Cell's pressure matters

"A model that describes dividing cells within human tissues from the perspective of physicists could help further the understanding of cancer growth.

Photo from: https://commons.wikimedia.org/wiki/File:South_African_Giraffes,_fighting.jpg

Jonas Ranft and team created a two-component mathematical model accounting for both the cells and the fluid caught in between. On the one hand, cells are modeled as behaving like a dividing fluid subject to expansion. On the other hand, the interstitial fluid is akin to an ideal fluid that cannot be compressed. This model is designed to elucidate the nature of mechanical pressure exerted upon dividing cells by their surrounding tissues, referred to as homeostatic pressure.Physicists from the Curie Institute, France, explored the relative impact of the mechanical pressure induced by dividing cells in biological tissues. This approach complements traditional studies on genetic and biochemical signalling mechanisms to explain experimental observations of how biological tissues evolve. This work, recently published inEuropean Physical Journal E, could have significant implications for the understanding of cancer growth.

It replaces a previous single-component model they developed last year. Its assumption: the homeostatic pressure is proportional to the fluid pressure within the tissue. If that were the case, very tall organisms such as giraffes could not exist, because the cells in their lower body would die under pressure.

Thanks to the two-component model, the authors found that it is the cells' pressure and not the interstitial fluid's pressure that influences the level of cell division. When there are as many new cells created from cell division as cells dying from programmed cell death, or apoptosis, the homeostatic pressure is balanced. This leads to a steady state of the biological tissue. Going one step further, the authors pinpointed the range of fluid pressure required to drive cell flow within the body.

Such models could help gain a greater understanding of the importance of the disruption of homeostatic pressure in biological tissues caused by cancer cells that are characterized by abnormal levels of cell proliferation."

Springer Science+Business Media (2012, July 3). Giraffes are living proof that cells' pressure
matters. ScienceDaily. Retrieved April 22, 2013, from http://www.sciencedaily.com­/releases/2012/07/120703161526.htm

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Drug Destroys Human Cancer Stem Cells but Not Healthy Ones

A team of scientists at McMaster University has discovered a drug, thioridazine, successfully kills cancer stem cells in the human while avoiding the toxic side-effects of conventional cancer treatments.

"The unusual aspect of our finding is the way this human-ready drug actually kills cancer stem cells; by changing them into cells that are non-cancerous," said Mick Bhatia, the principal investigator for the study and scientific director of McMaster's Stem Cell and Cancer Research Institute in the Michael G. DeGroote School of Medicine.

Unlike chemotherapy and radiation, thioridazine appears to have no effect on normal stem cells.

The research, published May 24 in the science journal Cell, holds the promise of a new strategy and discovery pipeline for the development of anticancer drugs in the treatment of various cancers. The research team has identified another dozen drugs that have good potential for the same response.

For 15 years, some researchers have believed stem cells are the source of many cancers. In 1997, Canadian researchers first identified cancer stem cells in certain types of leukemia. Cancer stem cells have since been identified in blood, breast, brain, lung, gastrointestinal, prostate and ovarian cancer.

To test more than a dozen different compounds, McMaster researchers pioneered a fully automated robotic system to identify several drugs, including thioridazine.

"Now we can test thousands of compounds, eventually defining a candidate drug that has little effect on normal stem cells but kills the cells that start the tumor," said Bhatia.

The next step is to test thioridazine in clinical trials, focusing on patients with acute myeloid leukemia whose disease has relapsed after chemotherapy. Bhatia wants to find out if the drug can put their cancer into remission, and by targeting the root of the cancer (cancer stem cells) prevent the cancer from coming back. Researchers at McMaster have already designed how these trials would be done.

Bhatia's team found thioridazine works through the dopamine receptor on the surface of the cancer cells in both leukemia and breast cancer patients. This means it may be possible to use it as a biomarker that would allow early detection and treatment of breast cancer and early signs of leukemia progression, he said.

The research team's next step is to investigate the effectiveness of the drug in other types of cancer. In addition, the team will explore several drugs identified along with thioridazine. In the future, thousands of other compounds will be analyzed with McMaster robotic stem cell screening system in partnership with collaborations that include academic groups as well as industry.

"The goal for all of the partners is the same -- to find unique drugs to change the way we tackle and treat cancer," he said.

The research was supported by grants from the Canadian Institute of Health Research (CIHR), the Canadian Cancer Society Research Institute (CCSRI) and the Ontario Ministry of Economic Development and Innovation (MEDI)'s Ontario Consortium of Regenerating inducing Therapeutics (OCRiT).

Source: McMaster University [May 24, 2012]

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DNA replication protein also has a role in mitosis, cancer

The foundation of biological inheritance is DNA replication – a tightly coordinated process in which DNA is simultaneously copied at hundreds of thousands of different sites across the genome. If that copying mechanism doesn't work as it should, the result could be cells with missing or extra genetic material, a hallmark of the genomic instability seen in most birth defects and cancers.

Mitotic spindle-chromosome attachments, marked in green, become unstable (on the right) compared to normal (on the left) [Credit: Cook and Salmon labs, UNC School of Medicine]

University of North Carolina School of Medicine scientists have discovered that a protein known as Cdt1, which is required for DNA replication, also plays an important role in a later step of the cell cycle, mitosis. The finding presents a possible explanation for why so many cancers possess not just genomic instability, but also more or less than the usual 46 DNA-containing chromosomes.

The new research, which was published online ahead of print by the journal Nature Cell Biology, is the first to definitively show such a dual role for a DNA replication protein.

"It was such a surprise, because we thought we knew what this protein's job was – to load proteins onto the DNA in preparation for replication," said Jean Cook, PhD, associate professor of biochemistry and biophysics and pharmacology at the UNC School of Medicine and senior study author. "We had no idea it also had a night job, in a completely separate part of the cell cycle."

The cell cycle is the series of events that take place in a cell leading to its growth, replication and division into two daughter cells. It consists of four distinct phases: G1 (Gap 1), S (DNA synthesis), M (mitosis) and G2 (Gap 2). Cook's research focuses on G1, when Cdt1 places proteins onto the genetic material to get it ready to be copied.

In this study, Cook ran a molecular screen to identify other proteins that Cdt1 might be interacting with inside the cell. She expected to just find more entities that controlled replication, and was surprised to discover one that was involved in mitosis. That protein, called Hec1 for "highly expressed in cancer," helps to ensure that the duplicated chromosomes are equally divided into daughter cells during mitosis, or cell division. Cook hypothesized that either Hec1 had a job in DNA replication that nobody knew about, or that Cdt1 was the one with the side business.

