detaches electrons from atoms or molecules. Gamma rays, x rays and nuclear radiation
what is radiation which detaches electrons from atoms or molecules
Ionising Radiation
which tissues are sensitive to carcinogenic effects of ionising radiation
thyroid, bone, breast, haematopoetic tissue
name a bacteria carcinogen
Helicobacter Pylori
what is Helicobacter Pylori linked with
Gastric adenocarcinomas and some lymphomas
They releases toxins which activate oncoproteins such as CagA at SHP2 binding site
what Hormones are carcinogens
excess oestrogen (linked to excess adipose tissue)
anabolic steroids
growth hormones IGF1
Is age a factor in tumour development?
Older you are the more likely you are to get cancer
does diet impact as a carcinogen. If yes elaborate.
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
Some people have inherited mutations which predispose them to certain types of cancer. which ones.
BRCA1, BRCA 2, MEN syndromes (endocrine)
what makes cancer cells ‘behave’ badly
- 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)
What is metastasis?
The process by which tumour cells get from their site of origin (primary) to another part of the body (secondary)
how many steps of metastasis
6
what are the 6 steps of metastasis
- detachment
2.Invasion of surrounding tissue - Intravasation into vessels
- Evasion of host cell defenses
- Adherence to endothelium else where
- Extravasation of cells from vessel into surrounding tissue
what are some of the routes of metastasis
Haematogenous (by blood)
Lymphatic
Transcoelomic
across a body cavity (ie peritoneum)
