1) A drug first identified 150 years ago and used as a smooth-muscle relaxant might make tumors more sensitive to

radiation therapy, according to a recent study led by researchers at The Ohio State University Comprehensive
Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James).The
researchers found that the drug called papaverine, inhibits the respiration of mitochondria, the oxygen-consuming
and energy-making components of cells, and sensitizes model tumors to radiation. They found that the drug does
not affect the radiation sensitivity of well-oxygenated normal tissues.

Additionally, the researchers showed that modifying the papaverine molecule might improve the safety of the
molecule and could represent a new class of radiosensitizing drugs that have fewer side effects.

The researchers report their findings in the Proceedings of the National Academy of Sciences. The journal includes
a commentary noting that the study "represents a potential landmark in the six-decade-old quest to eliminate
hypoxia as a cause for radiotherapy treatment failure."

"We know that hypoxia limits the effectiveness of radiation therapy, and that's a serious clinical problem because
more than half of all people with cancer receive radiation therapy at some point in their care," says principal
investigator Nicholas Denko, PhD, MD, professor of radiation oncology at the OSUCCC -- James.

"We found that one dose of papaverine prior to radiation therapy reduces mitochondrial respiration, alleviates
hypoxia, and greatly enhances the responses of model tumors to radiation," Denko says.

Radiation kills cancer cells in two ways: directly, by damaging DNA, and indirectly, by generating reactive, damage-
causing molecules called oxygen radicals. Hypoxic conditions reduce the generation of radiation-induced DNA
damage and the effective toxicity of a dose of radiation.

"If malignant cells in hypoxic areas of a tumor survive radiation therapy, they can become a source of tumor
recurrence," Denko says. "It's critical that we find ways to overcome this form of treatment resistance."

Tumor hypoxia is a consequence of oxygen demand and supply. Cancer cells require high levels of oxygen to fuel
their rapid growth, which can be so great that it outpaces the delivery of oxygen from the blood supply. Poorly
formed blood vessels in the tumor are not efficient at delivering oxygen and other nutrients. Insufficient oxygen
causes pockets of dead, necrotic cells surrounded by areas of hypoxia. Cancer cells in hypoxic regions at a distance
from the blood vessel can also be beyond the reach of chemotherapy and be resistant to radiation.

Strategies to overcome radiation resistance typically focus on delivering more oxygen to the tumor, Denko says.
"But these attempts have met with little clinical success because tumors have poorly formed vasculature," he adds.
"We took the opposite approach. Rather than attempting to increase oxygen supply, we reduced the oxygen
demand, and these findings suggest that papaverine or a derivative is a promising metabolic radiosensitizer."

2) Harvard University researchers have bioengineered a three-dimensional model of a human left heart ventricle
that could be used to study diseases, test drugs and develop patient-specific treatments for heart conditions such
as arrhythmia.The tissue is engineered with a nanofiber scaffold seeded with human heart cells. The scaffold acts
like a 3D template, guiding the cells and their assembly into ventricle chambers that beat in vitro. This allows
researchers to study heart function using many of the same tools used in the clinic, including pressure-volume
loops and ultrasound.

The research is published in Nature Biomedical Engineering.

"Our group has spent a decade plus working up to the goal of building a whole heart and this is an important step
towards that goal," said Kit Parker, the Tarr Family Professor of Bioengineering and Applied Physics at the Harvard
John A. Paulson School of Engineering and Applied Sciences and senior author of the study. "The applications, from
regenerative cardiovascular medicine to its use as an in vitro model for drug discovery, are wide and varied."

Parker is also a Core Faculty Member of the Wyss Institute for Biologically Inspired Engineering at Harvard, the
Harvard Stem Cell Institute and the Harvard Materials Research Science and Engineering Center.
The research was a collaboration between SEAS, Wyss, Boston Children's Hospital and the Harvard Stem Cell
Institute (HSCI).

"The long-term objective of this project is to replace or supplement animal models with human models and
especially patient-specific human models," said Luke MacQueen, first author of the study and postdoctoral fellow
at SEAS and Wyss. "In the future, patient stem cells could be collected and used to build tissue models that
replicate some of the features of their whole organ."

