NYMPHAEA New Perfume Solid from Amrita Apothecary

HONEY LOTUS PERFUME SOLID

~ Nymphaea ~

A Lingering Aromatic for Biophilic Goddesses and Dancing Skin

For Women who wander somewhere between the Water Nymphs, Circus Silks, Garden Witches, Harps, Operas, Faery Lore, and Plant Addiction.

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Opening:

Clementine, Mandarin, Coriander, Roman Chamomile

Heart:

Beeswax, Jasmine Grandiflorum, Orange Blossom, White Lotus

Base Notes:

Cocoa, Peru Balsam, Himalayan Cedar, Jasmine Sambac.

Nymphaea is a decidedly feminine botanical perfume balm, carefully handcrafted and poured into a hand carved rosewood box. Concretes, attars, absolutes and oils are blended perfectly to illuminate the sweetness and round floral exaltation of Jasmine and Neroli, with none of the frequently unpleasant and aromatic conflicts of these two commanding flower queens.

Soft and gentle yet with beautiful holding power, Nymphaea lingers like a sensory dream ~ recalling visions of water lily encounters, romantic interludes under moonlit Jasmine vines, divinely joyful moments of belonging, and gracefully entwines the worlds of flower erotica and human devotion.

While each note plays an integral role in the perfume composition, they are there to hold, melt, highlight, and enrich the relationship of Jasmine and Neroli, the principal notes.

Things to do while wearing Nymphaea….

Take a ballet class

Dream

Wander in the fog

Kiss

Look closely at wild moss

Sip hot Cocoa

Write a love letter

Crochet with silk & wool

Make Vanilla extract

Go Ice Skating

Listen to Loreena McKennet

Play Chess

Read Jitterbug Perfume

Plant Narcissus

Paint with pastels

Schedule a massage

Make herbal honeys

~~~

Blends well with: Chandra, Mead, Consort, A Vacation.

~~~~~~

An Aromatic Treasure by Amrita Apothecary

2012

Available in the Shop

~~

Love,

Ananda

SCIENTISTS CREATE NEW PROTEIN BASED MATERIAL WITH SOME NERVE

Scientists at the University of California, Berkeley, have taken proteins from nerve cells and used them to create a "smart" material that is extremely sensitive to its environment. This marriage of materials science and biology could give birth to a flexible, sensitive coating that is easy and cheap to manufacture in large quantities.

The work, to be published Oct. 14, in the journal Nature Communications, could lead to new types of biological sensors, flow valves and controlled drug release systems, the researchers said. Biomedical applications include microfluidic devices that can handle and process very small volumes of liquid, such as samples of saliva or blood, for diagnostics.

"This work represents a unique convergence of the fields of biomimetic materials, biomolecular engineering and synthetic biology," said principal investigator Dr. Sanjay Kumar, UC Berkeley associate professor of bioengineering. "We created a new class of smart, protein-based materials whose structural principles are inspired by networks found in living cells."

Kumar's research team set out to create a biological version of a synthetic coating used in everyday liquid products, such as paint and liquid cosmetics, to keep small particles from clumping together. The synthetic coatings are often called polymer brushes because of their bristle-like appearance when attached to the particle surface.

To create the biological equivalent of a polymer brush, the researchers turned to neurofilaments, pipe cleaner-shaped proteins found in nerve cells. By acting as tiny, cylindrical polymer brushes, neurofilaments collectively assemble into a structural network that helps keep one end of the nerve cell propped open so that it can conduct electrical signals.

"We co-opted this protein and turned it into a polymer brush by cloning a portion of a gene that encodes one of the neurofilament bristles, re-engineering it such that we could attach the resulting protein to surfaces in a precise and oriented way, and then expressing the gene in bacteria to produce the protein in large, pure quantities," said Kumar. "We showed that our 'protein brush' had all the key properties of synthetic brushes, plus a number of advantages."

Kumar noted that neurofilaments are good candidates for protein brushes because they are intrinsically disordered proteins, so named because they don't have a fixed 3-D shape. The size and chemical sequence of these hair-like proteins are far easier to control when compared with their synthetic counterparts.

