Portable Breast Scanner Allows Cancer Detection in the Blink of an Eye

A new portable scanner based on radio frequency technology can show in a second the presence of tumors -- malignant and benign -- in the breast on a computer. The red dot indicates the presence of a tumor.

Women could have a fast test for breast cancer and instantly identify the presence of a tumor in the comfort of their own home thanks to groundbreaking new research from the University of Manchester.
Professor Zhipeng Wu has invented a portable scanner based on radio frequency technology, which is able to show in a second the presence of tumours -- malignant and benign -- in the breast on a computer.
Using radio frequency or microwave technology for breast cancer detection has been proven by researchers in the US, Canada and UK. However, up to now, it can take a few minutes for an image to be produced, and this had to be done in a hospital or specialist care centre.
Now Professor Wu, from the University's School of Electrical and Electronic Engineering, says concerned patients can receive real-time video images in using the radio frequency scanner which would clearly and simply show the presence of a tumour.
Not only is this a quicker and less-intrusive means of testing, it also means women can be tested at GP surgeries, which could help dramatically reduce waiting times and in some cases avoid unnecessary X-ray mammography. The scanner could also be used at home for continuous monitoring of breast health.
The patented real-time radio frequency scanner uses computer tomography and works by using the same technology as a mobile phone, but with only a tiny fraction of its power.
This makes it both safe and low-cost and the electronics can be housed in a case the size of a lunch box for compactness and portability. Other existing systems are much larger.
Breast cancer is the second biggest killer in women, accounting for 8.2% of all cancer deaths. October is National Breast Cancer Awareness month.
The usual way of detecting breast cancer up to now is mammography, which works well for women over the age of 50 and can give results of up to 95% accuracy.
But it is far less effective for younger women. The detection rate could be as low as 60% for women under the age of 50, which accounts for 20% of all breast cancer cases.
At that stage it is even more important get accurate diagnosis. Early diagnosis and treatment could save thousands of lives.
The main difference between the two methods is that mammography works on density, while radio frequency technique works on dielectric contrasts between normal and diseased breast tissues.
In Professor Wu's design, as soon as the breast enters the cup an image appears on screen.
The presence of a tumour or other abnormality will show up in red as the sensor detects the difference in tissue contrasts at radio frequencies. Malignant tissues have higher permittivity and conductivity and therefore appear differently than normal ones to a screen.
Up to 30 images are generated every second, meaning a breast scan could be over in a far shorter time than they are currently.
Professor Wu said: "The system we have is portable and as soon as you lie down you can get a scan -- it's real-time.
"The real-time imaging minimises the chance of missing a breast tumour during scanning.
"Other systems also need to use a liquid or gel as a matching substance, such as in an ultrasound, to work but with our system you don't need that -- it can be done simply in oil, milk, water or even with a bra on.
"Although there is still research to be done, the system has great potential to bring a new way for breast cancer diagnosis.
"This will benefit millions of women in both developed and developing countries bearing in mind that one in nine women may develop breast cancer in their lifetime."
Professor Wu submitted his innovation of the sensor system to the IET Innovation Awards. The technology has been shortlisted in both Electronics and Measurement in Action categories. The winners will be announced in November.

Potential Prostate Cancer Marker Discovered

Images from the desorption electrospray ionization mass spectrometry analysis of prostate tissue samples are shown next to stained slides of the same samples. The images show that cholesterol sulfate is present in cancerous tissue and precancerous legions called high grade prostatic intraepithelial neoplasia, or PIN. A Purdue University-led research team discovered that cholesterol sulfate is a potential marker for prostate cancer. (Credit: Demian Ifa/Purdue Center for Analytical Instrumentation Development)

Studies by a Purdue University-led team have revealed a potential marker for prostate cancer that could be the starting point for less invasive testing and improved diagnosis of the disease.