"An exciting door is opened to make more physiological models of actual patient diseases," said William Pu, the
Director of Basic and Translational Cardiovascular Research at Boston Children's Hospital, a Professor of Pediatrics
at Harvard Medical School, Principal Faculty member of HSCI and co-author of the paper. "Those models share not
only the patient mutations, but all of the genetic background of the patient."

The key to building a functional ventricle is recreating the tissue's unique structure. In native hearts, parallel
myocardial fibers act as a scaffold, guiding brick-shaped heart cells to align and assemble end-to-end, forming a
hollow, cone-shaped structure. When the heart beats, the cells expand and contract like an accordion.

To recreate that scaffold, the researchers used a nanofiber production platform known as pull spinning, developed
in Parker's Disease Biophysics Group. Pull spinning uses a high-speed rotating bristle that dips into a polymer
reservoir and pulls a droplet from the solution into a jet. The fiber travels in a spiral trajectory and solidifies before
detaching from the bristle and moving toward a collector.

To make the ventricle, the researchers used a combination of biodegradable polyester and gelatin fibers that were
collected on a rotating collector shaped like a bullet. Because the collector is spinning, all of the fibers align in the
same direction.

"It is important to recapitulate the structure of the natural muscle to obtain ventricles that function like their
natural counterparts," said MacQueen. "When the fibers are aligned, the cells will be aligned, which means they
will conduct and contract the way that native cells do."

After building the scaffold, the researchers cultured the ventricle with either rat myocytes or human
cardiomyocytes from induced stem cells. Within three to five days, a thin wall of tissue covered the scaffold and
cells were beating in synch. From there, researchers could control and monitor the calcium propagation and insert
a catheter to study the pressure and volume of the beating ventricle.

The researchers exposed the tissue to isoproterenol, a drug similar to adrenaline, and measured as the beat-rate
increased just as it would in human and rat hearts. The researchers also poked holes in the ventricle to mimic a
myocardial infarction, and studied the effect of the heart attack in a petri dish that resulted.

To better study the ventricle over long periods of time, the researchers built a self-contained bioreactor with
separate chambers for optional valve inserts, additional access ports for catheters and optional ventricular assist
capabilities.

Using human cardiomyocytes from induced stem cells, the researchers were able to culture the ventricles for 6
months and measure stable pressure-volume loops. "The fact that we can study this ventricle over long periods of
time is really good news for studying the progression of diseases in patients as well as drug therapies that take a
while to act," said MacQueen.

Next, the researchers aim to use patient-derived, pre-differentiated stem cells to seed the ventricles, which would
allow for more high-throughput production of the tissue.

"We started by learning how to build cardiac myocytes, then cardiac tissues, then muscular pumps in the form of
marine organism mimics, and now a ventricle," said Parker. "Along the way we have elucidated some of the
fundamental design laws of muscular pumps and developed ideas about how to fix the heart when these laws are
broken by disease. We have a long way to go to build a four-chamber heart but our progress is accelerating."
3) Phantoms are not just ghostly figures of our imagination, they are also numerical or physical models that
represent human characteristics and provide an inexpensive way to test electromagnetic applications. Sossena
Wood, a bioengineering PhD candidate at the University of Pittsburgh, has developed a realistic phantom head for
magnetic resonance research in the Swanson School of Engineering.Wood started her tenure at Pitt as an
undergraduate student in the Department of Electrical and Computer Engineering where she met Tamer Ibrahim,
an associate professor of bioengineering. She began research in his lab, the Radiofrequency (RF) Research Facility,
during her senior year and is now finishing her dissertation incorporating similar research as a graduate student in
the Department of Bioengineering.

Ibrahim envisioned designing a 3D printed phantom head to use with the uniquely designed ultrahigh field
technology in his lab. "In the RF Research Facility, we use a whole-body 7 Tesla magnetic resonance imager (7T
MRI), which is one of the strongest clinical human MRI devices in the world," said Ibrahim. 7T ultrahigh field
technology is a powerful tool, but unfortunately, there are a few setbacks that come with this type of imaging.

