 The founding members of the new UNLV Cancer Institute have joined together in an effort to fight cancer through their research. Find out how these committed scientists are trying to improve the prevention, detection, and treatment of the deadly disease. BY SUZAN DIBELLA 
n June of last year, a small group of UNLV scientists formally joined together in the pursuit of a noble shared goal: improving the diagnosis, treatment, and prevention of cancer.Representing three different UNLV colleges, the eight faculty members — all of whom had been conducting research on their own on various subjects related to cancer — officially became the founding members of the new UNLV Cancer Institute. The reason for formalizing the collaboration of these scientists was perhaps best articulated by UNLV President Carol C. Harter at the time she announced that the institute had been approved by the UCCSN Board of Regents. "For many years," she said, "we have had faculty scientists doing intriguing cancer research. We expect the new institute to serve as a valuable think-tank for our cancer researchers while also making them more visible to the external community." Today, the institute boasts an additional faculty member and more than eight months of formal collaboration. The team of scientists from the departments of chemistry, biology, electrical and computer engineering, mechanical engineering, and health physics meet regularly to share insights on their research and generate a valuable exchange of data and theories. But the collaboration doesn't stop on the UNLV campus; they are being joined in their research endeavors by several faculty members from the University of Nevada School of Medicine and several physicians from University Medical Center. At the same time, members of the institute continue to pursue increased grant funding; the group's status as an institute is expected to enhance the likelihood of members obtaining such funding. UNLV Magazine recently asked these scientists to describe their research. HereÕs what we found out.
Finding ways to stop cancer from moving around the body is cell biologist George Plopper's research challenge. He believes it could have a remarkable impact on the way cancer is treated. But to understand why it's so critical, he explains, you must first understand how cancer works.
He adds that the most common way to treat cancer is to stop cancer cells from growing at inappropriate times; the idea is that a non-growing or dead cancer cell can't interfere with other organs. "There are thousands of ways to stop cells from growing," he says. "The problem is that most of these treatments also stop normal healthy cells from growing, so that patients who receive these treatments often feel more sick than they did with just the cancer. This is why their hair falls out, they get diarrhea, or suffer other side effects from treatment. In simple terms, when one takes anti-cancer drugs, one enters a race to see which will die first: the cancer cells or the healthy cells. That 'race' can be devastating, and in many cases, the cancer cells outlive the normal cells, so that patients get horribly sick but die of organ failure anyway." But, Plopper says, if cancer cells remained in just one place, then treatment could be more effective and less destructive to the rest of the body. "One way to help increase the effectiveness of cancer treatments is to target the other behavior of cancer cells — namely their propensity to grow in inappropriate places in the body. To grow in a different part of the body, a cancer cell has to crawl, or move, from one organ to another. We want to stop that from happening. The idea here is that if one could at least make the cancer cells stay put in one place, we could target the cells locally with the thousands of treatments available and leave the rest of the body alone." But getting cancer cells to "sit still" in one part of the body is very hard to do, since researchers don't know what makes them want to get up and move in the first place. "Why on earth would a skin cell want to move into a lung? Really, nobody knows," Plopper says. "My research tries to address this question in two ways. First, we study how cancer cells move. We compare breast cancer cells to normal breast cells, and ask what differences between them might explain why the cancer cells move. We'd like to focus on these differences, and try to find a way of interfering with the biological processes in the cancer cells that make them move to other organs; if we could design drugs that interfere with this process, we could stop cancer cells from moving. Second, we test new drugs to see if they can interfere with cancer cell movement but leave the normal cells alone, even if nobody knows how they might work. The idea here is that, regardless of how they work, drugs that would keep cancer cells in one place would be useful in the clinic and would compliment existing treatments for cancers."
"Radiologists rely on the mammograms to detect any abnormal areas of the breast," says Bruce, a faculty member in UNLV's department of electrical and computer engineering. "Our goal is to provide them with a tool to increase the effectiveness of diagnosing breast cancer." To that end, her research includes developing computer systems that can automatically detect masses, highlight these areas for the radiologist to analyze, and make determinations about whether the mass is benign or malignant. In a state-of-the-art computer laboratory, Bruce and her research team train the computer systems to detect tumor images produced by the mammogram and then to make decisions, or diagnoses, based on the shape and texture of the tumors. She uses advanced mathematics and electrical engineering tools to train the computer systems. "We have a database of mammograms that we use to train and test our automated systems," she says. "The database of mammograms has been read by radiologists. The malignant tumors have been proven by biopsies, and each patient has had a one-year followup. So we know the correct diagnosis for each mammogram. We give this information to our computer systems for training purposes." During the training phase, she also sets aside a portion of the mammograms and does not tell the computer system the true diagnoses. "We then use these 'unknown' mammo-grams for testing the system," she says. "We keep track of how well the system is diagnosing the mammograms and use this information for improving our designs."
