DIPG Dialogue

Just One More Day is starting a new regular blog feature called DIPG Dialogue which will contain interviews with researchers, physicians and other advocates in the DIPG community.

Introduction

Dr Shaohua Yang, M.D. & Ph.D., is currently an assistant professor in the Department of Pharmacology and Neuroscience at the University of North Texas Health Science Center. He has had neurosurgery residency training at Beijing Neurosurgical Institute China, one of the largest neurosurgical centers in the world, and has extensive clinical experience with brainstem tumor. Dr Yang's primary research is funded in the field of stroke and neuroprotection by National Institute of Health. He also has been pursuing research with brainstem glioma. In the end of 2008, Dr. Yang published his results of a novel experiment in the Journal of Neurosurgery, in which C6 glioma cells were implanted into the pons of juvenile and adult rats.


Questions & Answers:

Dr. Yang, what did your study show?

First of all, I would like to thanks this blog to provide the opportunity to share my research with all of you, especially with the parents of the brainstem glioma patients.
It has been well known that the outcome of brainstem glioma is very different between children and adult. Brainstem glioma constitutes up to 20% of childhood brain tumor, and has the worst outcome of any brain tumor in children. Over 80% of brainstem gliomas in children are diffuse intrinsic brainstem gliomas, which mean that the tumor cells are tangled extensively with normal brainstem tissue and make surgical intervention even radiotherapy almost impossible. On the other hand, brainstem glioma in adult is less aggressive and grows focally, which may benefit from surgical intervention and radiotherapy. Therefore, the median survival of adult brainstem glioma patient is much longer than that of children.
It is generally believed that the difference between childhood and adult brainstem glioma is due to the different grade of gliomas in these two groups. Normally, low-grade brainstem gliomas are considered to have a characteristic pattern focal growth, while high-grade brainstem gliomas grow diffusely and aggressively. However, this is not always the case, low-grade gliomas such as fibrillary astrocytomes have also been found in association with diffuse brainstem gliomas. Furthermore, very few histological data are available for diffuse brainstem gliomas because very few surgical intervention has been conducted in this type of glioma as biopsy results do not alter the treatment strategy.
From my clinical experience, I have noticed that children brainstem is much softer than that of adult. Thus, I thought about that the anatomical, histological, and immunological diversity between children and adults may be also contribute to the different biological behavior of diffuse and focal brainstem gliomas in children and adults. We used C6 glioma cells, which were chemical-induced glioma cells in rats. We implanted C6 cells in brainstem of young and adult rats to see how these tumor cells grow. What we found is that the brainstem glioma in young and adult rats imitates the characteristics of brainstem gliomas in humans. Since we put the same cells into the brainstem of both young and adult rats, this result indicates that the growth pattern and invasiveness of brainstem glioma could be due the host factors.


Do you have any explanation of why there is this difference between the tumors made in the young versus the adult rats?

From these results, what we can conclude so far is that the host factors could contribute the difference between brainstem gliomas in the young versus adult rats. These factors include anatomical, histological, and immunological factors. The growth and invasiveness of the tumor cells are not only depended on the cells but also on the environment. Different from adults, children are still in the development stage. They keep growing everyday, not only the bone and muscles, but also their brain. The development need a large panel of growth related factors, which could also change the tumor cell behavior and make them grow faster and more invasive. In addition, the tumor behavior is also depended on the status of immune system. In our body, we have cells that could potentially change into cancer everyday. But, fortunately, almost all of them will be killed by our immune system. It has been believed that the brain is an immune privileged site. But, it is now clear that normal glial cells such as microglia do potentially function as immune cells in brain. In children, the immune system is not mature yet. Thus, the immunological factor could also contribute to this difference.


What do you see as the next step in understanding these differences?

As we mentioned early, factors as growth related factors and immune capacity in brain could contribute to the difference between young and adult brainstem glioma. But this is just a hypothesis so far. What we need to do is to test this hypothesis using this rat model and other methods. We can precisely target each factor, such as immune factor or any of the growth factors, to see which play major role in this difference. What I predict is that the difference is not likely due to a single factor but the combination effects of a group of factors. If we could identify these factors, we could be able to develop novel treatment for the brainstem gliomas in children.


Is it possible for this information to become clinically relevant for children who have these types of tumors?

For the modern medicine, no therapy could be developed without the basic and translational research. Our study demonstrated, for the first time, that this rat model of brainstem glioma in young and adults imitate the brainstem glioma in humans. Therefore, the use of this model could facilitate future studies to identify the factors contribute to the difference of brainstem glioma between children and adults, and to discovery of novel therapies to treat the diffuse brainstem glioma in children.


What barriers do you have in moving forward on such research?

The major barrier to move forward the research is the funding resources. The brainstem glioma is relative rare comparing to other cancers. Few people realize that brainstem tumors are the most common pediatric cancer other than leukemia and lymphoma. The funding resource for this devastating disease has been very limited. I conducted a search for the current and historical NIH grants (1972-2009) to brainstem tumor, and not even one has been found. It has been very few scientists and physician that have been devoted to study this disease. Even for the other well funded medical researches in US, we are facing the problem that less and less people are devoted into the research. It is hardly imaging that a very well educated Ph.D, after 4 years college and more than 5 years Ph.D study, the start salary for them is only little bit more than $35,000/yr. Sadly, we have been investing trillions of dollars for the war and bail out the banks, but we have just invested a tiny fraction of these into the research in the last decade to our own health problem. So, we need our whole society to realize this problem.


Reference-
Brainstem glioma progression in juvenile and adult rats. J Neurosurg. 2008 Nov;109(5):849-55