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Name some growth factors and hormones that stimulate cell growth?
EGF, VEGF, G-CSF
What are mitogens?
Interleukins that stimulate proliferation of lymphocytes
What are the phases of the cell cycle?
- G1= growth phase
- S= DNA synthesis
- G2= growth phase 2
- M= mitosis
What is known as the resting phase?
G0, rest or non-cycling cells
WHat is prophase?
chromatin condensation, mitotic spindle
What is prometaphase?
movement of chromosomes to middle of cell
What is metaphase?
Further condensation and alignment at central axis, two chromatids per chromoson
What is anaphase?
segregation/migration of chromatids towards opposite poles
What is telophase?
migration complete and they disperse, nuclear membrane forms
What is a neoplasm?
A clonal process that results in heterogeneity, unregulated proliferation that becomes autonomous
What two forms of gastric cancer are assoc. with H. Pylori?
Gastic carcinoma and gastric lymphoma
What are some descriptors or epithelial dysplasia (also in malignant neoplasms)
- 1. Nuclear pleomorphism
- 2. Hyperchromatic nuclei
- 3. Large nucleoli
- 4. Inc nucleus-to-cytoplasm ratio
- 5. High rate of adnormal mitosis
What is epithelial dysplasia known as in cervix?
Cervical intraepithelial neoplasia
Dysplasia in the skin?
What are two important factors in cancer success?
- 1. Transformed cell
- 2. Assoc. stromal cells
A neoplasm consists of ?
Parenchyma (tumor cells) and stroma (assoc. non-tumor cells)
Malignant tumors with the prefix sarcoma means?
They have little connective tissue stroma, so they are fleshy
Malignant tumors with the prefix carcinoma means?
Derived from any of the three germ layers
What is the benign counterpart of melanoma?
What is choristoma?
mophorphologically normal tissue in the wrong place
What is a hamartoma?
mass of disorganized buy mature cells/tissues normal to the specific site
Tumor growth rate depends on three factors?
- 1. The doubling time of tumor cells (109 doubling needed for clinical detection of tumor)
- 2. fraction of tumor cells that are in the replicative pool
- 3. Rate of cell shedding or death
Metastasis has routes, what are they?
Lymphatics: sentinenl lymph node "1st node that receives flow from primary tumor"
Hematogenous: veins more likely to liver lungs and vertebrae
Direct seeding of body cavities: pertioneal cavity most common
Name the seven fundamental changes of malignant phenotype?
- 1. Self-sufficiency in growth signals
- 2. Insensitivity to signals that inhibit growth
- 3. Resistance to apoptosis
- 4. Defects in DNA repair
- 5. No limits on replicative potential
- 6. Sustained angiogensis
- 7. can metastasize
How many alleles need to be damaged to convert protooncogenes to oncogenes?
How many alleles to make a tumor suppressor gene stop growth inhibition (p53, Rb)?
Genes that regulate apoptosis need one or both alleles damaged to stop regulation of apoptosis?
One or both
Genes involved in DNA repair need how many alleles damaged to go haywire?
What is central to malignant transformation?
Cell cycle control loss of normal
What is the Rb gene in charge of?
Cell cycle restriction point
Loss of function of both copies of Rb gene is seen in these cancers?
- 1. Retinoblastoma
- 2. Osteosarcoma
- 3. Lung-small cell carcinoma
- 4. Adenocarcinoma
- 5. Bladder carcinoma
What is a major cause of genetic instability in cancer cells?
Defect in cell cycle checkpoint components
What is the first checkpoint in the cell cycle?
regulated by p53, evas DNA damage, if not repaired cell death is initiated
What is the second checkpoint in the cell cycle?
Check quality of new DNA, p53 or other tumor suppressor genes work here
Name some other tumor suppressor genes?
E-cadherin: cell adhesion (carcinoma of stomach)
APC/B-catenin: signal transduction regulation (carcinoma stomach, colon, pancreas; melanoma, Familial adenomatous polyposis coli/colon cancer)
RB1: regulation of cell cycle (retinoblastoma)
What syndrome is assoc. with mutated suppressor gene p53?
Li-Fraumeni syndrome: Inheritance of one bad p53 allele makes an individual 25 times more likely to have cancer by age 50 yrs
Which genes in HPV interfere with cell cycle regulation?
What are koilocytes?
Infected keratinocytes with perinuclear clearing
What are the precursors to HPV-negative SCC?
- 1. loss of cell polarization
- 2. Expansion and crowding of basal layer, budding bulbous rete ridges
- 3. Disturbance in cell differentiation (premature differentiation or lack of it)
Some uncommon types of oral SCC?
- 1. Verrucous (shiny carpet)
- 2. Spindle-cell
- 3. Papillary
What chemo med for SCC?
What are some biologicals in trial phase for SCC?
- 1. Cetuximab (blocks EGFR)
- 2. STAT3 Inhibitor
What are the two vaccines for HPV?
Gardasil (types 16,18,6,11)
Cervarix (types 16,18)
HPV positive SCC is more susceptible to chemo and radiation