88.5 WFDD - glioblastoma: Recent Episodes
None
Left: Ravi Bellamkonda, Vinik Dean of the Pratt School of Engineering at Duke University
Right:A fluorescent stained image of a tumor marking bacterial nanocarriers in pink, cancer cell nuclei in blue, and human mitochondria (another indicator of tumor cells) in green.
Duke University
SciWorks Radio is a production of 88.5 WFDD and SciWorks, the Science Center and Environmental Park of Forsyth County, located in Winston-Salem.
Great strides have been made in treating various forms of cancer, thus extending lives. But for people with Glioblastoma, a particular type of aggressive brain cancer, very little has worked. Recently, however, a lot of research has been done at the nanoscale, modifying evolution’s 4 billion year progress to suit our own needs.
Check out some of these related SciWorks Radio episodes.
- SciWorks Radio : A Virus that Kills Cancer
- SciWorks Radio : Clever New Cancer Treatments Being Developed Locally
- SciWorks Radio : The Predictive Power Of The Junk In Your Genome
- SciWorks Radio : Tales Of The Genetically Altered, Superhero Bacteria Swarmbot
- SciWorks Radio : Microbes
A team of biomedical engineers, including Duke University Pratt School of Engineering’s Dean, Dr. Ravi Bellamkonda, has published their most recent innovation in the journal Molecular Therapy – Oncolytics.
This cancer is very invasive in the brain. It doesn’t stay in one place. When a tumor doesn’t have a boundary or a clear edge, then it becomes very challenging to remove it all. You leave some behind because the tumor is migrating and invading the rest of the brain.
Dr. Ravi Bellamkonda, Vinik Dean of the Pratt School of Engineering at Duke University interviews for SciWorks Radio at the Duke AV Studios. - Duke University
The principle we’re testing here is, how do you design a system where you have a therapy that goes everywhere, but is only toxic to the region that the tumor is in and not elsewhere?
Some current treatments involve forcing chemicals through the brain, in an attempt to engage all of the cancer cells. This is dicey because it also leaves healthy brain cells vulnerable to the treatment. Surgery is also of limited benefit.
Taking out one extra millimeter of brain could mean the difference between speech and no speech, between walking and not walking. And so, in an organ like the brain, it is particularly important to figure out a way not to kill the normal cells and kill a distributed tumor.
So how do you do this without harming the brain? The answer, in this case, comes in the form of a bacteria called Salmonella, which has been genetically modified so it won’t make anyone sick.
Shawn's note, *according to the CDC:
"Every year, Salmonella is estimated[PDF - 1 page] to cause one million foodborne illnesses in the United States, with 19,000 hospitalizations and 380 deaths. Most persons infected with Salmonella develop diarrhea, fever, and abdominal cramps 12 to 72 hours after infection. The illness usually lasts 4 to 7 days, and most persons recover without treatment. However, in some persons, the diarrhea may be so severe that the patient needs to be hospitalized."*
The reason Salmonella was interesting to us is it has this property of being able to move in what we call extracellular space. If I put this bacteria in one corner of the brain on the surface, they have the ability to go everywhere in the brain, but they don’t grow everywhere in the brain because we’ve engineered it such that it’s hungry for certain essential compounds that we call purines.
So, by doing that, only in the tumor regions which are rich in purines, do they actually multiply and grow.
That’s just the first step.
We can engineer it genetically to produce proteins that it does not normally produce. So we made Salmonella that made two proteins that work together really well to kill tumors. But we didn’t want them to make these proteins everywhere in the brain. Tumor regions have low oxygen tension. So we use that feature to our advantage and engineered this bacteria such that it only triggers these proteins being made when there is low oxygen tension.
So, the team used Salmonella because it’s mobile in the brain. They made it dependent on cancer-abundant purines. Then they programmed it to only produce cancer killing proteins in low oxygen areas, found only around brain tumors.
When the tumor is gone, the Salmonella dies off safely because it has essentially consumed all of its own food source.
Genius!
Using a lab rat model, this method has increased the survival rate by 20%.
We are now trying to understand why it is that, in 20% of the cases, we had complete cure, and in 80% of the cases, when we treated the rats in this case, we did not. It could be because in those cases for some reason, the bacteria that we injected were not as effective. Or it could be that there’s variation within tumors, and the really aggressive ones outpace the good that these bacteria can do. We see evidence that, even in the cases of the animals that did not respond, initially they did, and then the tumor overtakes that response. So don’t take me wrong. The 20% cure is amazing for a disease we did not move the needle at all on for so many years. We’re very excited about that. But we’re very interested in understanding how we can make that 40, 60, 80 percent of the cases... or 100% with some luck.