"As you move from lower to higher fields, the images produced become less uniform and localized heating
becomes more prevalent," explained Ibrahim. "We wanted to develop an anthropomorphic phantom head to help
us better understand these issues by providing a safer way to test the imaging. We use the device to analyze,
evaluate, and calibrate the MRI systems and instrumentation before testing new protocols on human subjects."

Researchers are currently using numerical simulations to study the effect of electromagnetic (EM) fields on
biological tissues at varying frequencies. Wood said, "EM numerical modeling has been a standard when analyzing
these interactions, and we wanted to create a phantom that resembled the human form for use in validating the
EM modeling, thereby providing a more realistic environment for testing."

Before Wood could print the 3D structure, she had to do computational work to build the digital blueprint for the
model. She started with a 3T MRI dataset of a healthy male, which she characterized by segmentation and broke
into eight tissue compartments, a feature that differentiates her model from other basic phantom heads.
According to Wood, these compartments help improve image accuracy by acting as a sort of "speed bump" for the
field.

After the computational preparations, Wood used an MRI scanner to produce a 3D-digital image of healthy male's
head and ran her model through computer-aided design, which is software used to create, modify, analyze, and
optimize a design.

The next step was to print the prototype, which took three semesters to complete. "We used a plastic developed
by DSM Somos® for our printing material because it allowed us to create durable and detailed parts with a similar
conductivity to the human body," said Wood. "To help the model further mimic a real environment, we created
filling ports on the prototype where we can deposit fluids that resemble various tissue types."

Now that Wood has a fully printed anthropomorphic phantom head, she is able to assemble it and begin testing.
The phantom has many applications including testing to see if certain implants are able to go inside of an MRI or
detecting the temperature rise in different tissues based on various RF instrumentation.

"With MR imaging, the power from the RF exposure is transformed into heat in the patient's tissue, which can
have detrimental effects on the patient's health, especially with implants if not monitored by the scanner"
explained Wood. "With our phantom head, we can test the safety of our imaging by putting probes inside of
certain regions of the head and measuring the effects," said Ibrahim.

Ibrahim and Wood hope that this model will eventually be developed commercially and provide others with the
ability to pursue research without relying on human testing.

4) Scientists at Tokyo Institute of Technology (Tokyo Tech) have discovered a means of reducing muscle atrophy by
the addition of the soy-derived isoflavone aglycone (AglyMax) to the diet of mice. This attenuation by soy
isoflavone is attributable to block the apoptosis-dependent pathway in muscle fiber. The AglyMax supplement also
anticipate to attenuate age-related muscle loss, sarcopenia.
Healthy muscles are integral to overall good health, as muscle mass is important for appropriate metabolism and
mobility. Unfortunately, as the population of ageing individuals increases worldwide, and people adopt a more
sedentary lifestyle, healthy muscles can be deprived of activity and gradually waste away. Such a process can also
occur in individuals with long term injuries. This condition, called atrophy, can result in a myriad of constraints in
an individual's life. Although adequate exercise and nutrition normally help maintain healthy muscle mass,
hormone therapy and dietary supplements have also been shown to be effective. In particular, isoflavones found
in soy products are known to possess marked anti-oxidant potential. Studies have also shown the beneficial effects
of isoflavones on muscle mass in mice and other rodents.

Kunihiro Sakuma and colleagues expanded on this knowledge and sought to investigate whether a dietary
isoflavone aglycone (AglyMax) could inhibit muscle atrophy? They used a mouse model to address this question. In
order to induce a muscle atrophy condition, they removed the sciatic nerve connection to the calf muscle of mice.
Consequently, the muscle was deprived of nerve stimulations, leading to gradual atrophy of the muscle and
catastrophic loss of muscle mass.

Two groups of mice with severed sciatic nerves of the left leg were fed either a normal diet or a diet supplemented
with AglyMax. After 2 weeks, the muscles from these mice were compared. The mice on the AglyMax diet were
found to have substantially thicker muscle fibers in the affected muscle, compared to those on a normal diet.

