Chronic Inflammation and Cancer Research
Transcript:
Guest: Dr.
Lina Obeid – General Internal Medicine / Geriatrics
Host: Dr.
Linda Austin – Psychiatry
Dr. Linda Austin:
I’m Dr. Linda Austin. I’m
talking, today, with Dr. Lina Obeid who is Professor of Medicine and one of our
most outstanding researchers here at the Medical University of South
Carolina. Dr. Obeid, you do some very
interesting work looking at inflammation and cancer. Can you tell us about that work?
Dr. Lina Obeid:
It’s becoming, now, more and more known that chronic inflammatory
stimuli, things that inflame, for example, tobacco use and lung cancer, tobacco
use can cause chronic inflammation of the underlying tissues that are exposed
to tobacco, and we know smoking leads to cancer. That’s very well established. So, it [inflammation] is the underlying
mechanism of why cancer develops. It is
the same thing with colon cancer. Colon cancer is thought to
be, definitely, an underlying inflammatory insult to the GI tract. So, those are the two cancers I’m very
interested in and I’m very interested in seeing what the role of inflammation
is in those cancers.
To do this, we work on these molecules that are
lipid-based, fatty-based. These
molecules form the components of cells, the cell wall. They cover cells and they cover intracellular
compartments. People thought they were
only structural components of cells.
But, in fact, we’ve shown that these are hydrolyzed, or broken down, to
give signals across cells. And we’ve
shown that some of these molecules are involved in the inflammatory response,
but specifically involved in a chronic inflammatory response that looks like it
leads to cancer. So, we feel like if we
inhibit some of these pathways, we could protect from these chronic
inflammatory stimuli and, hopefully, prevent cancer.
We’re studying these in colon and lung, and we have
two nice models. We have mouse models of
colon and lung cancer. So, in both of
these models, we have knocked out one specific gene that we know makes one of
these molecules that we’ve shown is involved in cellular inflammation. Now we’re trying to see if it’s involved in
tissue inflammation in a living model, in an animal, so that we can go on to do
studies in humans down the road.
In fact, we’ve just recently shown that, indeed, in
a mouse model of colon inflammation, and leading to colon cancer, this molecule
is definitely involved.
So, inhibiting the generation of this molecule (sphingosine 1-phosphate), by knocking out the gene (sphingosine kinase), the
protein, in mice, we can show that they’re [the mice] protected from
inflammatory bowel disease as well as from colon cancer.
Dr. Linda Austin:
Now, let’s back up a little bit because most of us think of inflammation,
and I think I remember learning in medical school that part of the body will
get red, swollen and hot, but you’re really talking about inflammation at the
level of a cell, right, what happens to a cell when that inflammation pathway
is triggered?
Dr. Lina Obeid:
Yes, definitely, what happens in the cell. So, in a cell, when there’s inflammation,
some things are released. They’re called
cytokines and lipid mediators and these mediate for white cells to be recruited
into the tissue to cause what you’re describing.
Dr. Linda Austin:
They’re kind of the linking molecules.
They trigger changes that happen.
Dr. Lina Obeid.
Yes. So, you have the linking
molecules that cause white cells to come into tissues. When white cells come into tissues, they cause,
what you said, hotness, fever and redness.
But this, obviously, is not seen inside
the lung and the colon. What you see
in those cases, sometimes, is bleeding, chronic diarrhea, chronic cough, mucus
generation. Those are the signs from
internal organs, as opposed to what you see when you have inflammation of the
skin and it’s obvious, right in front of you, red, hot, etc. So, this is different, in some respect,
because they [molecules] are inside the organs.
So, at the cellular level, cellular inflammation
leads to organ or tissue inflammation, which is what we’ve, basically,
seen. And inhibiting some molecules
within cells can inhibit the inflammatory action that leads to the white cell
recruitment and all the manifestations of inflammation. We can say, now, the sphingosine kinase gene
and the sphingosine phosphate lipid molecule are clearly involved in
inflammatory bowel disease, and in colon cancer. And we’re now looking at the model of lung
cancer, to try and see if that occurs as well.
We’re excited.
Dr. Linda Austin:
Oh, it’s very exciting.
Dr. Linda Obeid:
We have some inhibitors. We have
a very nice chemistry facility as part of our Department of Biochemistry, and
they can synthesize analogs to some of the molecules that we think are
involved. They can make these analogs
that inhibit, so we have, now, inhibitors coming down the pipeline that we’re
studying in cells. We show they work in
cells and we’re beginning to do animal studies on them. And if they work in animals, we’d have to,
maybe, be able to go into clinical trials with them. So, it’s really exciting.
Dr. Linda Austin:
How many are working in your lab right now, Lina?
Dr. Lina Obeid:
About 8-10 people, at all times.
People come and go. I would say,
between 8 and 10.
Dr. Linda Austin:
And how many grad students do you have?
Dr. Lina Obeid:
I have three MD/PhD students that are doing their actual PhD in my lab
and I have two graduate students. The
rest are postdoctoral fellows.
Dr. Linda Austin:
Congratulations on your great effort.
Dr. Lina Obeid:
Thanks.
Dr. Linda Austin:
Thank you so much for talking with us today.
Dr. Lina Obeid:
Thanks a lot.
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