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Medicines taking sting out of side effects

2006-01-17T19:00:00-05:00

No wonder chemotherapy can be hard to take.

The very first chemical ever used to fight cancer was, believe it or not, mustard gas.

Since then, physicians have found ways to ease patients’ suffering from many, but not all, of the harsh side effects.

They have good medicines to prevent nausea and vomiting, said Dr. Rudolph Navari, director of the Walther Cancer Institute at the University of Notre Dame.

It used to be that nine of 10 people receiving chemotherapy suffered nausea; with new drugs, that’s down to only about one in five.

“It is a relatively rare case that someone has intractable nausea that can’t be controlled,‘’ said Dr. Chil Kang, an oncologist-hematologist in South Bend. "We can get people through this much better than even five years ago.’’

Other medicines are available to boost patients’ supply of white blood cells. A drop in white blood cell counts, a side effect of chemo, makes people vulnerable to infections.

Navari said that before the invention of "stimulating factors,’’ which spur production of white blood cells, about a third of patients wound up in the hospital with an infection during the course of their chemo.

“Now it’s about 5 percent,’’ Navari said.

But loss of appetite and the resulting rapid weight loss remain unsolved problems for many patients, Kang said. "People say food tastes like cardboard and they don’t have any motivation to eat because taste is not there.’’

No medicines are available that effectively stimulate appetite for patients undergoing chemo. To make food even less attractive, chemotherapy also may cause painful mouth sores, not only in oral cancer, but in all types of cancer.

“The most I can do is play cheerleader,’’ Kang said.

It’s an important issue, he said, because studies have shown that chemotherapy is less effective when people lose weight rapidly or become dehydrated during treatment.

The therapy also works less well if people string out the treatments, which are usually given every three weeks or so. Such delays give cancer cells a chance to develop resistance.

“Our goal is ‘planned therapy on time,’ ‘’ said Kim Woofter, a cancer nurse and administrator at Michiana Hematology-Oncology Inc. "That provides the best survival benefit.’’

Chemotherapy was invented during World War II when doctors noticed that some people accidentally exposed to mustard gas had very low counts of white blood cells.

According to the American Cancer Society, they reasoned that mustard gas might be effective against lymphoma, an overgrowth of certain white blood cells called lymphocytes. They gave it to lymphoma patients in an injectable form, and it worked, but only temporarily.

Today, more than 100 kinds of chemotherapy are used, according to the ACS, all of which work by killing cells that grow rapidly.

Those rapidly growing cells include not only cancer, but healthy cells in the body that also have the property of fast growth: hair cells and cells in the stomach lining and mouth. The destruction of those healthy cells is one reason people suffer side effects during chemotherapy.

Fortunately, continuing research holds promise of further improvements.

A recent study led by Navari at Notre Dame found that the addition of a psychiatric drug called Zyprexa made anti-nausea medicines work better.

Another study, not yet published, assessed the value of screening cancer patients for depression and providing treatment to those found to have symptoms.

“Guess what?‘’ Navari said. "More of those who were treated got through chemotherapy.’’

TopicID: 15363

Driven by potential

2005-11-08T19:00:00-05:00

ND chemist studies compound he invented to treat stroke, cancer

SOUTH BEND — A molecule invented by a University of Notre Dame chemist has been shown to reduce brain damage from stroke and slow down cancer in recent experiments performed on mice.

University of Notre Dame chemist Shahriar Mobashery invented the compound, called SB-3CT, four years ago while he was a professor at Wayne State University and has continued to work on it over the past two years at ND.

Evidence for the compound’s effectiveness in mice — a clue but by no means a guarantee that it will work in people — has been boosted by two recent studies.

In July, a study based on research done in California showed that SB-3CT reduced brain damage in mice that had suffered strokes.

A month earlier, researchers in Germany reported that it had extended survival in mice with an aggressive form of lymphoma.

Mobashery said the studies show that SB-3CT deserves to be taken to the next level of drug development. That includes further animal tests to see exactly how the compound is metabolized and to gauge its toxicity.

“I’m personally committed to move this as far as I possibly can,’’ Mobashery said, noting that all of the research leading up to human trials can be done at ND.

Mobashery, who holds a patent on SB-3CT, said the molecule inhibits two naturally occurring enzymes, called gelatinases, that are culprits in a variety of diseases.

In ischemic strokes, the kind caused by clots that cut off blood flow to part of the brain, gelatinases are believed to promote the death of brain cells.

In cancer, Mobashery said they allow cancer cells to break away from tumors, freeing them to enter the bloodstream and spread throughout the body.

