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November 29, 2009, 11:11 PM CT

Workings of anti-cancer drug

Workings of anti-cancer drug
The copper sequestering drug tetrathiomolybdate (TM) has been shown in studies to be effective in the therapy of Wilson disease, a disease caused by an overload of copper, and certain metastatic cancers. That much is known. Very little, however, is known about how the drug works at the molecular level.

A newly released study led by Northwestern University scientists now has provided an invaluable clue: the three-dimensional structure of TM bound to copper-loaded metallochaperones. The drug sequesters the chaperone and its bound copper, preventing both from carrying out their normal functions in the cell. For patients with Wilson disease and certain cancers whose initial growth is helped by copper-dependent angiogenesis, this is very promising.

This knowledge opens the door to the development of new classes of pharmaceutical agents based on metal trafficking pathways, as well as the further development of more efficient TM-based drugs. The study will be published in Science Express Nov. 26.

"Essential metals are at the center of a number of emerging problems in health, medicine and the environment, and this work opens the door to new biological experiments," said Thomas V. O'Halloran, the study's senior author and the Charles E. and Emma H. Morrison Professor of Chemistry in the Weinberg College of Arts and Sciences at Northwestern. He and geneticist Valeria Culotta of Johns Hopkins University discovered the first copper chaperone function in 1997.........

Posted by: Janet      Read more         Source


November 19, 2009, 0:02 AM CT

Morphine may stimulate cancer growth

Morphine may stimulate cancer growth
Eventhough morphine has been the gold-standard therapy for postoperative and chronic cancer pain for two centuries, a growing body of evidence is showing that opiate-based painkillers can stimulate the growth and spread of cancer cells. Two new studies advance that argument and demonstrate how shielding lung cancer cells from opiates reduces cell proliferation, invasion and migration in both cell-culture and mouse models.

The reports--to be presented November 18, 2009, at "Molecular Targets and Cancer Therapeutics," a joint meeting in Boston of the American Association for Cancer Research, the National Cancer Institute, and the European Organization for Research and Treatment of Cancer--highlight the mu opiate receptor, where morphine works, as a potential therapeutic target.

"If confirmed clinically, this could change how we do surgical anesthesia for our cancer patients," said Patrick A. Singleton, PhD, assistant professor of medicine at the University of Chicago Medical Center and principal author of both studies. "It also suggests potential new applications for this novel class of drugs which should be explored".

The proposition that opiates influence cancer recurrence, prompted by several unrelated clinical and laboratory studies, has gradually gained support. It started with a 2002 palliative-care trial in which patients who received spinal rather than systemic pain relief survived longer. Soon after that, Singleton's colleague, anesthesiologist Jonathan Moss, noticed that several cancer patients receiving a selective opiate blocker in a compassionate-use protocol lived longer than expected. Two recent retrospective studies observed that breast and patients with prostate cancer who received regional rather than general anesthesia had fewer recurrences. In February, 2009, the Anesthesia Patient Safety Foundation highlighted the issue.........

Posted by: Janet      Read more         Source


November 18, 2009, 11:18 PM CT

Catching circulating cancer cells

Catching circulating cancer cells
Fluorescence micrographs and SEM images show how more cancer cells were captured on the silicon nanopillar (SiNP) substrate compared to the flat substrate.

Credit: UCLA

Just as fly paper captures insects, an innovative new device with nano-sized features developed by scientists at UCLA is able to grab cancer cells in the blood that have broken off from a tumor.

These cells, known as circulating tumor cells, or CTCs, can provide critical information for examining and diagnosing cancer metastasis, determining patient prognosis, and monitoring the effectiveness of therapies.

Metastasis the most common cause of cancer-related death in patients with solid tumors is caused by marauding tumor cells that leave the primary tumor site and ride in the bloodstream to set up colonies in other parts of the body.

