December 10, 2006, 9:20 PM CT

Enzyme That Aids Tumor Growth

Using an innovative profiling strategy, researchers at The Scripps Research Institute have characterized an enzyme that is "highly elevated" in aggressive human tumor cells. When the enzyme, KIAA1363, was inactivated, it impaired tumor growth and migration in both ovarian and breast cancer cells, suggesting that inhibitors of this enzyme may prove valuable in the therapy of multiple types of cancer.

The study is the cover story of the October 23 issue of the journal Chemistry & Biology.

"Using a combination of enzyme activity and metabolite profiling, we determined that this protein-whose function was previously unknown-serves as a key regulator of a lipid signaling network that contributes to cancer," said Benjamin F. Cravatt, a Scripps Research professor and a member of its Skaggs Institute for Chemical Biology who led the study. "The heightened expression of KIAA1363 in several cancers indicates that it may be a critical factor in tumorgenesis. In addition, network components, including KIAA1363 itself, might be considered potential diagnostic markers for ovary cancer".

This experimental method of integrated molecular profiling used in the study should also advance the functional study of metabolic enzymes in any biological system, as per Cravatt.........

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December 8, 2006, 5:08 AM CT

Viagra Against Cancer?

Sildenafil and other "impotence drugs" that boost the production of a gassy chemical messenger to dilate blood vessels and produce an erection now also show promise in unmasking cancer cells so that the immune system can recognize and attack them, say scientists at the Johns Hopkins Kimmel Cancer Center.

Tests at Hopkins on mice with implanted colon and breast tumors showed that tumor size decreased two- and threefold in sildenafil-treated animals, compared to mice that did not get the drug. In mice engineered to lack an immune system, tumors were unaffected, proof of principle, the scientists say, that the drug is abetting the immune system's own cellular response to cancer.

In a report published in the Nov. 27 issue of the Journal of Experimental Medicine, the Hopkins team says boosted levels of the chemical messenger nitric oxide appear to dampen the effects of a specialized cell that diverts the immune system away from tumors, allowing swarms of cancer-attacking T-cells to migrate to tumor sites in the rodents.

Lab-grown cancer cells treated with sildenafil showed similar results, as did tissue samples taken from 14 head and neck cancer and multiple myeloma patients.

Sildenafil, marketed under the trade name Viagra, is one of a class of drugs used to treat erectile dysfunction in millions of men, and in recent years, its ability to stimulate the production of NO has been investigated by experts in diseases linked to the activity of blood vessels and blood components.........

Posted by: Jessica      Permalink         Source

December 5, 2006, 8:13 PM CT

Why Cancer Drug Causes Side Effect

I broken pump can mean lots of trouble, particularly when it occurs in the micro-world of cells. A broken "pump" in the liver may fail to push these medicines into a "drain," as per researchers at St. Jude Childrens Research Hospital. The finding offers clinicians a way to identify patients who are likely to develop diarrhea as a side effect from taking these drugs, the scientists said.

The discovery also has implications for people taking other drugs, since this pump controls the blood levels of a number of of the prescription drugs on the market. This study is the first to show that a specific gene mutation disables the pumpa protein called ABCG2preventing it from disposing of these drugs. The mutation, a type of alteration called a single nucleotide polymorphism, is designated 421C>A in reference to the specific change in one of the DNA building blocks of the gene.

ABCG2 pushes drugs out of cells and back into the blood, or in the case of the liver, the pump pushes drugs into a tube-like structure called the bile canaliculum, which eventually leads to the intestine, from which it is excreted, as per the researchers. ABCG2 also pumps drugs out of the cells lining the intestine, preventing drugs taken by mouth from flooding into the body. Once past the intestine, blood vessels pick up the drugs and bring them to the liver and other parts of the body.........

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November 30, 2006, 4:20 AM CT

New Drug Will Help Smokers

Scientists in the Oregon Health & Science University Smoking Cessation Center are studying whether the newly FDA-approved drug varenicline (Chantix) - a drug they recently showed to be more effective than the smoking cessation drug bupropion (Zyban) in helping generally healthy smokers quit - also can help smokers with the devastating lung disease known as chronic obstructive pulmonary disease (COPD).

