October 12, 2006, 10:12 PM CT

Algae Provide Clues To Cancer

A microscopic green alga helped researchers at the Salk Institute for Biological Studies identify a novel function for the retinoblastoma protein (RB), which is known for its role as a tumor suppressor in mammalian cells. By coupling cell size with cell division, RB ensures that cells stay within an optimal size range.

Their findings, which would be reported in the October 13 online edition of PLoS Genetics, show that RB blocks cells from dividing before they reach a minimum size and could provide new insights into the origins of cancer.

"Being the right size is very important for cells because their physiology changes quite dramatically when the surface-to-volume ratio changes," explains senior author James Umen, Ph.D., an assistant professor and Hearst Endowment Chair in Salk's Plant Biology Laboratory. "The human body is composed of trillions of cells, each of which must coordinate its growth and division in order to maintain size equilibrium," he adds.

This process is very tightly regulated and any given cell type will always stay within a very narrow size range, but the means by which cell size is determined remain mysterious. In proliferating cells, control mechanisms termed checkpoints are thought to prevent cells from dividing until they reach a specific size, but the nature of the checkpoints has proved difficult to dissect.........

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October 12, 2006, 10:04 PM CT

Geometry Of Breast Cell Invasion

Apropos of National Breast Cancer Awareness month, scientists with the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) have created a first-of-its-kind model for studying how breast tissue is shaped and structured during development. The model may shed new light on how the misbehavior of only a few cells can facilitate metastatic invasion because it shows that the development of breast tissue, normal or abnormal, is controlled not only by genetics but also by geometry. Though created specifically for the study of breast tissue, this model should also be applicable to the study of tissue development in other organs as well.

"Our results reveal that tissue geometry can control the morphogenesis of breasts and other organs by defining the local cellular branching microenvironment," said Bissell, a Distinguished Scientist with Berkeley Lab's Life Sciences Division, who was the principal investigator for this study. "This finding is important not only for understanding how tissue and organs get their organized shapes and patterns, but may in the future reveal mechanisms to control cancer invasion and metastasis".

In a paper reported in the October 13, 2006 issue of the journal Science, Bissell and her collaborators describe a study in which the branching of mouse epithelial tubules (hollow tubes made from epithelial cells that form the network of milk ducts in the mature female breast) in culture were subjected to control through a three-dimensional micropatterned assay. Using a special algorithm to quantify the extent of branching, the scientists observed that the geometric shape of the tubules determines where branching takes place. This may potentially affect where and how a malignancy spreads.........

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October 9, 2006, 8:48 PM CT

Genome Id Method Against Cancer

A mathematical discovery has extended the reach of a novel genome mapping method to humans, potentially giving cancer biology a faster and more cost-effective tool than traditional DNA sequencing.

A student-led group from the laboratory of Michael Waterman, USC University Professor in molecular and computational biology, has developed an algorithm to handle the massive amounts of data created by a restriction mapping technology known as "optical mapping." Restriction maps provide coordinates on chromosomes analogous to mile markers on freeways.

Lead author Anton Valouev, a recent graduate of Waterman's lab and now a postdoctoral fellow at Stanford University, said the algorithm makes it possible to optically map the human genome.

"It carries tremendous benefits for medical applications, specifically for finding genomic abnormalities," he said.

The algorithm appears in this week's PNAS Early Edition.

Optical mapping was developed at New York University in the late 1990s by David Schwartz, now a professor of chemistry and genetics at the University of Wisconsin-Madison. Schwartz and a collaborator at Wisconsin, Shiguo Zhou, co-authored the PNAS paper.

The power of optical mapping lies in its ability to reveal the size and large-scale structure of a genome. The method uses fluorescence microscopy to image individual DNA molecules that have been divided into orderly fragments by so-called restriction enzymes.........

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October 9, 2006, 8:26 PM CT

How Cancer-drug Resistance Occurs

Using the worm Caenorhabditis elegans, scientists at UT Southwestern Medical Center have discovered a mechanism by which cancer cells become resistant to a specific class of drugs.

They observed that a mutation in a single protein in the worm renders a potential new cancer drug ineffective. The drug is a derivative of a compound called hemiasterlin. Because hemiasterlin compounds are being tested as a way to fight multi-drug resistance, this newly discovered resistance effect is problematic, the scientists said.

