From: intraphase@gmail.com

https://www.medicalnewstoday.com/articles/319467.php



Poliovirus kills off cancer cells, stops tumor regrowth
Published Thursday 21 September 2017
By Ana Sandoiu
t cells attacking cancer cells
The modified poliovirus appears to enable T cells to attack cancer cells Researchers from Duke University in Durham, NC, may have discovered a new way of killing off cancer cells.

The team was jointly led by Dr. Matthias Gromeier, a professor in the Department of Neurosurgery, and Prof. Smita Nair, who is an immunologist in the
Department of Surgery.

The new research - which is published in the journal Science Translational Medicine - shows how a modified poliovirus enables the body to use its own resources to fight off cancer. The modified virus bears the name of recombinant
oncolytic poliovirus (
PVS-RIPO).

PVS-RIPO has been in clinical trials since 2011 and preliminary results have offered hope to patients with one of the most aggressive forms of brain tumor: recurrent glioblastoma. So, the researchers set out to investigate more deeply how exactly PVS-
RIPO works.

Explaining the rationale behind their research endeavor, Dr. Gromeier says, "Knowing the steps that occur to generate an immune response will enable us to rationally decide whether and what other therapies make sense in combination with poliovirus to
improve patient survival."
Poliovirus attacks tumors, inhibits regrowth

The researchers examined the behavior of the poliovirus in two human cell lines: melanoma and triple-negative breast cancer. They observed that the poliovirus attaches itself to cancerous cells. These cells have an excess of the CD155 protein, which acts
as a receptor for the poliovirus.

Then, the poliovirus starts to attack the malignant cells, triggering the release of antigens from the tumor. Antigens are toxic substances that the body
does not recognize, therefore setting off an immune attack against them.

So, when the tumor cells release antigens, this alerts the body's immune system
to start attacking. At the same time, the poliovirus infects the dendritic cells and macrophages.

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Dendritic cells are cells whose role it is to process antigens and "present" them to T cells, which are a type of immune cell. Macrophages are another type of immune cell - namely, large white blood cells whose main role is to rid our bodies of debris
and toxic substances.

The cell culture results - which the researchers then verified in mouse models - showed that once PVS-RIPO infects the dendritic cells, these cells "tell" T cells to start the immune attack.

Once started, this process seems to be continuously successful. The cancer cells continue to be vulnerable to the immune system's attack over a longer period of time, which appears to stop the tumor from regrowing.

As Prof. Nair explains, "Not only is poliovirus killing tumor cells, it is also
infecting the antigen-presenting cells, which allows them to function in such a
way that they can now raise a T cell response that can recognize and infiltrate
a tumor."

"This is an encouraging finding, because it means the poliovirus stimulates
an innate inflammatory response."

Prof. Smita Nair

Speaking to Medical News Today about the clinical implications of the findings and the scientists' directions for future research, Dr. Gromeier said, "Our findings provide clear rationales for moving forward with clinical trials in breast cancer,
prostate cancer, and malignant melanoma."

"This includes novel combination treatments that we will pursue," he added.

More specifically, he explains, because the study revealed that after treatment
with the poliovirus "immune checkpoints are increased on immune cells," a future strategy the researchers plan to explore is "[oncolytic] poliovirus combined with immune
checkpoint blockade."

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From: intraphase@gmail.com

Nerve implant 'restores consciousness' to man in persistant vegetative state

https://www.theguardian.com/science/2017/sep/25/nerve-implant-restores-consciousness-to-man-in-vegetative-state

Stimulation of the vagus nerve allows patient who had been in a persistant vegetative state for 15 years to track objects with his eyes and respond to simple requests
Information sharing across all electrodes before and after vagus nerve stimulation (VNS). On the right, the warmer colours indicate an increase in connectivity among brain regions responsible for planned movements, spatial reasoning and attention.
On the right, the warmer colours indicate an increase in connectivity following
vagus nerve stimulation among brain regions responsible for planned movements, spatial reasoning and attention. Illustration: Corazzol et al.



A 35-year-old man who had been in a persistant vegetative state (PVS) for 15 years has shown signs of consciousness after receiving a pioneering therapy involving nerve stimulation.

The treatment challenges a widely-accepted view that there is no prospect of a patient recovering consciousness if they have been in PVS for longer than 12 months.

Since sustaining severe brain injuries in a car accident, the man had been completely unaware of the world around him. But when fitted with an implant to stimulate the vagus nerve, which travels into the brain stem, the man appeared to flicker back into
a state of consciousness.

