Re: Telomeres, mutation rates and "breakthroughs"

From: Robert J. Bradbury (
Date: Mon May 01 2000 - 15:31:32 MDT

On Mon, 1 May 2000, John Clark wrote:

> I could say yes but you probably get cancer lots of times and never even
> know it

This is a good point John. The individual who won the Infinity Prize
at the A4M conference for the development of angiogenesis inhibitors,
had some slides showing the difference in size between leasions before
and after they turned on the genes promoting angiogenesis. I believe he
commented that many tumor specialists believe that the elderly have many
microscopic proto-tumors that simply have not figured out how to turn on
the angiogenesis genes that allow them to grow to observable sizes.
But these are in indivuals 50 or more years old who obviously have
many kg of tissue that could potentially cause problems.

> because your immune system kills the tumor when it's still microscopic.
> A lab dish doesn't have much of an immune system.

Another good point. The recent work showing that you can "prime"
dendritic cells to display tumor proteins to the induce the
immune system into attacking a tumor clearly shows that the
immune system *can* recognize it as foreign and deal with it.
The problems that can occur are (a) the mutations may be in
protein sequences that are not displayed by an individual's
MHC sequences; and (b) the tumor cells can respond by activating
a program that induces apoptosis in the immune system cells
(a cancer cell counter-attack).

There has been very little work done (to my knowledge) on
how frequently your immune system removes proto-tumors
because it is very difficult to observe micro-scale
cytocide that leaves behind few if any traces. The fact
that there are vaccines against some forms of cancer on
the horizon would argue that the immune system can be
trained to do it, so it is likely to be occuring at least
in some individuals as a natural defense.

What you would like to do in the long run is develop cell lines
for tissues that "must" divide, that are highly effective at
displaying any mutations in the genes responsible for the
regulation of cell replication, then train the immune system
to be highly effective at recognizing cells displaying those
mutations. You then replace your normal tissues with those
engineered to wave red flags in front of your immune system
when they begin to run amok.

Good discussion.

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