T2 - Neoplasia 4 - Moroz/biology Of The Neoplastic Cell

Front 1

differentiated vs. undifferentiated - which has a worse outcome? what about speed of differentiation? How can you tell speed (lecture objective)

also, how do you tell DNA index?

Back 1

recall that benign tumors are always well-differentiated, and that malignant tumors are usually not well differentiated or completely not - so undifferentiated is bad.

speed of growth is weird - the faster it grows, the better it'll respond to drugs. So a fast growing, well-differnetiated cancer sounds like the best option.

speed of differentiation can come from immunohistochemistry, cell sorting, counting cells in mitosis, mitotic index, PCNA, etc.

DNA index =
sample cells in G0/G1 divided by STANDARDS in Go/G1.

If 1, have diploid (46n)
if 2, have tetraploid (92n)
if .5, haploid = 23n
anything else = anuploidy.

Front 2

outline the cell cycle, the important phases, and regulators of it:

Back 2

most cells in quaiscent G0 phase.

for this class, we get to combine G1 and S into one phase, and G2/M into a second.

CyclinD/CDK4 and CK6 control the G1/S checkpoint. Note that p53, the tumor suppressor, is capable of arresting the cell at BOTH.

Cip/Kip, as well as INK4/ARF are INHIBITORY pathways.

CyclinD and CDK overexpression are DRIVERS of cell division.
note that MYC can drive cell division, but I think it's through transcription of polymerases more than it is controlling cell cycle checkpoints.

Front 3

objective - what's a labile cell? what about quiescent? what's permanent?

Back 3

labile = cells that divide throughout life, don't spend much time in G0 phase. relatively rare, include GI cells and bone marrow cells (RBC's)

Permanent cells - don't have the ability to multiply. I'd guess nerve and striated muscle?

Quaiscent cells - arrested in G0, able to replicate when given stimuli to do so. Most of the body's cells are like this.

Front 4

Apoptosis - what are the characteristics of apoptotic cells and compare the phenomenon to necrosis -

Back 4

apoptotic cells have BLEBBING later on.

first, get cytosol condensation and chromatin separation.

then, chromatin gets degraded by endonucleases and little pieces of cell BLEB off, get eaten by macrophages. KARYOHEXIS. no inflammation results. can affect only a single cell.

in necrosis, it's a group of cells that got assaulted. Get CELLULAR SWELLING, not shrinkage. KaryoLYSIS, not KaryoHexis.

from ATP depletion or membrane injury. Get inflammation and FIBROSIS

Front 5

talk about how apoptosis can happen: talk about regulators.

Back 5

two mechanisms - intrinsic vs. extrinsic. both involve executioner CASPASE 9.

extrinsic = FAS pathway.

big time cancer related regulators of apoptosis - think BCL-2 (oncogene, this binds up BAX and prevents leakage of cytochrome C = STOP AOPOTOSIS, so lots of BCL-2 = cancer).

remember that p53, in addition to stopping the cell cycle in the presence of DNA damage, can induce BAX expression which will make cytochrome C leak out and activate Caspase 9 and kill the cell.

Front 6

in what disease is BCL-2 overexpressed?

what's one word we should associate with BCL-2 activity?

Back 6

see it in B-cell follicular lymphoma.


associate MINI-RNA's with it. not sure how they work, but it's a buzz word.

B-cells depend on being able to undergo apoptosis. If there's too much BCL-2 production, all the BAX gets bound up and there's no intrinsic apoptosis pathway. cells keep living, get swollen lymph nodes.

Front 7

how does APC work?

Back 7

WNT pathway typically transcribes lot of genes = cell proliferation.
WNT is driven by Beta-Catenin.

APC is an important degrader of beta-catenin.

So, APC is a tumor suppressor - without it, you get too much beta catenin and too much WNT, too many cells.

Front 8

we talked about how to calculate DNA index - what is it really a measure of?

Back 8

Differentiation - cells that are MORE differentiated should behave more normally, and therefore should have a normal DNA content (diploid = 1 = 46n).

those with weird DNA concentrations are LESS differentiated and more weird = more deadly.

Front 9

go through how RB works, and how p53 works. Detials.

Back 9

Rb:
normally, you get a growth factor that increases cyclin D. Cyclin D and CDK4/6 can turn OFF Rb, to allow the cell cycle to proceed. Without Rb, E2f is allowed to float around promoting cell growth, so you can get Cyclin E made, to finish G1/S.

p53 works with p16 (Cip/Kip) to arrest cells. and upregulated Bax to do apoptosis. Also remember that it uses MicroRNA's.