"In biology, precision is critical," said Kumar. "Proteins are generally synthesized with the exact same sequence every time; the length and biochemical order of the protein sequence affects all of its properties, including structure and the ability to bind to other molecules and catalyze biochemical reactions. This kind of sequence precision is difficult if not impossible to achieve in the laboratory using the tools of chemical synthesis. By harnessing the precision of biology and letting the bacterial cell do all the work for us, we were able to control the exact length and sequence of the bristles of our protein brush."

The researchers showed that the protein brushes could be grafted onto surfaces, and that they dramatically expand and collapse in reaction to changes in acidity and salinity. Materials that are environmentally sensitive in this way are often referred to as "smart" materials because of their ability to adaptively respond to specific stimuli.

LINK BETWEEN NEW BORN HEALTH AND VITAMIN D

The impact vitamin A has on newborns is virtually unknown, but Penn State nutrition researchers have published two papers that may provide a framework for future investigations of the vitamin and neonatal health.

After supplementing newborn rats with vitamin A, the researchers found that vitamin A distribution within the body increases suddenly but temporarily, with a significant amount found in tissues other than the liver. Vitamin A in adults is usually found in significant amounts in the liver.

Nutrition experts know that vitamin A is necessary for prenatal growth and development, as well as in older children; but the role of vitamin A remains unclear for the neonatal period. Stores of the vitamin become depleted as the fetus reaches full term, to the point where newborns are nearly depleted of vitamin A. Neonates born in developing countries are likely to have even lower amounts of vitamin A in their bodies.

"The World Health Organization recommends periodic vitamin A supplements to children living in developing countries," said A. Catharine Ross, professor of nutritional sciences and Dorothy Foehr Huck Chair. "Giving large doses of vitamin A to children 6 months to 5 years old has shown to decrease mortality by 23 percent. However, studies in children under 6 months have been inconclusive."

Ross and colleagues studied levels of vitamin A in rat pups for two weeks, from 4 days old to 18 days old, similar to neonatal age in children. Half the pups received a vitamin A supplement while the others did not receive any supplement -- serving as the control.

The researchers measured the pups' rate of vitamin A metabolism by sampling various organs and found that vitamin A was used very quickly. Retinol, which is a form that vitamin A takes in the body, isn't broken down immediately and is recycled between plasma and tissues. The pups that received the supplement experienced lower rates of recycling, however they had greater uptake of vitamin A in extravascular tissues.

The supplemented rats were also found to have an increased uptake of chylomicron retinyl ester -- another form that vitamin A takes in the body -- in the lungs, intestines and remaining tissue, and a decrease in retinol turnover out of the liver, compared to the unsupplemented rats, Ross and colleagues report in two recent articles published in the Journal of Lipid Research.

The researchers speculate that since the neonates are born with a low vitamin A level but have a high demand for it, the uptake of retinyl ester in tissues other than the liver is an adaptive mechanism to make more vitamin A available for use.

"This research provides us with a blueprint for humans, giving us a baseline set of data, in order to let us make comparisons in the future," said Ross. "By being able to better understand infants' nutritional needs, evidence-based dietary intake recommendations could be made and infant mortality could potentially be reduced, particularly in developing countries."

Also working on this research were Libo Tan, graduate student and postdoctoral fellow in nutritional sciences; Amanda E. Wray, research technologist in nutritional sciences; and Michael H. Green, professor of nutritional sciences.

 

Repairing Damaged Nerves New Developments

You may have to stretch your imagination somewhat to see how the treatments talked about in today's article from sciencedaily.com (see link below) will eventually lead to simple treatments for our sort of neuropathy. However, you can follow the logic and because these scientists are dealing with worst-case-scenarios in terms of nerve damage, it is to be hoped that certain principles may eventually be applied to less traumatic neuropathies. In our case we'll have to wait for top-down solutions. Nerve damage caused by war or accident wounds is clearly of a different order than the neuropathy we suffer from with whole bodies but one would think that all progress in nerve repair, will eventually be relevant to us.

Step Forward in Effort to Regenerate Damaged Nerves
ScienceDaily (Feb. 21, 2012)

The carnage evident in disasters like car wrecks or wartime battles is oftentimes mirrored within the bodies of the people involved. A severe wound can leave blood vessels and nerves severed, bones broken, and cellular wreckage strewn throughout the body -- a debris field within the body itself.