The team used a new analysis technique to create a profile of the lipids, or fats, found in prostate tissue and discovered a molecular compound that appears to be useful in identifying cancerous and precancerous tissue. The profile revealed that cholesterol sulfate is a compound that is absent in healthy prostate tissue, but is a major fat found in prostate cancer tumors.
Graham Cooks, Purdue's Henry Bohn Hass Distinguished Professor of Chemistry, and Timothy Ratliff, the Robert Wallace Miller Director of the Purdue Center for Cancer Research, led the team.
"It was surprising to find a single compound that is distinctly present in cancerous tissue and not present in healthy tissue," said Cooks, who is co-director of Purdue's Center for Analytical Instrumentation Development. "We've been able to differentiate cancerous from healthy tissue using this new method in the past, but the difference was in the amounts of the same chemical compounds found in healthy tissue. There was no single differentiator of which one could say if it was present there was cancerous tissue."
Ratliff said this characteristic makes the compound a potential marker for the disease, which could lead to new blood or urine tests to screen for prostate cancer.
"Aside from skin cancer, prostate cancer is the most common cancer in men and is the second leading cause of cancer-related deaths," Ratliff said. "Unfortunately, the current screening test has a significant number of false positives because it uses a marker that is present with other non-cancerous conditions. As a result, many men have unnecessary biopsies, which are invasive, expensive and have the potential to cause infection. This new compound appears to be highly specific to prostate cancer cells, which would mean very few false positives."
The current prostate cancer test screens for a protein called prostate-specific antigen, or PSA, that is produced by the cells of the prostate. Elevated levels of PSA in the blood can signify prostate cancer, but non-cancerous conditions such as an enlarged or inflamed prostate also cause an increase in its levels, he said.
The findings of the study, which was funded by the Purdue University Center for Cancer Research and the National Institutes of Health, were published in the journal Analytical Chemistry.
The study was performed in collaboration with physician scientists from Indiana University School of Medicine, who co-authored the paper. They also provided the tissue samples and pathological analysis of the samples to check the new technique's results.
The team used a mass spectrometry analysis technique developed by Cooks and coworkers called desorption electrospray ionization, or DESI, to measure and compare the chemical characteristics of 68 samples of normal and cancerous prostate tissue.
Mass spectrometry works by first turning molecules into ions, or electrically charged versions of themselves, so that they can be identified by their mass. Conventional mass spectrometry requires chemical separations, manipulations of samples and containment in a vacuum chamber for ionization and analysis. The DESI technique eliminates these requirements by performing the ionization step in the air or directly on surfaces outside of the mass spectrometers, making the process much simpler, faster and more applicable to medical examination or surgical settings.
Cooks' research team also has developed software that turns the distribution and intensity of selected ions within a sample into a computer-generated image, much like what would be seen from a stained slide under the microscope. This chemical map of the sample can precisely show the location of cancerous tissue and the borders of tumors, Cooks said.
Livia Eberlin, co-author of the paper and a graduate student in Cooks' group, said the study showed promise in detecting precancerous lesions, as well.
"The DESI examination was able to distinguish a precancerous lesion in a small area of a sample made up of mostly healthy tissue," Eberlin said. "By evaluating the difference in the chemistry of cells, this technique can detect differences in diseased tissue that are otherwise indistinguishable. It could provide a new tool for pathologists to complement microscopic examination."
The team also plans to study differences in the chemistry of different types of prostate cancer tumors to see if there is a way to identify which are aggressive and which are not, she said.
Ratliff said the inability to tell the difference between aggressive and nonaggressive forms of prostate cancer causes problems in its treatment.
"A nonaggressive form of prostate cancer can be very slow to progress, and sometimes it is in the best interest of the patient not to go through rigorous treatments that reduce one's quality of life," he said. "The tests currently used to determine the probability that the cancer is an aggressive form are not very accurate, and about 30 percent of patients are misdiagnosed as having an aggressive form."
Additional co-authors of the paper include graduate students Allison Dill and Anthony Costa, and post doctoral researcher Demian Ifa from Purdue's Department of Chemistry and the Center for Analytical Instrumentation Development; Dr. Liang Cheng from the Indiana University School of Medicine Department of Pathology and Laboratory Medicine; and Dr. Timothy Masterson and Dr. Michael Koch from the Indiana University School of Medicine Department of Urology.
The team is already in the process of performing larger studies and plans to investigate the biological processes responsible for the expression of cholesterol sulfate in cancerous tissue.

Nanoparticles Shrink Tumors in Mice

The application of nanotechnology in the field of drug delivery has attracted much attention in recent years. In cancer research, nanotechnology holds great promise for the development of targeted, localized delivery of anticancer drugs, in which only cancer cells are affected.