He started to track objects with his eyes, began to stay awake while being read
a story and his eyes opened wide in surprise when the examiner suddenly moved her face close to the patient’s. He could even respond to some simple requests, such as
turning his head when asked – although this took about a minute.
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Angela Sirigu, who led the work at the Institut des Sciences Cognitives Marc Jeannerod in Lyon, France, said: “He is still paralysed, he cannot talk, but he can respond. Now he is more aware.”

Niels Birbaumer, of the University of Tübingen and a pioneer of brain-computer
interfaces to help patients with neurological disorders communicate, said the findings, published in the journal Current Biology, raised pressing ethical issues. “Many of
these patients may and will have been neglected, and passive euthanasia may happen often in a vegetative state,” he said. “This paper is a warning to all those believing that this state is hopeless after a year.”

The vagus nerve, which the treatment targeted, connects the brain to almost all
the vital organs in the body, running from the brain stem down both sides of the neck, across the chest and into the abdomen. In the brain, it is linked directly to two
regions known to play roles in alertness and consciousness.

In surgery lasting about 20 minutes, a small implant was placed around the vagus nerve in the man’s neck. After one month of vagal nerve stimulation, the patient’s attention, movements and brain activity significantly improved and he had shifted into
a state of minimal consciousness.

Recordings of brain activity also revealed major changes, with signs of increased electrical communication between brain regions and significantly more
activity in areas linked to movement, sensation and awareness.

Similar stimulation has already been shown to help some patients with epilepsy and depression.

Sirigu and her team now hope to apply the same technique to patients with less serious brain injuries, where even more substantial improvements might be possible. There may even be patients, she said, whose cortex (the part of the brain used for
cognitive tasks) is intact, but who have brain stem injuries that have led to limited awareness or consciousness.

The findings offer hope to the families of patients in PVS that it may one day be possible to re-establish some basic form of communication. However, some might also question whether such patients would wish to be made more acutely aware of being in a
severely injured state.
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“I cannot answer to this question,” said Sirigu. “Personally I think it’s better to be aware, even if it’s a bad state, to be conscious of what’s happening. Then you can have a decision if you want to go on or if you
want [euthanasia].”

Damian Cruse, a cognitive neuroscientist at the University of Birmingham, described the findings as “pretty exciting”, adding that in future it might
be possible to combine vagal nerve stimulation with other forms of rehabilitation.

“If you can just push the patient over the threshold so they can start responding to external stimulation you can maybe help them follow speech therapy and get them to a level where they can start to communicate,” he said.

During the past decade, scientists have made major advances in communicating with “locked in” patients using various forms of brain-computer interface.

These have allowed paralysed patients, some of whom had been assumed to be in PVS, to answer “yes” or “no” to questions to let their family and friends know their wishes and their state of wellbeing.

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* Origin: www.darkrealms.ca (1:229/2)

From: david.j.worrell@gmail.com

On Tuesday, September 26, 2017 at 10:50:28 AM UTC-7, LowRider44M wrote:

A 35-year-old man who had been in a persistant vegetative state (PVS) for 15

years has shown signs of consciousness after receiving a pioneering therapy involving nerve stimulation.

Wow, I wonder if this therapy might work on Slider and thang?

--- SoupGate-Win32 v1.05
* Origin: www.darkrealms.ca (1:229/2)

From: slider@anashram.org

On Tue, 26 Sep 2017 21:45:03 +0100, Jeremy H. Denisovan <david.j.worrell@gmail.com> wrote:

On Tuesday, September 26, 2017 at 10:50:28 AM UTC-7, LowRider44M wrote:

A 35-year-old man who had been in a persistant vegetative state (PVS)
for 15 years has shown signs of consciousness after receiving a
pioneering therapy involving nerve stimulation.

Wow, I wonder if this therapy might work on Slider and thang?

### - haha physician heal thyself??

iow: try it on yourself first, and if there's 'any' improvement whatsoever thang will try it next :)

plus here's how to make it actually work for us by proxy jeremy: just ramp
it up to around 60 amps, plug yourself in, flip the switch, and OUR
problem goes away virtually instantaneously! tada! ;)

pretty neat huh :)))

--- SoupGate-Win32 v1.05
* Origin: www.darkrealms.ca (1:229/2)

From: intraphase@gmail.com

On Tuesday, September 26, 2017 at 4:45:04 PM UTC-4, Jeremy H. Denisovan wrote:

On Tuesday, September 26, 2017 at 10:50:28 AM UTC-7, LowRider44M wrote:

A 35-year-old man who had been in a persistant vegetative state (PVS) for

15 years has shown signs of consciousness after receiving a pioneering therapy involving nerve stimulation.