It's scenes like this that neurosurgeon Jason Huang, M.D., confronts every day. Severe damage to nerves is one of the most challenging wounds to treat for Huang and colleagues. It's a type of wound suffered by people who are the victims of gunshots or stabbings, by those who have been involved in car accidents -- or by soldiers injured on the battlefield, like those whom Huang treated in Iraq.

Now, back in his university laboratory, Huang and his team have taken a step forward toward the goal of repairing nerves in such patients more effectively. In a paper published in the journal PLoS ONE, Huang and colleagues at the University of Rochester Medical Center report that a surprising set of cells may hold potential for nerve transplants.

In a study in rats, Huang's group found that dorsal root ganglion neurons, or DRG cells, help create thick, healthy nerves, without provoking unwanted attention from the immune system.

The finding is one step toward better treatment for the more than 350,000 patients each year in the United States who have serious injuries to their peripheral nerves. Huang's laboratory is one of a handful developing new technologies to treat such wounds.

"These are very serious injuries, and patients really suffer, many for a very long time," said Huang, associate professor of Neurosurgery and chief of Neurosurgery at Highland Hospital, an affiliate of the University of Rochester Medical Center. "There are a variety of options, but none of them is ideal.

"Our long-term goal is to grow living nerves in the laboratory, then transplant them into patients and cut down the amount of time it takes for those nerves to work," added Huang, whose project was funded by the National Institute of Neurological Disorders and Stroke and by the University of Rochester Medical Center.

For a damaged nerve to repair itself, the two disconnected but healthy portions of the nerve must somehow find each other through a maze of tissue and connect together. This happens naturally for a very small wound -- much like our skin grows back over a small cut -- but for some nerve injuries, the gap is simply too large, and the nerve won't grow back without intervention.

For surgeons like Huang, the preferred option is to transplant nerve tissue from elsewhere in the patient's own body -- for instance, a section of a nerve in the leg -- into the wounded area. The transplanted nerve serves as scaffolding, a guide of sorts for a new nerve to grow and bridge the gap. Since the tissue comes from the patient, the body accepts the new nerve and doesn't attack it.

But for many patients, this treatment isn't an option. They might have severe wounds to other parts of the body, so that extra nerve tissue isn't available. Alternatives can include a nerve transplant from a cadaver or an animal, but those bring other challenges, such as the lifelong need for powerful immunosuppressant drugs, and are rarely used.

One technology used by Huang and other neurosurgeons is the NeuraGen Nerve Guide, a hollow, absorbable collagen tube through which nerve fibers can grow and find each other. The technology is often used to repair nerve damage over short distances less than half an inch long.

In the PLoS One study, Huang's team compared several methods to try to bridge a nerve gap of about half an inch in rats. The team transplanted nerve cells from a different type of rat into the wound site and compared results when the NeuraGen technology was was used alone or when it was paired with DRG cells or with other cells known as Schwann cells.

After four months, the team found that the tubes equipped with either DRG or Schwann cells helped bring about healthier nerves. In addition, the DRG cells provoked less unwanted attention from the immune system than the Schwann cells, which attracted twice as many macrophages and more of the immune compound interferon gamma.

While both Schwann and DRG cells are known players in nerve regeneration, Schwann cells have been considered more often as potential partners in the nerve transplantation process, even though they pose considerable challenges because of the immune system's response to them.

"The conventional wisdom has been that Schwann cells play a critical role in the regenerative process," said Huang, who is a scientist in the Center for Neural Development and Disease. "While we know this is true, we have shown that DRG cells can play an important role also. We think DRG cells could be a rich resource for nerve regeneration."

In a related line of research, Huang along with colleagues in the laboratory of Douglas H. Smith, M.D. , at the University of Pennsylvania are creating DRG cells in the laboratory by stretching them, which coaxes them to grow about one inch every three weeks. The idea is to grow nerves several inches long in the laboratory, then transplant them into the patient, instead of waiting months after surgery for the nerve endings to travel that distance within the patient to ultimately hook up.

http://www.sciencedaily.com/releases/2012/02/120221125018.htm

NEW WINDOW OF OPPORTUNITY TO PREVENT CARDIOVASCULAR DISEASES

Future prevention and treatment strategies for vascular diseases may lie in the evaluation of early brain imaging tests long before heart attacks or strokes occur, according to a systematic review conducted by a team of cardiologists, neuroscientists, and psychiatrists from Icahn School of Medicine at Mount Sinai and published in the October issue of JACC Cardiovascular Imaging.

