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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Can Measles Save Us from Cancer?

November 19, 2014 by

Nov. 14, 2014

By Medical Discovery News

Red blood cells

Today, the words measles, mumps, and rubella (MMR) sound foreign to children. But before a vaccine prevented these three viruses, three to four million American children contracted measles, a possibly serious respiratory disease that can lead to pneumonia, and 40 percent of them required hospitalization each year. The vaccine is 95 percent effective, and in 2012 only 55 cases of measles were reported in the U.S., mostly due to traveling abroad.

Now, a study has demonstrated that the measles virus might actually be a useful treatment, for cancer. It sounds strange – using one serious disease to fight off another – but scientists have found a way to direct the cell-killing powers of viruses to cancer cells. The use of viruses to destroy cancer cells, called oncolytic virotherapy, has been investigated since the 1950s. Other viruses such as herpes and pox have also been used as treatments for other diseases, but the measles virus’s potential to fight cancer is very promising.

The Mayo Clinic in Rochester, Minn., utilized a modified measles virus called MV-NIS. To create this version of the virus, scientists inserted a gene for the protein sodium iodide symporter. This protein helps concentrate iodine in the human thyroid. Therefore, when this genetically engineered measles virus infects tumor cells and replicates, it produces this protein that binds to and concentrates iodine.

This is important because researchers can then inject a patient with radioactive iodine, which shows up on a 3-D imaging technique called SPECT-CT. Using the images, they can observe where cancer cells are at any site in the body. The engineered virus attacks and kills tumor cells but leaves normal cells alone. This works because the virus detects a protein called CD46 on the surface of a cancer cell, then enters the cell and replicates itself, killing the cancer cell.

The first clinical trial consisted of only two myeloma patients who had exhausted all other treatment options. Each patient was injected with one ultra-high dose (the equivalent of 100 million doses of the vaccine) of MV-NIS intravenously.

The results were astounding. The number of myeloma cells in both patients dramatically declined. One patient became cancer free and has remained so, while the other patient’s life was prolonged during this late-stage cancer. Advanced myeloma affects plasma cells, a type of white blood cell that produces antibodies, and is difficult to treat so this result is unprecedented.

MV-NIS is not yet ready for widespread use, but scientists will continue to build off this newfound virotherapy. Already, they plan to experiment with using another radioactive iodine molecules to additionally attack the tumor cells, uniting virotherapy with localized radiation treatment for myeloma. Stay tuned for updates on this promising discovery.

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More Bad News for Smokers

October 27, 2014 by

Oct. 24, 2014

By Medical Discovery News

Lung X-ray

Smoking isn’t the only thing that raises your risk of lung cancer. As it turns out, your DNA can have that effect too.

A scientific study scanned the genomes, the entire genetic code, of 11,000 people of European descent in an effort to identify if there was any correlation between gene sequences and a common form of lung cancer, non-small cell carcinoma. They discovered that variants of certain genes increase a person’s susceptibility to developing lung cancer, especially in smokers.

One of the three gene variants they identified, named BRCA2, can double a smoker’s chance for developing lung cancer. BRCA2 is a tumor suppressor gene. It encodes a protein involved in the repair of damaged DNA, which is critical to ensure the stability of cell’s genetic material. When cellular DNA is damaged, there are several ways for the body to detect and repair that damage. If the damage to DNA cannot be repaired, then the cell is programmed to die by a process called apoptosis in order to prevent the damage being passed on to its daughter cells.

Like other tumor suppressor genes, the BRCA2 protein helps to repair breaks in DNA. It also prevents damaged cells from growing and dividing too rapidly. Variants of BRCA2 associated with breast, ovarian, and now lung cancers produce proteins that do not repair DNA damage properly. This causes cells to accumulate additional mutations, which can lead to cells that grow and divide uncontrollably. Such mutations lead to an increased risk of developing cancer.

Scientists have discovered over 800 mutations of BRCA2 that cause disease, including breast, ovarian, lung, prostate, pancreatic, fallopian, and melanoma cancers. Most of the mutations result from the insertion or deletion of a few letters of genetic code into the part of the gene that code for a protein. This disrupts the production of the BRCA2 protein and results in a shortened and nonfunctional form of the BRCA2 protein.

Lung cancer is a leading killer of Americans. Nearly 160,000 Americans will die from lung cancer this year, representing 27 percent of all cancer deaths. Active smoking causes close to 90 percent of lung cancers.

The good news from this discovery is that since scientists first linked BRCA2 to an increased risk of breast cancer, new therapies have been developed. Current treatments for breast and ovarian cancers could be effective with BRCA2-associated lung cancers, such as PARP inhibition.  PARP1 is another protein involved in repairing DNA damage. When one of two strands of DNA are broken or nicked, PARP1 moves to the region and recruits other proteins to the site to repair the damage. Many chemotherapy agents kill cancer cells by inducing DNA damage in the tumor and inhibiting PARP1. This doesn’t allow cancer cells to repair damage and makes them more susceptible to chemotherapy and radiation therapy. Now that we know this gene is linked to lung cancer, such therapies may be more effective in treating lung cancer and saving lives.