The only current treatment for ischemic stroke is a clot-busting drug (t-PA) that must be given within three hours of the onset of symptoms. Most people having strokes aren’t taken to the hospital quickly enough to receive it.

But the tests in California found that SB-3CT had a beneficial effect in mice brains up to six hours after the start of stroke. That implies that SB-3CT, if it works in people, might provide a larger window of opportunity for them to get to the hospital and receive treatment.

Tests at the Burnham Institute in LaJolla, Calif., showed that it reduced tissue loss in mice brains by 70 percent. The study appeared in the Journal of Neuroscience.

The cancer study in Germany involved mice that had been genetically altered to develop a very aggressive form of lymphoma. SB-3CT slowed liver metastasis in these mice and extended their survival by 30 percent to 40 percent, according to a study in the May edition of the journal Cancer Research.

But a senior principal investigator at the National Cancer Institute expressed some doubt about the promise gelatinase inhibitors may hold in stopping cancer.

Dr. William Stetler-Stevenson, a senior principal investigator in NCI’s cell and cancer biology branch, said the strategy was extensively studied in the 1990s — with discouraging results. The approach worked well in mice, but benefits were not seen in people, he said.

“We’ve been down this road,’’ he said.

Mobashery said earlier drug studies involved substances that inhibited a whole class of enzymes called matrix metalloproteinases. They were "broad-spectrum’’ in their effect.

His molecule is different in that it inhibits only two — MMP-2 and MMP-9 — that he and other scientists believe are involved in cancer metastasis. So far, he said, SB-3CT is the only chemical proven to be selective against that pair.

Stetler-Stevenson, however, said that while he believes that MMP-2 and MMP-9 are culprits in stroke and heart attack, they may not be the most important targets in cancer.

“There is a significant amount of evidence that other MMPs may be better targets in respect to cancer,‘’ he said. "But in stroke and cardiac disease they may play an important role.’’

Only more research, time-consuming and costly, will determine whether SB-3CT will give doctors new weapons and against what diseases.