For the review, Mount Sinai researchers examined all relevant brain imaging studies conducted over the last 33 years. They looked at studies that used every available brain imaging modality in patients with vascular disease risk factors but no symptoms that would lead to a diagnosis of diseased blood vessels (vascular disease) in the heart or brain, or periphery (e.g. arms and legs).

The review demonstrates that patients with high blood pressure, diabetes, obesity, high cholesterol, smoking, or metabolic syndrome, but no symptoms, still had visible signs on their neuroimaging scans of structural and functional brain changes long before the development of any events related to vascular diseases of the heart (heart attack) or brain (stroke).

"This is the first time we have been able to disentangle the brain effects of vascular disease risk factors from the brain effects of cardiovascular and cerebrovascular disease and/or events after they develop," says the article's lead author, Joseph I. Friedman, MD, Associate Professor in the Departments of Psychiatry and Neuroscience at Icahn School of Medicine at Mount Sinai. "Moreover, subtle cognitive impairment is an important clinical manifestation of these vascular disease risk factor-related brain imaging changes in these otherwise healthy persons."

Dr. Friedman added that, because diminished cognitive capacity adversely impacts a person's ability to benefit from treatment for these medical conditions, early identification of these brain changes may "present a new window of opportunity" for doctors to intervene early and improve prevention of advancement from vascular disease risk factors to established cardiovascular and cerebrovascular diseases. His team is currently testing these hypotheses in ongoing studies at Mount Sinai.

"Patients need to start today to control their vascular risk factors, otherwise their brains may forever harbor physical changes leading to devastating heart and vascular conditions impacting their future overall health and even cognitive decline causing diseases like dementia or when it exists it can accelerate Alzheimer's," says study author, Valentin Fuster, MD, PhD, Director of Mount Sinai Heart, Physician-in-Chief of The Mount Sinai Hospital, and Chief of the Division of Cardiology at Icahn School of Medicine at Mount Sinai. "Our publication raises the possibility that these early brain changes are major warning signs of what the future may hold for these asymptomatic patients. These high risk patients, along with their doctors, hold the power to modify their daily vascular risk factors to help halt the future course of the manifestation of their potentially looming cardiovascular diseases."

"We hope our publication serves as a primer for cardiologists and other doctors interpreting the early neuroimaging data of their patients who may be high risk for vascular disease," says senior article author Jagat Narula, MD, PhD, Director of Cardiovascular Imaging, Professor of Medicine and Philip J. and Harriet L. Goodhart Chair in Cardiology at Icahn School of Medicine at Mount Sinai. "These subtle brain changes are clues to us physicians that our patients need to start to lower their vascular risk factors always and way before symptoms or a cardiac or brain event happens. This simple step to lower vascular risk factors can have huge impacts on global prevention efforts of cardiovascular diseases."

Researchers identified the following impact of key vascular risk factors on the structural and functional brain health of asymptomatic patients:

o Hypertension is associated with globally appreciable brain volume reductions, connecting brain fiber abnormalities, reduced brain blood flow, and alterations in the normal pattern of synchronized brain activity between different regions.

o Diabetes is associated with connecting brain fiber abnormalities, reduced brain blood flow, and alterations in the normal pattern of synchronized brain activity between different regions.

o Obesity is associated with brain volume reductions, reduced brain blood flow and metabolism.

o High total cholesterol and LDL cholesterol are associated with brain volume reductions, and connecting brain fiber abnormalities. In addition, high triglycerides is associated with reduced brain blood flow, and high total cholesterol is associated with reduced brain metabolism.

o Smoking is associated with brain volume reductions, and alterations of the normal pattern of blood flow. In addition, it causes reduced MAO B (Monoamine Oxidase B) which metabolizes dopamine, the neurotransmitter chemical that controls the brain's reward and pleasure zones.

o Metabolic Syndrome is associated with a greater burden of silent brain infarcts (SBIs), visible only on MRI, which represents subclinical cerebrovascular disease. In addition, it is associated with connecting brain fiber abnormalities, and alterations in the normal pattern of synchronized brain activity between different regions.