The scientists also sought to determine the way in which isoflavones reduced muscle atrophy. In doing so, they
found that isoflavone-based diet inhibited muscle cell death (apoptosis).

Despite such crucial insights, the scientists evaluated the effect of the soy supplementation in denervated muscles
only; therefore, it remains to be seen whether soy-supplementation plays a similar therapeutic role for other
conditions, like ageing related atrophy. There is hope that future studies will clarify both the role that isoflavones
play in modulating muscle atrophy, as well as its possible therapeutic application in individuals with muscle
atrophy due to ageing or illness.

5) A ten-year decline in the blood cholesterol of heart attack patients in Malaysia suggests that statins are having a
positive impact, according to an observational study in nearly 49,000 patients presented at the ASEAN Federation
of Cardiology Congress 2017 (AFCC2017).

AFCC2017 is being hosted by the Brunei Cardiac Society, with the support of the ASEAN Federation of Cardiology,
on 3 to 5 November in Brunei Darussalam. Experts from the European Society of Cardiology (ESC) will present a
special programme.1

"Lifestyle changes appear to be responsible for falls in blood cholesterol in the general populations of developed
nations while statins have reduced cholesterol in patients with heart disease," said lead author Dr Sazzli Kasim,
Chair, Malaysian Society of Atherosclerosis and Associate Professor of Medicine, University Technology MARA,
Shah Alam, Malaysia.2,3,4

"Blood cholesterol is still on the rise in the general population of developing countries like Malaysia," he
continued.5 "This study investigated trends in cholesterol levels in Malaysian patients with acute coronary
syndromes."

The study included 48 851 patients who had an acute coronary syndrome between 2006 and 2015 in Malaysia and
were enrolled in the National Cardiovascular Disease Database Acute Coronary Syndrome (NCVD-ACS) Registry.
This ongoing registry is maintained by the National Heart Association Malaysia with the support of the Ministry of
Health Malaysia. Total cholesterol was assessed on entry to the registry.

The researchers examined trends in cholesterol levels of ACS patients over the ten year period and compared
them to previously published values for the entire population.

The investigators found a significant trend for declining total cholesterol from 2006 to 2015 in the ACS population
(p =0.012). This was opposite to the total cholesterol trend in the Malaysian population.
ACS patients with a history of coronary heart disease had almost twice the declining rate in cholesterol as those
with no history of coronary heart disease.

When the researchers examined total cholesterol by type of ACS, they found that patients with unstable angina
had the lowest total cholesterol but the steepest rate of decline, followed by patients with non-ST-elevation
myocardial infarction and then patients with ST-elevation myocardial infarction.

Dr Kasim said: "We found that blood cholesterol levels have been falling in Malaysian patients with acute coronary
syndromes, which is the opposite of the national trend."

"Since cholesterol levels have increased significantly in the Malaysian population as a whole, it is highly doubtful
that lifestyle change is the reason for the declining cholesterol trend we observed in the ACS population," he
continued.

Dr Kasim said: "While this was an observational study and we cannot infer causality, it seems likely that cholesterol
levels decreased as the result of lipid lowering medication such as statins. ACS patients with a history of coronary
heart disease, who were more likely to be taking statins, had a more rapid decline in cholesterol levels than those
without a history of coronary heart disease."

He concluded: "These results appear to mimic findings from developed countries in previous years and show that
the Malaysian population is reaching similar health milestones. The findings also highlight the need to increase
awareness of the harm of raised lipid values and the treatment available."

Dr Ezam Emran, scientific chair of AFCC2017, said: "This large study suggests that statins are being effectively used
by heart attack patients in Malaysia. Rising lipid levels in the general population need to be tackled by promoting
healthier lifestyles."

Professor Michel Komajda, a past president of the ESC and course director of the ESC programme in Brunei, said:
"The benefits of statins for preventing a second heart attack are unequivocal, as highlighted by the 2017 ESC
guidelines.6 Patients should also be encouraged to quit smoking, adopt a healthier diet and be physically active."

Materials provided by European Society of Cardiology (ESC). Note: Content may be edited for style and length.

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