A dorsal view of a mouse showing accumulation of nanoparticles in a tumor four hours after intravenous administration. Bright fluorescence is observed predominantly in the tumor.

Such targeted-therapy methods would represent a major advance over current chemotherapy, in which anticancer drugs are distributed throughout the body, attacking healthy cells along with cancer cells and causing a number of adverse side effects.
By carrying out comprehensive studies on mice with human tumors, UCLA scientists have obtained results that move the research one step closer to this goal. In a paper published July 8 in the journal Small, researchers at UCLA's California NanoSystems Institute and Jonsson Comprehensive Cancer Center demonstrate that mesoporous silica nanoparticles (MSNs), tiny particles with thousands of pores, can store and deliver chemotherapeutic drugs in vivo and effectively suppress tumors in mice.
The researchers also showed that MSNs accumulate almost exclusively in tumors after administration and that the nanoparticles are excreted from the body after they have delivered their chemotherapeutic drugs.
The study was conducted jointly in the laboratories of Fuyu Tamanoi, a UCLA professor of microbiology, immunology and molecular genetics and director of the signal transduction and therapeutics program at UCLA's Jonsson Comprehensive Cancer Center, and Jeffrey Zink, a UCLA professor of chemistry and biochemistry. Tamanoi and Zink are researchers at the California NanoSystems Institute (CNSI) and are two of the co-directors of the CNSI's Nano Machine Center for Targeted Delivery and On-Demand Release. The lead investigator on the research is Jie Lu, a postdoctoral fellow in Tamanoi's lab. Monty Liong and Zongxi Li, researchers from Zink's lab, also contributed to this work.
In the study, researchers found that MSNs circulate in the bloodstream for extended periods of time and accumulate predominantly in tumors. The tumor accumulation could be further improved by attaching a targeting moiety to MSNs, the researchers said.
The treatment of mice with camptothecin-loaded MSNs led to shrinkage and regression of xenograft tumors. By the end of the treatment, the mice were essentially tumor free, and acute and long-term toxicity of MSNs to the mice was negligible. Mice with breast cancer were used in this study, but the researchers have recently obtained similar results using mice with human pancreatic cancer.
"Our present study shows, for the first time, that MSNs are effective for anticancer drug delivery and that the capacity for tumor suppression is significant," Tamanoi said.
"Two properties of these nanoparticles are important," Lu said. "First, their ability to accumulate in tumors is excellent. They appear to evade the surveillance mechanism that normally removes materials foreign to the body. Second, most of the nanoparticles that were injected into the mice were excreted out through urine and feces within four days. The latter results are quite interesting and might explain the low toxicity observed in the biocompatabilty experiments we conducted."
Researchers at the Nano Machine Center for Targeted Delivery and On-Demand Release are modifying MSNs -- which are easily modifiable -- so that the nanoparticles can be equipped with nanomachines. For example, nanovalves are being attached at the opening of the pores to control the release of anticancer drugs. In addition, the interior of the pores is being modified so that the light-induced release of anticancer drugs can be achieved.
"We can modify both the particles themselves and also the attachments on the particles in a wide variety of ways, which makes this material particularly attractive for engineering drug-delivery vehicles," Zink said.
The team is now planning future research that involves testing MSNs in a variety of animal-model systems and carrying out extensive studies on the safety of MSNs.
"Comprehensive investigation with practical dosages which are adequate and suitable for in vivo delivery of anticancer drugs is needed before MSNs can reach clinics as a drug-delivery system," Tamanoi said.
The research received support from National Institutes of Health and the National Science Foundation. In addition, NanoPacific Holdings Inc. provided critical support for the animal experiments.

