A Close-Up Look at Metastasis

June 12, 2015 by

By Medical Discovery News

May 29, 2015

A Close-Up Look at Metastasis

One of the things that make cancer cells so deadly is metastasis, their ability to dislodge from their original location and migrate to other tissues. Most people who die of cancer are victims of this process. Even if a tumor is removed surgically, doctors can’t be certain that some of the tumor cells haven’t already metastasized, hence the need for treatments such as chemotherapy to target those cells. Unsurprisingly, metastasis is a subject of intense research, and luckily scientists now have a new tool to help them understand how tumor cells move.

While most tumors have the ability to metastasize to many different tissues, they prefer to spread to certain ones, like those in the bones, liver, and lungs. Cancer begins to spread by invading nearby tissue, then through a process called intravasation, tumor cells enter a blood or lymphatic vessel, allowing them to circulate to other parts of the body.

When tumor cells stop moving in a tiny blood vessel called a capillary, the can move out of the blood vessel and into the tissue, which is called extravasation. They will proliferate in this new location and release signals to stimulate the production of new blood vessels to satisfy the oxygen and nutrient demands of the tumor, a process called angiogenesis. Not all cells of the tumor are equally capable of metastasizing, and depending on the new environment they may not be able to grow in their new locations. In general, cells in metastatic tumors acquire additional genetic mutations that make them better able to relocate to other sites in the body. In some cancers, the metastatic cells have evolved to be remarkably different from the original tumor cells, which may contribute to the failure of treatments, the identity of the original cancer, and the recurrence of cancer.

Engineers and scientists at Johns Hopkins University have reproduced the 3-D extracellular matrix (ECM) that surrounds human cells. They also created an artificial blood vessel that runs through the matrix to simulate the flow of blood or lymph. They then added breast cancer cells either individually or in clumps.

Using fluorescent microscopy, they studied how the tumor cells interacted with the model to investigate how tumor cells get into and out of vessels, a key step in metastasis. They found that the tumor cells first dissolved some of the ECM to form a tunnel. The cells moved back and forth within this tunnel, occasionally coming into contact with the vessel. Then the cancer cells attached to the vessel through a long process, finally sitting on the surface of the blood vessel. They appear to change shape and move along the outer surface of the blood vessel. After a few days, the cancer cells force their way between the outer cells of the vessel and are swept away by the fluid moving through it.

About 60-70 percent of cancer patients are already at the stage of metastasis by the time they have been diagnosed. This new device will allow scientists to gain a better understanding of the processes and molecular players in metastasis, which will hopefully lead to new interventions or therapies that could interrupt or prevent this process.

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You’re More Like Your Mother Than You Know

May 24, 2015 by

May 22, 2015

By Medical Discovery News

Photo of mother and child

While the benefits of breast feeding have been well-documented, scientists were surprised to learn of another one: breast milk contains a mother’s stem cells that become a part of different organs of the baby’s body.

Breast feeding protects infants against infections early in life and reduces their risk of juvenile diabetes, heart disease, and cancer as children. It also helps mothers lose weight after giving birth and lowers their risk of osteoporosis and uterine and ovarian cancer.

In addition, seven years ago scientists discovered the presence of mammary stem cells in breast milk. The mammary gland is unique in its ability to go through different stages in anticipation of producing milk, then a period of milk secretion followed by a return to the non-lactating state. All of this can occur as many times as necessary. This massive restructuring of the breast suggested the presence of stem cells.

Human breast milk contains about 14,000 cells in each milliliter. Most of these are the epithelial cells that are abundant in the breast and cells of the immune system. Some of the cells in breast milk had a molecule called nestin on the surface, which in adults is a marker for multipotent stem cells that can develop into many different types of cells, like those in the brain, pancreas, liver, skin, and bone marrow. When scientists transplanted a single nestin-positive stem cells into the fat pad of a grown mouse, it reconstituted a functional mammary gland. Scientists wondered if such cells were serving the same function in humans.