Cook partnered with Hec1 expert Edward (Ted) D. Salmon, PhD, professor of biology and co-senior author in this study, to explore these two possibilities. After letting Cdt1 do its replication job, the researchers interfered with the protein's function to see if it adversely affected mitosis. Using a high-powered microscope that records images of live cells, they showed that cells where Cdt1 function had been blocked did not undergo mitosis properly.

Once the researchers knew that Cdt1 was involved in mitosis, they wanted to pinpoint its role in that critical process. They further combined their genetic, microscopy and computational methods to demonstrate that without Cdt1, Hec1 fails to adopt the conformation inside the cells necessary to connect the chromosomes with the structure that pulls them apart into their separate daughter cells.

Cook says cells that make aberrant amounts of Cdt1, like that seen in cancer, can therefore experience problems in both replication and mitosis. One current clinical trial is actually trying to ramp up the amount of Cdt1 in cancer cells, in the hopes of pushing them from an already precarious position into a fatal one.

Source: University of North Carolina Health Care [May 13, 2012]

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New twist on ancient math problem could improve medicine, microelectronics

A hidden facet of a math problem that goes back to Sanskrit scrolls has just been exposed by nanotechnology researchers at the University of Michigan and the University of Connecticut.

A hidden facet of a math problem that goes back to Sanskrit scrolls has just been exposed by nanotechnology researchers [Credit: © bivainis/Fotolia]

It turns out we've been missing a version of the famous "packing problem," and its new guise could have implications for cancer treatment, secure wireless networks, microelectronics and demolitions, the researchers say.

Called the "filling problem," it seeks the best way to cover the inside of an object with a particular shape, such as filling a triangle with discs of varying sizes. Unlike the traditional packing problem, the discs can overlap. It also differs from the "covering problem" because the discs can't extend beyond the triangle's boundaries.

"Besides introducing the problem, we also provided a solution in two dimensions," said Sharon Glotzer, U-M professor of chemical engineering.

That solution makes it immediately applicable to treating tumors using fewer shots with radiation beams or speeding up the manufacturing of silicon chips for microprocessors.

The key to solutions in any dimension is to find a shape's "skeleton," said Carolyn Phillips, a postdoctoral fellow at Argonne National Laboratory who recently completed her Ph.D. in Glotzer's group and solved the problem as part of her dissertation.

"Every shape you want to fill has a backbone that goes through the center of the shape, like a spine," she said.

For a pentagon, the skeleton looks like a stick-drawing of a starfish. The discs that fill the pentagon best will always have their centers on one of those lines.

Junctions between lines in the skeleton are special points that Glotzer's team refers to as "traps." The pentagon only has one trap, right at its center, but more complicated shapes can contain multiple traps. In most optimal solutions, each trap has a disc centered over it, Phillips said.

Other discs in the pattern change size and move around, depending on how many discs are allowed, but those over the traps are always the same. Phillips suspects that if a design uses enough discs, every trap will have a disc centered over it.

In their paper, published online today in Physical Review Letters, the researchers report the rules for how to find the ideal size and spacing of the discs that fill a shape. In the future, they expect to reveal an algorithm that can take the desired shape and the number of discs, or the shape and percentage of the area to be filled, and spit out the best pattern to fill it.

Extending the approach into three dimensions, Glotzer proposes that it could decide the placement of wireless routers in a building where the signal must not be available to a potential hacker in the parking lot. Alternatively, it could help demolition workers to set off precision explosions, ensuring that the blast covers the desired region but doesn't extend beyond a building's outer walls.

Phillips expects filling solutions to be scientifically useful as well. Glotzer's team developed the new problem by trying to find a way to represent many-sided shapes for their computer models of nanoparticles. In addition to nanotechnology, biology and medicine often need models for complex shapes, such as those of proteins.

"You don't want to model every single one of the thousands of atoms that make up this protein," Phillips said. "You want a minimal model that gives the shape, allowing the proteins to interact in a lock-and-key way, as they do in nature."

The filling approach may prove a perfect fit for a variety of fields.

Author: Katherine McAlpine | Source: University of Michigan [May 10, 2012]

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Transplanted gene-modified blood stem cells protect brain cancer patients from toxic side effects of chemotherapy

For the first time, scientists at Fred Hutchinson Cancer Research Center have transplanted brain cancer patients' own gene-modified blood stem cells in order to protect their bone marrow against the toxic side effects of chemotherapy. Initial results of the ongoing, small clinical trial of three patients with glioblastoma showed that two patients survived longer than predicted if they had not been given the transplants, and a third patient remains alive with no disease progression almost three years after treatment.

"We found that patients were able to tolerate the chemotherapy better and without negative side effects after transplantation of the gene-modified stem cells than patients in previous studies who received the same type of chemotherapy without a transplant of gene-modified stem cells," said Hans-Peter Kiem, M.D., senior and corresponding author of the study published in the May 9 issue of Science Translational Medicine.

Kiem, a member of the Clinical Research Division at the Hutchinson Center, said that a major barrier to effective use of chemotherapy to treat cancers like glioblastoma has been the toxicity of chemotherapy drugs to other organs, primarily bone marrow. This results in decreased blood cell counts, increased susceptibility to infections and other side effects. Discontinuing or delaying treatment or reducing the chemotherapy dose is generally required, but that often results in less effective treatment.

In the current study, Kiem and colleagues focused on patients with glioblastoma, an invariably fatal cancer. Many of these patients have a gene called MGMT (O6-methylguanine-DNA-methyltransferase) that is turned on because the promoter for this gene is unmethylated. MGMT is a DNA repair enzyme that counteracts the toxic effect of some chemotherapy agents like temozolomide. Patients with such an unmethylated promoter status have a particularly poor prognosis.

A drug called benzylguanine can block the MGMT gene and make tumor cells sensitive to chemotherapy again, but when given with chemotherapy, the toxic effects of this combination are too much for bone marrow cells, which results in marrow suppression.

By giving bone marrow stem cells P140K, which is a modified version of MGMT, those cells are protected from the toxic effects of benzylguanine and chemotherapy, while the tumor cells are still sensitive to chemotherapy. "P140K can repair the damage caused by chemotherapy and is impervious to the effects of benzylguanine," Kiem said.

