"Oh, it's just devastating. It's like your life, your life's over."
That's the first thing that went through John Worch's mind last April when he found out he had stage four Glioblastoma - the deadliest kind of brain tumor. The elementary school principal, who also serves in the National Guard, had the three and a half inch tumor removed.
But in February, it started growing back. John got in touch with neuro-oncologist Doctor Andrew Brenner who enrolled him into a first-of-its-kind gene therapy study. As part of the one-time treatment, John was injected with a cold virus.
"But instead of the virus carrying its own DNA, it carries our engineered DNA," said Dr. Andrew Brenner Neuro-oncologist
San Antonio, TX.
The doctor says the virus delivers that engineered gene to cells around the brain tumor signaling them to die.
"It basically causes the tumor to starve. No nutrients. No oxygen."
Doctor Brenner says right now, only three people in the world are taking part in the study.
"But of the patients who have been treated, none of them have had tumor growth."
A promising sign, but Brenner says it's too early to draw any conclusions.
"You hope as time goes on, the more it gets starved, the more it will shrink and die away."
John says he feels better since the treatment. He hopes the innovative therapy will allow him to keep working with these children and be here for his own.
"I'm hoping to see them grow up into adults and have their own families. That's what I hope to see," said John Worch.
For more information on other series produced by Ivanhoe Broadcast News contact John Cherry at (407) 691-1500, email@example.com.
TOPIC: THE COLD VIRUS ATTACKS BRAIN TUMORS
REPORT: MB #3303
WHAT IS A BRAIN TUMOR? A brain tumor is a mass of excess cells that grows in the brain. Tumors can be benign or malignant: benign tumors are not cancerous and are not usually life-threatening, while malignant tumors are cancerous and can be life-threatening. Benign tumors can usually be removed without issue. Primary brain tumors develop in the brain, whereas secondary, or metastatic tumors, originate elsewhere and move to the brain. Symptoms of a brain tumor include frequent headaches, unexplained nausea or vomiting, blurred or double vision, difficulties with balance or speaking, hearing problems and personality changes, among others. (SOURCE: http://www.mayoclinic.com)
TYPES OF BRAIN TUMOR: Primary brain tumors are usually named for the part of the brain or the cells from which they originate. While there are many types of brain tumors, the most common types in adults are:
• Astrocytoma- These tumors originate from star-shaped cells called astrocytes and normally occur in the cerebrum.
• Meningioma- This type of tumor is usually benign and slow-growing and arises in the meninges. It can be any grade.
• Oligodendroglioma- This type of tumor usually occurs in the cerebrum and originates from the fatty cells that cover nerves in the brain. It is most common in middle-aged adults.
Doctors rate tumors by grade, with grade I being the least harmful and grade IV being the most harmful.
• Grade I tumors are benign, and they grow slowly. The cells in a grade I tumor mostly look like normal cells.
• Grade II tumors are malignant. The cells look less normal than those of a grade I tumor.
• Grade III tumors are also malignant and actively growing. The cells of a grade III tumor look very different than normal cells.
• Grade IV tumors are the worst kind. They are malignant, and they tend to grow rapidly, with highly abnormal-looking cells.
(SOURCE: http://www.cancer.gov/cancertopics/wyntk/brain/page3 )
TREATMENTS: Most brain tumors are treated by surgery, radiation, chemotherapy, or some combination of the three. Surgery removes the tumor from the brain and is usually the first treatment option. Radiation uses X-rays, gamma rays or protons to kill tumor cells and generally comes after surgery. Chemotherapy kills the tumor using drugs.
Recent research has looked at using oncolytic viruses to kill brain tumors. Oncolytic viruses are viruses that are specifically programmed to target and kill tumor cells. The virus is injected into the blood stream and is encoded to only kill tumor cells and to only replicate itself if there are tumor cells present. Therefore, when the virus has successfully eradicated the tumor, it stops replicating and dies.
FOR MORE INFORMATION, PLEASE CONTACT:
Elizabeth Allen, Media Communications Officer
UT Health Science Center San Antonio
San Antonio, TX
THE FOLLOWING IS AN IN-DEPTH INTERVIEW WITH THE DOCTOR FROM THE STORY ABOVE:
Dr. Andrew Brenner, neuro-oncologist, at The University of Texas Health Science Center at San Antonio's Cancer Therapy & Research Center, discusses a new way to fight brain tumors.