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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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An Itchy Situation

November 2, 2013 by

Nov. 1, 2013

By Medical Discovery News

Anyone ever bitten by a mosquito can attest to its itchy consequences. New research has discovered just how our bodies detect and process itching, leading to a better understanding of our reaction to itching and hopefully better treatments for it.

The clinical term for an itch is pruritus, and at least 16 percent of people experience an itch that just doesn’t go away. The most common dermatological complaint, long-term itching can be caused by chronic renal disease, cirrhosis, some cancers, multiple sclerosis, diabetes, shingles, allergic reactions, drug reactions, and pregnancy.

Prolonged itching and scratching can increase the intensity of the itch, possibly leading to neurodermatitis, a condition in which a frequently scratched area of skin becomes thick and leathery. The patches can be raw, red, or darker than the rest of the skin. Persistent scratching can also lead to a bacterial skin infection, permanent scars, or changes in skin color. The super strong pain reliever morphine can cause such a severe whole-body itch that some patients choose to forgo it and live with the pain.

Sensory neurons called TRPV1 cells detect itchy substances on skin. TRPV1 cells have long nerve fibers that extend into skin, muscle, and other tissues to help monitor conditions. It has not been clear how these neurons sort through different sensations like pain and temperature and route the signal along the proper pathway to the appropriate area of the brain for perception.

New research has revealed a small group of those neurons produce a substance called natriuretic polypeptide b (Nppb), a hormone known to be involved in regulating the heart. Surprisingly, when Nppb is produced by TRPV1 cells it acts as a neurotransmitter, a chemical messenger secreted by neurons to carry, boost, and control signals between neurons and other cells.

When scientists genetically modified mice to eliminate Nppb, they did not itch. Nppb binds to a specific receptor called Npra on particular nerves in the spinal column. When those cells were eliminated in mice, again, they did not itch. Interestingly, removing these cells did not impact other sensory sensations such as temperature, pain, and touch.

A similar transmission presumably exists in humans, but that has not yet been determined. Knowing which molecules and cells are involved will help scientists study how humans perceive itch signals. Before these findings, scientists thought a molecule called gastrin releasing peptide was responsible for transmitting the itch signal from nerves, and that itching was a low level form of pain.

Understanding the itch signaling pathway offers the opportunity to create drugs that specifically block that signal and alleviate unpleasant and chronic itching with fewer side effects.

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Thalidomide: A Nightmare Revisited

September 22, 2013 by

Spet. 20, 2013

By Medical Discovery News

While thalidomide is now being tapped for its cancer-fighting properties, it has a more notorious history. Starting in 1957, doctors recommended thalidomide as a mild over-the-counter sleeping pill supposedly safe enough for even pregnant women. That it also reduced morning sickness made it even more popular. The company that made thalidomide aggressively marketed the drug in 46 countries even after the wife of an employee who took the drug before its release gave birth to a child with no ears. Within two years, an estimated 1 million people in West Germany were taking the drug daily. However, thousands of babies born with severely malformed limbs revealed that this drug was not safe, but that connection was not made until 1961.

German pharmaceutical company Chemie Grünenthal GmbH originally developed thalidomide to treat convulsions, but users reported feeling sleepy. During testing, the company discovered that it was almost impossible to take enough thalidomide to be fatal. The company did not test the drug’s effects during pregnancy. Though approved for use in Germany and elsewhere in Europe, a U.S. Food and Drug Administration medical officer named Frances Oldham Kelsey denied its license because there was insufficient clinical evidence about its side effects. This decision limited the impact of the drug in America. In 1962, President John F. Kennedy awarded Kelsey the President’s Medal for Distinguished Federal Civilian Service. 

Warnings of the drug’s possible toxicity began to emerge in 1959. Adults taking the drug reported peripheral neuritis or inflammation of the nerves and the resulting nervous system damage. Even after an Australian and a German physician independently linked thalidomide to birth defects in 1961, it was four months before the company withdrew the drug from the market, and it was banned even later in some countries. It is thought that at least 100,000 pregnant women were affected by the drug leading to more than 90,000 miscarriages. Even a single dose of thalidomide during early pregnancy may cause severe birth defects. About 40 percent of babies exposed to the drug die before or soon after delivery. Over 10,000 children were born with thalidomide-related birth defects such as missing or shortened limbs. Still others were born deaf and blind, some had curved spines and some had damaged hearts and brains and many other abnormalities.

The company refused to pay compensation for many years until 1970 when they established a $28 million fund in return for legal immunity. When those funds were depleted, the German government paid compensation to victims. In 2009, Grünenthal provided another $63 million in compensation. The company did not publicly apologize for its actions until August 2012.  However, dissatisfaction with that statement and the level of compensation by the company continues.

Researchers are actively seeking drugs that work similarly to thalidomide but without the side effects. The thalidomide tragedy prompted creation of and reforms in the laws and policies that govern drug testing and approval, reducing the chances of another such incident, but it must not be forgotten lest history repeats itself.

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A Top 10 List To Die For

September 13, 2013 by

Sept. 13, 2013

By Medical Discovery News

How are you going to die?