The current gold standard for examining the disease status of tumors is an analysis of metastatic solid biopsy samples, but in the early stages of metastasis, it is often difficult to identify a biopsy site. By capturing CTCs, doctors can essentially perform a "liquid" biopsy, allowing for early detection and diagnosis, as well as improved therapy monitoring.

To date, several methods have been developed to track these cells, but the UCLA team's novel "fly paper" approach appears to be faster and cheaper than others and it appears to capture far more CTCs.

As per a research findings published this month in the journal Angewandte Chemie, the UCLA team developed a 1-by-2-centimeter silicon chip that is covered with densely packed nanopillars and looks like a shag carpet. To test cell-capture performance, scientists incubated the nanopillar chip in a culture medium with breast cancer cells. As a control, they performed a parallel experiment with a cell-capture method that uses a chip with a flat surface. Both structures were coated with anti-EpCAM, an antibody protein that can help recognize and capture tumor cells.........

Posted by: Janet      Read more         Source


November 17, 2009, 7:59 AM CT

Structural brain changes in Alzheimer's disease

Structural brain changes in Alzheimer's disease
Serial MRI brain scans, taken six months apart, show progression from mild cognitive impairment to Alzheimer's disease, with significant atrophy (blue) and ventricle enlargement (orange/red).

Credit: University of California, San Diego, UCSD

In a study that promises to improve diagnosis and monitoring of Alzheimer's disease, researchers at the University of California, San Diego have developed a fast and accurate method for quantifying subtle, sub-regional brain volume loss using magnetic resonance imaging (MRI). The study will be published the week of November 16 in the Proceedings of the National Academy of Sciences (PNAS).

By applying the techniques to the newly completed dataset of the multi-institution Alzheimer's Disease Neuroimaging Initiative (ADNI), the researchers demonstrated that such sub-regional brain volume measurements outperform available measures for tracking severity of Alzheimer's disease, including widely used cognitive testing and measures of global brain-volume loss.

The general pattern of brain atrophy resulting from Alzheimer's disease has long been known through autopsy studies, but exploiting this knowledge toward accurate diagnosis and monitoring of the disease has only recently been made possible by improvements in computational algorithms that automate identification of brain structures with MRI. The new methods described in the study provide rapid identification of brain sub-regions combined with measures of change in these regions across time. The methods require at least two brain scans to be performed on the same MRI scanner over a period of several months. The new research shows that changes in the brain's memory regions, in particular a region of the temporal lobe called the entorhinal cortex, offer sensitive measures of the early stages of the disease.........

Posted by: Daniel      Read more         Source


November 17, 2009, 7:55 AM CT

Nanoparticles causes DNA damage in mice

Nanoparticles causes DNA damage in mice
Titanium dioxide (TiO2) nanoparticles, found in everything from cosmetics to sunscreen to paint to vitamins, caused systemic genetic damage in mice, as per a comprehensive study conducted by scientists at UCLA's Jonsson Comprehensive Cancer Center.

The TiO2 nanoparticles induced single- and double-strand DNA breaks and also caused chromosomal damage as well as inflammation, all of which increase the risk for cancer. The UCLA study is the first to show that the nanoparticles had such an effect, said Robert Schiestl, a professor of pathology, radiation oncology and environmental health sciences, a Jonsson Cancer Center scientist and the study's senior author.

Once in the system, the TiO2 nanoparticles accumulate in different organs because the body has no way to eliminate them. And because they are so small, they can go everywhere in the body, even through cells, and may interfere with sub-cellular mechanisms.

The study appears this week in the journal Cancer Research

In the past, these TiO2 nanoparticles have been considered non-toxic in that they do not incite a chemical reaction. Instead, it is surface interactions that the nanoparticles have within their environment- in this case inside a mouse - that is causing the genetic damage, Schiestl said. They wander throughout the body causing oxidative stress, which can lead to cell death.........

Posted by: Scott      Read more         Source


November 17, 2009, 7:47 AM CT

What makes pandemic H1N1 tick?