However, further research revealed quite a surprise. First, they genetically modified mice to produce a protein that makes the cells glow red under fluorescent light. Mothers with this new feature were given normal pups to nurse. When they were examined as adult mice, they had cells that glowed red like the mice they had nursed from in their blood, brain, thymus, pancreas, spleen, and kidneys. These cells became functional cells within these organs, so the ones in the brain behaved like neurons and those in the liver made albumin. Based on this experiment, breast milk stem cells travel into the baby’s blood and become functional parts of various organs, at least in mice.

In the laboratory, these stem cells have also shown the ability to differentiate into breast cells that produce milk in a petri dish, as well as bone cells, joint cells, brain cells, heart cells, liver cells, and pancreatic cells that synthesize insulin. In addition, this study may have also discovered a non-invasive, ethical, and sustainable source of multipotent stems.

We don’t yet fully understand the role of these cells in offspring, whether they maintain a tolerance for the mother’s milk, play a role in normal growth and development, or both. Until then, know that your mother is more a part of you than you ever realized.

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Chocolate on My Mind

April 25, 2015 by

April 10, 2015

By Medical Discovery News

Chocolate

Peanuts creator Charles Schulz once said, “All you need is love. But a little chocolate now and then doesn’t hurt.” New research shows he might be right. In one study, certain compounds in cocoa called flavanols reversed age-related memory problems.

Flavanols, found in a variety of plants, are potent antioxidants that help cells in the body deal with free radicals. Free radicals arise from normal cellular processes as well as from exposure to environmental contaminants, especially cigarette smoke. Unless your body gets rid of free radicals, they can damage proteins, lipids, and even your genetic information. You can get flavanols from tea, red wine, berries, cocoa, and chocolate. Flavanols are what give cocoa that strong, bitter, and pungent taste. Cocoa is processed through fermentation, alkalization, and roasting among other methods, which can influence how much of the good flavanols are lost. Among the products made from cocoa, those with the highest levels of flavanol are cocoa powders not processed by the Dutch method, followed by unsweetened baking chocolate, dark chocolate and semi-sweet chips, then milk chocolate, and finally chocolate syrup contained the least.

In the latest study, a cocoa drink specially formulated by the Mars food company to retain flavanols was compared with another drink that contained very little flavanols. The study asked 37 randomly selected adults aged 50 to 69 to take one of the drinks. One group consumed 900 milligrams per day of flavanols and the others consumed only 10 milligrams per day for three months. Brain imaging and memory tests were administered before and after the trial.

Those who consumed the high levels of cocoa flavanols had better brain function and improved memories. Before the study, the subjects on average demonstrated the memory of a typical 60-year-old person. At the end, those who consumed more flavanols exhibited the memory capabilities more closely resembling a 30- to 40-year-old. Unfortunately, the average candy bar contains only about 40 milligrams of flavanol, so you would have to eat 23 of them a day to equal the amount of flavanol used in the study, which would lead to other health problems like obesity and diabetes.

Other studies have similarly revealed that high-flavanol cocoa beverages cause regional changes in the brain’s blood flow, suggesting that it could be used to treat vascular impairments within the brain. Flavanols have also been reported to reduce blood pressure and other factors that lead to cardiovascular disease, improve insulin sensitivity, modulate platelet activity thereby reducing the risk of blood clots, and improve the activities of the endothelial cells that line our blood vessels. The Kuna indians living on the San Blas Islands near Panama, who consume a type of cocoa rich in flavanol on a daily basis, have unusually low rates of hypertension, cardiovascular disease, cancer, and diabetes.

These studies need to be repeated with larger groups to confirm the benefits of consuming flavanols and to ensure that there are no negative effects. Still, if a cocoa beverage high in flavanols could be mass produced and marketed, we could improve human health in a very tasty way.

