Cellular Basis of Cancer Flashcards
neoplasia oncology benign malignant anaplasia
neoplasia= new growth
oncology= study of tumors or neoplasms
benign= localised growth that will not spread to other sites
malignant tumors= destroy surrounding tissue structures and spreads to other sites. grows rapidly, uncapsulated, consists of different types of cells.
anaplasia- lack of differentiation
benign vs malignant tumours and their potential to spread
benign tumours grow and compress on local structures but do not spread to distant sites
malignant tumours can invade and destroy adjacent structures and spread to distant sites
how might tumours spread?
lymphatic spread- sentinel node is the first node in the regional lymphatic basin that receives lymph flow from the primary tumour
tumours can spread with direct seeding of body cavities.
what are some examples ofcarcinogens
environmental factors infectious agents smoking alcohol consumptions diet obesity environmental carcinogens age acquired predisposing conditions chronic inflammation and cancer precursor lesions and cancer (Barretts oesophagus) immunodeficiency states
what are some example of microbial carcinogenesis?
oncogenic RNA viruses (human T cell leukaemia virus type 1) oncogenic DNA (HPV) Epstein Barr Virus (Burkitt lymphoma)
hallmarks of cancer
- sustaining proliferative signalling
- evade growth suppressors
- activating invasion and metastasis
- enable replicative immortality
- inducing angiogenesis
- resisting cell death
- sustaining proliferative signalling
what are oncogenes?
oncogenes promote autonomous cell growth in cancer cells
(stuck on acceleration)
proto oncogenes are unmutated cellular counterparts.
tumor supressor genes
tumour suppressor genes usually apply breaks to cell proliferation. abnormalities in these lead to failure of growth inhibition
- two-hit hypothesis (RB)
- p53 central monitor of stress in cell
p53- Li Fraumeni syndrome
two hit hypothesis
two mutations involving both alleles of a tumour suppressor gene (RB) = retinoblastoma
familial- inherit one defective copy (first hit) and the other copy is normal.
sporadic cases- both normal RB alleles. undergo somatic mutations
Lynch syndrome
linked with colon cancer and endometrial cancers
mismatch repair defect leads to a microsatellite instability (tandem repeats)
staging cancer
tumor size
the extent of spread to regional lymph nodes
presence of absence of blood-borne metastasis
diagnosis of cancer
clinical data
radiological images
cytology / FNA
histology: tissue scretions processed and sustained with haemotoxyline and eosin
immunohistochemistry categorisation of undifferentiated malignant tumors site of origin flow cytometry hereditary predisposition (BRcA1)
cancer definition
uncontrolled proliferation of cells that arise from virtually any cell type in the body
normal cell cycle
G0 phase= quiescent phase
G1 phase= growth phase. organelles duplicate
*G1 checkpoint
S phase= synthesis of DNA
G2 = growth and prepares for M phase
*G2 checkpoint
M phase= mitosis. the cell divides into 2 identical daughter cells.
can re-enter or go into G0
cyclins and CKDS
these drive the cell cycle.
in G1, CKD 4 and 6 are produced. cyclin binds to CDK which causes a reaction of E2F and Rb spitting. this allows progression to the S phase.
S phase produces another CDK1/2 and cyclinA
G2 CDK 1 and Cyclin B
- too low cyclin= does not progress
- too much cyclin= continuous growth/proliferation
cancer mutations
- point mutation (single change in nucleotide)
- DNA amplification. (a certain gene is amplified many times)
- chromosomal rearrangement
- epigenetic modifications (silence / more active DNA genes)
* ACTIVATION OF ONCOGENES (RAS, MYC gene)
* INACTIVATION OF TUMOR SUPPRESSOR GENE (p53, BRACA1/2)
Oncogene activation
RAS
cell normally contains the RAS gene which makes the RAS protein
next to it is a growth factor receptor.
growth factor stimulates growth factor receptor which activates the RAS protein.
RAS protein causes a cascade of intracellular phosphorylation
this activates a transcription factor which will read the DNA gene to make proteins for cell growth (cyclin and CDK)
*if there is a mutation in the RAS gene you make genes that are always active= cascade of phosphorylation = overproduction. stuck on acceleration.
oncogene activation
MYC gene
MYC gene is important for cell growth and cell survival.
mutation= more of this.
Tumour suppressor gene
p53
if there is damaged DNA the cells make p53 for cell arrest like p21.
p21 usually causes cell arrest by inhibiting the CDK and cyclins (inhibits the drivers of the cell cycle)
p53 makes cells for apoptosis
***if there is inactivation of tumour suppressor gene then there is no surveillance of abnormal cells. no cell arrest or cell repair or apoptosis.
immunological surveillance
natural physiological function to recognise and destroy transformed cells before they grow into tumors.
Tumors can inhibit t cell recognition, t cell function
central tolerance: newly formed T cells udnergo screening in the thymus. self peptides are removed. prevents attacking self.
however tumor cells are seen as ‘self’ so it’s not good for attacking/detecting these.
peripheral tolerance
Anergy - renderedanergic(unresponsive)
May have the potential for self-reactivity
Activation Induced Cell Death (AICD) - Presentation of common proteins such as haemoglobin by APC leading to deletion
Immunological ignorance - Auto-reactive T cells may never come in contact with their auto-antigen
Sequestration - Prevention of antigen contact
(across a blood-brain barrier) eg. myelin
HPV caccine
cervarix type 16,18
gardasil type 6 , 11, 16, 18
offered to girls 12-13 y/o
immunise before sexually active