'Microtentacles' on Tumor Cells Appear to Play Role in How Breast Cancer Spreads

Two breast tumor cells attaching to each other. The red color shows the surface of both tumor cells, while the green color shows how the microtentacles from one cell encircle the neighboring cell

Researchers at the University of Maryland Marlene and Stewart Greenebaum Cancer Center have discovered that "microtentacles," or extensions of the plasma membrane of breast cancer cells, appear to play a key role in how cancers spread to distant locations in the body. Targeting these microtentacles might prove to be a new way to prevent or slow the growth of these secondary cancers, the scientists say.
They report in an article to be published online March 15, 2010, in the journal Oncogene that a protein called "tau" promotes the formation of these microtentacles on breast tumor cells which break away from primary cancers and circulate in the bloodstream. While twisted remnants of tau protein have been seen in the brain tissue of patients with Alzheimer's disease, this is the first report that tau could play a role in tumor metastasis by changing the shape of cancer cells. These tau-induced microtentacles can help the cells reattach to the walls of small blood vessels to create new pockets of cancer.
"Our study demonstrates that tau promotes the creation of microtentacles in breast tumor cells. These microtentacles increase the ability of circulating breast tumor cells to reattach in the small capillaries of the lung, where they can survive until they can seed new cancers," says the senior author, Stuart S. Martin, Ph.D., a researcher at the University of Maryland Greenebaum Cancer Center and associate professor of physiology at the University of Maryland School of Medicine. Michael A. Matrone, Ph.D., is the study's lead author.
Healthy cells are programmed to die -- a process called apoptosis -- after they break off of epithelial layers that cover internal organs in the body. They also can be crushed if they are forced through small capillaries. However, cancer cells are able to survive for weeks, months and even years in the body. Once they are trapped in small blood vessels, the cells can squeeze through microscopic gaps in the vessels' lining and spread to organs such as the brain, lung and liver.
"We hope that through our research, we will be able to identify drugs that will target the growth of these microtentacles and help to stop the spread of the original cancer. Drugs that reduce tau expression may hold potential to inhibit tumor metastasis," Dr. Martin says.
He notes that metastatic cancers are the leading cause of death in people with cancer, but methods used to treat primary tumors have limited success in treating metastatic cancer. In breast cancer, metastases can develop years after primary tumors are first discovered.
Tau is present in a subset of chemotherapy-resistant breast cancers and is also associated with poor prognosis, but Dr. Martin adds, "While tau expression has been studied in breast cancers for contributing to chemotherapy resistance, the protein's role in tumor cells circulating in the bloodstream hasn't been investigated. And that's the focus of our research."
In this recent study, the University of Maryland researchers analyzed breast tumor cells from 102 patients and found that 52 percent had tau in their metastatic tumors and 26 percent (27 patients) showed a significant increase in tau as their cancer progressed. Twenty-two of these patients even had tau in metastatic tumors despite having none in their primary tumors.
Dr. Martin says more studies are needed to determine if tau is a clear predictor of metastasis. Given the complex nature of tumors, there most likely are other factors involved in causing cancers to spread, he says.
"Metastasis is a very major concern for people diagnosed with cancer, and the discovery of these microtentacles and the role that tau plays in their formation is a very exciting development that holds great promise for developing new drugs," says E. Albert Reece, M.D., Ph.D., M.B.A., acting president of the University of Maryland, Baltimore, and dean of the University of Maryland School of Medicine.
The University of Maryland, Baltimore, has filed patents on the microtentacle discoveries of Dr. Martin's lab group and is looking to partner with biopharmaceutical companies on new drug development. The researchers identified these cell extensions while they were studying the effects of two drugs that prevent cell division, or mitosis. Most chemotherapy drugs target cell division, aiming to slow or stop tumor growth.
Dr. Martin says his team found that a popular chemotherapy drug, taxol, actually causes cancer cell microtentacles to grow longer and allows tumor cells to reattach faster, which may have important treatment implications for breast cancer patients. Their studies are continuing.
"We think more research is needed into how chemotherapies that slow down cell division affect metastasis. The timing of giving these drugs can be particularly important. If you treat people with taxol before surgery to shrink the primary tumor, levels of circulating tumor cells go up 1,000 to 10,000 fold, potentially increasing metastasis," he adds.
The study being published in Oncogene was funded by grants from the National Cancer Institute, the USA Medical Research and Materiel Command, and the Flight Attendants Medical Research Institute.

Chemotherapy Plus Synthetic Compound Provides Potent Anti-Tumor Effect in Pancreatic Cancers

Human pancreatic cancer cells dramatically regress when treated with chemotherapy in combination with a synthetic compound that mimics the action of a naturally occurring "death-promoting" protein found in cells, researchers at UT Southwestern Medical Center have found.