Can you discuss brain tumors and ultimately how they grow and evolve?
Dr. Andrew Brenner: Ultimately, brain tumors aren’t the most common type of tumor. Overall, while they are still a huge problem, the general representation is relatively low. The less common something is, the harder it is to determine the cause for it. A lot of studies have been done. One of the things that we do know about the cause of brain tumors is what we refer to as ‘ionizing radiation,’ which is different from other types of radiation from what we call the electromagnetic spectrum. For example, all of the people in Japan right now who are around that reactor – the reactor is ionizing radiation, and basically what that means is that the radiation can react with the DNA directly and moreover cause damage directly to the cells as well as the proteins. Ionizing radiation is well known in terms of causing brain tumors. In terms of other things, there really isn’t a lot of association that we can see. There are myriad things however that are being investigated. One thing that is interesting is that we do occasionally find some virus DNA in tumor cells. There has been some speculation that viruses perhaps play a role in brain tumor formation, but it has yet to be proven. I think that it is going to be something that as technology continues to advance and we learn more and more about tumors, we will gain further insight into how exactly these tumors evolve.
How many people are diagnosed with this condition every year?
Dr. Andrew Brenner: There are about 13,500 cases diagnosed annually in the United States of the most aggressive form, which is glioblastoma multiforme (GBM). We see probably a total of 20,000 malignant primary brain tumors in the United States annually. We probably see an equal amount of more benign tumors. Overall, I would say approximately 50,000 brain tumors are diagnosed annually in the United States alone. The less aggressive ones, which don’t cause any limitation (generally speaking) in terms of people’s lifespan; like meningiomas, which come from the lining of the brain – they don’t actually invade the brain but rather push on it. Generally, they can be cut out and treated via radiation; that treatment typically offers patients positive results. However, the ones that develop within the brain rather than the lining, those tend to be the more aggressive and invasive ones. They are either developed from astrocytes, which are the cells that have to help protect the nerves, interact with the blood cells, in addition to performing a variety of dynamic processes within the brain; they even guide nerves along their route to form the proper connections, and so they are a very dynamic cell type and they are one of the most common cells in the brain besides nerves. Those tend to form the most tumors more than likely because they are the most prevalent cells in the brain. There are more of those cell types within the brain than any other cell besides the aforementioned nerves. Then there are some other cells in the brain called oligodendrocytes. They are basically the insulation along the nerves to keep the signal from short-circuiting basically. Again, those are called oligodendrocytes, and we see countless tumors from those. Furthermore, the cells that line the ventricles of the brain are called ependymal cells, and then from the peripheral nerves as well. They are all problematic. You have to think of the astrocyte tube – the ones from the astrocytes; since they are the most common and they often times tend to be rather aggressive and invasive. The average survival with somebody possessing the highest grade (grade 4) astrocytic tumors, or glioblastoma, is just over a year. We used to say about 13 ½ months, however, that number is getting longer as we continue to develop novel therapies. We more than likely are up to a year and a half. But still, at a year and a half we still have a long, long, long ways to go. We have a lot of work still to do.
So there are aggressive and detrimental forms of this cancer that are fatal?
Dr. Andrew Brenner: Indeed.
Where do all of the myths about brain cancer coming from cell phone usage come from?
