Neoplasia 2 (Doc + Ppt) Flashcards
Gatekeeper or Caretaker gene?
DNA repair
caretaker
Gatekeeper or Caretaker gene?
tumor suppressor gene or oncogene
gatekeeper
Gatekeeper or Caretaker gene?
ecodes products that monitors cell death and proliferation
gatekeeper
When DNA is damaged, evading apoptosis is mediated by ____
p53 (mutated)
What is the genetic mechanism that leads to 85% of follicular B cell lymphoma?
translocation bwtn chromosome 14 and 18 that fuses the BCL-2 gene on 18 to the IgH gene promoter on 14 –> BCL2 is OVER expressed -> anti-apoptotic environment
**IgH promoter is VERY active bc it is involved in heavy chain rearrangements
Growth of a new blood vessel is required for tumors to grow over _____
2 mm
Describe what sort of molecular changes have occurred in tumor cells to allow them to sustain angiogenesis.
- mutated p53 decreases the expression of TSP-1 -> agiogenesis is NOT inhibited
- Tumor hypoxia -> decrease expression of VHL -> HIF-1alpha is not degraded -> HIF-1alpha causes VEGF production -> angiogenesis induced
What are the anti-angiogenic factors that tumors must overcome in order to inc in size?
angiostatin
endostatin
vasculostatin
Describe the significance of bevacizumab.
anti-VEGF agent that was developed in hopes of being a cure all for solid tumors
BUT it was not a cure all bc tons of tiny foci of cancer (less than 2 mm each) can have their lethal effect without sustained angiogenesis
What is TSP-1 (thrombospondin-1)?
induced by p53 and it inhibits angiogenesis
What are potent inducers of angiogeneis?
VEGF and FGF
What are some examples of syndromes caused by defective DNA repair/caretaker genes? (6)
- BRCA1 and BRCA2 assc breast and ovarian cancer
- HNPCC (hereditary nonpolyposis colorectal cancer)
- Xeroderma pigmentosum
- ataxia telangiectasia
- Bloom syndrome
- Fanconi anemia
___% of breast cancers are assc with mutations in BRCA1 or BRCA2
3%
What are the 4 steps of invasion by malignancy?
- detachment of tumor cells from e/o
- degrade basement membrane
- attachment of tumor cells to basement membrane
- migration thru interstitium
How do tumor cells detach from e/o?
- downreg E-cadherin
- mutate catenin
*E-cad is extracell “glue” and B-cat is intracell part of the anchoring complex
How do tumor cells degrade the basement membrane and ECM?
secrete MMPs (spc MMP-9)
How do tumor cells migrate thru the interstitium once they passed thru the basement membrane?
Secrete autocrine motility factor
Describe the pattern of colon cancer metastases.
-> lymph nodes -> liver
Describe the pattern of prostate and breast cancer metastases.
-> lymph nodes -> bone
What is the mechanism of metastatic organ tropism (aka movement of cancer to a different organ)
differential conc of adhesion molecule expresson on endothlium of diff organs and chemokines (CXCR4 and CCR7)
What is the significance of tumor embolism?
tumor cells invade veins -> right heart -> lungs -> clot forms -> clot organized by fibroblasts -> pulmonary hypertension -> right heart failure
What are the categories of chemical carcinogens?
promoter, initiator, direct, or indirect
What type of carcinogen causes a mutation that are reversible in the cell but are irreversible in the progeny if it is not repaired?
Initiators
What type of chemical carcinogen causes reversible proliferation (aka induces proliferation not causes mutation)
promoter
What type of chemical carcinogen are reactive electrophiles?
direct
What type of chemical carcinogens require metabolic activation? (commonly by CYP450s)
indirect
What are the 3 most common and important chemical carcinogens in Dr. Nichols’ world?
estrogen
anti-cancer drugs
alcohol
What are the microbial carcinogens listed in the doc and what type of cancer do they cause?
- HPV: uterine cervival, mouth , upper GI
- HCV and HBV: liver
- EBV: lymphoma (in immunocompromised)
- H. pylori: stomach and lymphoma
What immune cells are the principle effectors cells of the immune system that mediate a response to a tumor?