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Biological Fountain of Youth

April 25, 2015 by

March 27, 2015

By Medical Discovery News

The Biological Fountain of Youth

Over 500 years ago, Ponce de Leon landed in Florida as part of his search for the fountain of youth – magical waters that reverse aging, prevent illness, and grant immortality. He never found it, and neither has anyone else. While immortality is still impossible, we have come a long way in understanding the aging process.

We do not know the precise mechanism of aging, but there are some fundamental processes in our bodies that begin to change and this can drive aging. There are several theories of aging under intense scientific investigation.

A widely accepted theory of aging today is called evolutionary senescence, which mainly hinges on the concept of mutation accumulation. As we age, our cells accumulate mutations in our genetic material or DNA, which affects the ability of our cells to replicate and our tissues to regenerate. Also, some of our genes are designed to enhance reproduction early in life, but can cause problems later. Since genes can only be passed on during reproduction, which generally occurs earlier in life, genes that have negative effects later in life are not removed from the population – we are stuck with them! A good example is a gene called p53, which controls the fate of damaged cells by preventing their replication or directing them to die. This is important in preventing cancer in young people, but it may negatively impact our ability to replace aging cells in tissues as we grow older.

Another widely discussed theory centers on the maintenance of our genomes. As we get older, we accumulate damage to our DNA, which affects cellular function and our ability to renew tissues in the body. In a sense, this is a high mileage effect. Take for example the production of free radical molecules. These highly reactive molecules are normally produced in mitochondria, which use oxygen to produce cellular energy, a process that creates free radical molecules as a by-product. These free radical molecules lead to oxidative damage of DNA and other cellular components.

There is also evidence the neuroendocrine system (hormones that affect neurological function) influences aging. For example, a reduction in hormone levels can lead to a lengthening of life, at least in experimental animals. We are beginning to suspect that the insulin-related hormonal pathway may play a significant role in aging, at least in mice. Mutations that reduce the amount of this circulating hormone extend life.

A relatively new model of aging involves the replication of chromosomes as cells divide. When cells replicate, specialized structures at the ends of chromosomes called telomeres are shortened. Shortened telomeres are linked to decreased viability and increased cancer risk. Cells whose telomeres reach a critical length can no longer divide and are described as senescent.

We are expanding our understanding of how aging occurs. The search for a modern-day fountain of youth will require a great deal of dedicated work by biomedical scientists to safely improve and extend human life.

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Cancer Goggles

June 6, 2014 by

June 6, 2014

By Medical Discovery News

Cutting people open and sewing them back up for a living is a pretty stressful occupation to begin with, but some surgeons have tougher jobs than others. Cancer surgeons are charged with removing all tumor cells on the first try. But tumor growth can be irregular and it can be hard to distinguish cancer cells from normal cells during an operation. Imaging techniques like MRIs and CT scans can give surgeons a road map to the tumor, but they offer only limited help once an incision has been made.

This is because these images are merely snapshots – a single frame and dimension. Even three-dimensional images can only be viewed one frame at a time. In addition, the inside of the body is dynamic and it takes a skilled surgeon to understand the orientation of tissues and the precise margins where tumor tissue ends and regular tissue begins. 

Because of this challenge, surgeons often have to remove healthy tissue to be sure all tumor cells are gone. This requires a special step: staining the removed tissue then looking at it under a microscope to identify the cells. The surgeon wants to be sure a margin of healthy tissue is removed so no tumor cells remain.

If tumor cells remain, they will grow and second operation may be necessary to remove more cancerous tissue. Again, the removal of additional healthy tissue will be necessary. But what if a surgeon could distinguish cancer cells from normal cells during surgery? It seems impossible. Each cell is microscopic, thousandths of a millimeter. Just observing cells takes special staining and high-powered optics.

But scientists at the University of Missouri and Washington University in St. Louis are working on the impossible. They are developing cancer goggles that will allow surgeons see tumor cells right in the operating room. This new technology uses LS301, a fluorescent dye combined with a short chain of amino acids called peptide, that is only absorbed by cancer cells and glows under infrared light. This dye specifically stains cells from prostrate, colon, breast, and liver cancers among others. Patients can be injected with the dye beforehand and it will last through a procedure.

