A Close-Up Look at Metastasis

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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Medicine: A Team Sport

Dec. 19, 2014

By Medical Discovery News

Medicine: A Team Sport

Imagine if public use of social media influenced healthcare in the United States. The result would be medical care that’s more patient-centric and data-driven.  Luckily, we don’t have to wait for these two platforms to converge, because it’s already on the horizon. Called participatory medicine, it’s based on four components termed P4: preventive, predictive, personalized, and participatory. This focuses on the patient not just as a recipient of care, but as an active and contributing part of maintaining health and diagnosing and treating disease.

Think of participatory medicine as a team sport that includes a patient, patient groups, specialized social networks, the entire care team, and clinical researchers. All team members have access to the patient’s data and participate equally in making decisions. This is a seismic shift from the traditional doctor-patient relationship, where a patient is generally a passive recipient of healthcare decisions. But in participatory medicine, patients have more control of their health and are accepted as partners in healthcare decisions.

Patient-sponsored social networks may drive participatory medicine into the healthcare industry. Such social networking can provide information about this new approach to medicine and educate other patients. There are already strong social networks for some chronic diseases, offering education, information about clinical studies, clinical advances, and updates on clinical trials. For example, the National Parkinson’s Foundation provides information about this disease, lists clinical trials, reviews the latest research, and has a hotline for people with questions. Parkinson’s patients can stay informed on the current practices and where treatments are heading with the latest information from ongoing clinical trials.

To succeed, participatory medicine will require the compilation of huge sets of data. This data might include the complete genomic sequence of every patient. Such a thing was unheard of just five years ago, but the more affordable cost of genome sequencing can now make this a reality. Comparing the genomic sequence and data sets of people with the same disease could provide clues about how they can stay as healthy as possible and how to reduce the incidence of that disease by examining possible genetic and environmental causes. Already, comparisons of cancer patients’ genomes have revealed that certain mutated genes, such as the BRCA1 gene linked to breast and ovarian cancer, could be responsible for cancerous growths. This has also lead to the development of drugs that specifically target cancer-invoking genes to combat the cancer. Such individualized cancer therapies all started with the analysis of large data sets. Once established, this new way of applying medicine will drive down the cost of healthcare and make trial-and-error treatments obsolete.

Large, longitudinal studies plan to take the medical application of data analysis to the next level by following 100,000 people for 30 years. Every year, researchers will collect a panel of multiple lab measurements from subjects and interview them to determine their overall health and environment. The database generated will provide answers to how we remain healthy and what genetic and environmental factors are associated with different states of disease. This will transform medicine’s ability to keep people healthy and allow early prediction for those likely to develop certain diseases.

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Cancer Goggles

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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Aging and Our Biological Clock

May 9, 2014

By Medical Discovery News

Unlike a mechanical clock our biological clocks do not run at a constant speed

The questions of how we age and how our bodies know what to do during that process have puzzled scientists for years. The answers lay in our biological clocks, which aren’t fully understood. Some scientists think that if we can learn how our biological clocks work, we would hold the key to slowing down or even reversing aging.

A group from the University of California, Los Angeles (UCLA) achieved astounding results that offer insight into the mechanisms of aging. They used existing sets of data to compare DNA patterns in normal and cancerous tissue samples from humans. They examined almost 8,000 samples from more than 50 different people that were taken from various places in or on the body. This allowed them to take a comprehensive look at the changes that occur throughout the body during the aging process and how tissues of the body keep time. 

Most, but not all, tissues had a biological age that matched their chronological age. The biological age of a tissue is the age it appears to be or behaves at. Chronological age is just a person’s overall age.

For example, women’s breast tissues age much faster than the rest of their bodies. In a healthy woman, breast tissues had a biological age two to three years older than the woman’s age. In a woman who had breast cancer, the cancer cells were an astounding 36 years older than the rest of her body! And even the healthy tissues surrounding those cancer cells were affected – they were up to 12 years older than the rest of the body. Maybe this age difference explains why breast cancer is so prevalent in women.

The results also show that biological clocks do not run at a constant rate. The clock advances much faster from birth through adolescence. When we reach our 20s the clock slows to a steadier rate.

Stem cells, cells that are basically clean slates and can develop into any type of cell in the body, are age zero according to the biological clock. This makes sense since embryos and umbilical cords have stem cells. So, if adult cells can be reprogrammed into stem cells, their biological clocks could potentially be reset as well. Could this be the key to being forever young?

This discovery could possible reverse the aging process, a scientific Fountain of Youth.  But first, the actual connection between the biological clock and aging still needs to be defined more precisely. Then we can move on to questions like whether slowing the aging process also reduces the incidence of cancerous diseases.

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