"This therapy is analogous to firing at both tumor cells and bone marrow cells, but giving the bone marrow cells protective shields while the tumor cells are unshielded," said Jennifer Adair, Ph.D., who shares first authorship of the study with Brian Beard, Ph.D., both members of Kiem's lab.

The three patients in this study survived an average of 22 months after receiving transplants of their own circulating blood stem cells. One, an Alaskan man, remains alive 34 months after treatment. Median survival for patients with this type of high-risk glioblastoma without a transplant is just over a year.

"Glioblastoma remains one of the most devastating cancers with a median survival of only 12 to 15 months for patients with unmethylated MGMT," said Maciej Mrugala, M.D., the lead neuro oncologist for this study.

As many as 50 percent to 60 percent of glioblastoma patients harbor such chemotherapy-resistant tumors, which makes gene-modified stem cell transplant therapy applicable to a large number of these patients. In addition, there are also other brain tumors such as neuroblastoma or other solid tumors with MGMT-mediated chemo resistance that might benefit from this approach.

The researchers also found that chemotherapy increased the number of gene-modified blood and bone marrow cells in these patients. Kiem said this finding will have implications for other stem cell gene therapy applications where defective bone marrow stem cells can be corrected by gene therapy but their numbers need to be increased to produce a therapeutic benefit, or for patients with HIV/AIDS to increase the number of HIV-resistant stem and T cells.

The clinical trial is open and is recruiting more patients. For more information go to: http://clinicaltrials.gov/ct2/show/NCT00669669.

Source: Fred Hutchinson Cancer Research Center [May 09, 2012]

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Study reveals huge genetic diversity in cells shed by tumors

The cells that slough off from a cancerous tumor into the bloodstream are a genetically diverse bunch, Stanford University School of Medicine researchers have found. Some have genes turned on that give them the potential to lodge themselves in new places, helping a cancer spread between organs. Others have completely different patterns of gene expression and might be more benign, or less likely to survive in a new tissue. Some cells may even express genes that could predict their response to a specific therapy. Even within one patient, the tumor cells that make it into circulating blood vary drastically.

The finding underscores how multiple types of treatment may be required to cure what appears outwardly as a single type of cancer, the researchers say. And it hints that the current cell-line models of human cancers, which showed patterns that differed from the tumor cells shed from human patients, need to be improved upon.

The new study, which will be published online May 7 in PLoS ONE, is the first to look at so-called circulating tumor cells one by one, rather than taking the average of many of the cells. And it's the first to show the extent of the genetic differences between such cells.

"Within a single blood draw from a single patient, we're seeing heterogeneous populations of circulating tumor cells," said senior study author Stefanie Jeffrey, MD, professor of surgery and chief of surgical oncology research.

For over a century, scientists have known that circulating tumor cells, or CTCs, are shed from tumors and move through the bloodstreams of cancer patients. And over the past five years, there's been a growing sense among many cancer researchers that these cells — accessible by a quick blood draw — could be the key to tracking tumors non-invasively. But separating CTCs from blood cells is hard; there can be as few as one or two CTCs in every milliliter of a person's blood, mixed among billions of other blood cells.

To make their latest discovery, Jeffrey, along with an interdisciplinary team of engineers, quantitative biologists, genome scientists and clinicians, relied on a technology they developed in 2008. Called the MagSweeper, it's a device that lets them isolate live CTCs with very high purity from patient blood samples, based on the presence of a particular protein — EpCAM — that's on the surface of cancer cells but not healthy blood cells.

With the goal of studying CTCs from breast cancer patients, the team first tested whether they could accurately detect the expression levels of 95 different genes in single cells from seven different cell-line models of breast cancer — a proof of principle since they already knew the genetics of these tumors. These included four cell lines generally used by breast cancer researchers and pharmaceutical scientists worldwide and three cell lines specially generated from patients' primary tumors.

"Most researchers look at just a few genes or proteins at a time in CTCs, usually by adding fluorescent antibodies to their samples consisting of many cells," said Jeffrey. "We wanted to measure the expression of 95 genes at once and didn't want to pool our cells together, so that we could detect differences between individual tumor cells."

So once Jeffrey and her collaborators isolated CTCs using the MagSweeper, they turned to a different kind of technology: real-time PCR microfluidic chips, invented by a Stanford collaborator, Stephen Quake, PhD, professor of bioengineering. They purified genetic material from each CTC and used the high-throughput technology to measure the levels of all 95 genes at once. The results on the cell-line-derived cells were a success; the genes in the CTCs reflected the known properties of the mouse cell-line models. So the team moved on to testing the 95 genes in CTCs from 50 human breast cancer patients — 30 with cancer that had spread to other organs, 20 with only primary breast tumors.

"In the patients, we ended up with 32 of the genes that were most dominantly expressed," said Jeffrey. "And by looking at levels of those genes, we could see at least two distinct groups of circulating tumors cells." Depending on which genes they used to divide the CTCs into groups, there were as many as five groups, she said, each with different combinations of genes turned on and off. And if they'd chosen genes other than the 95 they'd picked, they likely would have seen different patterns of grouping. However, because the same individual CTCs tended to group together in multiple different analyses, these cells likely represent different types of spreading cancer cells.

The diversity, Jeffrey said, means that tumors may contain multiple types of cancer cells that may get into the bloodstream, and a single biopsy from a patient's tumor doesn't necessarily reflect all the molecular changes that are driving a cancer forward and helping it spread. Moreover, different cells may require different therapies. One breast cancer patient studied, for example, had some CTCs positive for the marker HER2 and others lacked the marker. When the patient was treated with a drug designed to target HER2-positive cancers, the CTCs lacking the molecule remained in her bloodstream.

When the team went on to compare the diverse genetic profiles of the breast cancer patients' CTCs with the cells they'd studied from the cell lines, they were in for another surprise: None of the human CTCs had the same gene patterns as any of the cell-line models.

"These models are what people are using for drug discovery and initial drug testing," said Jeffrey, "but our finding suggests that perhaps they're not that helpful as models of spreading cancers." While the human cell-line cells did show diversity between each of the seven cell lines, they didn't fall into any of the same genetic profiles as the CTCs from human blood samples.

These results don't have immediate impacts for cancer patients in the clinic because more work is needed to discover whether different types of CTCs respond to different therapies and whether that will be clinically useful for guiding treatment decisions. But the finding is a step forward in understanding the basic science behind the bits of tumors that circulate in the blood. It's the first time that scientists have used high-throughput gene analysis to study individual CTCs, and opens the door for future experiments that delve even more into the cell diversity. The Stanford team is now working on different methods of using CTCs for drug testing as well as studying the relationship between CTC genetic profiles and cancer treatment outcomes. They've also expanded their work to include primary lung and pancreatic cancers as well as breast tumors.