Researchers led by Dr. Rolf Brekken have shown in mice that pancreatic cancer cells dramatically regress when treated with chemotherapy in combination with a synthetic "death-promoting" compound. 

The research, conducted in mice, appears in the March 23 issue of Cancer Research and could lead to more effective therapies for pancreatic and possibly other cancers, the researchers said.
"This compound enhanced the efficacy of chemotherapy and improved survival in multiple animal models of pancreatic cancer," said Dr. Rolf Brekken, associate professor of surgery and pharmacology and the study's senior author. "We now have multiple lines of evidence in animals showing that this combination is having a potent effect on pancreatic cancer, which is a devastating disease."
In this study, Dr. Brekken and his team transplanted human pancreatic tumors into mice, then allowed the tumors to grow to a significant size. They then administered a synthetic compound called JP1201 in combination with gemcitabine, a chemotherapeutic drug that is considered the standard of care for patients with pancreatic cancer. They found that the drug combination caused regression of the tumors.
"There was a 50 percent regression in tumor size during a two-week treatment of the mice," Dr. Brekken said. "We also looked at survival groups of the animals, which is often depressing in human therapeutic studies for pancreatic cancer because virtually nothing works. We found not only significant decrease in tumor size, but meaningful prolongation of life with the drug combination."
The drug combination was also effective in an aggressive model of spontaneous pancreatic cancer in mice.
The compound JP1201 was created in 2004 by UT Southwestern researchers to mimic the action of a protein called Smac. The researchers discovered Smac in 2000 and found that this protein plays a key role in the normal self-destruction process present in every cell.
Cell death, or apoptosis, is activated when a cell needs to be terminated, such as when a cell is defective or is no longer needed for normal growth and development. In cancer cells, this self-destruct mechanism is faulty and lead to breaks in the cell-death cascade of events. The synthetic Smac, or Smac mimetic, developed at UT Southwestern inhibits these breaks, allowing the cell to die.
"In essence, we're inhibiting an inhibitor," Dr. Brekken said. "And we're allowing the apoptotic cascade to kick off, resulting in the death of cancer cells."
UT Southwestern researchers are using Smac mimetics in breast and lung cancer research, as well. Dr. Brekken said the next step is to develop a compound based on JP1201 that can be tested in humans in clinical trials.
Other UT Southwestern researchers involved in the study included lead author Dr. Sean Dineen, surgery resident; Dr. Christina Roland, surgery resident; Rachel Greer, student research assistant in the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research; Juliet Carbon, senior research associate in surgery and in the Hamon Center; Jason Toombs, research assistant in surgery and in the Hamon Center; Dr. Puja Gupta, a pediatric hematology/oncology fellow; Dr. Noelle Williams, associate professor of biochemistry; and Dr. John Minna, director of the W.A. "Tex" and Deborah Moncrief Jr. Center for Cancer Genetics and of the Hamon Center.
The research was supported by Susan G. Komen for the Cure and Joyant Pharmaceuticals, a Dallas-based company and UT Southwestern spinoff that is developing medical applications of Smac-mimetic compounds.