What makes pandemic H1N1 tick?
Dr. Richard Scheuermann, professor of pathology and clinical sciences at UT Southwestern Medical Center.
As the number of deaths correlation to the pandemic H1N1 virus, usually known as "swine flu," continues to rise, scientists have been scrambling to decipher its inner workings and explain why the incidence is lower than expected in elderly adults.

In a study available online and appearing in a future issue of Proceedings of the National Academy of Sciences, a UT Southwestern Medical Center researcher and his collaborators in California show that the molecular makeup of the current H1N1 flu strain is strikingly different from prior H1N1 strains as well as the normal seasonal flu, particularly in structural parts of the virus normally recognized by the immune system.

Previous research has shown that an individual's immune system is triggered to fight off pathogens such as influenza when specific components of the immune system - namely antibodies, B-cells and T cells - recognize parts of a virus known as epitopes. An individual's ability to recognize those epitopes - spurred by past infections or vaccinations - helps prevent future infections. The challenge is that these epitopes vary among flu strains.

"We hypothesize that older people are somewhat protected because the epitopes present in flu strains before 1957 appears to be similar to those found in the current H1N1 strain, or at least similar enough that the immune system of the previously infected person recognizes the pathogen and knows to attack," said Dr. Richard Scheuermann, professor of pathology and clinical sciences at UT Southwestern and a co-author of the paper. "Those born more recently have virtually no pre-existing immunity to this pandemic H1N1 strain because they have never been exposed to anything like it".........

Posted by: Mark      Read more         Source


November 11, 2009, 9:57 PM CT

A view inside the body

A view inside the body
Iowa State University engineers Eliot Winer, left, and James Oliver have developed technology that converts 2-D medical scans into detailed 3-D images that can be used to plan a surgery or teach a lesson in anatomy.
James Oliver picked up an Xbox game controller, looked up to a video screen and used the device's buttons and joystick to fly through a patient's chest cavity for an up-close look at the bottom of the heart.

And there was a sight doctors had never seen before: an accurate, 3-D view inside a patient's body accessible with a personal computer. A view doctors can shift, adjust, turn, zoom and replay at will. Software that uses real patient data from CT and MRI scans. Software doctors can use to plan a surgery or a round of radiation treatment. Software that can be used to teach physiology and anatomy. Software that puts virtual reality technology developed at Iowa State University to work helping doctors and patients, teachers and students. Software that's now being sold by an Ames startup company, BodyViz.com.

Two-dimensional imaging technologies have been used in medicine for a long time, said Eliot Winer, an Iowa State associate professor of mechanical engineering and an associate director of Iowa State's Virtual Reality Applications Center. But those flat images aren't easily read and understood by anybody but specialists.

"If I'm a surgeon or an oncologist or a primary care physician, I deal with patients in 3-D," Winer said.

And so Winer and Oliver, an Iowa State professor of mechanical engineering and director of the university's CyberInnovation Institute, began to develop technology that converts the flat images of medical scans into 3-D images that are easy to see, manipulate and understand. Thom Lobe, a pediatric surgeon based at Blank Children's Hospital in Des Moines, helped the engineers design a tool doctors could use.........

Posted by: Scott      Read more         Source


November 11, 2009, 9:53 PM CT

What helps you to live longer?

What helps you to live longer?
Yousin Suh, Ph.D.
A team led by scientists at Albert Einstein College of Medicine of Yeshiva University has found a clear link between living to 100 and inheriting a hyperactive version of an enzyme that rebuilds telomeres - the tip ends of chromosomes. The findings appear in the latest issue of the Proceedings of the National Academy of Sciences.

Telomeres play crucial roles in aging, cancer and other biological processes. Their importance was recognized last month, when three researchers were awarded the 2009 Nobel Prize in Physiology and Medicine for determining the structure of telomeres and discovering how they protect chromosomes from degrading.