Source: Stanford University Medical Center [May 07, 2012]

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Genetic Pathway Impacting the Spread of Cancer Cells Discovered

In a new study from Lawson Health Research Institute, Dr. Joseph Torchia has identified a new genetic pathway influencing the spread of cancer cells. The discovery of this mechanism could lead to new avenues for treatment. Regular cell division is regulated by methylation, a series of chemical changes. Methylation modifies DNA to ensure cells divide at a healthy, balanced rate. In cancer, the methylation process is unbalanced, causing cells to resist regulation and divide uncontrollably.

Research suggests changes in genetics play a role in this process, yet little is known about the mechanism. In a new study led by Dr. Torchia and his colleagues, a hormone called Transforming Growth Factor Beta (TGF-β) is starting to show the answers. Using genetic sequencing, they analyzed the effects of TGF-β on DNA methylation to reveal a never-before- seen pathway.

When TGF-β comes into contact with a cell it activates the tumor-suppressing gene, which stops the cells from dividing. According to Dr. Torchia's group, ZNF217, a cancer-causing gene, can interfere with this process by binding to the DNA. This prevents the tumour-suppressing genes from activating, and the cells continue to divide.

These results characterize the dynamic processes underlying cell division, suggesting genetic influencers must be balanced to keep cell division under control. Most importantly, they provide hope for new cancer therapies. "This link between methylation and TGF-β has never been shown before," Dr. Torchia says. "If we understand how methylation is regulated, and identify the machinery that's involved, we may be able to target some of the machinery therapeutically and turn these genes back on to fight the cancer."

Source: Lawson Health Research Institute [May 03, 2012]

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DNA sequencing lays foundation for personalized cancer treatment

Scientists at Washington University School of Medicine in St. Louis are using powerful DNA sequencing technology not only to identify mutations at the root of a patient's tumor – considered key to personalizing cancer treatment – but to map the genetic evolution of disease and monitor response to treatment. 

The Genomics of Drug Sensitivity in Cancer project released its first results on July 15th. Researchers released a first dataset from a study that will expose 1,000 cancer cell lines (including ovarian) to 400 anticancer treatments [Washington University]

"We're finding clinically relevant information in the tumor samples we're sequencing for discovery-oriented research studies," says Elaine Mardis, PhD, co-director of The Genome Institute at the School of Medicine. "Genome analysis can play a role at multiple time points during a patient's treatment, to identify 'driver' mutations in the tumor genome and to determine whether cells carrying those mutations have been eliminated by treatment." 

This work is helping to guide the design of future cancer clinical trials in which treatment decisions are based on results of sequencing, says Mardis, who is speaking April 1 at the opening plenary session of the American Association for Cancer Research annual meeting in Chicago. She also is affiliated with the Siteman Cancer Center at the School of Medicine and Barnes-Jewish Hospital. 

To date, Mardis and her colleagues have sequenced all the DNA – the genome – of tumor cells from more than 700 cancer patients. By comparing the genetic sequences in the tumor cells to healthy cells from the same patient, they can identify mutations underlying each patient's cancer. 

Already, information gleaned through whole-genome sequencing is pushing researchers to reclassify tumors based on their genetic makeup rather than their location in the body. In patients with breast cancer, for example, Mardis and her colleagues have found numerous driver mutations in genes that have not previously been associated with breast tumors. 

A number of these genes have been identified in prostate, colorectal, lung or skin cancer, as well as leukemia and other cancers. Drugs that target mutations in these genes, including imatinib, ruxolitinib and sunitinib, while not approved for breast cancer, are already on the market for other cancers. 

"We are finding genetic mutations in multiple tumor types that could potentially be targeted with drugs that are already available," Mardis says. 

She predicts, however, that it may require a paradigm change for oncologists to evaluate the potential benefits of individualized cancer therapy. While clinical trials typically involve randomly assigning patients to a particular treatment regimen, a personalized medicine approach calls for choosing drugs based on the underlying mutations in each patient's tumor. 

"Having all treatment options available for every patient doesn't fit neatly into the confines of a carefully designed clinical trial," Mardis acknowledges. "We're going to need more flexibility." 

When during the course of cancer mutations develop also is likely to be important in decisions about treatment. In a recent study, Mardis and her team mapped the genetic evolution of leukemia and found clues to suggest that targeted cancer drugs should be aimed at mutations that develop early in the course of the disease. 

Using "deep digital sequencing," a technique developed at The Genome Institute, they sequenced individual mutations in patients' tumor samples more than 1,000 times each. This provides a read-out of the frequency of each mutation in a patient's tumor genome and allowed the researchers to map the genetic evolution of cancer cells as the disease progressed. 

They found that as cancer evolves, tumors acquire new mutations but always retain the original cluster of mutations that made the cells cancerous in the first place. Their discovery suggests that drugs targeted to cancer may be more effective if they are directed toward genetic changes that occur early in the course of cancer. Drugs that target mutations found exclusively in later-evolving cancer cells likely may not have much effect on the disease because they would not kill all the tumor cells. 

Mardis says that sequencing the entire genome of cancer cells is essential to piecing together an accurate picture of the way cancer cells evolve. If the researchers had sequenced only the small portion of the genome that involves genes, they would not have had the statistical power to track the frequency of mutations over time. (Only 1 to 2 percent of the genome consists of genes.) 

In another study, a phase III clinical trial of post-menopausal women with estrogen-receptor positive breast cancer, the Washington University researchers have shown that sequencing can help to predict which women will respond to treatment with aromatase inhibitors. These estrogen-lowering drugs are often prescribed to shrink breast tumors before surgery. But only about half of women with estrogen-receptor positive breast cancer respond to these drugs, and doctors have not been able to predict which patients will benefit. 

Interestingly, by sequencing patients' breast tumors before and after aromatase inhibitor therapy, the researchers identified substantive genomic changes that had occurred in responsive patients, whereas the genomes of unresponsive patients remained largely unchanged by the therapy. 

"No one has ever looked at treatment response at this level of resolution," Mardis says. "It's so obvious who is responding." 

