altered Salmonella typhimurium
that showed no toxicity and a lack of the enzyme purine holds promise in
the treatment of brain tumor.
- Brain tumor cells
are rich in purine, which leads the bacterium to the tumor cells. P53 and
azurin aid in killing the tumor cells.
- 20% improvement
in survival was noticed in the experimental studies, indicating the
potential use of this bacterium in the treatment of glioblastomas.
team of biomedical engineers from Duke University are using a strain of salmonella
, which is known for its
ability to cause food poisoning, in their fight against brain cancer.
Glioblastoma is an aggressive form of brain cancer
for which therapy has been difficult due
to the blood brain barrier preventing the passage of drugs to the brain.
Surgery too has proven to be ineffective as even small remnants of cells can
lead to the growth and development of the tumor.
research team from Duke University wanted an aggressive treatment method that
would aid in curbing the aggressive disease. This prompted them to focus on the
bacterium Salmonella typhimurium
was altered to form a cancer striking missile through genetic engineering. When
these genetically altered Salmonella
were tested in rats, there was a 20% increase in the survival rate over 100
days, which could be correlated to 10 human years with complete remission of
the tumor. The improvement in the survival rate of the rats with glioblastoma
is considered a huge success by the team of researchers, considering that
glioblastoma is very aggressive and difficult to treat.
‘Treatment of glioblastoma using genetically altered Salmonella typhimurium could herald a more specific method of treatment.’
results of the study were published in the Journal Molecular Therapy- Oncolytics
research was conducted in the laboratory of Dr. Ravi Bellamkonda who is the
Dean of Duke's School of Engineering. Very few people survive glioblastoma for
a long period and so, a 20% increase in survival rate was very encouraging and
phenomenal, according to the researchers who undertook the study.
idea to introduce Salmonella typhimurium
was obtained from earlier studies that showed that the presence of infection
activated the immune system to attack the tumors. Although later studies that
dealt with the use of genetically detoxified Salmonella
did not prove effective.
order to convert the intestinal bacteria into an organism that would seek out
cancer cells, Bellamkonda along with senior author Nalini Mehta selected a
detoxified strain of S. typhimurium
which lacked a vital enzyme called purine.
This forced the bacteria to look
for supplies of this enzyme. Tumors happen to be rich in purine, which
directs these detoxified bacteria to the tumors in large numbers.
Killing Tumor Cells
bacteria were also genetically altered to produce two compounds called p53 and
Azurin which prompted the cells to commit suicide when there was a low level of
oxygen. During the growth of cancers, the cells divide and grow very rapidly
leading to a condition of low oxygen.
Ravi Bellamkonda said that the major challenge in treating the gliomas is that
there was no clear demarcation between cancerous cells and non-cancerous cells,
which increased the difficulty of removing the cancer using surgical methods.
The scientist further stated that designing bacteria that would seek out the
tumors and ill specifically tumor cells due to the hypoxic (deprived of
adequate oxygen) conditions maintained and due to the rich source of purine was
exciting. The toxicity of the bacterium was deactivated which meant that they
would not lead to infections on their own. When asked about how the bacterium
would be cleared, Dr. Ravi stated that since their natural food source would be
depleted as soon as the tumor is cleared, the bacterium would be wiped out too.
Delivery of the Bacteria
research team injected the altered bacterium directly into the brain of the
rats under study. The course of action among human trials would be an inclusion
of the bacterium after surgical removal of the primary tumor. The treatment was
found to be successful in 20% of the rats and led to regression of the tumor,
increasing their life by 100 days.
Among the 80% of the rats for which the
treatment did not increase survival, it did not affect the length of time the
rats survived. The failure to treat these rats were concluded to be due to:
- Poor bacterial
- Aggressive growth
of the tumor which far exceeded the growth of the bacterium.
the rats showed an initial improvement, irrespective of the survival rate in
the end. The researchers believe this required a need to monitor the
progression of the treatment and the need to provide continued doses over a
period of time. This was the first attempt by the research team to identify a
novel method of treatment of glioblastomas and they have been successful in
identifying certain nuances that increased the survival rate, at least for some
research team is now working on altering the bacteria to produce drugs that
would have a stronger effect on the tumors. The researchers are, however,
cautious as the drugs will not be very specific to the tumors and could lead to
the development of side effects.
tumors develop from the astrocytes, which are star-shaped cells with glue like
and form the supportive tissue of the brain. They are highly malignant,
reproduce quickly and are supported by an extensive network of blood vessels.
tumors are found in the cerebral hemispheres of the brain, but can also be
found at different places in the brain and the
are a combination of
different cell types and could also contain cystic mineral, blood vessels,
mixed grade of cells and calcium deposits.
glioblastoma, a large number of tumor cells develop and are suitable nourished
by considerable blood supply. There are dead cells that are found in the center
of the tumor but since these cells originate in the brain, they grow well in
the brain but rarely spread to other parts of the body, and they are nourished
by an ample blood supply.
common symptoms are increased pressure in the brain, headache, nausea,
vomiting, drowsiness, weakness in one part of the body, memory or speech
difficulties and eye problems.
- 15.4% of all
primary brain tumors
- 60-75% of all
- More frequent
in older adults and constitute only 3% of childhood brain
The cause or the exact mechanism is
unknown for glioblastoma. They are difficult to treat as they consist of
different types of cells and do not respond well to therapies.
current study that uses genetically altered Salmonella
holds promise in the treatment of this form of cancer, an
increase in the survival rate and remission of cancer has for so long been
elusive in the treatment methods utilized thus far.
- Nalini Mehta, Johnathan G. Lyon, Ketki Patil, Nassir Mokarram, Christine Kim, Ravi V. Bellamkonda,"Bacterial Carriers for Glioblastoma Therapy." Molecular Therapy - Oncolytics, 2016. DOI: 10.1016/j.omto.2016.12.003
- Glioblastoma (GBM) - (http://www.abta.org/brain-tumor-information/types-of tumors/glioblastoma.html)