Genetic Variant Offers Protection Against Tuberculosis and Leprosy

When people get exposed to the mycobacterium responsible for tuberculosis (TB), some will become sick with a disease that is a major cause of mortality around the world while others simply don't. Now, researchers reporting in the March 5th issue of the journal Cell, a Cell Press publication, can point to one important reason for this variation in susceptibility or resistance: genetic differences among individuals in levels of an immune enzyme (LTA4H) that is involved in the production of leukotriene B, a pro-inflammatory fatty acid immune signaling molecule.
It turns out individuals who are heterozygous for LTA4H, meaning they carry two versions of the enzyme-encoding gene and produce an average amount of the enzyme (not too little or too much), are less likely to succumb to tuberculosis. They also appear to gain protection against leprosy, a disease which is also caused by mycobacterial infection.
"TB is obviously a big problem," said Lalita Ramakrishnan of the University of Washington. "There isn't a good vaccine, notwithstanding the fact that the TB vaccine has been administered to more people than any other. On top of that, it requires long-term treatment for cure and there is an epidemic of drug-resistant TB. Increasingly, people are becoming infected with strains that are resistant to every antibiotic. On this backdrop, it made sense to go back to the drawing board and try to understand the pathogenesis of the disease."
In the new study, Ramakrishnan and her colleague David Tobin did just that, in an unbiased screen for TB susceptibility genes in the zebrafish. They then collaborated with University of Washington human geneticists Jay Vary, Thomas Hawn and Mary-Claire King and others in Vietnam and Nepal to validate their findings in human populations.
A second study in the same issue of Cell approached the question in another way. Kanury Rao and his colleagues at the International Centre for Genetic Engineering and Biotechnology in India used a genome-wide analysis to produce what now becomes a resource for TB researchers everywhere. They uncovered all of the "cellular machinery" within human macrophages -- the cells primarily targeted by TB -- that interact with the infectious mycobacteria and allow the infection to stably persist.
Rao's team uncovered 275 players within host cells that interact with each other to form a dense network. That picture allowed the researchers to make a detailed molecular-level description of what he refers to as "functional modules" within host cells that are engaged and perturbed by TB infection. Interestingly, they showed that the shape of that interaction varies depending on which isolated strain of TB one considers, suggesting that the different strains rely on somewhat different tactics for successful infection.
Rao's findings offer new leads in the fight against TB, he says. "We identify a core set of molecules which can be targeted through drug development efforts to treat both drug sensitive and multiple drug resistant forms of TB infection. Rather than targeting the pathogen itself, our studies highlight an alternate strategy wherein the host factors required to support pathogen survival can be used as targets for TB therapy."
The discovery of LTA4H as a TB susceptibility gene may have clinical implications too, even if it doesn't offer a direct path to a better vaccine, Ramakrishnan says. For one thing, the finding that medium activity of the immune enzyme is best when it comes to TB might help to explain something that has been known but not well understood in clinical circles: people with hard-to-treat TB sometimes improve when they are given anti-inflammatory, immunosuppressive therapies along with more standard drug treatments alone.
Ramakrishnan also notes that the same polymorphisms in LTA4H they uncovered were earlier linked to heart disease. That suggests that drugs that target this pathway in heart disease might be useful in the context of TB, she says.
The connection between infectious disease and heart disease also has implications for understanding the evolution of the immune system's inflammatory responses. "In general, people have thought that inflammation is a positive when it comes to fighting infection, but then it can cause modern-day disease," Ramakrishnan says. The finding that it is heterozygotes -- with intermediate activity of the immunity enzyme -- who fare best in the context of TB and leprosy suggests that in these infections also, inflammation has to be finely tuned for optimal protection.
The researchers include David M. Tobin, University of Washington, Seattle, WA; Jay C. Vary, Jr., University of Washington, Seattle, WA; John P. Ray, University of Washington, Seattle, WA; Gregory S. Walsh, Howard Hughes Medical Institute and Division of Basic Science, Fred Hutchinson Cancer Research Center, Seattle, WA; Sarah J. Dunstan, Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, Oxford University, Oxford, UK; Nguyen D. Bang, Pham Ngoc Thach Hospital for Tuberculosis and Lung Disease, Ho Chi Minh City, Vietnam; Deanna A. Hagge, Mycobacterial Research Laboratory, Anandaban Hospital, Kathmandu, Nepal; Saraswoti Khadge, Mycobacterial Research Laboratory, Anandaban Hospital, Kathmandu, Nepal; Mary-Claire King, University of Washington, Seattle, WA; Thomas R. Hawn, University of Washington, Seattle, WA; Cecilia B. Moens, Howard Hughes Medical Institute and Division of Basic Science, Fred Hutchinson Cancer Research Center, Seattle, WA; and Lalita Ramakrishnan, University of Washington, Seattle, WA.

