Neoplasia 2 Flashcards
what are the two main factors of carcinogenesis?
genetic and environmental
what are the important genes in carcinogenesis?
oncogenes, tumour suppressory genes, DNA repair genes, miRNAs
what does DNA damage lead to?
altered gene expression and then altered cell function
what are proto-oncogenes?
normal genes which regulate cell division
what are the roles of proto-oncogenes?
growth factors, growth factor receptors, signal transducers, control of gene expression
what do oncogenes produce?
oncoproteins
what are abnormal variants of proto-oncogenes called?
oncogenes
if tight regulation is lost, what can oncogenes do
mutations, excess activity of product, enhanced transcription
what do the mutations in the oncogenes cause?
increased activity of the product
what is the cause of excess amounts of the normal product?
duplication of the gene, viral product
what occurs in enhanced transcription?
translocation or chromosome rearrangement
what do tumour suppressor genes do?
act to inhibit cell division and suppress growth
what do tumour suppressor genes require?
loss of both alleles
give an example of a tumour suppressor gene
retinoblastoma gene
what are the inherited factors of cancer?
inherited cancer syndromes, familial cancer, defective DNA repair
what are the inherited cancer syndromes?
single mutant genes, often tumour suppressor genes, retinoblastoma, some colon cancers
what are the familial cancers?
family clusters, genes and pattern of inheritance, breast, ovary and colon
what results due to defective DNA repair
increased sensitivity to carcinogens and general increased cancer risk
give an example of a defective DNA repair cancer
xeroderma pigmentosum
what is P53?
the guardian of the genome
when does P53 act?
just before the restriction point in the cell cycle
what are the 2 main functions of P53 in response to damaged DNA
stops the cell cycle to allow DNA repair or apoptosis (if repair is not possible)
what happens to P53 during cancer?
it is often inactivated by mutation or deletion or viral proteins (HPV)
what is affected if P53 is mutated/deleted?
other cell division controls, DNA repair mechanisms, apoptosis inhibited, stimulation of blood vessel formation, destructive enzymes activated, cell motility increased
what are the hallmarks of cancer?
insensitivity to anti-growth signals, tissue invasion and metastasis, limitless replicative potential, sustained angiogenesis, evading apoptosis, self-sufficiency in growth signals
what is the process of carcinogenesis?
multistep - initiation, promotion, progression
what are the modes of spread of malignant tumours?
local spread, lymphatic spread, blood spread (haematogenous), transcoelomic spread, intraepithelial spread
what is metastasis?
the spread of malignant cells to distant organ forming secondary tumours
how do carcinomas spread?
lymphatic and later blood
how do sarcomas spread
blood (lymphatic spread is rare)
where do cancers of the lung spread to?
local nodes, liver, bone and brain
where do cancers of the tongue spread to?
neck nodes, later lung and spine
what are the steps of metastasis?
intravasation, survival in the circulation, arrest in organ, extravasation, survival of cells after extravasation, initial growth of cells after extravasation, persistence of growth
what can tumour cells do?
alter adhesion molecules, make poor basement membrane, increase protease production or reduce inhibitors, alter extracellular matrix
when talking about grading and staging, what does grade mean?
biological nature of the tumour (histopathology)
when talking about grading and staging, what does stage mean?
extent of spread (clinical)
what is grading?
a histological assessment of invasion into underlying tissue and cellular atypia
what does cellular atypia include?
mitotic activity, nuclear pleomorphism, differentiation, necrosis
what are the methods of grading?
numerical, low/intermediate/high, degree of differentiation (SCC)
what type of grading is used for squamous cell carcinomas?
degree of differentiation
what does pleomorphism cover?
variation in cell shape and size, variation in nuclear shape and size
what can be seen in cells of a malignant tumour?
numerous mitoses, abnormal mitoses, variable differentiation
what does staging mean?
the extent or severity of a persons cancer
what does knowing the staging of the cancer help?
planning treatment and estimating the persons prognosis
what is used to determine staging?
physical exams, imaging procedures, laboratory tests, pathology and surgical reports
what system is used for staging of oral cancer?
TNM
what does T stand for in TNM?
tumour size
what does N stand for in TNM?
lymph node involvement
what does M stand for in TNM?
presence of metastases
what are the clinical effects of lung cancer?
cough, haemoptysis, chest pain, pneumonia
what are the systemic effects of cancer often caused by?
cytokines or hormones released by tumour cells or dysfunction of the organ
what are the systemic effects of cancer?
fever, anorexia, weight loss/cachexia, neurological problems e.g. neuropathy, endocrine sydromes e.g. Cushings syndrome, metabolic effects e.g. hypercalcaemia
how do you treat malignant tumours?
surgery, chemotherapy and radiotherapy
what is tumour immunology?
immune surveillance
what can tumour immunology do?
suppress or enhance carcinogenesis
what is elimination-equilibrium-escape
how does the immune system recognise tumour cells
what are the tumour associated antigens?
products of mutated genes, overexpressed proteins, viral proteins, oncofetal antigens
what is elimination?
cell mediated immune response
what immune cells contribute to elimination?
CD8+, NKC (first line of defence against tumour cells), macrophages
what can immunodeficiency lead to?
an increased incidence of malignant tumours
what does elimination lead to?
escape
what is escape
how do tumour cells evade the immune response
how do tumour cells escape?
acquire molecular changes such as alter tumour antigen expression (lack of T cell recognition), activation of immunoregulatory pathways leading to T cell unresponsiveness and apoptosis, immunosuppressive factors e.g. cytokines (inhibit T cell response)
what is immunotherapy?
using the patients own immune response to control and destroy malignant cells
what are the methods of immunotherapy?
active immunisation, reversal of immunosuppression, adopted cell transfer, strengthening natural immune responses
when is immunotherapy used?
in advanced stage of disease
when is immunotherapy most successful?
in haematological malignancies