Mirogabalin A New Drug For Neuropathy

Today's post from medivizor.com (see link below) looks at a new drug designed to treat neuropathic symptoms. It looks as though it may be a possible substitute for Lyrica (pregabalin) but with less side-effects and that has to be a good thing considering the bad press that pregabalin gets. As so often, the article is aimed at diabetics with neuropathy but if it's a possible substitute for pregabalin, then it will be prescribed for many people with neuropathy from other causes. The problem is, there has only been one small study on humans to date and whether the conclusions drawn are enough to convince you or not, there needs to be more research, especially on the effects on the various major forms and causes of neuropathy. Pregabalin, for instance, is issued to some neuropathy patients and is not recommended for others, depending on the cause of the nerve damage - clarity and evidence are essential.

Mirogabalin: a potential new drug to treat pain in diabetics with peripheral neuropathy
Posted by Medivizor on Jul 10, 2015 in Diabetes mellitus

In a nutshell

This study examined whether mirogabalin is safe and effective in diabetics with peripheral neuropathy. 

Some background

Chronic high blood glucose levels can lead to damage to blood vessels in patients with diabetes. This can result in various complications, such as eye disease, kidney disease and diabetic neuropathy. Diabetic neuropathy is a condition in which the nervous system becomes injured. Approximately 50% of diabetics who have neuropathy experience peripheral neuropathic pain (PNP – chronic pain in legs and arms). PNP can result in depression, anxiety and sleep disorders.

Pregabalin (Lyrica) is a drug currently used to treat PNP, however it is poorly tolerated. In addition, 50% of patients require pregabalin along with another drug in order to achieve pain relief. Mirogabalin is a similar drug to pregabalin, but is believed to have fewer side effects. Its use in treating PNP is currently being investigated.

Methods & findings

This study aimed to determine the safety and most effective dose of mirogabalin.

This study involved 452 diabetic patients divided into 7 groups. One group of patients received a placebo (a substance with no therapeutic effect). 5 groups received mirogabalin at different doses (5, 10, 15, 20 or 30 mg per day). One group received 300 mg pregabalin daily. Participants received the drug or placebo for 5 weeks.

Participants recorded their pain score at the start of the study and throughout the study. All participants had an average daily pain score greater than 4 (maximum score of 11). Mirogabalin had a clinically significant effect if it reduced the daily pain score by 1.

In comparison to the placebo group, participants receiving mirogabalin had a greater decrease in pain. This decrease was greater with a higher dose (pain score difference of -0.53 for 10 mg vs. -1.01 for 30 mg). This decrease was also greater than participants using pregabalin (pain score difference of -0.05 for pregabalin compared to placebo).

61% of participants experienced side effects. 9.4% experienced mild to moderate dizziness, while 6.1% experienced headaches.

The bottom line

This study concluded that 30 mg of mirogabalin reduces pain in diabetics with PNP and is well-tolerated. 

The fine print

This study only assessed the effects of mirogabalin over 5 weeks. It is not known whether mirogabalin is safe or effective for long-term use. As some participants experienced side effects, this drug may not be suitable for all patients. The author received funding from Daiichi Sankyo, the company who developed the drug.

Published By :
Diabetes Care

Date :

Sep 17, 2014

Original Title :

Efficacy and Safety of Mirogabalin (DS-5565) for the Treatment of Diabetic Peripheral Neuropathic Pain: A Randomized, Double-Blind, Placebo- and Active Comparator-Controlled, Adaptive Proof-of-Concept Phase 2 Study.

https://medivizor.com/blog/SampleLibrary/diabetes-mellitus/mirogabalin-a-potential-new-drug-to-treat-pain-in-diabetics-with-peripheral-neuropathy/