Vitamin D Crucial to Activating Immune Defenses

Scientists at the University of Copenhagen have discovered that Vitamin D is crucial to activating our immune defenses and that without sufficient intake of the vitamin, the killer cells of the immune system -- T cells -- will not be able to react to and fight off serious infections in the body.
For T cells to detect and kill foreign pathogens such as clumps of bacteria or viruses, the cells must first be 'triggered' into action and 'transform' from inactive and harmless immune cells into killer cells that are primed to seek out and destroy all traces of a foreign pathogen.
The researchers found that the T cells rely on vitamin D in order to activate and they would remain dormant, 'naïve' to the possibility of threat if vitamin D is lacking in the blood.
Chemical Reaction that Enables Activation
In order for the specialized immune cells (T cells) to protect the body from dangerous viruses or bacteria, the T cells must first be exposed to traces of the foreign pathogen. This occurs when they are presented by other immune cells in the body (known as macrophages) with suspicious 'cell fragments' or 'traces' of the pathogen. The T cells then bind to the fragment and divide and multiply into hundreds of identical cells that are all focused on the same pathogen type. The sequence of chemical changes that the T cells undergo enables them to both be 'sensitized to' and able to deliver a targeted immune response.
Professor Carsten Geisler from the Department of International Health, Immunology and Microbiology explains that "when a T cell is exposed to a foreign pathogen, it extends a signaling device or 'antenna' known as a vitamin D receptor, with which it searches for vitamin D. This means that the T cell must have vitamin D or activation of the cell will cease. If the T cells cannot find enough vitamin D in the blood, they won't even begin to mobilize. "
T cells that are successfully activated transform into one of two types of immune cell. They either become killer cells that will attack and destroy all cells carrying traces of a foreign pathogen or they become helper cells that assist the immune system in acquiring "memory." The helper cells send messages to the immune system, passing on knowledge about the pathogen so that the immune system can recognize and remember it at their next encounter. T cells form part of the adaptive immune system, which means that they function by teaching the immune system to recognize and adapt to constantly changing threats.
Activating and Deactivating the Immune System
For the research team, identifying the role of vitamin D in the activation of T cells has been a major breakthrough. "Scientists have known for a long time that vitamin D is important for calcium absorption and the vitamin has also been implicated in diseases such as cancer and multiple sclerosis, but what we didn't realize is how crucial vitamin D is for actually activating the immune system -- which we know now. "
The discovery, the scientists believe, provides much needed information about the immune system and will help them regulate the immune response. This is important not only in fighting disease but also in dealing with anti-immune reactions of the body and the rejection of transplanted organs. Active T cells multiply at an explosive rate and can create an inflammatory environment with serious consequences for the body. After organ transplants, e.g. T cells can attack the donor organ as a "foreign invader." In autoimmune disease, hypersensitive T cells mistake fragments of the body's own cells for foreign pathogens, leading to the body launching an attack upon itself.
The research team was also able to track the biochemical sequence of the transformation of an inactive T cell to an active cell, and thus would be able to intervene at several points to modulate the immune response. Inactive or 'naïve' T cells crucially contain neither the vitamin D receptor nor a specific molecule (PLC-gamma1) that would enable the cell to deliver an antigen specific response.
The findings, continues Professor Geisler "could help us to combat infectious diseases and global epidemics. They will be of particular use when developing new vaccines, which work precisely on the basis of both training our immune systems to react and suppressing the body's natural defenses in situations where this is important -- as is the case with organ transplants and autoimmune disease."
Most Vitamin D is produced as a natural byproduct of the skin's exposure to sunlight. It can also be found in fish liver oil, eggs and fatty fish such as salmon, herring and mackerel or taken as a dietary supplement. No definitive studies have been carried out for the optimal daily dosage of vitamin D but as a large proportion of the population have very low concentrations of vitamin D in the blood, a number of experts recommend between 25-50mg micrograms a day

