Neoplasia 2 Flashcards
What are the markers of differentiation of neoplastic cells?
-
Cell morphology:
- - neoplastic cells often lose any recognizable gross & histological appearance. -
Cell function:
- - usually lost in malignant tumors.
- - regulatory mechanisms are lost. -
Cell Behavior:
- - increasingly aggressive with loss of differentiation and function.
Species differences in tumor function:
Example: Granulosa Cell tumor
Which type of animals are prone to these tumors.
Comment on Granulosa cell tumors of the Mare.
- Balance of hormones is important
- Many produce steroids
- estrogen
- testosterone
- progesterone
- example: Mares with graunulosa cell tumor will produce and over-secrete testosterone causing anestrous, nymphomania, stallion like behavior.
- Granulosa cell tumors are common in large animals. They are usually non malignant and rarely metastasize.
Discuss the events occuring when a bitch has a granulosa cell tumor.
- +/- malignancy
- Produces:
1. Estrogens: therefore prolonging estrus.
and
2. Progesterone: causing
**– Cystic Endometrial Hyperplasia
– Pyometra. **
What are some histological feature of malignancy?
- neoplastic cells will have a **LARGE NUCLEUS with prominant nucleoli. **
- - Nucles is pale and shows ANISOKARYOSIS which is variability in nucleus size. - **Increased mitosis and abnormal mitotic figures. **
Mitotic figures are black and fuzzy shaped (normally they are symmetrical)
Summarize the histological features of malignancy:
- Large open, pale nucleui with prominant nucleolus.
- Increased Mitosis
- Abnormal mitotic figures
- Multiple Nucleoli in a single nucleus.
- Bizarre cells
Benign vs. Malignant rate of growth:
Cell population may increase due to increased proliferation or decreased cell death.
Normal checkpoints in the cell cycle are used to ensure normal cells are being formed.
- G1S checkpoint
- G2M checkpoint
Proliferative Activity: Normal versus tumor cells.
What is the most effective way tumor cells are produced?
Most mature tissues are made up of labile, stable, and permanent cells. The most effective way to increase proliferation of cells (rapid growth) is to resume quiescent stable cells in the G0 phase back into the cell cycle.
What are the Mechanims of tumor growth?
- Altered proliferation potential
- - can shorten the cell cycle
- - convert quiescent cells into dividing cells (stable –> labile) - neoplast cells can:
**a. escape normal limits on cell division.
b. independent of external growth factors
c. not susceptible to apoptotic factors**
therefore: increase in cell #’s
3. re express telomerase:
- - **enzyme allowing replication and expansion of telomeres
- - important in immortality. **
4. Growth modulation in normal tissue
- - constant transfer of information between cells ( can be inhibitory, stimulatory, hormonal transfers)
5. Neoplastic cells lose dependence
**– They are not responsive to needs of whole organism.
- They drive their own replication **
6. Neoplastic cells are resistant to apoptosis.
- They drive their own replication **
**– functional inactivation of p53 gene. **
- overall growth rate increased.
- activate survival signalling pathways (independent of exogenous sruvival factors)
- inactivate death factor signalling pathways ( evade apoptosis)
Telomerase:
- Telomerase is the enzyme that allows telomere replication.
- Embyronic cells express Telomerase
- Extreme ends of DNA templates (telomeres) not duplicated at cell divison. This means that very short telomeres cannot divide. A signal that the cell is close to its death.
- Neoplastic cells often regain the ability to produce telomerase therefore the telomerese do not shorten, no signal for cell death, cell keeps dividing, and IMMORTALITY.
Apoptosis:
What is its physiological purpose?
How is it pathologically induced?
- normally allows tissue homeostasis.
- Pathologically induced:
a. withdrawal of survival factors
b. binding of death factors
- - Fas ligand
- - TNF- alpha
c. hypoxia
d. DNA damage
- p53
e. cytotoxic immune cells
- T lymphocytes
- NK cells
- Caspases (intracellular proteases) are final effectors.
What are morphological markers of apoptosis?
- margination of chromatin
- condensation and fragmentaiton of nucleus
- Condensation of cells with preservation of organelles.
Tumor growth:
What occurs as the tumor cell population increases?
• As the tumour cell population expands a higher percentage of cells leave the replicative pool by reverting to G0, differentiation and death.
Carcinogenesis:
Tumors arise from clonal growth of cells which ahve mutations in 4 classes of genes:
- Cell Growth regulators
- proto oncogenes
- tumor suppressor genes - Apoptosis regulators
- DNA repair regulators.
What are other important growth factors in tumor growth?
- Blood supply
- Extrinsic growth regulating factors
- Efficacy of Host immune response
- emergency of sub populations of aggressive tumor cells.
Comment on the latency period in tumor growth.
Animal can have a tumor for a long time before it become clinically apparent. By the time it is clinically apparent it is already too late and near the death stage.
The Process:
1 normal cell transforms into a single tumor cell.
The single tumor cell undergoes 30 doublings and becomes the smallest clinically detectable mass ( 1 gram)
From there the cell only have to undergo 10 more doublings before it becomes the maximum mass (10^12) compatible with life. At this point it is already too late to tx effectively.
