Cancers Flashcards
Meta plastic
Replacement of one cell lineage with another
Dysphasia
Abnormal tissue architecture
Cancers neoplasia
Forms new tissues / neoplasm
Benign mild dysplasia restricted to one location
Malignant cells invade other tissue highly dysplastic
Chronic myeloid leukaemia
Philadelphia chromosome
Chromosome 22 cut and bound to 9
BCR and ABL rearrangement and expression of fusion protein
The fused product is deregulated stimulation the production of leukaemia cells.
Gleevec
Treatment for CML
RB knock out
Requires 2 hits of mitosis recombination
Hyperplasia
Excessive growth
RTK
Receptors dimerise causing a conformational change and transphosphorylate together at the c terminal removing the activation loop from the catalytic cleft
Deregulation of RTK
Mutations can cause it to not require a stimulus to signal causing the cell to constantly grow
Raw
Cell cycle control
Allows the cell to proliferate if no mitogen is present
Small gtpase catalysed by GEF and inactivates by GAP
GEF
Catalyse exchange of gdp for gtp
GAP
Catalyse exchange of gtp for gdp
Ras mutations
Mutation at gly12 causes valine to be there instead so gtp cannot be hydrolysed
SH2
Binds to the RTK phosphate before binding sh3 and sos to plasma membrane
SOS
Ras GEF
RAS induced proliferation
GTP bound form exposes a loop which binds molecules such as RAF p13k
RAF induces the MAPK pathway
GF RTK RAS RAF MEK ERK pathway
Brings cells out of G0 and into the cell cycle
Rb
Regulates cell cycle at the R point
TGF beta
Regulates cell cycle until Rpoint as a growth inhibitor
P53
Tumour suppressor gene
Monitors three stages of cell cycle
G1
S
G2
Blocks continuation if DNA damage is detected or if replication is incomplete
Cycling and CDK
Conserved alpha helix binding
Responsible for substrate recognition
Cyclin D
Present when mitogens bind
Inactivation of RB
Cyclin CDK hyper phosphorylated
P13K
Stimulated by IGFR RTK
Generates second messenger pip3
Which phosphorylated akt at the membrane by
P53 mutations
Missense
Often in dna specific binding domain
Mdm2
Conjugated ubiquitin to p53 which is then degraded
Blocked by atm and atr
Nutlin
Mdm2 mimetic
SV40
Codes for oncoprotein that inhibits p53 and pRB
Tolomerase
TTAGGG enzyme
Prevent Philadelphia chromosome
GRN 163l
Prevents telomerase extension
Hypoxia
Hif1 alpha binds beta causing transcription of VEGF
Normoxia
Proline hydroxylase adds oxygen to th proline residues on hif1 alpha then pvhl poly ubiquitylation then causes it degradation
Angiogenesis
Peri sites move away from the capillary before the basement membrane breaks down and migrate to the peri vascular space before proliferating and adhering to each other then everything adds itself to it again
Treatment for angiogenesis
Inhibit the cascade or block the ability of endothelial cells to break down the matrix
Or anti VEGF antibodies block its binding
Endostatins inhibit cell growth
Sources of energy I. Tumour cells
Glycolysis
Gluatmineolysis replenishes citric acid intermediates
E cadherin
Present in epithelial cells crosslinking actin by the c terminus
Very low level present in carcinoma
Invadapodia
Actin polymerisation forms a protrusion into the basement membrane mediated by arp23 and cdc42
Matrix metala pro teases then released from the ends of the filaments and expand the gap in the basement membrane
RGD
Interferes with integrin binding to the ecm preventing metastasis
Rho GTPase
Members of the Ras superfamily
Can be sequestered in membrane by GDI
Intrinsic inflammatory pathway
Activated by various oncogenes such as RAS or EGFR
Chromosomal rearrangement in the absence of a suppressor gene and create a inflammatory micro environment
Extrinsic
Inflammatory conditions augment the risk of cancer
Pathways convergence
Activate transcription factors such as Nfkb and hif1 and produce cox2 resulting in activation of leukocytes and the cytokines then activate the inflammatory pathway
Chronic liver inflammation
NSAIDs and anti TNF alpha drugs highly reduce incidence
Veclade
Inhibits the proteasome by interfering with the degradation of iKB triggering apoptosis as the Nfkb cannot be broken down
NSAIDs such as aspirin
Reduce incidence of cancer as prostaglandins cannot be formed properly