In addition, the researchers have identified a series of mutations in the breast tumors that have corresponding small-molecule inhibitor drugs that target defective proteins. This finding indicates that for women who are not responding to aromatase inhibitors, treatment options may include combining conventional chemotherapy with the indicated small-molecule inhibitor. 

"We felt it was important to show there could be therapeutic options available to patients who are resistant to aromatase inhibitors," Mardis says. "As we move forward, we think sequencing will contribute crucial information to determining the best treatment options for patients."  

Source: Washington University School of Medicine [April 01, 2012]

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Getting Cancer Cells to Swallow Poison

Honing chemotherapy delivery to cancer cells is a challenge for many researchers. Getting the cancer cells to take the chemotherapy "bait" is a greater challenge. But perhaps such a challenge has not been met with greater success than by the nanotechnology research team of Omid Farokhzad, MD, Brigham and Women's Hospital (BWH) Department of Anesthesiology Perioperative and Pain Medicine and Research. 

Ligand-nanoparticle components (in green) targeting and binding to cells [Credit: Image courtesy of Brigham and Women's Hospital]

In their latest study with researchers from Massachusetts Institute of Technology (MIT) and Massachusetts General Hospital, the BWH team created a drug delivery system that is able to effectively deliver a tremendous amount of chemotherapeutic drugs to prostate cancer cells. 

The study is electronically published in the January 3, 2012 issue of ACS Nano. 

The process involved is akin to building and equipping a car with the finest features, adding a passenger (in this case the cancer drug), and sending it off to its destination (in this case the cancer cell). 

To design the "vehicle," researchers used a selection strategy developed by Farokhzad's team that allowed them to essentially select for ligands (molecules that bind to the cell surface) that could specifically target prostate cancer cells. The researchers then attached nanoparticles containing chemotherapy, in this case docetaxel, to these hand-picked ligands. 

To understand Farokhzad's selection strategy, one must understand ligand behavior. While most ligands mainly have the ability to bind to cells, the strategy of Farokhzad and his colleagues allowed them to select specific ligands that were not only able to bind to prostate cancer cells, but also possessed two other important features: 1) they were smart enough to distinguish between cancer and non-cancer cells and 2) they were designed to be swallowed by cancer cells. 

"Most ligands are engulfed by cells, but not efficiently," said Farokhzad. "We designed one that is intended to be engulfed." 

Moreover, the ability for a ligand to intentionally be engulfed by a cell is crucial in drug delivery since it enables a significant amount of drug to enter the cancer cell, as opposed to remaining outside on the cell surface. This is a more effective method for cancer therapy. 

Another important aspect of this drug delivery design is that these ligand-nanoparticle components are able to interact with multiple cancer markers (antigens) on the cell surface. Unlike other drug delivery systems, this makes it versatile and potentially more broadly applicable. 

According to the study's lead author, ZeyuXiao, PhD, a researcher in the BWH Laboratory of Nanomedicine and Biomaterials, current strategies for targeting nanoparticles for cancer therapy rely on combining nanoparticles with ligands that can target well-known cancer markers. Such strategies can be difficult to execute since most cancer cells do not have identifiable cell surface markers to distinguish themselves from normal cells. 

"In this study, we developed a unique strategy that enables the nanoparticles to specifically target and efficiently be engulfed into any desired types and sub-types of cancer cells, even if their cancer markers are unknown," said Xiao. "Our strategy simplifies the development process of targeted nanoparticles and broadens their applications in cancer therapy." 

This research was supported by the National Institutes of Health, the David Koch-Prostate Cancer Foundation, and the USA Department of Defense Prostate Cancer Research Program. 

Source: Brigham and Women's Hospital [January 09, 2012]

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Researchers map potential genetic origins, pathways of lung cancer in never-smokers

Researchers have begun to identify which mutations and pathway changes lead to lung cancer in never-smokers — a first step in developing potential therapeutic targets. 

Never-smokers (defined as an individual who smoked fewer than 100 cigarettes in his or her lifetime) are estimated to account for 10 percent of lung cancer cases. However, in the past, researchers have not examined this patient population as extensively as they have studied patients with lung cancer who smoked, according to Timothy G. Whitsett, Ph.D., senior postdoctoral fellow in the cancer and cell biology division at the Translational Genomics Research Institute (TGen). 

He presented findings on potential gene mutations and pathway alterations that could lead to lung cancer in never-smokers at the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer: Biology, Therapy and Personalized Medicine, held Jan. 8-11, 2012. 

"This is the starting point. We certainly have a lot of pathways and gene expression alterations that we're going to be very interested in confirming and looking at in larger cohorts of patients," Whitsett said. "This is a very important subset of patients with lung cancer, and our research looks to identify pathways and genes that are potentially driving this form of cancer." 

Whitsett and his colleagues looked at three female patients with adenocarcinoma: one never-smoker with early-stage disease, one never-smoker with late-stage disease, and, as a comparison, one smoker with early-stage disease. The team performed whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) on each patient to identify gene mutations and pathway alterations that could have led to the development and progression of their specific lung cancers. 

"In the never-smoker with early-stage cancer, there were very few mutations in the genome, but when we looked at the whole transcriptome, we saw differences in gene expression," said Whitsett. 

In the never-smoker with late-stage disease, the researchers found mutations in what Whitsett called "classic tumor-suppressor genes." He and his colleagues hypothesized that mutations of the tumor-suppressor genes might be a factor in late-stage lung cancer in never-smokers. 

Notably, Whitsett and his colleagues reported that these never-smokers' tumors lacked alterations in common genes associated with lung cancer such as EGFR, KRAS and EML/ALK translocations. This finding makes these patients ideal cases for the discovery of new mutations that may drive lung adenocarcinomas in never-smokers, according to the researchers. 

Whitsett said that using WGS and WTS to identify cancer origins "has become a way to really dive down into an individual tumor to try to understand the pathways that may be driving that tumor and identify what therapeutic interventions may be possible." 

The researchers are now validating these findings in about 30 never-smokers with lung adenocarcinoma and about 60 clinically matched smokers with lung adenocarcinoma.  

Source: American Association for Cancer Research [January 09, 2012]

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Scientists identify lung cancer stem cells and new drug targets

Singapore scientists, headed by Dr. Bing Lim, Associate Director of Cancer Stem Cell Biology at the Genome Institute of Singapore (GIS), a research institute under the umbrella of the Agency for Science, Technology and Research (A*STAR), and Dr Elaine Lim, medical oncologist affiliated with Tan Tock Seng Hospital (TTSH) and National Cancer Centre Singapore (NCCS), have, for the first time, identified a gene responsible for lung cancer. The finding, reported in the advanced online issue of Cell on 5 January 2012, is a huge step towards finding a cure for the disease. 

