Neoplasia Material Flashcards
Major cause of relapse in cancer?
Minimal residual disease
Ending given to:
1) benign EPITHELIAL tumor
2) benign CT tumor
1) papilloma or adenoma
2) -oma
Ending given to:
1) malignant epithelial tumors
2) malignant CT tumors
1) carcinoma; adenocarcinoma
2) -sarcoma
An abnormal pattern of tissue growth that can be precursor to neoplasia? Is it reversible?
Dysplasia
usually irreversible
T/F: neoplasia is almost always irreversible
True
Define:
1) Hamartoma
2) Choristoma
1) CT or epithelial cells found in their normal location but in a DISORGANIZED manner
2) ectopic rest of normal tissue (excess of tissue in an abnormal situation)
T/F: Neoplasms contain ONLY neoplastic cells
False (contain non-neoplatic cells too)
Name the theory:
1) “neoplasm arises from a lurking bad stem cell in the tissue”
2) neoplasm arises from cumulative alteration of a normal cell in a tissue
1) Cancer stem cell theory
2) Stochastic model
Name the 6 hallmarks of neoplasia
1) Sustained proliferative signaling
2) evading growth suppressors
3) activating invasion and metastasis
4) enabling replicative immortality
5) inducing angiogenesis
6) resisting cell death
Name 2 emerging hallmarks of neoplasia
1) deregulating cellular energetics
2) avoiding immune destruction
Name two enabling characteristics of neoplasia
1) Genome instability
2) tumor-promoting inflammation
Which cell types are more susceptible to developing neoplasia (at any age)?
Continously cycling & quiescent stable cells
Name 5 ways to achieve proliferative signaling
1) produce more growth factor
2) express more GF receptors
3) mutate the GF receptor
4) Ras mutation
5) mutate intracellular signaling cascade (Raf)
Describe the two hit model of tumor suppressor gene loss
Both alleles that code for the tumor suppressor gene are eliminated (1 congenital, 1 acquired; or both acquired)
Important tumor suppressor genes:
1) internal controllers of cell proliferation
2) contact inhibition of cell proliferation
1) RB, P53
2) NF2, APC
Over expression of this anti-apoptotic protein can lead to the development of neoplasms
Bcl-2
How do cancer cells achieve replicative immortality?
counter telomere erosion
Name 2 mechanisms by which cancer cells counter telomere erosion
1) upregulate telomerase (makes telomere longer)
2) Alternative lengthening telomere (ALT)
A cancer drug that targets VEGF would be useful for preventing what hallmark of neoplasia?
Angiogenesis
High levels of this protein are the reason newly formed vessels are unstable, leaky, and have abnormal function
Angiopoietin 2
AP1 promotes maturation
When epithelial cell metastasize, what is the first feature they lose to be able to do so?
Cell-to-cell adhesion
Cells must have what ability in order to be able to invade?
Motility
Describe the role of Stathmin in metasasis
Stathmin regulates microtubule dynamics in the cell; when mutated, it loses its ability to stabilize the tubules in the presence of ECM–>cell becomes rounded and gains amoeboid-like motility
T/F: Metastasis is a random process
False (seed & soil)
certain cancers have preferential sites of metastasis
The idea that cancer cell prefer glycolysis, even in the presence of oxygen
Warburg effect
Describe the basis for PET scans
cancer cells have upregulation of glucose transport into the cell–>PET looks for areas of increased glucose uptake
3 phases of immunosurveillance
1) elimination
2) equilibrium
3) escape
2 reasons tumors can ‘escape’ the immune response
immune exhaustion
production of immunosuppressive tumor environment
Describe the function of PD-1 in association with tumor suppression
PD-1 is a T-cell receptor used as an “off” signal; Tumor cells have a PD-1 ligand they use to bind T-cells and shut them down prematurely (to avoid apoptosis)
Cancer cells have a defect in this mechanism that detects errors in newly synthesized DNA
Mistmatch repair (MMR)
2 mechanisms by which inflammation can give rise to cancer
1) inflammtory cells increase concentrations of growth and survival factors
2) reactive oxygen species and free radicals result in genetic damage (mutations)
Birt-Hogg-Dube syndrome in german shepherds is an example of what type of cause of cancer?
Genetic predisposition
BHD syndrome is due to loss of which specific suppressor gene?