COPD is the fourth leading cause of death in the United States. It is a disease that leads to progressive loss of lung function and is primarily a smoker's disease because very few nonsmokers are at risk for COPD. Once it has taken a firm hold, COPD has a debilitating effect on patients' lives, lifestyles and their families. They develop chronic cough, shortness of breath and difficulty breathing with exertion. Over time, as breathing becomes more and more difficult, the disease limits their ability to be active, and reduced activity further limits their quality of life. While both men and women smokers are at risk for these devastating effects, women smokers are more vulnerable than men.

Gail Cary, 73, Beaverton, Ore., has COPD. She smoked two packs a day for decades before quitting seven months ago with the support of OHSU Smoking Cessation Center staff.

"I always had an ill feeling, felt uncomfortable about smoking. I was careful to hide it, but I coughed a lot and my clothes smelled of smoke," Carey said. "Seven months ago I had a very irregular heartbeat and went to the hospital in am ambulance. I told myself if I get home, the cigarettes are gone. I felt so guilty. Since I've quit, I've felt a lot better emotionally. I'm thinking positively and I don't cough. I'm not going to go back".........

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November 29, 2006, 4:39 AM CT

Scientists Working In A 'Boundary-less' Environment

A cadre of world-renowned researchers working in the most promising areas of cancer research have come together to work as a team at one institution Memorial Health to accelerate findings for the prevention and therapy of cancer.

The new approach to making advances in cancer research is focused on a "boundary-less" environment which the researchers expect will stimulate faster, cross-disciplinary results and increased collaboration between researchers and physicians. The "boundary-less" approach applies to all aspects of the research and even extends to the physical facility which features a laboratory that literally has no internal walls.

This team of scientists, all recruited from top institutions in the United States, is focused exclusively on translational or "bench to bedside" research of molecular genetics, allowing them to work closely with physicians to translate laboratory findings into individualized therapys, earlier diagnostics, and new cancer prevention methods for patients.

Tapped to lead Memorial Health's newly created Laboratory Research Program, Jeff Boyd, Ph.D., a distinguished scientist from Memorial-Sloan Kettering Cancer Center in New York City, selected some of the nation's top research talent including Dominique Broccoli, Ph.D., Fox Chase Cancer Center; Nagendra Ningaraj, Ph.D., Vanderbilt University; Ranjan Perera, Ph.D., Burnham Institute, La Jolla, California; Apostolos Psychogios, M.D., Harvard University; John Risinger, Ph.D., National Cancer Institute; and, Cindy Yee, Ph.D., Memorial Sloan-Kettering Cancer Center.........

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November 28, 2006, 4:59 AM CT

Big Bias In Who Gets Screened For Breast Cancer

Certain women may miss out on routine tests that screen for early signs of breast cancer.

Elderly women, women with publicly funded health insurance and women who don't go to an obstetrician and gynecologist for routine exams are all less likely than others to get a clinical breast exam and a recommendation for a mammogram.

"A physician's recommendation is why a number of women undergo screening in the first place," said Rajesh Balkrishnan, the Merrell Dow professor of pharmacy at Ohio State University. "Foregoing these exams can increase a woman's risk of developing an advanced stage of breast cancer. There are several reasons why a doctor may not give a patient a clinical breast exam or recommend a mammogram".

Balkrishnan led a study that uncovered some of these possible reasons. The findings currently appear online at the website of the journal Breast Cancer Research and Treatment.

The scientists gathered data from the National Ambulatory Medical Care Survey (NAMCS), a database run by the Centers for Disease Control and Prevention. The NAMCS contains information on a nationally representative sample of practicing physicians and patient visits throughout the United States. The scientists restricted their data set to doctor office visits by women 40 and older from 1996 through 2004.........

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November 23, 2006, 5:22 AM CT

Prolonged Anthracycline Therapy Reduces Heart Problems

Stretching out a dose of chemotherapy over six or more hours may reduce the risk of heart problems caused by certain commonly used cancer drugs, according to a new review of recent research.

Anthracycline drugs like daunorubicin and doxorubicin are used to treat many types of solid tumors and blood cancers such as leukemias in adults and children.

Anthracycline therapy can be very successful at controlling cancer, but heart damage caused by anthracycline treatment is a considerable and serious problem, said Dr. Elvira van Dalen of the Emma Childrens Hospital in the Netherlands.