A small number of cells, known as cancer stem cells or tumor-initiating cells (TIC), are responsible for the promotion of tumor growth. Dr. Bing Lim’s team was successful in finding a marker, known as CD166, to identify these cells. With the finding of this marker, the team then made more inroads into the genomic study of the TICs, and discovered several genes that were important for the growth of cancer cells. 

The metabolic enzyme known as glycine decarboxylase (GLDC) is a normal occurring enzyme in cells, present in small quantities. The scientists discovered that in abnormal instances when the level of GLDC rises significantly, it causes changes in the behavior of the cell, making it cancerous. 

"The manuscript from Dr. Bing Lim's laboratory provides a very exciting breakthrough about the unique metabolism of tumor initiating cells” said Dr. Lewis Cantley of Harvard Medical School. “This study builds on recent observations that a subset of cancer cells have enhanced serine/glycine metabolism. Importantly it shows that the enzyme glycine decarboxylase, which contributes to nucleotide synthesis, is elevated in lung tumor initiating cells and that it is critical for the ability of these cells to form tumors in vivo. Since glycine decarboxylase does not appear to be generally required for the growth of normal adult tissues, these results raise the possibility that this enzyme could be a target for cancer therapy." 

“This research is exemplary of the synergy between cancer researchers and clinicians that led to a breakthrough in our understanding of the metabolic pathway in lung cancer. I congratulate Dr. Bing Lim and Dr. Elaine Lim for leading this impressive multi-institutional study,” said Dr. Huck Hui Ng, Acting Executive Director of GIS. “The discovery of the biomarker has profound implications in cancer diagnostics and stratified medicine. It is hopeful that the metabolic enzyme GLDC will be a good target for drug development by the pharmaceutical industries."  

Dr. Bing Lim added “This is one of the most satisfying pieces of work I have orchestrated and the biggest credit must go to my post doctoral fellow, Dr. Wen Cai Zhang, who took the project from first establishing a xenograft model for human lung cancer to the identification of CD166 as a marker for lung cancer stem cell and culminating with the amazing discovery of the impact of a regular metabolic enzyme in carcinogenesis. It is doubly satisfying that we may have also identified a major drug target for controlling cancers”. 

Dr. John Wong, Vice Provost (Academic Medicine) of the National University of Singapore, explained that “Lung cancer is one of the most common causes of cancer death in Singapore and the region. There is an urgent need to better understand what drives this disease, especially as lung cancer in Asians appears to have major biological differences compared to that commonly seen in the West. The authors of this seminal paper should be congratulated as they represent the best of Team Science in Singapore, comprising both basic scientists and clinician investigators, all working to develop better therapies for Singaporeans and the community we live in. The findings from Dr. Bing Lim’s team strongly support the cancer stem cell paradigm and similar studies in other cancers need to be done.” 

Elaine Lim, co-corresponding author and co-principal investigator in this project said, “This paper is the result of successful co-operation between scientists and doctors from the Singapore Lung Cancer Consortium, with the Stem Cell division in GIS. The thoracic surgeons from TTSH, NCCS and NUHS have made outstanding contributions to this homegrown scientific project” 

Prof Soo Khee Chee, Director of NCCS, said that “NCCS has made important contributions to medical research through the years, both in clinical as well as basic research. This paper is an example of a very satisfying outcome when medical doctors and scientists huddle together to produce high-quality work. Co-operation between seemingly disparate disciplines amongst the different institutions in Singapore, led by Elaine and Bing, was critical to this success – and there will be many more to come” 

“This study has made significant contributions to our fundamental understanding of lung cancer,” added Prof Philip Choo, Chief Executive Officer at TTSH. “The study also represents an exceptional step forward for medical research involving doctors and scientists. We look forward to more of such collaborative efforts in the future.” 

More information: The research findings described in the press release can be found in the 5 January 2011 advanced online issue of Cell under the title “Glycine Decarboxylase Activity Drives Non-Small Cell Lung Cancer Tumor- Initiating Cells and Tumorigenesis”. 

Source: Agency for Science Technology and Research (A*STAR) [January 06, 2012]

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Studies identify risk factors in rising trend of liver cancer

Doctors have known for years that the incidence of deadly liver cancer is on the rise, but what is causing that trend has remained a mystery. Two recent Mayo Clinic studies published in the January issue of Mayo Clinic Proceedings offer a clearer picture of the rise of hepatocellular carcinoma (HCC), or liver cancer, which has tripled in the U.S. in the last three decades and has a 10 to 12 percent five-year survival rate when detected in later stages.

"The studies illuminate the importance of identifying people with risk factors in certain populations to help catch the disease in its early, treatable stages," said W. Ray Kim, M.D., a specialist in Gastroenterology and Hepatology and principal investigator of one study.

Dr. Kim's research group looked at several decades of records in the Rochester Epidemiology Project, a database that accounts for an entire county's inpatient and outpatient care. The study found the overall incidence of HCC in the population (6.9 per 100,000) is higher than has been estimated for the nation based on data from the National Cancer Institute (5.1 per 100,000). The study also found that HCC, which two decades ago tended to be caused by liver-scarring diseases such as cirrhosis from alcohol consumption, is now occurring as a consequence of hepatitis C infection.

"The liver scarring from hepatitis C can take 20 to 30 years to develop into cancer," Dr. Kim says. "We're now seeing cancer patients in their 50s and 60s who contracted hepatitis C 30 years ago and didn't even know they were infected."

Eleven percent of cases were linked to obesity, in particular fatty liver disease.

"It's a small percentage of cases overall," Dr. Kim says. "But with the nationwide obesity epidemic, we believe the rates of liver cancer may dramatically increase in the foreseeable future."

Another study looked exclusively at the Somali population, which is growing in the U.S., particularly in Minnesota, where as many as 50,000 Somalis have settled in the last two decades. The East African country is known to have a high prevalence of hepatitis B, a risk factor for HCC.

Researchers investigating records in the Mayo Clinic Life Sciences System confirmed that hepatitis B remains a risk factor, but they were surprised to find that a significant percentage of liver cancer cases in the population are attributable to hepatitis C, which had not been known to be significantly prevalent.