Folliculin gene
Radiation, fiber, and vaccines in cats are examples of what type of cancer of cause?
Environmental–>physical
A carcinogen is considered _________ if it or its metabolite(s) bind to DNA and cause mutations
Genotoxic
Two categories of damage that carcinogens can cause that are non-genotoxic
Cytotoxic
Receptor mediated
Vaccine-induced sarcomas in cats are an example of what type of cytotoxic effect?
sustained inflammation (and growth factor release)
The carcinogenic compound involved in bracken fern toxicosis in cattle
Ptaquiloside (PTQ)
Concerning passive smoking and cancer in pets, there are studies that show a detectable association between environmental tobacco smoke and ___________ in dogs
Nasal cancer
(NOT lung cancer)
Name 3 typical retrovirus genes
GAG, POL, ENV
Describe the 2 mechanisms retroviruses use to cause cancer
1) viral oncogenes; homologous to a cellular proto-oncogene and causes sustained proliferation
2) Insertional mutagenesis; virus inserts its genome near a growth regulatory gene and it becomes overexpressed by viral promoters when the virus replicates
Feline leukemia virus is an example of _______ _______ (mechanism of retroviruses)
insertional mutagenesis
Bovine leukemia virus contains what “oncogene”?
Tax
Two ways “Tax” in BLV affects the host’s cells
1) causes growth-factor independent proliferation
2) upregulates Bcl-2 (anti-apoptotic)
What criteria is Tax lacking to consider it a true viral oncogene?
Lacks a cellular proto-oncogene homologue
This virus establishes infections only in keratinocytes of skin or mucous membranes
Papillomaviruses
What viral genes do papillomaviruses encode to cause cancer?
E6 & E7
Describe the functions of
1) E6
2) E7
(with papillomavirues)
E6–ubiquinates p53 (causes it to be degraded)
E7–competes for binding with RB (E2F is free to push cell cycle forward)
What general mechanism do Hepadnaviruses use to cause cancer?
cause chronic inflammation
Marek’s disease (herpesvirus) encodes what viral protein to cause cancer?
Meq
Bacteria & Metazoan cause cancer mainly through generation of?
Chronic inflammation
This type of neoplasm is transmitted by coitus and will usually spontaneously regress
Transmissible venereal tumor (TVT)
3 steps of stepwise tumor development
Initiation
Promotion
Progression
Which step of tumor development involves non-mutagenic, reversible effects, and results in a benign tumor?
Promotion
T/F: All malignant neoplasms come from a benign precursor
False
Direct effects of neoplasia are more commonly associated with what type of neoplasm
malignant
Disease or symptoms that are a consequence of the presence of cancer in the body
Paraneoplastic syndrome
Name an important systemic effect of cancer
Cachexia (weight loss and debility)
A protein found in circulation of cancer patients that mediates the breakdown of skeletal muscle protein
Proteolysis-inducing factor (PIF)
Most common endocrinopathies associated with cancer?
Hypercalcemia
Hypoglycemia
MOST cases of hypercalcemia of malignancy are due to?
Secretion of PTH or PTHrP by non-endocrine neoplasms
Which cancer of dogs is frequently associated with HCM?
adenocarcinoma of apocrine glands of anal sac
Biggest problem with management of early malignant disease?
Latent period (time before mass is clinically detectable)
Which method of diagnosing neoplasia is characterized by
1) an easily obtained sample
2) rapid analysis
3) variability in ability to distinguish neoplasia from non-neoplatic lesions
Cytological (cytology)
This method of cancer diagnosis can be used to establish epithelial vs. connective tissue neoplasms and uses specific and sensitive Ab reagents
Immunohistochemistry (IHC)
gold standard for phenotyping lymphomas
Why is PARR preferred over IHC in diagnosing lymphomas?
it can be performed on cells obtained from FNA (IHC requires a biopsy)
Concerning lymphomas in dogs, gene expression profiling can be used to differentiate survival for ________ but NOT _______
T-cell lymphoma
NOT B-cell lymphoma (had similar survival times)
An objective measure of the extent of disease
Stage
Name the 3 criteria that go into staging
TNM system
1) Tumor location and size
2) Lymph node involvement
3) metastasis
Determination regarding differentiation, growth, or invasiveness based on histological features
Grade
T/F: All tumors are graded using the same criteria
False