TopicID: 14503

Molecule by molecule: Researchers dig deep to find cancer's deadly secrets

2004-08-17T20:00:00-04:00

SOUTH BEND — Cancer researchers are taking on the dreaded disease one molecule at a time.p. They’re discovering in ever greater detail how cancer cells arise, take root, grow into tumors and — perhaps most crucial of all — spread and become killer diseases.p. Understanding the exact role a particular chemical plays in the progression of cancer gives scientists an edge: They can find another chemical that blocks it and halts the disease.p. But, at the same time, the complex biochemical portrait of cancer emerging now is showing just how varied and formidable the disease really is.p. It’s not one disease, but some say as many as 100 diseases. It has the capacity to mutate, like bacteria, and become resistant to treatment.p. Some observers — voices of skepticism intruding on an otherwise upbeat enterprise — even suggest that the “war on cancer” declared by President Nixon more than three decades ago is actually being lost.p. They argue that some fundamental flaws in the way research is being conducted is stifling true progress.p. Both the reasons for hope, and the enormity of the challenge, were evident at a recent scientific retreat for cancer researchers held at the University of Notre Dame.p. The three-day event brought together researchers from universities where the Indianapolis-based Walther Cancer Institute is currently funding research programs.p. Scientists gave talks or poster presentations on nearly 90 different studies now under way at Notre Dame, Indiana University, Purdue University, the University of Michigan and the University of California, San Diego.p. The researchers are optimistic, naturally, about the state of their chosen field.p. But it has become clear to optimists and pessimists alike that the naive days of searching for a single, miraculous “cure for cancer” are long gone, said Dr. John Durant, Walther Cancer medical director.p. “We’re not going to see ‘the cure’ for cancer,” he said. “This is not a war that will be won easily. It will be won in baby steps.”p. Searching for clues p. 91��Ƶ presented at the retreat involve virtually all the stages of a tumor’s life cycle, from breakdowns in the body’s system for repairing damaged DNA that lay the groundwork for later malignancies to the biochemical changes in cancer cells that coax them to leave their site of origin and begin their deadly journey to other organs.p. One study at ND, presented by bio-organic chemist Shahriar Mobashery, involves a chemical that might be able to stop metastasis — the process of cancer spread — in its tracks. It is metastasis, Mobashery said, that is especially dangerous.p. “The primary tumor is usually not fatal unless it’s a brain tumor,” he said.p. The promising inhibitor studied at ND — called SB-3CT — has been shown to slow down the spread of lymphoma cells to the liver and prostate cancer cells to bone in specially bred mice.p. So detailed is this study, that Mobashery was actually able to show a computer graphic depicting how the SB-3CT molecule binds with certain chemicals, called gelatinases, that are responsible for metastasis.p. An exciting time p. Mobashery’s colorful dance of atoms, impressive as it was, is not yet a medicine. The ND experiment, like all the others presented at the retreat, are only preliminary steps, and actual treatments based on the work are years away.p. Dr. Rudolph Navari, director of the Walther program at ND, said better treatments are certainly coming, from the work presented during the symposium or from the hundreds of other research projects going on around the country.p. Dr. Rudolph Navari, director of the Walther Cancer Research Center at the University of Notre Dame, talks about promising studies currently under way at ND during a recent scientific retreat for cancer researchers.p. At ND alone, he said, researchers are working with three promising compounds that have proven to kill cancer in mice.p. “We’ve had more new treatments come out in the last five years than in the previous 20,” said Navari, a physician who treats cancer patients in South Bend. “And many more will be coming out in the next five years. It’s an exciting time.”p. The enterprise of cancer research, however, has its critics.p. An influential article in the March 22 edition of Fortune magazine contends that the pace of progress in cancer research is so slow you might conclude the war is actually being lost.p. The article, by Clifton Leaf, points out that the percentage of Americans dying from cancer today is the same as it was in 1970 despite the expenditure of an estimated $200 billion on cancer research in the past three decades.p. By contrast, Leaf writes, the death rates for heart disease and stroke have plummeted by 59 percent and 69 percent, respectively, in the same period.p. Leaf, a cancer survivor, argues that much of today’s cancer research is flawed because it has the goal of shrinking tumors. That seems reasonable, but the fact is that cancer treatments often succeed in eliminating all visible tumors only to have the cancer quickly recur and kill the patient.p. Leaf also faults cancer researchers for their reliance on mice models as the measure of success for their laboratory experiments. Countless treatments that have worked in mice prove useless in people, he points out.p. Jack Dixon, dean of scientific affairs at the University of California, San Diego, doesn’t agree with Leaf’s article, but he took its title as inspiration. Dixon gave his presentation at ND the provocative title “Are We Really Losing the War on Cancer?”p. Dixon has studied two important families of genes called kinases and phosphophatases, which he said act respectively as the “gas” and the “brakes” on cell growth. An excess or shortage of either can lead to cancer. Scientists will learn how to target medicines at those proteins, he said, creating new cancer drugs that are more effective and have fewer side effects.p. Traditional radiation and chemotherapy take a less sophisticated approach.p. “With those, we’re basically trying to kill off your tumor cells before we kill you off,” Dixon said.p. Millions of survivors p. Durant, the Walther medical director, said the pace of progress against cancer may be slower than some people have expected, but it has been meaningful and real nonetheless.p. Durant said that when he began his career in oncology as a research fellow in 1963 in New York City, only one in three people survived cancer. Today, it’s estimated that about 64 percent of people diagnosed with cancer are cured of the disease.p. “That’s taken us from 1963 to 2004,” he said.p. The result is literally millions of people who are alive today because of the medical treatment they received. The National Cancer Institute and Centers for Disease Control and Prevention estimate that the number of cancer survivors increased from 3 million to nearly 10 million in the three decades between 1971 and 2001.p. Success in treatment of children with cancer during the same period is more impressive, Durant said.p. “When you realize that childhood cancer was just terrible, practically all of them died,” he said. “Today, leukemia in children rarely kills them, although we find that some get another malignancy in adulthood.”p. p. More on the Web p. To read about the research efforts of the Walther Cancer Institute, go to .p. To read Clifton Leaf’s article “Why we’re losing the war on cancer (and how to win it),” go to blog.aperio.com/articles/Fortune_Cancer.pdf.