New Channel Found To Protect Against Pain

Today's post from medicalxpress.com (see link below) discusses the finding of a new ion channel which is present in the membranes of neurons and protects against pain sensations. Now this won't mean much to the average reader but basically, the mechanisms in nerve cells that cause burning pain (typical of neuropathy) have been and remain very poorly understood. It's now believed that this pain comes from continuous activity in the bundles of nociceptor fibers in and around nerve cells. A sort of continuous vibration of those fibers that causes irritation. The newly discovered channel of potassium ions is thought to calm this activity down thus reducing pain. This means that they can now look into ways of strengthening these channels so that they give better protection and strengthen their own activity, thus in theory, reducing pain. Again, it all sounds gobbledegook for most people but it's vitally important that this sort of close inspection of how nerve cells work continues, so that in the not too distant future, effective solutions can be developed. How long will it take? How long is a piece of string? However, it is encouraging that this sort of work is going on in the background so that one day we might be able to get off the chemical medications that are pretty ineffective in controlling our neuropathic symptoms.

Researchers identify innate channel that protects against pain
Provided by University of Bristol January 21, 2014

Scientists have identified a channel present in many pain detecting sensory neurons that acts as a 'brake', limiting spontaneous pain. It is hoped that the new research, published today [22 January] in the Journal of Neuroscience, will ultimately contribute to new pain relief treatments.

Spontaneous pain is ongoing pathological pain that occurs constantly (slow burning pain) or intermittently (sharp shooting pain) without any obvious immediate cause or trigger. The slow burning pain is the cause of much suffering and debilitation. Because the mechanisms underlying this type of slow burning pain are poorly understood, it remains very difficult to treat effectively.

Spontaneous pain of peripheral origin is pathological, and is associated with many types of disease, inflammation or damage of tissues, organs or nerves (neuropathic pain). Examples of neuropathic pain are nerve injury/crush, post-operative pain, and painful diabetic neuropathy.

Previous research has shown that this spontaneous burning pain is caused by continuous activity in small sensory nerve fibers, known as C-fiber nociceptors (pain neurons). Greater activity translates into greater pain, but what causes or limits this activity remained poorly understood.

Now, new research from the University of Bristol, has identified a particular ion channel present exclusively in these C-fiber nociceptors This ion channel, known as TREK2, is present in the membranes of these neurons, and the researchers showed that it provides a natural innate protection against this pain.

Ion channels are specialised proteins that are selectively permeable to particular ions. They form pores through the neuronal membrane. Leak potassium channels are unusual, in that they are open most of the time allowing positive potassium ions (K+) to leak out of the cell. This K+ leakage is the main cause of the negative membrane potentials in all neurons. TREK2 is one of these leak potassium channels. Importantly, the C-nociceptors that express TREK2 have much more negative membrane potentials than those that do not.

Researchers showed that when TREK2 was removed from the proximity of the cell membrane, the potential in those neurons became less negative. In addition, when the neuron was prevented from synthesizing the TREK2, the membrane potential also became less negative.

They also found that spontaneous pain associated with skin inflammation, was increased by reducing the levels of synthesis of TREK2 in these C-fiber neurons.

They concluded that in these C-fiber nociceptors the TREK2 keeps membrane potentials more negative, stabilizing their membrane potential, reducing firing and thus limiting the amount of spontaneous burning pain.

Professor Sally Lawson, from the School of Physiology and Pharmacology at Bristol University, explained: "It became evident that TREK2 kept the C-fiber nociceptor membrane at a more negative potential. Despite the difficulties inherent in the study of spontaneous pain, and the lack of any drugs that can selectively block or activate TREK2, we demonstrated that TREK2 in C-fiber nociceptors is important for stabilizing their membrane potential and decreasing the likelihood of firing. It became apparent that TREK2 was thus likely to act as a natural innate protection against pain. Our data supported this, indicating that in chronic pain states, TREK2 is acting as a brake on the level of spontaneous pain."

Dr Cristian Acosta, the first author on the paper and now working at the Institute of Histology and Embriology of Mendoza in Argentina, said "Given the role of TREK2 in protecting against spontaneous pain, it is important to advance our understanding of the regulatory mechanisms controlling its expression and trafficking in these C-fiber nociceptors. We hope that this research will enable development of methods of enhancing the actions of TREK2 that could potentially some years hence provide relief for sufferers of ongoing spontaneous burning pain."