Dr. Andrew Brenner: I think that some of them are based on half-truths and they appear logical on the surface, but when you really dig into them it is very unlikely. I guess that you could say with cell phones . . . probably the jury is still out. You can look at a lot of data that has been published; especially within the last year there have been two vast studies. One is the Interphone study, which is what we call a case control study. What they did is they looked at people who had brain tumors in the regular population, and they looked at how much cell phone usage they had, and what they discovered was that there really isn’t a difference between people who have brain tumors and people who don’t in terms of cell phone usage. Moreover, there was another study that approached the subject in a different way. What they did was that they looked at the brain tumor incidents in the United States over the last 10 – 15 years in addition to looking at the cell phone usage in the last 10 – 15 years. In 1995, we had 20 million cell phone users. By last year, there was 280 million cell phone users . . . so almost one cell phone for every person in the United States. That is a lot of cell phones. During that time frame, we have not seen any rise in the number of brain tumors that were formed. In other words, you can say that if you expect cell phones to cause brain tumors, you should expect an increase in brain tumors with the increase in cell phone usage. That hasn’t panned out. I think that it is appropriate. There are still some concerns about the jury being out, especially for populations that have just started using the cell phone recently. You have to think about kids. It wasn’t affordable for children to be using cell phones. Now we have family plans that allow children to have their own cell phones. The actual phones are getting cheaper and cheaper in addition to the data plans. Almost all kids have cells phones, especially in that 13 – 17 age range. That is a relatively recent phenomenon. You can argue that the specific data collected in fact doesn’t involve that group (the young people). Is it possible that in 10 – 15 years we may see that number rise? Theoretically, that is possible. It is always good to have a healthy amount of skepticism. In either regard, you have to say if something is possible or not likely, but as of now we cannot make any definitive statements for that group. You can always approach it from a theoretical perspective – it is true that cell phones generate electromagnetic radiation . . . but so do we as humans and so does a light bulb. I like to put things into a normal perspective. If you think about the amount of energy a light bulb generates, one packet of that energy in a light bulb is about one million times stronger than one packet from a cell phone. So that packet has a better ability to penetrate tissue because it has more energy associated with it. If you think about the pure volume, we can measure that in terms of watts for example. If you look at a light bulb, it is typically 60 watts / 80 watts / 100 watts, and then if you look at a cell phone (nowadays) they are about half of a watt.
So you get more electromagnetic energy from a light bulb than the modern cell phone?
Dr. Andrew Brenner: Right. This is both evident in volume as well as intensity. So if you think about it in that perspective, it is rather unlikely that cell phones at that low of intensity and volume would generate any type of damage when we are incessantly exposed to incandescent in addition to other forms of electromagnetic radiation.
Can you discuss the study that found evidence of patient’s metabolism increasing as a result of the brain tumor?
Dr. Andrew Brenner: We don’t know exactly what that means. What they did in that study was radioactively labeled glucose (sugar molecules). It was a very low form of radiation; enough to detect with an instrument called a PET scanner, but not enough to do any actual harm – we use these types of radio nuclei or radioisotopes. We use those for all types of diagnostic imaging. Perhaps you have heard of PET scanning? We do that for cancer in addition to a variety of different things. You can also do it to look at the usage of sugar for activity of the brain. What they did in that study was they had volunteers who had a cell phone on both ears (one was off and one was on). What they then did was measure the usage of glucose in the brain. What they found was a specific area (generally two areas) – one right above the eyes known as the orbital frontal cortex – increased in activity and sugar usage. The other is the temporal lobe (located close to the ear). They saw an increase in activity in these PET scans, and ultimately determined that those areas where the ones that had the most exposure to the electromagnetic radiation from the cell phones. Now it is possible that since cell phones work in the microwave range that it is purely heat related. As microwaves are absorbed, they generally create heat. Normally that is not a big deal because you are exposed to the sun and that in fact already generates heat. Whether that has some long-term significance, we don’t know. If you look at the epidemiology data (referred to earlier in the interview) – the studies of people as a group; we don’t see that they do make a difference, but it is an intriguing finding, however, nothing more at this point. It does merit further investigation. There are other things that could happen. If you are constantly activating a part of the brain, perhaps that could affect the overall function of that particular part in the long run – modified behaviors and such.
Is there any validity in the notion that power lines, sports drinks and MSG having an effect in the development of progression of brain tumors? Where do those myths come from?
Dr. Andrew Brenner: Again, most of the examples that you chose have some half-truths to them. If you look at MSG (monosodium glutamate), you will notice that glutamate is in fact an amino acid, but in the brain it is used as a neurotransmitter used to convey information and send signals back and forth between nerves. The theory is that you are stimulating the brain. If you are stimulating the brain, you can cause increased tumor formation. Furthermore, there are some studies that illustrate that glutamate can be used by tumor cells to sort of clear the way around them through a process called excitotoxicity. It is a real scientific finding that the glioma cells, or those brain tumor cells, actually secrete a lot of this glutamate and ultimately make themselves immune to it, and that over stimulates nerves in the area. When those cells become over stimulated they die. However, when you talk about ingesting glutamate you have to remember something else: It is an amino acid, and our body is great at regulating our amino acid intake, and on top of that there is a blood brain barrier. Amino acids do not cross over into the brain unless the brain wants them to. It is very tightly regulated. We’re not going to increase the amount of glutamate just by eating some more. It will be dumped in the urine if there is excess, and the blood brain barrier will keep it out if there is excess in the blood.