TopicID: 6501

ND's Haiti mission not impossible. The target: Elephantiasis

2003-09-22T20:00:00-04:00

SOUTH BEND — Although there are many diseases more deadly than elephantiasis, few can match it for creating lifelong misery and disfigurement.p. It causes grotesque swelling of the body, typically of people’s legs, of women’s breasts and of men’s genitals.p. In impoverished countries like Haiti, where hygiene is generally poor, the swelling is aggravated by disastrous skin infections.p. When the infections rage in affected limbs, heat generated in the skin can become so intense that it leaves second-degree burns. The infections also cause eruptions that become putrid and make people smell bad.p. About a quarter of the 8.3 million people who live in Haiti are infected with tiny, parasitic worms that cause lymphatic filariasis, according to the Rev. Thomas Streit, a biology professor who is director of the University of Notre Dame’s Haiti Program .p. (Lymphatic filariasis is the name of the disease, while the term elephantiasis describes the disfiguring symptoms.)p. Most infected Haitians have not yet developed symptoms and are not sick. By contrast, those who already are badly disfigured are shunned and cut off from normal social contact and jobs.p. A common belief is that people with elephantiasis have been hit with a voodoo curse.p. "The disease doesn’t kill people,‘’ Streit said. "In Haiti, some say it kills people’s spirits.‘’p. p. Targeted for elimination p. p. It is in Haiti, nonetheless, that Streit and a group of collaborators are pursuing a hopeful idea: that elephantiasis can not only be prevented from maiming new victims but actually eliminated from the environment altogether.p. For a half century, Notre Dame scientists have been studying mosquito-borne diseases that plague people in hot, sticky places like Haiti, Streit said.p. Researchers at the university’s Center for Tropical Disease Research and Training are continuing the tradition by looking into malaria and dengue fever.p. The university’s current effort in Haiti is actually part of a worldwide campaign — backed by the World Health Organization and U.S. Centers for Disease Control and Prevention — aimed at wiping out lymphatic filariasis from all corners of the globe. The disease is prevalent in 80 countries, and 120 million people are infected.p. Streit, the scientist-priest, has been studying diseases in Haiti since 1993, the year before he received his doctorate in vector biology at Notre Dame . His efforts received a gigantic boost in early 2000 when the Bill and Melinda Gates Foundation awarded the university a grant of $5.2 million to lay the groundwork for a campaign to eliminate lymphatic filariasis in Haiti.p. Three and a half years later, the goal is beginning to come into view, said Michele Sexton, the program director. As a first step, the program “mapped’’ the disease, to identify where transmission is high and low. Then a treatment phase was started involving mass distribution of pills and the fortification of salt with anti-worm medicine. The fourth year of mass treatment begins next month.p. Thousands already treated
p. Last year, the program succeeded in treating almost 450,000 people with a medicine that wipes out immature worms from a person’s system and prevents adult worms from reproducing and reinfecting the bloodstream for a year, Sexton said.p. To banish the disease from the island country, research by Streit and others suggests, it will be necessary to treat virtually everyone in high-risk areas once a year for five years.p. Preventive treatment is relatively simple, especially compared with combating something like ”caps">HIV, which mutates so rapidly a vaccine may not be possible.p. All it takes is for a person to take one pill a year, Streit said. And because the parasitic worms’ only reservoir — where it lives and reproduces — is within people, world health officials have concluded that lymphatic filariasis can be made to vanish.p. "It will disappear on its own, as it has in developed countries,‘’ said Streit, noting that the disease occurred in Charleston, S.C., in colonial times.p. The tiny, mosquito-borne worm causes elephantiasis by damaging tissues in people’s lymphatic nodes and channels, the circulatory system for the body’s immune system.p. Elephantiasis is essentially the same condition as lymphedema, Streit said, the swelling well-known to women who have had lymph nodes removed as part of breast cancer surgery.p. Lymphatic filariasis occurs today only in tropical countries that are also very poor and undeveloped.p. And in Haiti, it’s the country’s incredible poverty and lack of development, rather than any complexity of the disease itself, that presents the biggest challenge to wiping it out, Sexton said. Haiti is so poor that Sexton said she has difficulty describing it to her friends at Notre Dame. She spends about half of each year at ND and the other half in Leogane, a city of about 200,000, where the university has built a center.p. "It’s hard for them to understand,‘’ she said.p. A disease born of poverty