The research, funded by the Wellcome Trust, was carried out in the School of Physiology and Pharmacology at the University of Bristol.

Explore further: Short circuit in molecular switch intensifies pain

More information: 'TREK2 Expressed Selectively in IB4-Binding C-Fiber Nociceptors Hyperpolarizes Their Membrane Potentials and Limits Spontaneous Pain' by Cristian Acosta, Laiche Djouhri, Roger Watkins, Carol Berry, Kirsty Bromage and Sally Lawson in the Journal of Neuroscience.

Journal reference: Journal of Neuroscience

http://medicalxpress.com/news/2014-01-innate-channel-pain.html 

CANCER NEW DEVICE YIELDS CLOSE UP LOOK AT METASTASIS

Johns Hopkins engineers have invented a lab device to give cancer researchers an unprecedented microscopic look at metastasis, the complex way that tumor cells spread through the body, causing more than 90 percent of cancer-related deaths. By shedding light on precisely how tumor cells travel, the device could uncover new ways to keep cancer in check

The inventors, from the university's Whiting School of Engineering and its Institute for NanoBioTechnology (INBT), published details and images from their new system recently in the journal Cancer Research. Their article reported on successful tests that captured video of human breast cancer cells as they burrowed through reconstituted body tissue material and made their way into an artificial blood vessel.

"There's still so much we don't know about exactly how tumor cells migrate through the body, partly because, even using our best imaging technology, we haven't been able to see precisely how these individual cells move into blood vessels," said Andrew D. Wong, a Department of Materials Science and Engineering doctoral student who was lead author of the journal article. "Our new tool gives us a clearer, close-up look at this process."

With this novel lab platform, Wong said, the researchers were able to record video of the movement of individual cancer cells as they crawled through a three-dimensional collagen matrix. This material resembles the human tissue that surrounds tumors when cancer cells break away and try to relocate elsewhere in the body. This process is called invasion.

Wong also collected video of single cancer cells prying and pushing their way through the wall of an artificial vessel lined with human endothelial cells, the same kind that line human blood vessels. By entering the bloodstream through this process, called intravasion, cancer cells are able to hitch a ride to other parts of the body and begin to form deadly new tumors.

To view these important early stages of metastasis, Wong replicated these processes in a small transparent chip that incorporates the artificial blood vessel and the surrounding tissue material. A nutrient-rich solution flows through the artificial vessel, mimicking the properties of blood. The breast cancer cells, inserted individually and in clusters in the tissue near the vessel, are labeled with fluorescent tags, enabling their behavior to be seen, tracked and recorded via a microscopic viewing system.

Wong's doctoral advisor, Peter Searson, the Joseph R. and Lynn C. Reynolds Professor of Materials Science and Engineering and director of the INBT, said his graduate student took on this challenging project nearly five years ago -- and ultimately produced impressive results.

"Andrew was able to build a functional artificial blood vessel and a microenvironment that lets us capture the details of the metastatic process," said Searson, who was the corresponding author of the Cancer Research article. "In the past, it's been virtually impossible to see the steps involved in this process with this level of clarity. We've taken a significant leap forward."

This improved view should give cancer researchers a much clearer look at the complex physical and biochemical interplay that takes place when cells leave a tumor, move through the surrounding tissue and approach a blood vessel. For example, the new lab device enabled the inventors to see detailed images of a cancer cell as it found a weak spot in the vessel wall, exerted pressure on it and squeezed through far enough so that the force of the passing current swept it into the circulating fluid.

"Cancer cells would have a tough time leaving the original tumor site if it weren't for their ability to enter our bloodstream and gain access to distant sites," Wong said. "So it's actually the entry of cancer cells into the bloodstream that allows the cancer to spread very quickly."

Knowing more about this process could unearth a key to thwarting metastasis.

"This device allows us to look at the major steps of metastasis as well as to test different treatment strategies at a relatively fast pace," Wong said. "If we can find a way to stop one of these steps in the metastatic cascade, we may be able to find a new strategy to slow down or even stop the spread of cancer."

Next, the researchers plan to use the device to try out various cancer-fighting drugs within this device to get a better look at how the medications perform and how they might be improved.