Telomeres are relatively short sections of specialized DNA that sit at the ends of all chromosomes. One of the Nobel Prize winners, Elizabeth Blackburn, Ph.D., of the University of California at San Francisco, has compared telomeres to the plastic tips at the ends of shoelaces that prevent the laces from unraveling.

Each time a cell divides, its telomeres erode slightly and become progressively shorter with each cell division. Eventually, telomeres become so short that their host cells stop dividing and lapse into a condition called cell senescence. As a result, vital tissues and important organs begin to fail and the classical signs of aging ensue.........

Posted by: Scott      Read more         Source


November 10, 2009, 8:52 AM CT

Stem cells help paralyzed rats to walk

Stem cells help paralyzed rats to walk
Hans Keirstead, Jason Sharp and colleagues have found that human embryonic stem cells restore limb function in rats with neck spinal cord injuries.
Photo by Kerrin Piche Serna / University Communications
The first human embryonic stem cell therapy approved by the FDA for human testing has been shown to restore limb function in rats with neck spinal cord injuries - a finding that could expand the clinical trial to include people with cervical damage.

In January, the U.S. Food & Drug Administration gave Geron Corp. of Menlo Park, Calif., permission to test the UC Irvine therapy in individuals with thoracic spinal cord injuries, which occur below the neck. However, trying it in those with cervical damage wasn't approved because preclinical testing with rats hadn't been completed.

Results of the cervical study currently appear online in the journal Stem Cells. UCI scientist Hans Keirstead hopes the data will prompt the FDA to authorize clinical testing of the therapy in people with both types of spinal cord damage. About 52 percent of spinal cord injuries are cervical and 48 percent thoracic.

"People with cervical damage often have lost or impaired limb movement and bowel, bladder or sexual function, and currently there's no effective therapy. It's a challenging existence," said Keirstead, a primary author of the study. "What our treatment did to injured rodents is phenomenal. If we see even a fraction of that benefit in humans, it will be nothing short of a home run".........

Posted by: Scott      Read more         Source


November 9, 2009, 8:18 AM CT

Learning bacterial communications

Learning bacterial communications
Peiter C. Dorrestein, PhD is a researcher at University of California - San Diego.

Credit: UC San Diego School of Medicine

Using imaging mass spectrometry, scientists at the University of California, San Diego have developed tools that will enable researchers to visualize how different cell populations of cells communicate. Their study shows how bacteria talk to one another an understanding that may lead to new therapeutic discoveries for diseases ranging from cancer to diabetes and allergies.

In the paper reported in the November 8 issue of Nature Chemical Biology, Pieter C. Dorrestein, PhD, assistant professor at UC San Diego's Skaggs School of Pharmacy and Pharmaceutical Sciences, and his colleagues describe an approach they developed to describe how bacteria interface with other bacteria in a laboratory setting. Dorrestein and post-doctoral students Yu-Liang Yang and Yuquan Xu, along with Paul Straight from Texas A&M University, utilized technology called natural product MALDI-TOF (Matrix Assisted Laser Desorption Ionization-Time of Flight) imaging mass spectrometry to uniquely translate the language of bacteria.

Microbial interactions, such as signaling, have generally been considered by researchers in terms of an individual, predominant chemical activity. However, a single bacterial species is capable of producing a number of bioactive compounds that can alter neighboring organisms. The approach developed by the UCSD research team enabled them to observe the effects of multiple microbial signals in an interspecies interaction, revealing that chemical "conversations" between bacteria involve a number of signals that function simultaneously.........

Posted by: Mark      Read more         Source



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Did you know?
Scientists at Yale have brought to light a mechanism that regulates the way an internal organelle, the Golgi apparatus, duplicates as cells prepare to divide, according to a report in Science Express.Graham Warren, professor of cell biology, and colleagues at Yale study Trypanosoma brucei, the parasite that causes Sleeping Sickness. Like a number of parasites, it is exceptionally streamlined and has only one of each internal organelle, making it ideal for studying processes of more complex organisms that have a number of copies in each cell.

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