neoplasia I&II

Question 1

differentiation

Answer 1

neoplastic cells resemble normal tissue - more likely to be benign and not spread if well differentiated

Question 2

anaplasia

Answer 2

lack of differentiation - malignancy hallmark

Question 3

dysplasia

Answer 3

disordered growth

Question 4

pleomorphism

Answer 4

variation in size and shape

Question 5

benign tumors

Answer 5

• remain localized

- do not spread - no invasion

Question 6

malignant tumors - cancers

Answer 6

• invade and destroy - metastasize
• grow rapidly
• dysplasia
• pleomorphism

Question 7

oncogenic RNA viruses

Answer 7

human T cell leukemia virus type I (HTLV-2)

-pro growth and pro genomic unstable proteins

Question 8

oncogenic DNA viruses

Answer 8

HPV, epstein barr, Hepatitis B and C

-HepB,C –> chronic inflammation and hepatocyte death

Question 9

H. Pylori - bacteria

Answer 9

stomach cancer due to chronic inflammation and endothelial cell proliferation

Question 10

what mutation can constitutively activate cell proliferation?

Answer 10

RAS mutation

• Myc
• cyclin D

Question 11

tumor suppressor genes - 2 hit hypothesis

Answer 11

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

Question 12

what are the main tumor suppressor genes?

Answer 12

p53 and retinoblastoma (RB)

Question 13

Retinoblastoma

Answer 13

• 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

Question 14

telomeres

Answer 14

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

Question 15

Warburg effect

Answer 15

cancer cell rely heavily on glycolysis –> need glycolytic intermediates for rapid growth
-even with excess O2, still run glycolysis instead of TCA

Question 16

angiogenesis

Answer 16

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

Question 17

hypoxia stimulation of VEGF

Answer 17

HIF-1alpha

• normal O2 –> hydroxylated –> degraded by proteasome
• hypoxia –> not hydroxylated –> stimulate VEGF gene transcription

Question 18

how do cancers evade the immune response?

Answer 18

can upregulate PDL-1 ligands binding to the PD-1 receptor on T cells suppressing the immune response

Question 19

role of inflammation in cancer

Answer 19

• can increase the risk for tumor development
• ex. IBD, pancreatitis, COPD, Barrett’s esophagus
• aspirin helps prevent colon cancer (Lynch syndrome)

Question 20

paraneoplastic syndromes

Answer 20

cannot be explained by location or tissue

• Cushing syndrome - excess corticotropin –> pituitary tumors (ademos) or small cell lung carcinoma
• hypercalcemia - most common

Question 21

traditional chemo

Answer 21

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

Question 22

target chemo therapies

Answer 22

specific molecular targets

• tarceva - EGFR
• Herceptin - HER2 (breast)
• Imatinib - BCR-ABL