"DNA is the genetic blueprint within every cell of the body that dictates cellular behavior," Gary says. "I study natural biochemical systems that repair damaged DNA." DNA, he explains, becomes damaged to some extent all the time; it is an inevitable part of life. Some environmental factors, such as sunlight, cigarette smoke, and pollution, can accelerate the rate of DNA damage. "If left unrepaired," he notes, "this damage causes changes in DNA, called mutations, that make the cell behave abnormally. If normal cells acquire DNA mutations that cause them to grow uncontrollably, they can become cancer cells." Therefore, he points out, protecting DNA from damage is very important in preventing cancer. "Fortunately, normal cells have a built-in way to prevent mutations," he says. "They have biochemical systems that find sections of DNA that have been damaged, and they restore them to their original condition. The more efficiently these systems work, the lower our risk of getting cancer will be." Hence, his research seeks to discover the details of how DNA repair biochemistry works in the effort to enhance the human body's natural ability to prevent cancer. "We study the properties of specific repair proteins to see what they do individually and also how they work together as a molecular team to repair DNA. We want to learn the precise role of each protein, and then assemble this information to form a model that describes the repair process as a series of steps leading to the end point, which is completely repaired DNA. Along the way, we learn the requirements and vulnerabilities associated with each step; these are the potential sources of problems in terms of cancer development."
"Patients with malignant brain tumors have a very poor prognosis," says Madsen, a UNLV health physics professor. "The best available treatment — using surgery, chemotherapy, and radiation therapy — results in typical survival of about 10 months. When the treatment fails, it's usually due to the reappearance of the tumor at the original site. This is due to the fact that the tumor cells not removed during surgery are very resistant to chemotherapy and/or radiation therapy." One treatment that holds promise, Madsen says, is photodynamic therapy, in which laser light is used to activate a cancer-killing drug that has already been administered to the patient. "My primary research focus is to evaluate the effectiveness of photodynamic therapy, or PDT as it's called, in the treatment of aggressive brain tumors," he says. "PDT is a two-stage treatment. In the first stage, a drug is administered to the patient; the drug accumulates in the tumor and, in the second stage, it is activated with laser light. The activated drug leads to the eventual destruction of the tumor tissue." The effectiveness of this treatment, he says, depends, in part, on being able to deliver the laser light to the tumor. This is usually accomplished by the insertion of optical fibers into the tumor tissue or the cavity in which the tumor is situated, Madsen says. "The drug can also be used as a diagnostic tool to locate tumor cells. This is possible since the drug emits light when it interacts with the laser. This light can be seen with a special type of camera." Madsen's research has already attracted the attention of several neurosurgeons who have wanted to use the therapy in clinical trials; he is now collaborating with them to develop experimental PDT treatment for cancer patients in California and Norway.
"The spaces between blood vessel walls and surrounding tissue is normally large enough to allow only water and nutrients to pass through," Fu says. "However, when the size of that space increases due to illness, larger molecules and cells, including cancer cells, can cross the vessel wall, leading to a greater likelihood that cancer will spread throughout the body via the bloodstream." Through her research, she explains, she hopes to better understand what chemicals affect the integrity of the blood vessel walls; her goal is to find ways to prevent cancer cells from permeating those walls and then traveling throughout the body. Another related aspect of her research involves discovering ways of helping cancer-fighting drugs reach cancerous tumors. Once again, she is examining the permeability of the vessel walls to analyze the steps of drug delivery to tumors through the blood vessels surrounding it. "New and more effective anti-cancer agents are being developed these days, but the clinical results have not met the high expectations of researchers," she says. "One of the many difficulties is that it is hard for these agents to make their way into the blood vessels of the tumor and into the cancer cells." If successful, her research will yield mathematical models that will be used by other researchers to determine how much and how frequently cancer-fighting drugs should be administered to patients.
