Cancer first half.. Flashcards
Difference between well differentiated tumour and a poorly differentiated tumour and prognosis
Well differentiated = closely resembles origin ( better)
poorly - little resemblance (worst)
undiff = cells of origin unknown
Name 4 properties of a benign tumour
grows by expansion
compresses adjacent tissue
DOES NOT infiltrate
stays at the site of origin
name 4 properties of a malignant tumour
expands and infiltrates
compresses and invades adjacent tissue
metastasises in the blood
irregular outline
carcinoma
malignant epithelial
adenoma
benign epithelial
leiomysarcoma
malignant smooth muscle
osteoma
benign bone
rhabdomyloma
benign striated muscle
lipoma
benign adipose
chrondrosarcoma
malignant cartilige
tetratomas
germ cell 3 laters
embryonal
embryogenic blast tissue
how does a benign tumour grow in a solid organ and on epithelial surface
1 - expands and compresses grows spherically
2- direction of least resistance , papillary shape
5 properties of malignant tumour
nuclear hyperchromatism high nuclear:cytoplasmic ratio pleomorphism high mitotic count abnormal mitosis
difference between malignant tumour and dysplasia
loss of differentiation is dysplasia differentiation varies in malignant
what is a carcinoma in situ
dysplasia in epithelium has signs of a malignant tumour but not invading
describe 3 ways cancers spread
1) serosal surfaces
2) lymph - in lumen of lymph, into lymph draining system, proliferate in the subscapularsinus and replace node
3) blood - invade vessel wall and into lumen, get stuck in small capillary and grows (distal metastasis)
name 5 effects of a benign tumour
can metastasise pressure on adjacent vital structures can get stuck in bronchioles interfere with endocrine (pituitary) bleeding
name some common sites of BBM
brain, liver, adrenals, bone, lungs
name the 5 ways of diagnosing cancer
tumor marker history imaging physical exam biopsy
What do HCG, AFP and PSA detect
HCG - trophoblast tumours
AFP - liver and germ cell tumours
PSA - pituitary tumors
3 places you can detect tumour markers
csf, blood, urine
what do you asses in histology of a tumour
degree of differentiation and how far spread
common cancer cytogenetics test
cervical smear - exfoliate top layer
3 things that determine the stage of a tumour
if it has metastasised
invasion
size of primary origin
Dukes colorectal staging?
A doesn’t pass muscle
B passes
C infiltrate nodes
describe a cells entry back into the cell cycle
PDGF and FGF stimulate TFs c-cos c-jun and c-myc. These are all competency factors and immediate early genes. (G1a)
TFs transribe proteins CYCLIN D and EZE which stimulate the cell to go into re entry.
(delayed responce) (G1b)
progression factors finally cause the cell to reenter G1
which cyclins are expressed where in the cell cycle
DE in G1 cdk 6 and 4
A in S cdk 2
B in M and G2 cdk 1
name 3 things that can activate oncogenes
mutation
gene amplification
translocation
what are protooncogenes and oncogenes
- protooncogenes any component of the growth signalling cascade
- oncogenes are protooncogenes that dont need a signal to activate - mutated
what do p53 and Rb check
TSG. they prevent progression of the cell cycle,
all DNA replicated?
favourable environment?
RNA virus tumour 4 types
B eccentric core C centric code (90%) D bullet shaped core
A- intracellularly
viral genes and what they code for
gag - G antigens (core protein )
pol - polmerase (enzymes)
env - envelope
scr - silent
describe -ve RNA virus replication
1) RNA virus lysis with cell and releases 2 single stranded RNA into virus
2) Reverse transcription of RNA - proviral DNA
3) RNA depredates and used to make new DNA complementary strand. Contains identicle LTRs
4) proviral DNA integrated into cells DNA and transcribed into mRNA (DNA polymerase)
5) viral proteins made
6) proteins and RNA bud off to make new virus particle
how does sarcoma and leukaemia virus replicate
sarcoma - SRC contains silent oncogene
leukaemia - integrates next to silent human protooncogene. rightward LTR has a strong promoter so protooncogene is expressed
name 4 functions of oncogene products (how they cause cancer)
hormones - monkey virus makes PDGF which tells all cells to divide
receptors - think theyve got a ligand attached - constant signals to divide
g proteins - GTAase mutation therefor GTP constantly bound
TF switch on cell growth
descrive monkeyvirus
-in non permissive cells e.g. human can only do early phase
this means early phase proteins e.g. T antigens are produced and the cell can not progress
-in permissive cells e.g. monkey cells can do early and late phase. this means late phase proteins e.g. VP123 can be produced. new virus buds off and cell is lysed
two types of DNA virus life cycle
lytic- early and late phase. permissive cells. cell lysis
transforming - only early phase, non permissive causes cell to divide
how do DNA virus replicate
DNA gets transcribed to mRNA then viral proteins made from that
how to DNA virus cause cancer
early phase viral proteins e,g, E6.
