neoplasia I&II Flashcards
differentiation
neoplastic cells resemble normal tissue - more likely to be benign and not spread if well differentiated
anaplasia
lack of differentiation - malignancy hallmark
dysplasia
disordered growth
pleomorphism
variation in size and shape
benign tumors
- remain localized
- do not spread - no invasion
malignant tumors - cancers
- invade and destroy - metastasize
- grow rapidly
- dysplasia
- pleomorphism
oncogenic RNA viruses
human T cell leukemia virus type I (HTLV-2)
-pro growth and pro genomic unstable proteins
oncogenic DNA viruses
HPV, epstein barr, Hepatitis B and C
-HepB,C –> chronic inflammation and hepatocyte death
H. Pylori - bacteria
stomach cancer due to chronic inflammation and endothelial cell proliferation
what mutation can constitutively activate cell proliferation?
RAS mutation
- Myc
- cyclin D
tumor suppressor genes - 2 hit hypothesis
both alleles have to be affected/mutated to cause cancer
- 1st mutation in a tumor suppressor allele (usually point mutation)
- 2nd mutation in other allele –> turn off tumor suppressor –> proliferation
what are the main tumor suppressor genes?
p53 and retinoblastoma (RB)
Retinoblastoma
- growth factors (EGF,PDGF) –> hyperphosphorylate RB –> release E2F –> bind to TF to stimulate S phase –> cell cycle progression
- growth inhibitor (TGFbeta, p53) –> hypophosphorylation of RB –> E2F remains bound –> stay in G1 phase and do not progress
- cyclin D/CDK4,6 –> initial phosphorylation
- cyclin E/CDK2 –> hyperphosphorylation
telomeres
DNA on the ends of the chromosome
- degrade over time through cell divisions
- progressive loss of tumor suppressor genes
- chromosome breaks and fusions
- cancer cells –> acquire telomerase –> rebuild telomeres to prevent degradation
Warburg effect
cancer cell rely heavily on glycolysis –> need glycolytic intermediates for rapid growth
-even with excess O2, still run glycolysis instead of TCA
angiogenesis
sprouting of blood vessels from new endothelial cells
- when cells do not receive enough O2/circulation
- release VEGF –> form tip cell, stalk, tube –> fusion of blood vessels
- high VEGF release in cancer cells –> more permeable
hypoxia stimulation of VEGF
HIF-1alpha
- normal O2 –> hydroxylated –> degraded by proteasome
- hypoxia –> not hydroxylated –> stimulate VEGF gene transcription
how do cancers evade the immune response?
can upregulate PDL-1 ligands binding to the PD-1 receptor on T cells suppressing the immune response
role of inflammation in cancer
- can increase the risk for tumor development
- ex. IBD, pancreatitis, COPD, Barrett’s esophagus
- aspirin helps prevent colon cancer (Lynch syndrome)
paraneoplastic syndromes
cannot be explained by location or tissue
- Cushing syndrome - excess corticotropin –> pituitary tumors (ademos) or small cell lung carcinoma
- hypercalcemia - most common
traditional chemo
non-specific - kills all types of cells, not just cancer cells
- DNA damaging, DNA/RNA synthesis inhibitors
- ex. cisplatin, gemcitabine, 5-FU
- hair loss & GI
target chemo therapies
specific molecular targets
- tarceva - EGFR
- Herceptin - HER2 (breast)
- Imatinib - BCR-ABL