So MSG being the cause of the formation of tumors in the brain is in due course a myth?
Dr. Andrew Brenner: Yes.
What about power lines? Is there any truth to that?
Dr. Andrew Brenner: It’s basically the same thing. It is electromagnetic radiation. Now, electromagnetic radiation sounds exceptionally scary, but again when we talk about electromagnetic radiation it is an entire spectrum. All it means is something is being emitted in a wave form. That can be heat, light particles, microwaves or perhaps ionizing radiation (ultraviolet rays, x-ray radiation, etc.). The reality is that the huge power lines that we see hanging all around our neighborhoods, those emit what is called ultra low frequency electromagnetic radiation. It is so low in energy that it is probably 1,000 fold or less than that of a cell phone. When you then talk about a cell phone being a million times less than a light bulb, you are talking about the energy associated with those towers, it is hundreds of millions times less than that of a light bulb.
So where has all of this paranoia come from?
Dr. Andrew Brenner: It’s the words “electromagnetic radiation.” I think that is the main thing. So far there has been no proof that the electromagnetic radiation is significant in terms of anything. We have been surrounded by electromagnetic radiation for eons. The sun generates it. We walk out and are among the ultraviolet rays all of the time. We have DNA repair mechanisms in our bodies that repair damage when it occurs, and with these very, very low energy forms of waves out there . . . it is not likely that they are causing any significant problems.
So if you live by power lines than you are probably okay?
Dr. Andrew Brenner: That is correct.
What about sports drinks? Do these novel beverages designed to rehydrate and fuel the body pose any threat to it?
Dr. Andrew Brenner: The idea that sports drinks have any effect whatsoever developed online and went viral. Basically, I think that it started in Europe and the way it went was that the sports drinks had something in them called glucuronolactone; that glucuronolactone was something that was used in the Vietnam era to promote alertness and cohesiveness among soldiers. What they found was that it caused brain tumors and they stopped using it. It is not regulated by the FDA or any European agencies, so they are free to put them in the sports drinks, and you should not drink the sports drinks because they have that brain tumor forming sugar in there. The reality is no government ever used glucuronolactone. It was never shown to be harmful in any way whatsoever. It is actually a byproduct of our normal metabolism. It is made by our liver all of the time. It is used in our tissues (skin) as well as various other tissues throughout our body. It is an essential sugar form that is without any harm. The European agencies have performed studies on glucuronolactone and determined there are no unsafe properties. They really didn’t find any harm with it, but what they discovered was less than 3 grams per day of glucuronolactone had no effect whatsoever on anything. In order to get 3 grams per day, you would actually have to drink well more than 10 sports drinks per day.
Do you think that the caffeine would hurt you more than the glucuronolactone?
Dr. Andrew Brenner: Probably.
Theoretically, you could be in front of a microwave, on a cell phone, drinking a sports drink, and still be okay. Is that accurate?
Dr. Andrew Brenner: More than likely you would be fine, unless someone came along and did something else to hurt you. I don’t think any of those things will have a detrimental effect on your well-being.
Is the theory behind microwaves causing brain tumors basically on the same line as the aforementioned examples?
Dr. Andrew Brenner: We haven’t seen any rise in the number of brain tumors with the emergence of microwaves. Microwaves generate heat. Heat is absorbed. It can’t really penetrate, and it doesn’t have enough energy associated with it to displace DNA or proteins. With that being said, it seems (like the other examples) to be virtually harmless in terms of brain tumor formation as a cause of electromagnetic radiation. Which is one of the reasons that there one in almost every household.
Can you talk a little bit about the new-fangled treatments for brain cancer, and how these therapies are helping patients restore their quality of life?
