Disorders of Growth & Neoplasia 4/5 Flashcards
how do the cells in a tumour appear
monoclonal
from one parent cell which has undergone genetic change
PROGENY
how does the clone expand in a tumour
uncontrolled proliferation as lack normal control mechanism
tumours become —-
heterogenous
mix genetic profiles
diff properties and mutations
what is the tumour progression
normal cell
transformed cell - mutation
clonal expansion
tumour progression
further tumour progression
what is metastatic property
can go spread elsewhere
what are some examples of changes in a transformed cell
altered nuclear/cyto ratio
altered DNA content
altered surface change
growth at very low cell densities in vitro
what si the aetiology of cancer
not single disease diff forms other factors involved -geographic - age - gender -geentic
what are some environmental factors assc with carcinogenesis
chemicals
radiation
viruses
unknown
what is chemical carcinogenesis
chems implications to cause cancer
animal studies
epidemiology
what are some cancers linked to smoking
lung
laryngeal
oral
bladder
is smoke a bur chemical
no
- polyacrylic hydrocarbons
- Ni + Cd
wha does asbestos and nitrosamines cause
asbestos - insulation - mesothelioma
nitrosamines - diet - gastric carcinoma
what re the nurses of action of chems
direct action
metab conv to active form
weak/strong carcinogens
synergistic effects
what is a simplified theory of carcinogens
initiation - DNA damage and mutation
promotion - clonal expansion of abnormal cells leading to cancer
what can radiotherapy do
lead to later development of second cancer
what is radiation evidence linked to cancer
ionising radiation can induce cancers
what does ionising radiation do to dn
damages dna
how does ionising radiation damage dan
break single strand - repaired… inaccurate
break double strand - chromo break… chromo rearrange
what is UV radiation strongly implicated with
development of skin cancers
- basal cell carcinoma
- squamous cell carcinoma
- malignant melanoma
how does UV light effect the body
does not penetrate deeply therefore damage limited to skin
what does UV light induce formation of
pyramidine dimers =base pair sub during rep
can viruses cause cancer
yes
and contribute to development in diff ways
what is a retrovirus
RNA tumour virus
what are the genes retrovirus contains
viral oncogenes
what are viral oncogenes responsible for
malignant transformation in cells
how does the Viral RNA genome have an effect
copied into DNA by revise transcriptase and inserted into host genome — can influence adjacent genes
how do viruses act indirectly
cause tissue damage, lead to inc ell prolif and increased risk of mutations - HEP C
give some viruses examples
HPV
EBV
Hep C & B
what can HPV give rise to
cervical/anal/penile/oropharyngeal carcinoma
what can EBV give rise to
epstein-barr virus
nasopharyngeal carcinoma, burkitts/hogkins lymphoma
what does Hep B & C give rise to
hepatocellular carcinoma
give an example of a non malignant disease caused by virus
EBV
- infectious mononucleosis
oral hairy leukoplakia
what are some hosts defences
immune cells target tumour cells - destruct
lymphoid infiltrate
regression some cancers
immunodef states assc increase risk
is neoplasia genetic
yes genetic disease
what happens in consideration of neoplasia
tumour cells breed
all carcinogens mutagens
tumour cells - nuc abnormalities
altered DNA content
what are oncogenes
normal genes switched on when cell is needed and promote cell div when expressed are “porto-oncogenes”
what happens if oncogenes are inappropriately switch don
cell div at wrong time
oncogene –> oncoprotein
how do oncogenes act in manner
dominant
what are the categories of photo- oncogenes
genes prod GF/ GF receps
gene overexressed or muataed = diff recep
gene encode signal transducers
gene activate other genes to promote growth transcription factors
how are oncogenes activated
point mutations
gene amplification translocation between chromos
wha are tumour suppressor genes
genes that normally stop a cell grow, promote diff of cell to terminal state OR trigger checkP’s = cell arrest if dna damage occurs
how can normal tumour suppressor function be lost
inactivating mutations
deletions
viral protein = complexes
loss both copies f tumour suppressor gene
what re some examples of tumour suppressor genes
APC
TP53
Rb
what does activation of p53 do
regulation of transcription of down streak target genes
cell cycle arrest
cell death - apoptosis
how is tumour suppressor genes known
inherited cancers
what are 3 broad groups of familial cancer syndromes
familial cancer syndromes
familial cancers
autosomal recessive disorders (DNA repair defects)
what are familial cancer syndromes
increased risk of cancer due to transmission of single gene
Rb
who is retinoblastoma inherited
abnormal allele is inherited and has an effect after a sporadic occurrence previous
what ar familial cancers
in some fams is marked increase in incidence of common cancers
- breast
- ovary
what are some responsible genes in familial cancers
BRCA -1/2 in breast cancer
what are autosomal recessive disorders ) due to DNA repair defects)
eg lynch syndrome
due to impaired na repair
fail to mismatch
what can be done for relatives of affected ppl
screening, counselling and early treatment
what are telomeres
repeating DNA sequences found at end of chromosome
what are tele mores imp for
regulating the number of cells divisions a cell is capable of
what happens to the telemere after each division
shortens until cannot replicate anymore
what is telomerase
enzyme that lengthens teleomres in stem cells
- tumours have more of this
what are epigenetic effects
reversible, heritable altered gene expression without mutation
give some examples of epigenetic events
histone mod
dna mthylation
silenced tumour suppressors by hypermethylation
what is molecular carcinogenesis
multiple genetic abnormalities
what does molecular carcinogenesis involve
oncogenes and tumour suppressors
what si the presentation of cancer like
very vary
incidental screening
effect of primary OR metatstic lesion
dept on site
what can tumours present as consequence of
local disease
distant spread
non metatstic manifestation of malignancy
incidental findings
what are the symptoms of cancer
asymptomatic
vague
- tired, weight loss, fever, anorexia
sp symptoms
- primary/secondayr lesions
- skin/rash
paraneoplastic syndomres
what are paraneoplastic syndromes
symptoms that cannot be explained by effects of local or distant tumours
why is it imp ro recog paraneoplastic syndormes
may be first sign of underlying cancer
significant clinical effect itself
mimic metasstaci disease
give some examples of paraneoplastic syndromes
endocrinopathy
- hypercalcaemia
neuromuscular
- myasthenia
vascular
- nonbac thrombotic endocraditis
what si the presentation of oral cancer
vary white patch red speck patch lump ulcer not pain no sympt
what is commonly cancer screened
breast
ceervix
colorectal
what is the diagnosis
clinical signs cytology histopathology immunohistochem biomarkers imaging
what are courses of treatment
intent - curative/palliative surgery radiotherapy chemotherapy novel molecularly targeted therapies none