"The study suggests that screening for hepatitis C would be helpful for the Somali population and would enable close surveillance of liver cancer among those at risk," says lead author Abdirashid Shire, Ph.D., a Mayo Clinic researcher. "That would greatly improve treatment and survival of Somalis with this type of cancer."

Source: Mayo Clinic [January 03, 2012]

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Exercise cuts bowel cancer risk

Researchers at the University of Western Australia (UWA) and the Western Australian Institute for Medical Research (WAIMR) have found people who engage in vigorous physical activity may be protected against types of colorectal cancer. 

The study, published in the Cancer Causes Control journal, used a Western Australian cohort.  

Researchers examined 870 participants who had bowel cancer and a control group of 996 who did not have the disease. 

Study participants were asked to answer questions about their recreational physical activity, lifestyle, diet, medication and occupation. 

UWA PhD student Terry Boyle, also supported by the Lions Cancer Institute, says the study confirms previous research that shows the most physically active have a lower risk of bowel cancer than the least active.  

“It also gives us some clues as to what types of activity are the most effective at reducing bowel cancer risk,” Mr Boyle says.  

The study found people who performed regular vigorous physical activity over their lifetime had a 40 per cent reduced risk of cancer of the distal (lower) colon and rectum. 

“These results suggest that vigorous activity like jogging, cycling, swimming, tennis, hockey, netball and football may be the most effective physical activities to lower the risk of bowel cancer,” Mr Boyle says. 

Of the possible mechanisms linking physical activity and colon cancer, there is evidence to suggest that obesity and vitamin D may have a great effect on distal colon cancer than proximal colon cancer. 

While the link between physical activity and colon cancers remains opaque, this study supports the suggestion that lifestyle factors are more strongly tied to distal colon cancer than proximal colon cancer.  

Another finding showed physical activity performed after the age of 51 years, may be more beneficial in reducing the risk of distal colon cancer than physical activity performed earlier in life. 

“This shows that it really is never too late to start being physically active,” Mr Boyle says. 

Author: Gina Ravenscroft | Source: Science Network/Western Australia [December 20, 2011]

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Drugs used to overcome cancer may also combat antibiotic resistance

Drugs used to overcome cancer may also combat antibiotic resistance, finds a new study led by Gerry Wright, scientific director of the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University. 

"Our study found that certain proteins, called kinases, that confer antibiotic resistance are structurally related to proteins important in cancer," says Wright about the study published in Chemistry & Biology. 

"The pharmaceutical sector has made a big investment in targeting these proteins, so there are a lot of compounds and drugs out there that, although they were designed to overcome cancer, they can in fact be looked at with fresh eyes and maybe repurposed to address the problem of antibiotic resistance." 

The large-scale study involved screening 14 antibiotic resistant molecules against 80 chemically diverse protein kinase inhibitors. 

Antibiotic resistance is a problem growing in global scope, as more viruses have overcome currently available antibiotics. 

"As a result, new drugs and antibiotic strategies are urgently needed to fill the gap in infectious disease control," says Wright, adding he hopes future studies in combination therapies will provide new insight into antibiotic resistance. 

"One of the challenges facing the drug discovery community is the lack of new chemical scaffolds with antibiotic activity. This has led to the open question of whether all easily implementable antibiotic chemical scaffolds have already been exploited over the last 50 years: the so-called ''low hanging fruit''." 

Source: McMaster University [December 21, 2011]

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Study finds link between air pollution and increase in DNA damage

A study in the Czech Republic has found a link between exposure to certain air pollutants and an increase in DNA damage for people exposed to high levels of the pollution. 

They found that breathing small quantities of a polycyclic aromatic hydrocarbon (PAH), called benzo[a]pyrene (B[a]P), caused an increase in the number of certain 'biomarkers' in DNA associated with a higher risk of diseases, including cancer. 

Air pollution is a major problem around the world, particularly in urban areas. In attempt to control regional air pollution levels, the EU has introduced legal limits for exposure to a variety of different airborne pollutants. For B[a]P , the EU air quality standard is 1 nanogram per metre3 (ng/m3) as an annual average that has to be attained where possible throughout the EU. 

To measure the risk of DNA damage and risk to health caused by exposure to chemicals, such as PAHs, researchers sometimes use 'biomarkers' – these are biological features that can provide an indicative picture of risk and disease. 

Previous studies have suggested that 'DNA adducts' can be used as biomarkers to measure exposure to PAHs. These are, in effect, small molecules, such as PAHs, bound to the DNA. Similarly, 'chromosomal aberrations' - structural changes to a stretch of DNA - can be used as biomarkers to demonstrate the effect of some pollutants on DNA. 

To test whether there was a possible link between exposure to PAHs and the frequency of DNA adducts and chromosomal aberrations, the researchers, supported by the EU EnviRisk and INTARESE projects, examined DNA from 950 police officers and bus drivers in Prague. 

The participants, drawn from three separate studies conducted over a five-year period, all worked outdoors for more than eight hours a day. Each carried a device to measure their personal exposure to PAHs and DNA was extracted from the participants' white blood cells. 

The researchers also tested a new technique for identifying chromosomal aberrations called 'fluorescence in-situ hybridisation', or FISH, which is much more sensitive than previous techniques. 

The results revealed, for the first time, a significant relationship between exposure to PAHs, the number of DNA adducts and the number of chromosomal aberrations detected using FISH. In particular, PAH levels and the occurrence of the two biomarkers were higher in winter than in summer. 

In one of the studies, average personal exposure to B[a]P and PAHs in January was measured as 1.58 ng/m3 and 9.07 ng/m3, respectively. In June, this dropped to 0.18 ng/m3 and 1.92 ng/m3. 

The number of B[a]P-like DNA adducts and chromosomal aberrations were correspondingly much higher in January than in June. In fact, the number of DNA adducts strongly mirrored exposure to PAHs in the past 30 days. 

These findings are of concern because exposure to more than 1 ng/m3 of B[a]P has been found to put people at higher risk of developing cancer later in life. 

Previous studies have shown that DNA adducts can be an indicator for cancer several years after exposure and the findings of this study indicate that DNA adduct biomarkers and chromosomal aberrations measured using FISH could help health authorities identify individuals at higher risk of disease.  

Source: Click Green [December 18, 2011]

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Making Big Tobacco pay smokers' health bills: lessons from the United States

Reports that Nicola Roxon plans to encourage state governments to consider legal action to recover around A$31 billion in smoking-related health-care costs from the tobacco industry highlight the incoming attorney-general’s commendable commitment to reducing the impact of smoking-related illness and mortality. 