The biochemistry professor knows that when this protein is produced at high quantities in breast cancer tumors, patients have an 80 percent chance of having their tumor recur. When it is produced at low levels, the rate of recurrence is only 30 percent. "I study how hsp27 protects breast cancer cells from agents designed to kill them, thus allowing the tumors to recur," says Carper, who serves as director of the UNLV Cancer Institute. To conduct his research, Carper grows human breast cancer cells in his laboratory. Using genetic engineering techniques, he has constructed cell lines that make high or low levels of hsp27. "I then try and kill these cell lines with chemotherapeutic drugs to determine how hsp27 protects these cells," he says. "I examine whole cells, as well as DNA, RNA, and proteins removed from these human breast cancer cells. I also do some experiments in test tubes in which I mix together hsp27 and other proteins to see how they interact with each other." Carper hopes that his research might one day enable physicians to treat patients with breast cancer more effectively. "After surgical removal, the tumor would be evaluated for the presence of hsp27," he says. "If hsp27 was elevated, then a specific therapy — developed in my laboratory — would be given to kill any remaining tumor cells that had high levels of hsp27. This would decrease the rate of tumor recurrence and potentially improve survival of breast cancer patients."
Elegbede, a UNLV biochemistry professor since 1998, has discovered that a plant product called d-limonene, found in the skins of oranges, seems to have a powerful cancer-fighting ability in laboratory animals. But understanding just how this and other natural agents fight cancer again requires a lesson on how cancer begins, he says. "Cells grow by dividing according to their DNA message at certain times in the life cycle," Elegbede says. "When something happens to change the message that is carried by the DNA in new cells — a mutation — the cells usually have an internal mechanism that prevents the incorrect message from resulting in a change to the cell. That mechanism causes the cell to commit suicide, which we call 'apoptosis.' "We have found that in most cancer cells, something has gone wrong with the DNA that causes them to carry and maintain one of these incorrect messages. As a result, the cancer cells do not obey the internal signal to self-destruct and do not obey any of the control signals regulating their growth. Consequently, cancer cells grow out of control." Elegbede notes that researchers have found that just as some foods have cancer-causing properties, others have the potential to halt cancer growth or prevent it altogether. "Some of these components selectively cause the cancer cells to commit suicide while not having any deleterious effect on normal cells," he says. "My research is involved in understanding which of these food components have potential to cause, or more accurately, to remind cancer cells to self-destruct. Understanding how they are able to do this will help us in determining which of the compounds can be used for preventing and/or treating cancers in humans." D-limonene is one of those compounds, he says, noting that clinical trials designed to evaluate the substance's effect on humans are underway in several countries.
"Enzymes are molecules contained in our cells that help control biological processes like cell regeneration," says McKinstry. "In one of my research pro-jects we are synthesizing molecules called 'enzyme blockers' that will regulate abnormal enzyme activity that is associated with specific biological disorders such as cancer. "Another focus of my research is on combining molecules that will damage the DNA in cancer cells and stop them from reproducing," she says. "We take the basic molecular structure of a naturally occurring cancer-causing substance and then chemically alter it in order to develop new compounds that will be effective drugs for cancer therapy." Her research is conducted in a laboratory where the substances she studies are exposed to both very low and very high temperatures, as well as to the absence of oxygen and moisture. McKinstry's goals are straightforward: She wants to develop new drugs for treating cancer and then develop molecules that will stop cancer. "If we could stop cancer cells from growing or stop normal cells from becoming cancerous, cancer would become nonexistent," she says.
"The thymus gland, which is found in the body near the heart, produces proteins that help the immune system to work properly so that we do not become sick," he explains. "So we are using those proteins to develop substances that kill leukemia cells." The good news is that early results of his research show that these substances from the thymus gland can stop human leukemia cells from dividing, which limits their ability to spread throughout the body. "If we are correct in our central hypothesis that the thymus gland secretes hormones that prevent the occurrence or spread of cancer, then we will be able to isolate a thymic hormone and use it for the treatment of certain forms of cancer. Specifically, we have a thymic peptide that stops leukemia cells from growing in the laboratory. We hope that this thymic peptide will prevent leukemia cells from growing and spreading in the human body." In his laboratory, Spangelo, who also chairs the chemistry department, uses cancer cells taken from a leukemia patient to create cell lines for testing of various combinations of the thymic peptides. "It's our hope that these substances will act the same in the human body as they do in the lab," he says. Joining the UNLV Cancer Institute this year is nursing professor Susan Meacham, who is the director of the university's new nutrition sciences program. Meacham's research focuses on cancer-preventing foods. |
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