"A major problem for cancer treatment is that if cancer cells can survive long enough, they have a chance to undergo mutations that make them resistant to anticancer drugs," said Dr. Michael Roth, professor of biochemistry and senior author of a paper published this week in the online edition of the Proceedings of the National Academy of Sciences

One way that cancer cells resist multiple drugs is through the action of the multi-drug resistance protein, which pumps most drugs out of the cell before they can have any effect.

However, hemiasterlin bypasses this pump altogether and kills cancer cells by preventing them from dividing.

Derivatives of hemiasterlin are being tested as anti-cancer therapies, with one already in clinical study. The drug works by interfering with tubulin, which forms the structure that separates chromosomes as cells divide.........

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October 8, 2006, 6:18 PM CT

Breast Reconstruction Not Very Safe For Obese

Significantly obese women may wish to consider delaying breast reconstruction following mastectomy until they achieve a healthier body weight. As per findings presented today at the American Society of Plastic Surgeons (ASPS) Plastic Surgery 2006 conference in San Francisco, women who are significantly obese are at higher risk for complications and have a lower satisfaction rate than do normal and overweight patients.

"Just because someone is overweight doesn't mean they should not be entitled to undergo breast reconstruction after mastectomy," said Elisabeth Beahm, MD, ASPS Member Surgeon, author of the study, and associate professor at M. D. Anderson Cancer Center. "Feeling 'whole' can be an integral part of recovery from cancer, yet significant concerns have been raised about the wisdom of doing breast reconstruction in very obese patients due to a high complication rate.

The current retrospective study observed that patients with a BMI greater than 35 demonstrated significantly increased complication rates for all types of breast reconstruction, from implants to flaps. The complication rate approached 100 percent for morbidly obese patients with a BMI over 40.

"We investigated whether plastic surgeons can safely perform breast reconstruction for these patients or if we would be depriving them reconstruction simply because of empiric concerns for their weight," said Dr. Beahm. "We observed that significantly obese patients, those having a BMI of 35 or higher, had a higher risk for complications. Our experience suggests that in a number of cases it may be more prudent to delay breast reconstruction until the patient has lost weight".........

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October 3, 2006, 9:54 PM CT

Three Molecular Targets For Leukemia

he road to better treatment for the most common form of adult leukemia will require blocking multiple molecular pathways that fuel the disease, researchers at The University of Texas M. D. Anderson Cancer Center report in the Oct. 1 edition of the journal Blood.

The research team examined blood and bone marrow samples of 188 adults with acute myelogenous leukemia (AML) and then followed the patients' progress to gauge the cumulative impact of a trio of cell-signaling chain reactions on the disease.

"We found that the more of these pathways that are active in a patient, the worse their prognosis," says first author Steve Kornblau, M.D., associate professor in the Department of Blood and Marrow Transplantation.

Patients who had none of the three molecular cascades active had a median survival time of 78.6 weeks. For those with one highly active pathway, median survival was 57.9 weeks. With two, it was 42.3 weeks. Patients with high activation of all three pathways had a median survival time of just 23.4 weeks.

"Targeting just one of these pathways won't be effective because we also found that they cross-activate each other, they essentially cover for each other," Kornblau said. "New therapies will have to target multiple pathways to be effective".........

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October 3, 2006, 5:09 AM CT

Progress In Pancreatic Cancer Research

Researchers at SUNY Downstate Medical Center and the Brooklyn VA Hospital have found that when a human protein, PNC-28, is administered to pancreatic tumor cells in animals, the tumors are destroyed. The research was reported in the October 1st edition of the International Journal of Cancer.

Matthew R. Pincus, MD, PhD, professor of pathology at SUNY Downstate and chairman of pathology and laboratory medicine at the Brooklyn VA, said, "The results are very encouraging. PNC-28 may be an effective agent in treating cancers, especially if delivered directly to the tumor".

PNC-28 is a p53 peptide, a naturally occurring human protein known to suppress tumor growth. The researchers previously found that PNC-28 induces death of a variety of human tumor cell lines, including a pancreatic cancer cell line, while not harming healthy cells.