The legacy of the US Master Settlement Agreement holds significant lessons for policy makers in Australia [Credit: Razvan Caliman]

Such litigation is a potentially powerful way of countering the tobacco industry, but has been largely limited to the United States to date. As part of preliminary work on the proposal, Roxon has brought Matthew Myers, president of the leading US tobacco control organisation, Campaign for Tobacco-Free Kids, to Australia to discuss litigation with state officials. 

Myers, as The Australian points out, advised US attorneys-general during litigation against the tobacco industry in the late 1990s, and played a key role in negotiations that resulted in the controversial 1998 Master Settlement Agreement (MSA). 

While a spokeswoman for Roxon stated that Myers had been brought in to “share his extensive experience in tobacco-related litigation” and that the minister was “heartened by the support of such an esteemed anti-tobacco expert", the MSA has, in fact, had limited impact on the tobacco industry and effectively split the tobacco control community in the United States. 

Probably best known for its requirement that Philip Morris and other leading tobacco corporations make payments of US$246 billion to those states party to the settlement over a 25-year period, the MSA remains controversial within US tobacco control and broader public health circles, and it’s imperative that Australian officials consider the circumstances surrounding its progress carefully. 

The US Master Settlement Agreement 

The MSA was the result of secret negotiations between the tobacco industry, and attorneys-general and members of the tobacco control community including Myers. Critics of the negotiations claim the tobacco industry was on the defensive in the late 1990s – facing a combination of dozens of state lawsuits, damaging insights into its long-standing knowledge of the harms of smoking, and falling stock prices – and that state lawsuits should have been allowed to go to trial. In effect, the negotiations let the industry off the ropes. 

Under the terms of the MSA, the tobacco industry paid US$246 billion, agreed to fund a national initiative to reduce smoking and accepted limited restrictions on advertising. In return, outstanding litigation was dropped by the 46 states party to the settlement, and future state-level litigation was pre-empted. 

The final terms have been described by Allan Brandt, professor of history of medicine at Harvard Medical School and author of the book The Cigarette Century, as “a pale reflection” of earlier proposed settlements. As many had predicted, tobacco corporations passed the costs of the MSA on to consumers through sharp price hikes essentially making the agreement, Brandt contends, little more than a new excise tax on cigarettes. 

Settlement results 

Ostensible marketing restrictions in the agreement contained so many loopholes that spending on cigarette advertising and promotion has, in fact, increased dramatically in the United States since 1998. Not only has the MSA had virtually no impact on tobacco industry income or marketing practice, signatory states have realised little benefit from it. 

And while it may appear impressive, the agreed multi-billion dollar payment was insufficient to cover the costs of treating smoking-related illnesses and, more significantly, there were no assurances included in the settlement that monies received by the states would be dedicated to health-care and tobacco control programs. 

In many cases these funds have disappeared into general revenues, making state politicians reliant on this unexpected income, and effectively making the states partners of the tobacco industry. As Brandt argues, any new legal challenges to the industry have become “threats to the states' cash flow”. 

Australia’s tobacco control legislation is considerably more advanced than that in the United States, so concerns that the MSA does little to curtail industry advertising are largely irrelevant here. But the legacy of the MSA does hold significant lessons for policy makers in this country assessing the advisability of mounting legal action to secure compensation for smoking-related health-care costs. 

Most importantly, the MSA demonstrates that litigation, once launched, will have to be pursued diligently and without recourse to negotiated settlements with the industry. 

The experience of US states also underlines the importance of installing a regulatory mechanism that ensures any monies recovered from the industry are used to underwrite health costs related to tobacco use. Given his central role in the MSA negotiations, Myers' best advice to Australian policy makers may well be about what not to do in future litigation. 

Author: Ross MacKenzie | Source: The Conversation [December 16, 2011]

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Endorphin Plays Traffic Cop to Organs

Spleen to the left, appendix to the right: In order for the body to sort itself out properly, two substances have to trigger a complex chain reaction, according to the latest findings at the University of Hohenheim published in the journal Current Biology. 

The distribution of the “happy hormone”, endorphin serotonin (in red) in a 10-hour old frog embryo showing how serotonin collects in the outer cells, yet only in the upper part [Credit: University of Hohenheim]

It's all a matter of communication: Studies with frogs have shown zoologists at the University of Hohenheim that two chemical messengers are responsible for cell communication in the embryo, a fact that was unknown until now. Only when these two substances cooperate do the heart, liver and spleen move into their correct positions. Both substances are also vital to the bodies of fully-grown adults. A disturbance of their interplay could potentially lead to cancer. 

The chemical messenger serotonin is generally known as an endorphin, or "happy hormone." In fact, the substance actually is responsible for regulating many bodily functions, such as in the brain, the nerves in the stomach and the entire intestinal tract. 

A similar kind of multitalented chemical messenger is wnt. This substance is responsible for the development of the head-tail axis in frogs and for the growth of a fly's wings. 

Now a project team working under the auspices of Prof. Dr. Martin Blum, specialist for developmental biology, has found out that both of these substances are in charge of the asymmetrical right-left development in embryos. In the early stages of an embryo's development, they are partly in charge of the communication between cells and thus ensure that all organs find their way to their proper locations. 

The river that moves embryos 

Serotonin and wnt trigger a rather complex process. After fertilisation, the egg cell begins and then continues to divide in symmetrical fashion. Even after only a few hours, serotonin and wnt command special cells to grow very fine hairs which rotate quickly, acting like a propeller. 

This coordinated movement brings the fluid on the surface of the cells into motion, causing a determined flow from right to left. 

It is this stimulus that activates the genes which are responsible for directing the body's organs to their proper location. This can only happen when both messengers, serotonin and wnt, are allowed to interact freely. "If one or the other is lacking, then the process doesn't even get started, resulting in defects in the embryo." 

Possible starting point for new form of cancer treatment 

Adults also seem to require the perfect and uninhibited interplay between serotonin and wnt. If this is not the case, then "cells divide which shouldn't divide," Prof. Dr. Blum explains. One possible result: cancer. 

This new discovery on the basic research level by scientists in Hohenheim might, therefore, be the starting point for new methods of treating cancer, a topic which the members of Prof. Dr. Blum's team want to explore in-depth with colleagues from the University of Heidelberg. 

Source: University of Hohenheim via AlphaGalileo [December 15, 2011]

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