CD8 T cells (secondary = NK cells, macrophages, and Abs)
What does the immune system recognize in defense against tumors?
- Tumor Ags
- mut oncogene products and other mut gene products
- overly or abnormally expressed protein
- oncogenic viral protéins
- oncofetal protein
- altered self cell surface glycolipids and glycoprotiens
What are examples of oncofetal Ags that are recognized by CD8 T cells?
CEA and AFP
What are examples of altered self cell surface glycoproteins and glycolipids that are recognized by CD8 T cells?
CA-125 and CA-19-9
How can tumors resist the immune system? (8)
- selective growth of Ag-negative cells
- dec MHC
- no costimulatory molecules made
- Ag masking
- make TGF-beta
- engage CTLA-4 (T cell inhib receptor)
- activate T regs\
- express FasL which can engage Fas receptor on immune cells to kill them
What are direct effects (négative ones) that benign tumors can have? (5)
- cause obstruction
- secrete hormones
- ulcerate -> bleeding -> infection
- infarct
- rupture
What is the term for symptoms not attributable to direct effects of tumors?
paraneoplastic
T or F: Cachexia is a paraneoplastic condition
F
Paraneoplastic condition arise in ___% of cancer pts.
10%
What is Cachexia?
catabolic state of severe wasting that is mediated by TNF
What is the most common paraneoplastic condition?
Hypercalemia
What are the symptoms of paraneoplastic hypercalemia?
nausea, vomiting, and altered mental status (disorientation, lethargy, seizures)
T or F: Paraneoplastic syndroms manifest in the more progressive phases of cancer?
F: they can be the earliest manifestation of occult tumor
T or F: paraneoplastic syndroms are never fatal
F: they can be fatal
T or F: Paraneoplastic conditions can mimic metastatic disease
T
What is cushing syndrome? What causes it? (assuming the paraneoplastic kind)
pituitary adenomas or small cell carcinoma of the lung that make ACTH
causes. ..
- weight gain (central obesity)
- inappropriate antidiuretic hormone (SIADH)
- hypoglycemia
- carcinoid syndrome (serotonin)
- Eaton-Lambert syndrome
What consists of attacks of cutaneous flushing?
carcinoid syndrome
Cancer causes a _____ state.
hypercoagulable
What is the différence between cancer stage and cancer grade?
stage = anatomical extent of tumor (size and spread)
Grade = extent of tumor cell differentiation
T or F: Stage carries far more prognosis than grade.
T
What are examples of tumor serum markers?
PSA CA-125 CA-19-9 HCG AFP CEA Igs
What is a tissue sample obtained by surgical or endoscopic forceps, incision, or excision?
Biopsy
What is a sample of cells exfoliated or aspirated from te body?
cytology
_____ gene directly control tumor growth
Gatekeeper
_____ genes affect genetic stability
caretaker
Are BRCA gene gatekeepers or caretakers?
DNA repair genes = caretaker
What is the difference between normal and cancerous glandular tissue of the breast?
Cancer = 1 layer of cells Normal = 2 layers of cells
What tumor cell surface receptors mediate invasion into tissues?
Laminin and fibronectin receptors
What mediates migration of tumor cell migration (after it breaks thru the basement membrane?
Secretion of autocrine motility factor and fibronectin
What chemokines mediate metastases in breast cancer?
CXCR4 and CCR7
What is the difference between initiators and promoters?
Initiators cause irreversible mutations in progeny if not reversed in mutated cells while promoters cause reversible proliferation of initiated cells
T or F: radiation exposure causes cancer almost immediately after the exposure
F: it has long latent periods before cancer develops (years to decades)
What type of malignant tumors does radiation cause?
Sarcomas
Nuclear power plat leaks cause what kind of cancer?
Thyroid
What is the mechanism of paraneoplastic hypercalcemia?
Parathyroid hormone related protein (PTHRP)
What is the treatment for paraneoplastic hyperkalemia?
Hydration and bisphosphates
What is the most common type of lung cancer type to cause hypercalcemia?
Squamous cell carcinoma
**microscopically seen w/ keratin pearl
What tests are run on biopsies?
Immunohistochemistry
Flow cytometry
Molecular testing