p. In most of Haiti, the sewage system consists of open ditches or ponds near where people live.p. Mosquitoes breed rampantly in this water, and most people don’t have screens in their houses or mosquito nets around their beds to protect them from being bitten.p. Education has been a big, but by no means insurmountable, challenge, Streit said.p. Most people infected with the worms don’t have symptoms and don’t feel sick. But the pill quickly kills all the young worms in their systems, and that makes the person feel sick and have a fever for a day or two.p. "So you’re asking people who aren’t sick to take a pill that makes them feel sick,‘’ he said. "Some thought the people wouldn’t be able to understand this, but they do.‘’p. Sexton said the program’s Haiti staff and its helpers — fewer than 100 people in all, including workers from the country’s limited public health system — continually puts on educational shows in the country’s communes, political units that are roughly the equivalent of counties.p. The presentations are shown at night and include a video presentation that explains the real causes of elephantiasis. With no electricity in their homes and not much else to do at night, the people turn out in droves in a mood of festive excitement.p. "People love it. It’s a big community event,‘’ Streit said. "The people are incredibly receptive and appreciative.’‘p. But the cost of giving pills this way is high, and treating the whole country would bust the program’s budget. So to reach the goal of universal treatment more affordably, Sexton said, the program wants to put the filariasis medicine in the country’s salt supply.p. Again, cultural barriers stand in the way.p. Salt production in Haiti, far from being centralized, is largely accomplished by individuals who produce raw salt from ocean water and sell it to cooperatives.p. Politicians in Haiti have been reluctant to pass a law regulating salt production and requiring that it be fortified for fear such a measure would either throw lots of people out of work or, more likely, be mostly ignored.p. A salty political issue
p. For decades, the law has required that salt sold in the United States be fortified with iodine, an additive that can create a 10-point advantage in IQ for a child who would otherwise be deficient. Streit said he believes that if Haiti passes a law to require that iodine be put in salt, it will be a simple matter to have the anti-worm medicine added as well.p. "It works,‘’ Streit said. "The question will be whether we can overcome political and legal obstacles so that we can do the whole supply.’‘p. Unfortunately, the medicine in either form does not appear to kill the adult worms, which can live for six years in the human body. And the medicine does nothing to reverse damage to lymphatic tissues that causes elephantiasis.p. But treatments for lymphedema, including massage techniques and special attention to hygiene, also dramatically reduce the grotesque appearance of elephantiasis, Streit said.p. The Haiti program has been teaching people scarred by the disease, including men who have been branded "town monsters’’ because of their odor, to self-treat their conditions.p. There is also a good surgical treatment for the debilitating effect the disease has on the male scrotum, a condition that doctors call hydrocele. It’s a common affliction in Haiti and even occurs in teenagers, Streit said.p. "Could you imagine being 14 or 15 and having no chance of intimacy in your life?‘’ he said.p. Streit said the Haiti program needs more money and more volunteers to complete its mission.p. It needs volunteer lawyers to help with legal and political ramifications of the salt fortification project, marketers to get the word out about the program and urologists to perform the operation that restores male potency.p. The Rev. Theodore M. Hesburgh, Notre Dame’s president emeritus , said he believes elephantiasis can be wiped out of Haiti, but only if more money and volunteers are added to the project.p. "I think it can be done because it’s medically possible and because it’s been done in other places,‘’ said Hesburgh, who is the university’s main contact with the Global Alliance for the Elimination of Lymphatic Filariasis. "It can be done there, but it will take a lot of money and a lot of volunteers.‘’p. Streit said he expects to reach the goal of universal treatment by the end of the decade. Then that level of coverage must be continued for five years or less in order to eliminate the disease.p. "We’re reaching out with our expertise and, if you will, our very soul to eliminate enormous suffering,‘’ Streit said. "They suffer from this for their whole lives.’’