This Time Round, the theme music for SciWorks Radio, appears as a generous contribution by the band Storyman and courtesy of UFOmusic.com.
biomedical #engineering #science #biology #salmonella #cancer #glioblastoma #duke university #pratt school of engineering #ravi bellamkonda #journal molecular therapy #oncolytics #shawn fitzmaurice #wfdd #sciworks #winston-salem
Science Normal Tweet
"Glioblastoma - MR sagittal with contrast" by Christaras A - Created myself from anonymized patient MR. Licensed under CC BY 2.5 via Commons - https://commons.wikimedia.org
Glioblastoma - MR sagittal with contrast" by Christaras A
SciWorks Radio is a production of 88.5 WFDD and SciWorks, the Science Center and Environmental Park of Forsyth County, located in Winston-Salem. Follow Shawn on Twitter @SCIFitz.
According to the American Cancer Society, cancer, in its various forms, killed almost 600,000 Americans in 2014. The good news, according to their 2011 annual report, is that death rates have decreased. Over the span of time between 1990 and 2007, an estimated 900,000 lives were spared. Improvements in prevention, early detection, and treatment are cited for this. There is still no cure, but treatments are becoming more and more advanced and, well, clever. Here in Winston-Salem, a team led by Dr. Waldemar Debinski, director of the Brain Tumor Center of Excellence at Wake Forest Baptist, has been awarded a $1.5 million grant by the National Cancer Institute (NCI) of the National Institutes of Health, to advance treatments for glioblastoma, or GBM; a highly malignant form of brain tumor.
Brain tumors represent a particular problem in oncology. Brain tumors are localized to the brain and are separated from the blood stream. It is more difficult to get to them with drugs. At the same time, some forms of brain tumors, such as glioblastoma, the one we are specifically focusing on, are growing very fast and are very aggressive, and they also spread quickly in the brain.
The NIH grant is allowing Dr. Debinski to focus on three advanced forms of molecular treatment.
One is on specific delivery of drugs to the sites in tumor cells where they really act. We can deliver drugs to the nuclei, we can also deliver drugs to lysosomes, and we can deliver drugs to mitochondria. So, if we treat somebody with traditional chemotherapeutics, the drug is going to go all over, but not exactly to the sites where it works. I’ll give you an example: Some drugs work in the nuclei of cells, it’s a house to DNA, and many of the chemotherapeutics interfere with the DNA. The best approach would be to deliver the drugs straight to the DNA. And so, we can actually do that. The second part of the grant, we have identified a relatively small peptide, that is a small protein. This can be used for imaging and if it’s for imaging it also means for diagnostic purposes. At the same time, it can deliver drug-loads. This peptide has interesting characteristics because it can cross the blood-brain barrier. This is the barrier that delineates the brain from the rest of the organs. And it’s also the barrier for standard drugs, and, because of that, brain tumors are so difficult to treat. But this peptide has the capacity to actually get into tumors when it’s in the brain. The third part of the story is pure immunotherapy. We are trying to design and build a super-antibody that will have several functions, including the possibility to destroy the cancer cells, also to activate the immune system, which is usually suppressed in the patients with GBM or with other kinds of cancers. The antibody is a defined structure and has defined elements performing specific functions, and we can exchange those elements for other elements of different functions. And by this, producing a multifunctional antibody.
To recap, Dr. Debinski’s team is advancing methods to deliver drugs to very specific parts of multiple cells (for example, all cell nuclei, and only the nuclei, in a tumor), delivering drug loads across the highly impermeable blood-brain barrier, and the manufacture of a super-antibody to kill cancer cells and awaken the immune system. But with this, and many other projects like it worldwide, how close are we to a cure for cancer?
I think that now, in the field of neuro-oncology, we have achieved a critical mass of people interested in working on brain tumors. Working from different angles, and trying to understand the disease, and also trying to design new therapeutic approaches. And I remain optimistic that, in the next decades, we’ll be making much faster progress, and bring almost an end to cancer as we see it now.
This Time Round, the theme music for SciWorks Radio, appears as a generous contribution by the band Storyman and courtesy of UFOmusic.com.
american cancer society #dr. waldemar debinski #wake forest baptist #tumor center of excellence at wake forest baptist #national cancer institute #national institutes of health #glioblastoma
Science Normal Tweet