Cancer Flashcards
examples of post-mitotic cells
*significance: tumors not associated with these cell types
skeletal muscle, cardiac muscle, mature neurons
Highest incidence and highest mortality
- prostate/breast
- lung
- colon/rectum
1 and 2 flipped for death
Expt to prove tumor cells are monoclonal
- random X inactivation in females, tumors express one or other allele of a distinguishable gene product
cancer cell heterogeneity
At different stages in cancer progression, cells face different selective pressures that promote the survival of cells that have acquired a particular variation
CSC and therapy hypotheses
- Hierarchic CSC model - conventional therapy: CSCs are more resistant than differentiated cells to therapy and persist, quick relapse
- Hierarchic CSC model - CSC-specific therapy: in theory, CSC ablation should lead to decline of malignancy
- dynamic CSC - CSC-specific therapy: differentiated cells can reacquire CSC features through signaling from stromal cells and relapse will ensue
Warburg Effect
Even in presence of O2, cancer cells have elevated levels of glycolysis. Can take advantage of this by giving tagged glucose to see on PET scan
cyclins and CDKs of G1 to S transition
cyclin D/CDK 4 and 6
cyclin E/CDK 2
cyclins and CDKs of S phase
cyclin A/CDK 2 and 1
cyclin and CDK of G2 to M
cyclin B/CDK 1
inhibitors of cyclin D/CDK 4 and 6
p15, p16, p18, p19
inhibitors of all CDKs
p21, p27, p57
What is most severe histological feature?
anaplasia, lack resemblance to normal counterpart. not good sign!
pleomorphism
variation in cell size and shape
clonal selection and tumor progression
- clonal selection: initial mutation that confers growth advantage to cell and its progeny
- tumor progression: additional mutations that occur that give further growth advantage and account for malignant characteristics of a tumor
grading vs staging
just looking at tumor vs. looking at tumors invasiveness (use for prognosis)
lymphatic spread vs hematogenous spread
- lymphatic is common for carcinomas
- hematologic is common for sarcomas: metastasis to liver, lung, bone, and brain are common
IHC
used to determine what tissue type tumor came from, or to see if anaplasia is present keratin: epithelial vimentin: mesenchymal LCA: lymphoid S100: neural and melanocytic
flow cytometry
used to classify lymphoma/leukemia by surface antigens
- T/B cell, myeloid, degree of differentiation
- also used for apoptosis assay
FISH for cancer
detects loss of tumor suppressors, amplification of oncogenes, and translocations
PCR for cancer
assess for specific mutations
RT-PCR
RNA into cDNA
i.e. BCR-ABL fusion protein
PSA
IHC
- high false positive, secreted into blood in prostate ca
TTF1
IHC
thyroid transcription factor 1
- positive in many lung cancers, as well as thyroid cancer
myogenin
IHC
- expressed in rhabdomyosarcoma (recapitulates early muscle)
Ki67
nuclear proliferation marker
high Ki67 = low doubling time
- can sometimes be helpful
C-Kit/CD1117
- often seen in GIST (GI stromal tumor)
tyrosine protein kinase that can be mutated, cancer may be respond to Gleevac
p53 mutation and IHC
seen as positive in nuclear staining, longer half life and accumulates in cell
percentage of cancers attributable to infection in developing countries
26%
percentage of cancers familial vs. sporadic
familial: 5-10%
sporadic: 70-80%
family cluster: 15-20%
Characteristics of known carcinogen
- ca epidemiology studies
- clinical studies
- study of tissues/cells from exposed human
reasonably anticipated to be carcinogen
- multiple species
- multiple tissue sites
- multiple routes of exposure
- structurally related to known carcinogen
- similar mechanism
Oncogenic viruses
- HTLV: leukemia/lympomas
- HPV: cervical
- EBV: Burkitt’s lympoma
- HCV: liver
HPV mechanism
- E6 degrades p53
- E7 binds RB, removing its inhibitory effects on E2F –> proliferation
H. pylori
only known bacterium implicated in genesis of cancer (adenocarcinomas and gastric lymphomas)
two cytogenetic manifestations of gene amplification
HSR (FISH)
double minutes
n-Myc
commonly found in neuroblastoma
c-Myc
Burkitt’s Lymphoma
L-Myc
small cell lung carcinoma
proto-oncogene family erb B (EGFR)
80% squamous cell carcinoma of lung
50% glioblastoma
80-100% tumors of head and neck
proto-oncogene family Ras
90% pancreas
50% colon
50% thyroid
30% lung
proto-oncogene family Myc
- L-Myc: small lung cell carcinoma
- c-Myc: Burkitt’s lymphoma
- n-Myc: neuroblastoma
CML chromosomes
(9;22) abl kinase, bcr regulator
Burkitt’s Lymphoma translocation
(8;14) myc on 8 near Ig regulator on 14
Promyelocytic leukemia
t(15;17) –> treat with all trans RA to release NCOR/HDAC and allow promyelocytes to differentiate
Myelomonocytic leukemia
inv(16)
Myeloblastic leukemia
(8;21)
Ewing Sarcoma
t(11;22)
Meningioma
Monosomy 22
Retinoblastoma
del(13)(q14)
alveolar rhabdomyosarcoma
t(2;13)
synovial sarcoma
t(X,18)