The Centers for Disease Control would answer that life expectancy depends greatly on where someone lives. Life expectancy in the United States ranks 40th in the world with 77.97 years.That addresses when someone might die but what about how? Most likely, it will be from one of these top 10 causes, based on how many Americans they kill each year.

10) Suicide – 38,285. Many factors are now known to influence suicide: mental illnesses, genetics, certain pharmaceuticals, traumatic brain injuries, drug and alcohol abuse, and chemical or hormonal imbalances. To decrease these rates, education about the signs preceding suicide and accessible treatment is necessary.

9) Kidney Disorders – 45,731. Although dialysis can help people survive a little longer without a kidney, it is no cure. Kidney damage can occur from infection, high blood pressure, or toxic reactions to drugs, leading to chronic kidney disease that affects more than 26 million Americans.

8) Influenza and Pneumonia – 53,667. Both these diseases mostly affect the very old, very young, or those with immune system problems. This figure could be lowered with vaccinations.

7) Diabetes – 73,282. The rate of diabetes is increasing, with one in 500 children being diagnosed, corresponding to trends in obesity, diet, exercise, and aging. Lifestyle changes could decrease diabetes rates.

6) Alzheimer’s – 84,691. This form of dementia affects older adults, mostly over 60, and is caused by the build-up of beta-amyloid protein plaques in the brain. There is currently no cure.

5) Accidents – 122,777. The leading cause of accidental deaths depends on age. For children and young adults it’s car accidents, adults over 35 are most likely to accidentally overdose on drugs, and for those over 65 it’s most likely to be related to a fall.

4) Stroke – 128,931. A stroke occurs when an area of the brain does not receive oxygen due to a ruptured or blocked blood vessel. Those with high blood pressure, diabetics, smokers, and alcoholics are at the highest risk. The good news is that deaths from strokes decreased by almost 45 percent in 10 years but still leads to more than 250,000 hospitalizations yearly.

3) Chronic Lower Respiratory Diseases – 143,382. These diseases of the lungs and airways include bronchitis and emphysema, although the latter kills 20 times more than the former. Smoking is the leading cause of this condition.

2) Cancer – 575,313. Lung, colon, breast, pancreatic, and prostate cancers have the most victims out of more than 200 different types affecting more than 60 different organs. Another piece of good news is that five-year survival rates have increased about 15 percent since the 1970s.

1) Heart Disease – 596,339. Advances in science have improved care, reducing these deaths by 18 percent in 10 years. However, as 25 percent of adults have high blood pressure, 67 percent are overweight, and 20 percent smoke, Americans have plenty of risk factors to improve on.

The United States has maintained its leadership role in biomedical science and needs to continue this in the future. Support biomedical research – your life may depend on that next scientific advance.

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Cancer-Fighting Bacteria

August 30, 2013 by

Aug. 30, 2013

By Medical Discovery News

Anyone who has experienced the nightmare of food poisoning would probably steer clear of any chance of that. But now, one of the very causes of such illnesses is being tested as a way to treat cancer.

Typically, Listeria monocytogenes infects people when they eat contaminated foods, resulting in 1,600 cases of listeriosis food poisoning each year. The symptoms are fever and muscle aches sometimes along with diarrhea or other gastrointestinal symptoms. It primarily affects the elderly, newborns, or pregnant women, although occasionally people without these risk factors also become ill. In people with compromised immune systems, symptoms can include headaches, stiff necks, confusion, and convulsions. For some, the infection can lead to septicemia, which means that bacteria are in the blood and can lead to a much more rapid deterioration. Listeriosis can also lead to meningitis, a possibly fatal condition in which the bacteria infect the membranes that cover the brain and spinal column. In older adults and people with other serious medical problems, even immediate treatment may not be effective and they can die. 

But a weakened form of the bacterium might be able to deliver radiation directly to cancer cells and effectively kill them. Scientists genetically engineered listeria cells so they were coated with a protein called a monoclonal antibody. Then they attached a radioactive compound called rhenium-188 to the protein. When injected into mice with human cancerous tumors, these modified bacteria cells delivered radioactivity to the tumor cells without harming normal cells. 

The real advantage of this new approach is that it not only targets the primary tumor, but is even better at finding cancer cells that have migrated to other locations in the body. These other metastatic cancer cells are very difficult to target with other therapies. Scientists were unable to find any damage to normal tissues from either the bacteria cells or the radioactive rhenium. Both the bacteria and the rhenium were no longer detectable in the mice one week after the last treatment.

For the experiment, scientists used pancreatic cancer cells. Pancreatic cancer is the most lethal type of cancer, leaving only 4 percent of its victims alive five years after diagnosis. Its location makes diagnosis difficult, and because symptoms often aren’t recognized until the cancer is too advanced to survive, it’s usually too late. If the tumor is confined to the pancreas, then surgery is an option. Chemotherapy and radiation are also used to kill the cancer cells. That’s where this new treatment comes in.

Although this method must be refined to ensure that the bacteria used are as safe as possible and that no dangerous levels of radiation are released and accumulate in the body, it offers hope to the 40,000 people diagnosed with pancreatic cancer each year.

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