TopicID: 3964

Knowledge power. Want to improve the effectiveness of cancer medicine? Take time to educate the patient

2003-08-23T20:00:00-04:00

Not all improvements in chemotherapy come from test tubes in the labs of pharmaceutical companies.p. A recent study by University of Notre Dame researchers suggests patient education might also be a key ingredient in successful medical treatment of cancer.p. Their study, which involved nearly 250 local patients, found that people benefited from having a full understanding of what lay in store for them before they began their battle with cancer.p. That knowledge included some potentially harsh doses of reality, including their chances of survival with and without treatment, how chemotherapy would make them feel and how both their illness and their medicine were likely to change their finances and their lives.p. Dr. Rudolph Navari, director of ND’s Walther Cancer Research Center, said the study compared 239 patients who went to see four local cancer specialists after being diagnosed with a malignancy.p. The patients ranged in age from 27 to 85, with the average age being about 63. They were about evenly split between men and women.p. Some of the patients received extra education to help them understand their situation while others did not, said Navari, who is also a practicing oncologist in South Bend.p. Those chosen, at random, for the "educational intervention’’ were given a prompt sheet listing nine suggested questions for them to ask the oncologist.p. They also were shown a 35-minute video depicting five different vignettes of patient-doctor interaction.p. The researchers wanted to see if the education would improve the course of treatment, Navari said.p. And they found that it did. A big improvement.p. Knowledge is power
Patients who received the educational intervention were more likely to complete their course of chemotherapy rather than giving up and quitting early. And they were less likely to experience serious side effects.p. One possible explanation: Expecting hardship makes it easier to endure.p. "If you know you’re going to lose your hair, if you understand that’s going to happen, you’re less likely to stop treatment,‘’ Navari said.p. Among breast cancer patients, 86 percent of those who received the extra education had either completed their treatment or were still on course after six months. That compares with only 63 percent of those who do not receive the educational intervention.p. Similarly, 78 percent of colon cancer patients who received extra education completed their treatment, compared with 59 percent for those who didn’t.p. The results for toxicity were also impressive. Thirty percent of breast cancer patients in the non-intervention group reported having serious toxic side effects, compared with only 12 percent of those who did receive intervention.p. Besides having the advantage of being forewarned, Navari said, people who received the added education may have chosen treatments that were less toxic and more compatible with their lifestyles than they otherwise might have.p. The study found that most patients didn’t truly understand their cancer diagnosis after it was first given to them by their primary care doctor or surgeon, even though modern practice calls for full disclosure by the diagnosing physician.p. That may be because of shortcomings in doctors’ communication skills.p. Or, the study suggests, it may be because patients, having just gotten some very bad news, are still too anxious to comprehend what they’re told about their condition. They may be in a state of denial.p. "Once they hear the word ‘cancer,’ they may not hear much else, even if the doctor goes on to give them a lengthy, detailed explanation,‘’ Navari said.p. Benefits of question-asking
The study suggests patients learn more if they go into their meeting with the oncologist armed with a set of questions.p. The "question-asking’’ technique, through the use of a prompt sheet of suggested queries, may have helped patients participate more actively in the treatment decision, Navari said, even though they may still wind up simply asking the doctors what to do.p. "It’s a two-way thing,‘’ he said. "Often after a lot of questions, the person will just ask the doctor, ’What would you do if it were you, or your loved one?’ ‘’p. Navari said the researchers will continue to follow patients included in the study group to see if the educational intervention has an even bigger impact: allowing cancer patients to live longer.p. Navari said the study’s findings also highlight the importance of doctors having good communications skills, what people often refer to as having a good "bedside manner.‘’ The National Board of Medical Examiners recently announced that, starting next year, medical students will have to pass a live-action exam of their communications skills before they are certified as doctors.p. "Having a good bedside manner is simply communicating information patients need to know in a way that indicates you care about them,’’ he said. "The more patients know about what they have, the better off they are. It’s all tied together.’’

TopicID: 3969

Putting hydrogen to work

2003-07-06T20:00:00-04:00

SOUTH BEND — A small tank of hydrogen makes a camp lantern glow in one of the University of Notre Dame’s underground engineering labs.p. Hydrogen flows through a series of hoses, valves and gauges into what looks like a square stack of black wafers. Metal plates on each side of the stack are wired to the light.p. The tabletop array, rigged up to demonstrate why hydrogen fuel cells are so promising and may change the world, also demonstrates the many reasons why the fuel cells may fizzle instead.p. Despite the fact it’s holding the lightest element there is, this tank is surprisingly heavy. The black wafers that strip electrical current from hydrogen are bulky and expensive.p. Anyone in their right mind would pop a couple of old-fashioned D batteries into their lantern rather than cart this contraption to the woods.p. “The big problem with hydrogen fuel cells is going to be cost,” Paul McGinn, an ND professor of biochemical and chemical engineering, said. “It’s going to have to compete with what’s already out there.”p. McGinn is among the army of researchers around the world who are chipping away at the technical problems that now block hydrogen fuel cells from making it big in the market.p. He’s the lead scientist on a team of Notre Dame researchers (and one from Indiana University Northwest) recently awarded a $1.6 million grant from the U.S. Army’s Communications and Electronics Command.p. The ND team is looking for novel materials that can be substituted in the fuel cells to make them cost less, weigh less, work better or otherwise improve.p. Hydrogen fuel cells are ballyhooed as an environmentally sound alternative to fossil fuel because they use an abundant element as fuel and give off water as the main byproduct.p. The dream is to reduce both greenhouse gases and dependence on foreign oil in one stroke, converting society to a “hydrogen” economy. Everything from powering cars to heating houses can be accomplished with hydrogen fuel cells.p. What the Army wants from Notre Dame, McGinn said, are fundamental breakthroughs that lead to lighter, longer-lasting power sources for the many electronic devices that the modern soldier carries into battle.p. “The Army is interested in mobility, as we saw in the recent Iraq conflict,” he said. “They spend a huge amount of money bringing batteries to the battlefield.”p. One angle the ND researchers are taking in this quest is to search for an alternative to the platinum and other precious, non-corroding metals currently used in fuel cells.p. Platinum commonly serves as the key element in the catalyst that makes the cells work, McGinn said. They strip electrons off the hydrogen molecules and set up the electrical current that provides the power.p. One experiment under way at ND tests different combinations of five metals as potential catalysts. It’s being done in a lab two floors below ground level in the bottom of the Fitzpatrick Hall of Engineering.p. (The fact it’s so subterranean also has to do with the issue of dependence on foreign oil. The building was designed during the energy crisis of the late 1970s to have 60 percent of its space underground insulated by earth.)p. The metals are sprayed in thin layers on discs, which are then fed into a machine that evaluates their properties. Theory tells researchers which metals are most promising to try, McGinn said, but it takes actual trials to find the best combination.p. It’s a lottery with a big prize at stake. If the researchers find a combination that beats platinum, its contract with the Army allows the university to sell the information to private industry, McGinn said. Other results of the experiment will be published.p. Other ND researchers are looking at potential uses for carbon nanotubes in fuel cells as well as studying the “microfluidics,” or interplay of liquids and gases, within the cells.p. Nanotubes, tubes of carbon molecules that are very tiny and very strong, might help reduce the weight of hydrogen storage tanks. The tanks now being used are basically metal sponges, composed of hydrides that absorb hydrogen.p. There’s no guarantee ND’s research will bear fruit, just as the future of hydrogen fuel in the free market remains an open question.p. “Can we say for sure we’ll find something in the next six months?” McGinn said. “No, you can never say that.”p. p. Staff writer David Rumbach:
_ drumbach@sbtinfo.com _
(574) 235-6358 p. p. July 7,2003