Wow, I wonder if this therapy might work on Slider and thang?

:-)

So many breakthroughs I figured a cache thread.

--- SoupGate-Win32 v1.05
* Origin: www.darkrealms.ca (1:229/2)

From: intraphase@gmail.com

'Chemical surgery' used to mend harmful mutations in human embryos

https://www.theguardian.com/science/2017/sep/28/chemical-surgery-used-to-mend-harmful-mutations-in-human-embryos-base-editing

Scientists have used the technique, also known as ‘base editing’, for the first time in human embryos to change a single letter in a faulty gene
Instead of cutting right through the double strand of the DNA helix like Crispr, the new technique changes single letters, or bases, of the G, T, A and C that make up the genetic code.
Instead of cutting right through the double strand of the DNA helix like Crispr, the new technique changes single letters, or bases, of the G, T, A and C that make up the genetic code. Photograph: Alamy Stock Photo


Ian Sample Science editor
@iansample

Thursday 28 September 2017 06.35 EDT
Last modified on Thursday 28 September 2017 09.44 EDT

Researchers in China have used a procedure described as “chemical surgery” to mend harmful mutations in human embryos for the first time.

The scientists found that it was possible to repair a faulty gene that gives rise to a serious blood disorder called beta thalassemia which can be caused by
one misspelling in the DNA code.

None of the embryos treated in the experiments were used to produce babies, and
doing so would be illegal in the UK and many other countries. But the work proves that the method, known in genetics as “base editing”, could be an effective way to
prevent inherited diseases. Base editing was dubbed “chemical surgery” by its inventor, David Liu at Harvard University.

In the past decade, scientists have developed a range of powerful tools to edit
the genetic code, the most popular of which is called Crispr-Cas9. The method uses enzymes to make precision cuts in faulty genes which the body can then repair with the
correct DNA.
Q&A
What is Crispr?

In 2015, scientists led by Junjiu Huang at Sun Yat-sen University in Guangzhou,
China, tried to use Crispr to correct abnormal beta thalassemia genes in human embryos without much success. In the latest breakthrough, the same team turned to base editing
instead.

To perform the experiments, Huang first created a batch of cloned embryos. His team took skin cells from patients with beta thalassemia, removed their DNA-containing nuclei, and dropped them into donor eggs that had their own nuclei removed. The eggs
then developed into early stage embryos that carried the beta thalassemia mutation.

Base editing uses similar enzymes to Crispr, but instead of cutting right through the double strand of the DNA helix, the enzymes instead change single letters, or bases, of the G, T, A and C that make up the genetic code. For many
patients with beta
thalassemia, the disease is caused by a mutation that switches an A for a G.

Writing in the journal Protein and Cell, the researchers show that the new procedure worked to some extent. Humans carry two copies, or alleles, of every gene and in many cases both versions have to be “healthy” to avoid disease.
In the study, base
editing sometimes repaired only one faulty gene rather than both, creating so-called mosaic embryos that had both normal and mutant cells. “This looks very promising, but all the embryos from which they were able to get information from more than one
cell were clearly mosaic, with some cells still carrying both mutant alleles,” said Robin Lovell-Badge at the Francis Crick Institute in London. The Guardian's Science Weekly Editing the embryo: removing harmful gene mutations - Science Weekly podcast
Hannah Devlin explores the science and ethics behind a landmark study that successfully edited the genomes of developing embryos
Listen

The Chinese team has not suggested that the procedure is ready to use in humans, especially as they found that it sometimes created mutations instead of
fixing them. But researchers do see a role of gene editing in preventing heritable diseases from
being passed on.

“For many years, we have been saying that direct gene editing in embryos is some way in to the future. Now the future is here and there is much to consider,” said Darren Griffin, a geneticist at the University of Kent. “The paper itself represents
a significant technical advance because, rather than using the classic Crispr technology previously reported, the current ‘base editor’ technology is an adaptation that chemically alters the DNA bases themselves.

“While this is undoubtedly a highly significant advance, it is important not to get carried away about its widespread utility if put into clinical practice.
An embryo would still need to be diagnosed as abnormal, then the base editor applied, then re-
diagnosed to make sure that it had worked. This would be an involved procedure that would be very expensive.

“In the meantime, the ethical implications of gene manipulation in embryos need a thorough examination where safety is of paramount concern.”

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