Neoplasia IV Flashcards
anoikis
loss of adhesion to BM
extrinsic apoptosis
Fas/FasL
-FADD
caspase 8
intrinsic apoptosis
DNA damage
-mito cytochrome c
caspase 9
pro-apoptotic
BAX and BAK
anti-apoptotic
BCL-2
BH3-only proteins
sense death inducing stimuli
convergence of apoptosis pathways
caspase 3
FLIP
in tumors - prevent activation of caspase 8
p53 and apoptosis
increases BAX
BCL2 gene
protects tumor cells from apoptosis
telomerase
upregulated in tumors
angiogenesis in tumors
necessary to get larger than 1-2mm
bridge fusion breakage cycle
joining of ends of shortened chromosomes
-if cancer gets telomerase back - this can cause cells with really fucked up DNA
angiogenesis inhibitors
angiostatin
endostatin
vasculostatin
HIF-alpha
with hypoxia
-activates transcription of VEGF and bFGF
bFGF
pro-angiogenic
notch signaling
with VEGF
-regulates branching and density of vessels
p53
can stimulate anti-angiogenesis factors
mutations of RAS and MYC
up-regulate VEGF production
bevacizumab
anti-VEGF antibody
-Tx of multiple cancers
steps of metastasis through ECM
loosen tumor cell-cell interactions
degrade ECM
attachment to ECM
migration
E-cadherins
connected to beta-catenin
-disrupted with cell mestastasis
catenin
link E-cadherin to cytoskeleton
mutations in catenin - cancer
MMP
degradation of the BM and CT
ameboid migration
tumor cells squeeze through matrix
quicker
collagen IV
in BM
locomotion during metastasis
cytokine driven
platelet tumor aggregates
in bloodstream
-may favor cell survival and implant of tumor cells
CD44
on T cells and is used to migrate in lymphoid tissue
-binds hyaluronate
overexpression of CD44 may cause metastasis
most metastasis
first capillary bed they meet
breast cancer cells
secrete PTHRP
- stimulate RANK and RANK-L from osteoblast
- activate osteoclast degradation of bone matrix
clonal evolution model
as mutations accumulate
-subset of tumor cells that have right genes for metastasis arise
metastasis suppressor gene
loss of this gene promotes metastasis
metastasis oncogenes
favors development of metastasis
SNAIL and TWIST
mir335 and mir126
suppress metastasis of breast cancer
mir10b
promote metastasis
DNA repair systems
mismatch repair
nucleotide excision repair
recombination repair
HNPCC syndrome
defective mismath repair
genes MSH2 and MLH1
microsatellite instability
xeroderma pigmentosa
defective nucleotide excision repair
risk of cancers after UV exposure
blood syndrome
defective homologous recombination repair
ataxia-telangiectasia
defective homologous recombination repair
mutated ATM
-DNA damage by ionizing radiation
fanconi anemia
defective homologous recombination repair
BRCA1 and BRCA2
mutated in patients with breast cancer
stromal microenvironment
host stromal cells, ECM, and inflammation can modulate tumor growth
warburg effect
cancer cells use glycolysis
-increased need for glucose
“aerobic glycolysis”
pyruvate can be shunted to synthesis other cell constituents
mTOR pathway
stimulated by growth factors to increase glucose and AA uptake
PTEN
promotes autophagy
burkitt lymphoma
c-myc gene moved to Ig heavy chain gene locus
-causes overexpression
philadelphia chromosome
fusion of BCR-ABL genes
-from translocation
chromosome 9 and 22
constitutive kinase activity
hematopoietic malignancy
translocation
deletions
common in non-hematopoietic solid tumors
-ex. RB gene
N-myc gene amplification
in neuroblastoma
ERB-B2 gene amplification
in breast cancer
cancer cell epigenetics
global DNA hypomethylation and promoter localized hypermethylation (for tumor suppressors)
methylation
inactivates genes
evolution of colorectal cancer
mutation at APC - hyperproliferative
mutation at RAS - adenoma to intermediate adenoma
loss of tumor suppressor - late aenoma
loss of p53 - carcinoma
p53
on chromosome 17p
direct acting carcinogenic agents
no metabolic conversion necessary
indirect acting carcinogenic agents
require conversion first - usually cytochrome p450
ex/ polycyclic hydrocarbons
steps in chemical carcinogenesis
initiation followed by promotion
aflatoxin B1
from aspergillus
correlation with hepatocellular carcinoma
chemical carcinogen
sun light that causes cancer
mostly UVB
fair skinned in australia/new zealand - carcinoma and melanoma
cumulative - non-melanoma
intense intermittent - melanoma (sun bathing)
radiation induced neoplasms
myeloid leukemias
-followed by children thyroid cancer
helicobacterial pylori
gastric malignancy
HTLV1
RNA virus that causes cancer
-CD4 T cells
T cell leukemia,lymphoma in Japan and Caribbean
tax protein increases cell replication and interferes with repair
HPV
DNA viruses that causes cancer
-squamous cell carcinoma of the cervix
loss of E2 viral suppressor and over-expression of E6 and E7 oncoproteins
EBV
herpes virus that infects B cells
-B cell lymphoma in immunosuppressed patients
NOT burkitt lymphoma - this is a translocation of c-MYC
hepatocellular carcinoma
due to hepatitis virus B and C
H. pylori
gastric carcinoma
-pathway of prolonged chronic inflammation
marginal zone lymphoma
-MALToma (mucosa associated lymphoid tissue lymphoma