The research team has now given PNC-28 to laboratory animals to test its ability to block the growth of pancreatic cancer cells. When administered over a two-week period in the peritoneal cavities of mice containing simultaneously transplanted tumors, PNC-28 caused complete destruction of these tumors.

When delivered concurrently with tumor implantation, PNC-28 completely blocked tumor growth during the two-week period of administration and two weeks post-treatment, followed by weak tumor growth that leveled off at low tumor sizes.........

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October 1, 2006, 7:39 PM CT

Predicting drug sensitivity in lung cancer

What if we can clearly predict which of those patients with non-small cell lung cancer would respond to a cisplatin-based chemotherapy. This would benefit many patients with non-small cell lung cancer, since oncologists could use another drug combination to treat these patients. This is what researchers from MD Anderson Cancer Center is trying to achieve.

Non-small cell lung cancer cells with a defective version of a potential tumor suppressor gene are highly resistant to attack by a platinum-based drug commonly used to treat the disease, researchers at The University of Texas M. D. Anderson Cancer Center and The University of Texas Southwestern Medical Center at Dallas report in the cover article of the latest issue of Cancer Research.

The gene may provide a potential biomarker for selecting among chemotherapy choices for non-small-cell lung cancer as well as a therapeutic target for restoring the drug cisplatin's punch in treating resistant forms of the disease, says senior author Lin Ji, Ph.D., associate professor in M. D. Anderson's Department of Thoracic and Cardiovascular Surgery.

Researchers at the two institutions, working under a joint National Cancer Institute Specialized Program of Research Excellence (SPORE) in Lung Cancer grant, have identified three tumor-suppressor genes on chromosome 3. The latest paper refines the impact of one of those genes, NPRL2, on the most common form of lung cancer.........

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September 28, 2006, 9:38 PM CT

Anti-angiogenesis To Fight Cancer

A researcher at the University of Wisconsin-Madison School of Medicine and Public Health has discovered a new part of the complicated mechanism that governs the formation of blood vessels, or angiogenesis.

The finding may help halt tumor growth in cancer patients, says Emery Bresnick, the senior author on the study, a professor of pharmacology and member of the UW-Madison Paul P. Carbone Comprehensive Cancer Center.

The research, published in the Journal of Cell Biology on Sept. 25, is the first to connect a particular nervous-system chemical to the regulation of blood vessels.

Normally, blood vessels form when wounds heal and during menstruation, pregnancy and fetal development. But impaired blood-vessel development and function are also a major cause of blindness, and tumors rely on new blood vessels as they develop.

Like most critical body processes, angiogenesis is tightly controlled by multiple balancing mechanisms. When Bresnick and colleagues, including postdoctoral fellow Soumen Paul, began the new study, they were not looking into angiogenesis. Instead, they were studying a protein that regulates the maturation of blood cells, and noticed that it turns on a gene that makes a compound called neurokinin-B, or NK-B.

Aware that NK-B affects cells in the nervous system, Bresnick wondered, "Why would a protein involved in blood-cell formation turn on the gene for a compound that is supposedly involved in regulating the nervous system?".........

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September 26, 2006, 7:41 PM CT

Investigational Anti-cancer Drug AT9283

Astex Therapeutics today announced that it had begun dosing first patients in a Phase I/IIa clinical trial of its investigational anti-cancer drug AT9283. Astex discovered AT9283, a potent inhibitor of Aurora kinases, using its innovative fragment-based drug discovery technology, Pyramid-.

This is Astex's second product to enter clinical development. The company's lead product, AT7519, is already in a Phase I trial at sites in the US and the UK. This initial clinical trial of AT9283 is designed to assess safety and tolerability and may provide preliminary evidence of efficacy in patients with haematological malignancies. It is being conducted at the University of Texas MD Anderson Cancer Center, one of the world's leading oncology centres. Astex plans to initiate additional clinical studies of AT9283 in North America and Europe within the next six months.

In addition to its inhibition of Aurora kinases, AT9283 is highly active against the Gleevec® resistant T315I abl mutation and could benefit patients who have failed treatment with agents such as Gleevec® and Sprycel-. AT9283 is also a potent inhibitor of JAK-2 and the present trial will assess its activity in patients with myeloproliferative disorders associated with activating mutations of this protein.........

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