okay so we've talked today about cell phones and text messaging I'm just
kidding we're actually talking about the cell cycle and messaging within the cell
and how it relates to current disease and treatments for more lectures like
this please check us out at Med cram comm what I wanted to talk about it kind
of goes back a little bit to high school biology but this is really cool because
we're actually starting to see some of our discoveries that we've made years
ago come to fruition today so let me draw for you the cell cycle so if you
remember from high school biology there's a cycle where the cell
reproduces itself through the process of mitosis mitosis isn't the only thing
that happens it's just part of it you remember there is prophase metaphase
anaphase telophase well that has to do with mitosis so this is phase M okay but
that's kind of the last thing that happens usually what happens is the cell
stays in either g0 so that would be the pre synthetic phase or it goes into g1
now g1 is where it's preparing to divide and the first thing that it needs to do
before it does divide is it needs to replicate its DNA and that's called the
S phase S stands for synthetic and that's where you have chromosome
duplication it's very time consuming very energy consuming so once it
actually reproduces its DNA then it's then going to go into a pre mitotic
phase known as g2 and it will continue to grow until it's ready to actually go
through the division process so let's follow this around here you have a cell
it makes a decision to go through with dividing it's got to reproduce all of
its chromosomes all of its DNA then it's got to grow some more and then finally
divide and this could keep going in the case
cancer or it could exit and stay as a cell in g0 so what's really interesting
about this is that the body regulates this pretty well normally and there's a
restriction point right here right before the S phase okay so this is a
restriction point and it makes sense because you don't want to go through
this takes a lot of energy if things are not right okay and this is regulated by
cyclones which are proteins that make sure that it's ready to go through with
replication so this restriction point if it finds that it's not quite perfect or
not quite ready it will exit out of the system and you will get something called
senescence okay basically it's programmed death which causes some
inflammation for instance if there's oxidative stress if there is cellular
damage and it detects that so before it copies it it's going to say you know
what the cell is not ready to divide we should not be dividing the cell we're
going to replicate errors it's not a good idea so it exits the cell right
here before the S phase this is called the restriction point and it's cyclones
which mediate that okay now let's say that everything's good and it goes
through the S phase the next thing that's going to happen is there is
another checkpoint right before it goes through mitosis and actually divides so
in other words there is another checkpoint over here and it will look to
make sure that the DNA was reproduced correctly
so if it wasn't reproduced correctly then it'll say you know what we need to
just involute and die and that's called a proptosis now a pitocin is very
important because a pitocin give information okay but you could also get
replicative senescence which does cause inflammation okay now there are a couple
of other terms that you may not have heard of
one of them is Auto Fidji this is where the cell starts to break down itself and
starts eating itself it's like a catabolism state another word that you
may not have heard is necroptosis okay this is where the cell dies and it uses
something called an RI P which is kind of cute rest in peace but it's an RI P
kinase and this also can cause inflammation now there's another thing
called F ro cytosis and this is pretty cool because here you have phagocytosis
with leukocytes that actually eat up the trash and the cellular debris and it
reduces autoimmunity and it reduces inflammation so that's good okay so this
is generally the cell cycle that we're talking about there's a number of things
that can happen to cells in the cell cycle and the purpose of all of this is
to make sure that only good cells reproduce and bad cells stop reproducing
or they die and this is to prevent cancer when you go through the cell
cycle one of the things that happens when you do this synthetic phase is you
lose something called telomeres telomeres are the ends at the end of the
DNA so let's say this line here was the DNA there would be little telomeres at
the end because every single time you reproduce or duplicate a chromosome you
don't reproduce the whole thing you get a part of it cut off and so there is
something called telomerase --is which add on to the end well in certain cases
you don't have these enzymes because there's mutations in them and these
enzymes are things called te R T and T e rc so turts and turks
and they found that mutations in these have been found in patients with
idiopathic pulmonary fibrosis and also COPD in fact idiopathic
ptosis have mutations in both tert and Turk
whereas COPD just has mutations in Turk so once again we see the cellular basis
here of disease now the other thing I want to mention is this restriction
point and for that matter this one too in fact all of this is regulated very
strictly by receptors and we're going to talk about a specific receptor called an
intrinsic tyrosine kinase this intrinsic tyrosine kinase phosphorylates enzymes
which allows transcripts on the DNA to work and these intrinsic tyrosine
kinases can be activated by different receptors
and we're going to talk about those receptors next because if we can
eliminate the tyrosine kinase from signaling this to go through we can
potentially take cancer and arrest it in its tracks
so let's talk about that because that's pretty important okay so there's four
types of receptors that we're going to talk about there are receptors with
intrinsic tyrosine kinase activity and then we have receptors that are lacking
tyrosine kinase activity and then we have G proteins and steroid let's talk
about these receptors with intrinsic tyrosine kinase activity so these are
receptors that directly control the entry of cells into the cell cycle so
they directly control cell cycle you can see why this would be a target for
cancer treatments okay so what are the type of receptors that we're talking
about there is the epidermal growth factor there is the platelet-derived
growth factor there is the vascular endothelial growth factor fibrosis
growth factor and tgf-beta so these are all receptors
on the cell surface that interact directly with a intrinsic tyrosine
kinase which will directly control cell cycles so the purpose of this is to find
the receptors for all of these and to block it and if we can block it then
potentially we can prevent cancer from forming so the epidermal growth factor
receptor can be blocked by medications for instance get fit in nib you'll
notice that they all end in B's another one is ER l OT ini be another one is AF
a TI n ib so these are all receptor blockers okay platelet derived growth
factor veg F R and FG f R and things of that nature
these can be blocked at least these three right here can be blocked by
something called in the tid a nib and that was FDA approved back in 2014 for
the treatment of idiopathic pulmonary fibrosis so IPF and it kind of slows
down the progression again this is utilizing through a tyrosine kinase
receptor blocker now real quick cells that lack tyrosine kinase would be
receptors like il-2 three and a fair on gamma and they actually use something
called a jak kinase and then they signal to the cell using something called stats
these are second messenger things that go into the nucleus and transcribe from
there you may recall that G proteins use gtp and they use cyclic a.m. P as second
messengers and then finally steroid hormones our steroids of course that
kind of looked like vitamin D kind of drawing this
schematically here without spending too much time looks like a steroid and it
kind of cuts right through into the nucleus of the cell without any
receptors and it does transcription perhaps a better picture would be like
something like this okay so kind of like a vitamin D or cholesterol analogue okay
so this explained a little bit about cell cycling let's talk about cell
mediated immunity and helper T cells and things of that nature in the next
lecture hi I'm dr. Rajesh well we're excited to announce the launch of med
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