These special goggles will illuminate cancer cells with LS301 using an infrared light source. A surgeon can distinguish glowing cancer cells from normal cells and observe when they are completely removed. As a result, the surgeon would not need to remove a margin of healthy tissue to be sure all cancerous tissue is gone. This may greatly improve success rates from surgeries to remove cancerous growths. 

Currently, this technique is being perfected in veterinary surgeries to guide the removal of tumors in pets and is not yet ready for use with humans. If effective, it will be a great resource for patients undergoing tumor removal surgery in the future.

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Putting Your Bacteria to Work

April 4, 2014 by

April 4, 2014

By Medical Discovery News

A biotech startup company called uBiome has adopted the concept of crowd sourcing, using the Internet to rally people around a cause, for research on the human microbiome. The microbiome is all the microscopic flora and fauna that live in and on the human body. Humans have 10 times as many bacterial cells as human cells. But science is just beginning to understand the populations of the microbiome and how they affect a person’s health for good or bad.

What science already knows about the microbiome comes from the $173 million government-funded Human Microbiome Project (HMP). This project took five years and collected and sequenced the microbiome of 250 healthy people. It proved there are at least 1,000 different types of bacteria present on every person. The National Institutes of Health (NIH) has made the four terabytes of data from this project available to all researchers via the Microbiome Cloud Project.

Different anatomical sites of the body have different microbial populations. Additionally, the microbial populations that inhabit our bodies vary from person to person, but are very stable within an individual. Each person has their own distinct microbial signature that is unique to them. Most of these microbial species are actually helpful and protect against invading microbes that can cause disease. Some, like certain E. coli in the gut, actually produce essential vitamins that keep us healthy. Alterations in the human microbiome have been associated with diseases like autism, obesity, irritable bowel syndrome, and asthma. In some cases, correcting microbial populations associated with disease states may cure or help manage the disease.

A startup company called uMicrobiome is looking to sequence the microbiomes of at least 1,000 more people from all over the world, and they are trying to find volunteers using crowd sourcing. Anyone interested can go to the company’s Web site (ubiome.com), make a pledge, and request a sampling kit, which contains a swab for gently brushing areas of the ears, mouth, genitalia, or gastrointestinal tract. The swabs are placed into a solution that preserves and stabilizes the bacteria for transport back to the lab.

uMicrobiome examines samples for their 16S RNA sequences. These sequences are present in all microbes, but part of the sequence is unique to each different bacterium. This technology of DNA sequencing can determine the different types of bacteria present and their proportions in each sample.

The company puts the results on their Web site for individuals to access and analyze their microbiome. There are also software tools to help users interpret what they are seeing. uMicrobiome secures the data so that it cannot released in an identifiable form. A person can choose to share their data with other citizen scientists for scientific studies or compare their microbiome to others’.

So science to the citizens has arrived! Anyone can learn about their own microbial world and advance this field of science as well. 

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Organ Farming

March 15, 2014 by

March 14, 2014

By Medical Discovery News

Imagine that a patient needs an organ, like an airway to their lungs called a trachea. A scientist harvests some of the patient’s cells and attaches them to a scaffold the proper shape and size for the tube. The cells and scaffolds are placed into a tissue reactor and – ta da! – in a week or two there is an organ ready for the surgeon to transplant into the patient. While it sounds like a chapter from “Brave New World,” this science fiction scenario is a growing reality.

Bladders and ears have been grown in the laboratory, and hearts, eyes, and kidneys and other organs are in progress. These organs are close to the natural ones they’re copying – some even have their own immune system. In April 2013, surgeons at the Children’s Hospital of Illinois implanted a bioengineered trachea into a two-year-old child. This was the first surgery of its kind in the United States and one of only six worldwide.

