Chronic Inflammation and Cancer Research

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Chronic Inflammation and Cancer Research




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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