Neoplasia Flashcards
benign tumors
often encapsulated, surrounded by fibrous sheath of connective tissues; well-differentiated and morphology of normal cell
malignant tumors
variation in size and shape, nuclear/cytoplasmic ratio and are poorly differentiated
anaplastic
have lost differentiation markers
pleomorphism
variation in size and shape
hyperchromasia
increased DNA
cancer development
normal –> hyperplasia –> dysplastic growth –> carcinoma in situ –> invasive malignancy –> metastasis
benign
cells deviate only minimally from normal cells but in excessive number; hyperplasia and metaplasia
hyperplasia
appear normal but with excessive number of cells
metaplasia
displacement of normal cells with a normal cell type but in wrong spot
dysplasia
abnormal appearance and growth rate (cancer precursor)
carcinoma in situ
early form of cancer that is defined by the absence of basement membrane invasion
invasive cancer
cancer cells have breached the basement membrane
metastasis
cancer cells have migrated to distant sites
oncogene
a gene that transforms cells; cancer-inducing
tumor suppressor gene
constrains cell proliferation; loss leads to cancer
loss of p53
decreased apoptosis –> cancer
loss of APC
decreased cell cycle control -> cancer
kras mutation
oncogene is constitutively expressed
APC pathway
APC normally inhibits beta-catenin –> if lost, beta-catenin will remain on and increase proliferation and decrease differentiation
GAP inhibition
GTP is always bound leading to constitutive Ras activation
intratumor heterogeneity
not all cancer cells inside the same tumor have same behavior
interpatient heterogeneity
same cancer in different patients but tumors are heterogeneous
altered metabolism in cancer cells
will express PK-M2 to slow conversion of PEP to pyruvate, allowing glycolysis intermediates to build up and be used for NT synthesis; will express LDH for formation of lactate; take up more glucose for more energy
initiation
cause DNA mutation; effect is irreversible
promotion
induced by compounds (skin irritant, TPA) or endogenous conditions (hormones) that promote proliferation of cell giving rise to larger number of cells carrying mutation; NO EFFECT unless cell has been treated with initiator
progression
acquisition of further mutation by exposure to initiator or repeated promoter exposure
examples of initiator
cigarettes, red meat, radiation, ROS, alkylating agents
examples of promoters
cytotoxic or mitogeni agents (ethanol), estrogens, androgens, chronic inflammation
initiator only, single exposure
no change
promoter only, multiple exposures
no change
initiator + multiple promoters
papilloma
initiator + promoter in different area
no change
initiator + multiple promoters and then removal of promoter
papilloma regresses
initiator + continuous promoter exposure
advanced papilloma, even after promoter removal
papilloma + initiator
carcinoma
Cox-2 inhibition
shown to suppress development of carcinoma, indicating inflammation association
parenchyma
tumor classification and biological behavior
reactive stroma
modulate tumor growth and spread (connective tissue, blood vessels, fibroblasts)
invasion into distant sites
EMT transition for intravasation into vessels to travel to new place –> MET transition to set up colony once at new place
EMT
loss of E-cadherin and catenin, gain of vimentin and fibronectin; activation of snail, slug, twist
role of stroma in EMT
secretes growth factors such as EGF, HGF, TGF, FGF
angiogenesis in cancer
increase in HIF-1A leads to stimulation of VEG-F to make new blood vessels
macrophages in angiogenesis
produce IL-8 and VEGF and release MMPs to liberate angiogenic factors
properties of tumor vessel
higher permeability, increased leakage, more dense, more fragile, not many pericytes
avastin
VEGF antagonist (monoclonal antibody) to decrease angiogenesis
sunitinib
VEGF receptor antagonist that inhibit receptor tyrosine kinase activities
interferon
blocks IL-8 in kaposi sarcoma