She and her colleagues found that the rates of heart failure among adult patients receiving anthracycline therapy were significantly lower when the patients had an infusion of the drug that lasted six or more hours, compared to shorter infusions times.

In five studies involving 557 patients, the longer treatment cut the risk of heart failure by nearly 75 percent compared to the risk in patients who received the short treatment.

van Dalen said the prolonged dose of six hours or more might be justified if a patient is at high risk of heart damage or needs a high cumulative dose of the chemotherapy.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.........

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November 22, 2006, 4:45 AM CT

Side-effect-free chemotherapy

Treating cancer with chemotherapy can be as destructive to healthy cells as it is to tumour cells, causing notorious, debilitating side effects. US researchers have now developed an enzyme with the potential to eliminate the extreme fatigue, sickness and hair loss that result from this cell damage and strike fear into the hearts of cancer patients.

The researchers, led by Zaver Bhujwalla from Johns Hopkins University in Baltimore, developed a traceable enzyme to activate cancer prodrugs. The enzyme can be tracked on its journey within the body, to ensure that it has been cleared out of healthy tissue before the prodrug is introduced.

'Blood vessels of tumour cells are much leakier than normal, healthy vasculature so the enzyme leaks into the tumour but is cleared out of healthy tissue by the bloodstream,' Bhujwalla explained.

The enzyme, cytosine deaminase was chemically tagged with two tracers, gadolinium, which is a contrast agent that can be visualised using magnetic resonance imaging (MRI); and rhodamine, which is an optically visible tracer. Using rhodamine allowed the scientists to view sections of tissue microscopically and verify that their MRI images were accurate.

'This is the first time that a prodrug enzyme has been made visible with MRI,' Bhujwalla told Chemistry World. 'It's crucial because this type of imaging can be used in a clinical setting.'.........

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November 16, 2006, 9:40 PM CT

Tooth Whiteners Do Not Cause Cancer

Common tooth whitening products, which have been used by millions of people, are found to be safe and do not increase the risk of oral cancer when used as directed. This exhaustive review of the literature, including numerous unpublished clinical studies involving over 4,000 human subjects, appeared in an article by Dr. Ian Monroe entitled, " Use of Hydrogen Peroxide-Based Tooth Whitening Products and it Relationship to Oral Cancer," published in Journal of Esthetic and Restorative Dentistry.

Clinical and laboratory data on tooth whitening products show no evidence for the development of oral cancer or of other effects that could be linked to increased oral cancer risk. Exposures to hydrogen peroxide, generally the effective ingredient in tooth whiteners, are too low and of too short of a duration (30-60 minutes) to cause any oral tissue changes that could enhance risks for oral cancer development. Concentrations of hydrogen peroxide rapidly decline to near undetectable levels commonly within 15 to 60 minutes.

Given the likely use of tooth whitening products by smokers, the review also sought to examine any possibility of increased oral cancer development due to combined exposure (i.e., hydrogen peroxide and carcinogenic agents that are present in cigarette smoke). A possible combined-effect, as seen in the increased likelihood of lung cancer development in smokers also exposed to asbestos, was found to be groundless with regards to bleaching and smoking and further illustrates the relative safety of tooth whitening products.........

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November 15, 2006, 4:52 AM CT

Vascular Targeting Agent Halts Bone Metastasis

A novel vascular targeting agent completely prevented the development of bone tumors in 50 percent of the mice tested in a preclinical study, providing early evidence that it could treat, or thwart, growth of tumors in bone, a common destination for a number of cancers when they start to spread.

Researchers at The University of Texas M. D. Anderson Cancer Center reported in the journal Cancer Research that this "Trojan Horse" agent, VEGF121/rGel, stopped specialized cells within the bone from chewing up other bone material to make room for the implanted tumor to grow.

Although this study tested the ability of VEGF121/rGel to halt the growth of human prostate cancer cells in the bones of mice, scientists say it likely could help prevent the growth of other cancers in bones such as breast, multiple myeloma, lung and renal cell.

"Many tumors invade bone in the same way, so these findings suggest it may be possible to shut down this process regardless of the tumor type," says the study's lead author, Michael G. Rosenblum, Ph.D., professor in the Department of Experimental Therapeutics. "If that could be done - and we are a long way from determining if it is possible - we may be able to offer the first treatment that specifically targets bone metastasis".........

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