Dr. Andrew Brenner: Alas, as you mentioned, brain tumors still occur and know no boundaries in terms of age as well as demographics. Unfortunately, we have 30-year-old women with young children who have life threatening brain tumors without a cure. There still is a lot that we have to do to help increase survival for those patients. We are trying to develop very innovative types of therapies that don’t involve the typical paradigm of toxic drugs that cause hair loss in addition to problems like that. One thing that we have been looking at is a gene therapy. We have been working with a company outside of Israel for the past couple of years called Vascular Biogenics. What that basically is, is a cold virus; but instead of the virus carrying its own DNA, it carries our own engineered DNA. That cold virus delivers that DNA to all of the cold cells. It is only activated in the tumor environment, because the tumor secretes certain inflammatory molecules call TNF (tumor necrosis factor). When that is around, that gene is activated and it signals the cells to die. It basically kills off the blood cells anywhere there is a tumor. It basically causes the tumor to starve – no nutrition, no oxygen.
So it is sort of suffocating that tumor then?
Dr. Andrew Brenner: Pretty much.
Thus far, this study still remains rather minute, correct?
Dr. Andrew Brenner: We have done an earlier study with patients with all forms of cancer. It wasn’t restricted to any particular type. We treated over 25 patients; basically trying to determine the safety of it and the best possible dose to get the optimal results. Since that time, there have been two studies that have been ongoing. One is in thyroid cancer. We did see a very promising response in a patient with thyroid cancer. Based on what we know about thyroid cancer, it would make sense that this treatment would work for that. That particular study was open at the Mayo Clinic. The thing that we were particularly interested in was the formation and development of brain tumors, so we did study it in our animals, and we did see a very nice response there as well. This prompted us to open up this study. This is for patients with the most aggressive form of brain cancer: glioblastoma. Accordingly, we have enlisted 3 patients and they have yet to experience any problems thus far. We are planning on enrolling 25 yet again to aid in the study (specifically to look at primary brain tumors). It is our goal to learn more about the efficacy of it as well as the safety of it. As I just said, the patients enlisted in the study thus far have been doing fantastic. We hope that it continues to do as such in the future. Since we were involved in the development of it for brain tumors – we were the first to open it – Duke University and Dana-Farber Cancer Institute (Massachusetts General Hospital) will join us soon.
What kind of results have you seen from the people who have completed this treatment?
Dr. Andrew Brenner: Well, it is still very early so it is hard to make any conclusions. I should say that immediately. I can’t say that this truly works. It would be unreasonable to make a conclusion based on three patients so far. Of the patients that have been treated, none of them have experienced tumor growth.
So it stopped the growth of the tumor?
Dr. Andrew Brenner: Yes, which seems very promising at this point.
Is the principal enrolled in this particular study?
Dr. Andrew Brenner: Yes. He was the last patient treated with it.
So he has seen that growth stop as well?
Dr. Andrew Brenner: Well, his is the most recent since he was the last patient to be treated with it. We do have other patients that have been on it for longer and have experienced a more prolonged stoppage of growth.
What exactly does that “stoppage of growth” entail? Could this have the potential to be a cure for brain tumors in the future, or perhaps lead to its discovery?
Dr. Andrew Brenner: That’s what is hoped. As more time goes on, the more it gets starved, shrinks and eventually dies off. One problem is, as tissue dies in the brain it looks exceedingly similar to that of the tumor itself. We often times can’t tell if it has stopped or if it is dying. It looks very much the same. So you only will know over time after incessantly looking at the patients, and eventually it should decrease as the tissue is dying off. However, knowing that it is not growing is a remarkable thing as well.
Has there ever been a study like this that uses a virus to fight tumors, or is this a first of its kind?
Dr. Andrew Brenner: Viruses? Yes. A virus to deliver a gene? No. This is the first of its kind.
Is there anything else that you would like to add about the studies you are leading or working on?
Dr. Andrew Brenner: We currently have a lot of exciting studies that are ongoing or opening. Things are moving very quickly in terms of brain tumor research both here at our center as well as other centers across the country. We have just recently completed a study with a very promising drug, which we hope to bring back to the clinic within the next year. That one showed very good results for a number of our patients. We have different studies that all focus on different methods and techniques of blocking brain tumor growth that are opening up here within the next couple of weeks, and we are going to continue to add to those studies so that we have a variety of options available for patients with primary brain tumors as well as to try and increase survival rates for all of the people that are forced to live with this condition.