E6 can bind to p53 and Rb and cause them to be inactive therefor no defence against abnormal division
what increases a families risk of Rb
loss of normal chromosome
loss and reduplicate of abnormal Ch13
mitotic crossing over
inderpendant mutation
= loss of hetrozygosity - usually have 1 mutated 1 norm if lose normal then only have 1 mutated
Name 5 characteristics of cancer
disturb cellular arrangements = pain disturb normal pleomorphism - anaplasia metastasis - cell heterotopia new growth invasion adjacent tissue
How does the body respond to carcinogens once inhaled
phase 1 - makes it more reactive
phase 2 - couples with more water soluble so body can excrete
how does the reactivity of a compound relate to how carcinogenic it is
unreactive more carcinogenic as, more reactive react quicker so are rid quicker however these persist in cells
explain how BP is a carcinogen
phase one .. BP —AHH—> BP=o —EH—> HO–BP–OH —–AHH—> O=BP -OH-OH
phase 2 .. detoxified and excreted . conjugated with glutathione, sulfate, glucaronic acid
OR
attracted to e- on G. causes either
1) G - T not C as BP uses one of bonding positions - if in an oncogene can cause cancer
2) induces SOS repair (not always effective so can cause errors and mutations
effect of radiation on DNA
DIRECT - excitation and ionisation electrons causing ions - dimerisation of pyramiding in uv INDIRECT free radical formation
name 2 types of cancer that are limited to white peple sun exposed areas
squamous and basal cell carcinoma
what is XP and symptoms
recessive, unusual response to sunlight, loads of freckles, pigmentation abnormalities, skin cancer
explain how XP causes cancer
uv light causes free rad formation and TT dimers in DNA. These are usually cleaved by endonuclease but XP has definitional endonuclease. This means during dna replication DNA polymerase has to leave a gap in the dna where the TT dimer is. This causes SOS repair which isnt faithful and can cause errors + mutations
Name 5 things that can alter apoptosis of a cell
GF levels GIF environment secreted growth inhibitors intrinsic program of differentation/ apoptosis, tumour immune responce
name 5 things that a malignant cell must have
insensitivity to antigrowth signals sensitivity to growth signals evading apoptosis VEGS new blood vessels growth tissue evasion and metastasis
3 ways a cell evades apoptosis
upregs anti apoptotic
downregs apoptotic
loss of func of apoptotic factors
what does Wilfs tumour caused by
upref of GFs
what can breast cancer be caused by
increased TK receptors
what can cause GI stromal tumours and how do you treat
mutation in TK domain of c-kit. TK inhibitor (gleevec)
non hodgekins lymphonma is caused by?
B cells and T ells
Name the 2 main types of hodgekins lymphoma
nodular lymphocyte (good) neoplastic cells - classic hodge
describe... nodular sclerosing lymphocyte depleted lymphocyte rich mixed cellularity
1 - RS and lymph equal (diff architecture)
2 - more RS low LYMPH
3- low RS more LYMPH
4 - RS and lymph equal
describe embryonal tumour
blast tissue remnants. increased likely young children, highly malignant, can spread early by lymph and vv
where is a neuroblastoma
adrenal gland
whats special about a astrocytoma
its malignant but does not metastasise as cant adhere to any other body surfaces
describe the two types of tetroma
OVIAN - young woman - cysys. contains keratin . good prognosis
TESTIS - young men. painless swelling of testes, malignant . can use tumour markers and tests
describe variable expression
mutation in a single cancer gene can predispose to loads of diff tumours
describe age related penetrance
takes time for individual to accumulate ‘hits’
name 2 genes and cancers that are caused by mutations in protoncogenes
MET - hereditory papillary renal carcinoma
RET - multiple endocrine neoplasia
name 2 cancers that are caused by TS gene mutation
breast and ovarian BRCA1 BRCA2
APC 0 FAP
what are genes hMLH1
mutator genes, held repair DNA if get a mutation
outcome of being a high AHH inducer
high risk induce - diol made quicker, increase chances of it binding to dna