TopicID: 413

Tackling cancer's mysteries

2002-01-07T19:00:00-05:00

SOUTH BEND — Researchers at the University of Notre Dame will be getting $2 million more to unravel the inner workings of cancer cells and to pioneer new treatments and diagnostic tools.p. ND’s research program — called the Walther Cancer Research Center — is in line to receive the money from the Department of Defense. A bill appropriating the funds has been approved by both houses of Congress and is awaiting the president’s signature.

The grant will allow the center to expand a variety of projects being carried out by three groups of researchers, said Rudolph Navari, Walther Center director. The ND scientists in those groups are among researchers around the world who are delving into the molecular intricacies of cancer.

Thorny questions

Among the thorny issues they’re pursuing are the questions of how tumors coax nearby blood vessels to grow toward them and supply them with nutrients and oxygen and how individual cancer cells learn to change shape so they can flow through the bloodstream and spread to other organs.

The insights such researchers are finding seem, on the one hand, to make cancer seem all the more formidable, even cleverly malicious. But, in fact, understanding cancer on the deepest level of biochemical processes reveals strategies to diagnose and defeat it, Navari said.

For example, detailed study of angiogenesis — the process by which tumors hijack blood supplies — has led to the discovery of a protein fragment that appears in the urine of colon cancer patients at the same time tumors recur, Navari said.

The existence of that fragment suggests a new test that doctors might one day use to detect the recurrence of colon cancer much more quickly, when treatment works best and lives can still be saved.

“We know our current techniques (for detecting recurrence) are not very good,‘’ said Navari, a medical oncologist. "A CT scan, for example, only finds tumors that are 2 centimeters or more. The hope is that this will allow us to detect it much sooner.’’

Grant favors collaboration

The Department of Defense grant program now funding ND gives preference to research centers that stress collaboration between university departments, Navari said.

The Walther Center’s three teams of researchers are drawn from the chemistry, biochemistry, biology and premedical departments, he said. A fourth group, not involved in the new grant, explores ethical and social questions related to cancer care that people receive.

By working together, scientists from different disciplines hope to cut the time it takes to discover new treatments and advance them to clinical research. It’s not unusual for 20 years to lapse between the discovery of a potentially useful new cancer-fighting chemical and its actual use in people with cancer.

“Traditionally, departments work independently, and even within departments, professors pretty much do their own thing,‘’ Navari said. "One of the things we try to do here is to get people to talk to each other.’’

While chemists are making new molecules with potential for fighting cancer in the lab, biochemists and biologists are learning more about the molecular processes that make cancer tick. They can assess the effect of potential new drugs on healthy and malignant cells.

As a physician who treats patients in South Bend, Navari said he contributes a sense of what drugs and tests are needed most for people with cancer.