The patient receiving the transplant was a girl named Hannah Warren who was born without a trachea, commonly called a windpipe. Since birth, she’s had a plastic pipe inserted in her mouth that went down into her lungs, allowing her to breathe. She could not eat normally or even speak. With few options available, this type of congenital defect has always meant an early death; only a few children live past the age of six.  

Bioengineered organs could change that. The key is stem cells – cells that are at an early stage of development and through the influence of their environment can produce the many specialized cells of organs and tissues. In this case, doctors harvested the girl’s immature stem cells from the marrow inside her bones. The stem cells were taken to the lab and allowed to adhere to a plastic fiber model precisely the size (about one-half inch in diameter) and structure of the trachea she needed. Once placed in an incubator called a tissue bioreactor, the stem cells colonized the plastic and started growing. While they were growing, cells communicated with neighboring cells and worked together to produce all the cells needed for a functioning trachea. 

At the end of this process, Dr. Paolo Macchiarini implanted the trachea with promising results. Since the cells in the bioengineered trachea were based on ones from her body, her immune system didn’t recognize it as foreign and reject it, a big worry for transplant recipients. Without a plastic pipe in her mouth, Hannah was able to smile for the first time.

Unfortunately, while her trachea functioned well after the surgery, her esophagus never recovered. She underwent a second surgery to fix her esophagus and died from complications. Macchiarini said that her death was not due to the implanted trachea but her own “very fragile” tissue. He called Hannah a “pioneer” in the field of regenerative medicine and plans to conduct similar operations.

The next step for bioengineered organs is clinical trials leading to Food and Drug Administration approval. This would give more scientists and physicians the opportunity to improve organ “farming” and extend this field into a therapy that could benefit many.

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And The Winners Are

January 3, 2014 by

Jan. 3, 2014

By Medical Discovery News

The Nobel Prize

Inside each living cell is a complex system of roadways, each used to transport molecules so the cell can keep performing the processes it was made to do. Like highways that span from one state to another, cells can even use the roadways to deliver molecules to other cells. How cells are able to do this has been an intense area of study for years, and thanks to three Nobel prize-winning scientists, it’s a little more understood now.

This year’s Nobel Prize for Physiology or Medicine was awarded to scientists who have unraveled the mysteries of how cells route or traffic specific molecules to the correct locations.  The $1.4 million prize was split between Drs. James Rothman of Yale University, Randy Schekman of University of California-Berkeley, and Thomas Sudhof of Stanford University. Their work revealed a basic element of cell physiology that is essentially the same for all cells, from single-celled yeasts to complex mammals like humans.

The basic mode of transporting molecules in cells is in a vesicle – hollow, spherical structures that carry molecules inside. Molecules are packaged at different places in cells and then safely transported at the right time to the correct destination via vesicles. But how does this transportation container know where to drop off its delivery? With mail, a zip code is written on the outside of a letter specifying a precise location where it is to be delivered. With vesicles, there are specific proteins on the outside surface of the sphere that specify where its cargo is to be delivered, whether it’s within a cell or to the cell’s surface, to be released from the cell to other cells. With the right cellular zip code, molecules are delivered to the right place.

Schekman discovered the genes and proteins that regulate these vesicles. They are the traffic cops that control vesicle traffic through the cells. He found that different genes and proteins determined whether a vesicle delivered its contents to the cell’s surface or to different compartments inside a cell. While he studied this in yeast cells, similar genes and proteins have been found in more complex animals such as mice and humans.

Rothman found the specific proteins on the surfaces of vesicles that represent molecular zip codes and allow the vesicles to interact with proteins at their correct destinations. The interaction between these two groups of complementary proteins causes the vesicle to fuse with the membrane at its intended destination and release its contents.

Sudhof revealed how nerve cells communicate with each other and how calcium ions control this activity. He found that calcium ions act as a trigger, causing vesicles to fuse with cell surfaces and release the molecules to interact with neighboring cells, transmitting signals along a nerve.

This transportation system is used for critical functions in humans, like brain signals and immune responses, so problems within the system can cause disease. These pioneers have provided an incredible understanding upon which others can continue to build.

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