“I can identify the areas, particularly in breast and prostate cancer, where we don’t have good treatments,’’ he said.

Cells targeted for genetic analysis

The cancer work is being done at labs in buildings throughout the campus. The researchers come from across the country and around the world and include both undergraduates in their early 20s and established scientists.

In one of the labs, Matt Feldman, a graduate student in biochemistry, uses two high-tech devices to explore subtle genetic differences in healthy and cancerous mice.

Feldman uses a laser capture microdissector to isolate individual cancer cells from mouse tissue. He can even hand-pick cells from the border between cancerous and normal tissue, and then compare healthy and diseased cells that were, literally, next-door neighbors.

After being isolated by the microdissector, sick cells are analyzed using a device that compares their entire genome, consisting of 6,000 genes, to those of three normal mice. The normal mice genomes are contained within small plastic chips, called microarrays, that cost $750 each and can only be used once, said Victoria A. Ploplis, associate chemistry and biochemistry professor.

The purpose of the genetic analysis is to find variations in gene expression that are associated with the disease, Ploplis said. Since the researchers are looking at the entire genome of the mouse, it’s possible for entirely unexpected genes to emerge as key players in disease.

“This is discovery research,‘’ Ploplis said. "We’re looking at everything.’’

The mice used by the gene-targeting group at the Walther Center are produced in the university’s Transgene Center. They are genetically altered to produce too much or too little of various proteins, enabling researchers to explore how various abnormalities influence cancer and other diseases, Director Francis Castellino said.

Looking to mice for answers

Research at the Transgene Center, which keeps an inventory of 5,000 transgenic mice, focuses mainly on genes and proteins involved in blood-clotting, Castellino said. Abnormal clotting is, of course, a factor in heart attacks and atherosclerosis, but it’s associated with cancer as well, Navari said. Physicians have long observed that cancer patients often develop abnormal clotting.

“We have taken these mice, which are deficient in certain clotting proteins, and transplanted tumors into them and found the tumors grow a lot slower,‘’ Navari said. "So maybe it’s possible to design a drug to reduce this protein in cancer patients, and slow down the cancer growth.’’

In a chemistry lab, Pingyu Ding, a visiting scholar from China, synthesizes a promising new molecule believed to have the remarkable ability to attach itself to the surface of prostate cancer cells, and not to anything else.

The excitement about this compound, called a prostate specific membrane antigen, is that it might lead to a screening test that is far superior to the largely ambiguous PSA test now given to middle-aged men, said Paul Helquist, chemistry and biochemistry professor.

One could, for example, attach a fluorescent compound to the molecule so that when it binds to prostate cancer cells, they light up on diagnostic scans and reveal their presence, said Helquist, who heads up the Walther Center’s drug design group. Or one could go one step further and attach a cell-killing drug directly to the molecule, enabling it to seek out prostate cancer like a smart bomb.

Hope from a sea slug

Another promising molecule being studied by the chemistry department is derived from a black sea slug found on a Japanese island just off Okinawa. The extract from the ugly slugs — which look like "balls of tar,’’ Helquist said — was identified as a potential anti-cancer agent 12 years ago. But the information sat unused until recently when a researcher named John Kane isolated the active chemicals and start making it in the lab at Notre Dame.

Lab tests have confirmed that very tiny amounts of the drug cause breast cancer cells to break up and self-destruct, Helquist said. The next steps are to make sure the compound, called iejimalide, doesn’t do the same thing to healthy cells and to see whether it works in living mice.

“That’s the extent of work that could be done at a typical university,‘’ Helquist said. "If a compound meets all these tests, there would be a transfer of technology to a pharmaceutical concern.’’

What makes cancer spread?

In the biology department, Crislyn D’Souza-Schorey is exploring one of cancer’s most dangerous tricks: the ability to detach from its site of origin, change shape and move around the body to invade different organs. Her research looks specifically at breast cancer and other cancers that occur in surface tissues called epithelia.

Her research feeds into one of the great mysteries of cancer: What triggers cancerous tumors to begin spreading, she said.

“The ultimate goal is to control or prevent metastasis,’’ she said.

The cancer research at Notre Dame is not unusual. Universities around the world are doing similar work. It is unusual, however, for Notre Dame to be as heavily involved in medical research as it is, given the fact that it does not have a medical school.

“You won’t find another chemistry department in the country doing what we’re doing,’’ Castellino said.

The new grant approved by Congress is the second one that the Defense Department has awarded to ND, Helquist said. The original grant, now being used, was for $1 million

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