Blocking Inflammation Receptor Kills Breast Cancer Stem Cells, Study Finds

Scientists at the University of Michigan Comprehensive Cancer Center have uncovered an important link between inflammation and breast cancer stem cells that suggests a new way to target cells that are resistant to current treatments.
The researchers identified a receptor, CXCR1, on the cancer stem cells which triggers growth of stem cells in response to inflammation and tissue damage. A drug originally developed to prevent organ transplant rejection blocks this receptor, killing breast cancer stem cells and preventing their metastasis in mice, according to the study.
Cancer stem cells, the small number of cells that fuel a tumor's growth, are believed to be resistant to current chemotherapies and radiation treatment, which researchers say may be the reason cancer so often returns after treatment.
"Developing treatments to effectively target the cancer stem cell population is essential for improving outcomes. This work suggests a new strategy to target cancer stem cells that can be readily translated into the clinic," says senior study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center. Wicha was part of the team that first identified stem cells in breast cancer.
Results of the current study appear online Jan. 4 in the Journal of Clinical Investigation and will appear in the journal's February print issue.
CXCR1 is a receptor for Interleukin-8, or IL-8, a protein produced during chronic inflammation and tissue injury. When tumors are exposed to chemotherapy, the dying cells produce IL-8, which stimulates cancer stem cells to replicate. Addition of the drug repertaxin to chemotherapy specifically targets and kills breast cancer stem cells by blocking CXCR1.
Mice treated with repertaxin or the combination of repertaxin and chemotherapy had dramatically fewer cancer stem cells than those treated with chemotherapy alone. In addition, repertaxin-treated mice developed significantly fewer metastases than mice treated with chemotherapy alone.
"These studies suggest that important links between inflammation, tissue damage and breast cancer may be mediated by cancer stem cells. Furthermore, anti-inflammatory drugs such as repertaxin may provide a means of blocking these interactions, thereby targeting breast cancer stem cells," Wicha says.
Repertaxin has been tested in early phase clinical trials to prevent rejection after organ transplantation. In these studies, side effects seem to be minimal. There are no reports of using repertaxin to treat cancer.
Note to patients: This work was done in cell cultures and mice. Repertaxin is not available to patients at this time and no clinical trials are yet planned.
Breast cancer statisitics: 194,280 Americans will be diagnosed with breast cancer this year and 40,610 will die from the disease, according to the American Cancer Society.
Additional authors: Christophe Ginestier, Suling Liu, Mark Diebel, Hasan Korkaya, Ming Luo, Marty Brown, Jun-Lin Guan, Gabriela Dontu, all from U-M; and Julien Wicinski, Olivier Cabaud, Emmanuelle Charafe-Jauffret, Daniel Birnbaum, all from Universite de la Mediterranee, Marseille, France
Funding: National Institutes of Health, Breast Cancer Foundation, Taubman Institute, Department of Defense, Inserm, Institut Paoli-Calmettes, Institut National du Cancer, Ligue Nationale Contre le Cancer
Disclosure: The University of Michigan has filed for patent protection on this technology, and is currently looking for a commercialization partner to help bring the technology to market.

Natural Compounds in Pomegranates May Prevent Growth of Hormone-Dependent Breast Cancer

Eating fruit, such as pomegranates, that contain anti-aromatase phytochemicals reduces the incidence of hormone-dependent breast cancer, according to results of a study published in the January issue of Cancer Prevention Research, a journal of the American Association for Cancer Research.

Pomegranate is enriched in a series of compounds known as ellagitannins that, as shown in this study, appear to be responsible for the anti-proliferative effect of the pomegranate.
"Phytochemicals suppress estrogen production that prevents the proliferation of breast cancer cells and the growth of estrogen-responsive tumors," said principal investigator Shiuan Chen, Ph.D., director of the Division of Tumor Cell Biology and co-leader of the Breast Cancer Research Program at City of Hope in Duarte, Calif.
Previous research has shown that pomegranate juice -- punica granatum L -- is high in antioxidant activity, which is generally attributed to the fruit's high polyphenol content. Ellagic acid found in pomegranates inhibits aromatase, an enzyme that converts androgen to estrogen. Aromatase plays a key role in breast carcinogenesis; therefore, the growth of breast cancer is inhibited.
Chen, along with Lynn Adams, Ph.D., a research fellow at Beckman Research Institute of City of Hope, and colleagues, evaluated whether phytochemicals in pomegranates can suppress aromatase and ultimately inhibit cancer growth.
After screening and examining a panel of 10 ellagitannin-derived compounds in pomegranates, the investigators found that those compounds have the potential to prevent estrogen-responsive breast cancers. Urolithin B, which is a metabolite produced from ellagic acid and related compounds, significantly inhibited cell growth.
"We were surprised by our findings," said Chen. "We previously found other fruits, such as grapes, to be capable of the inhibition of aromatase. But, phytochemicals in pomegranates and in grapes are different."
According to Gary Stoner, Ph.D., professor in the Department of Internal Medicine at Ohio State University, additional studies will be needed to confirm the chemopreventive action of Urolithin B against hormone-dependent breast cancer.
"This is an in vitro study in which relatively high levels of ellagitannin compounds were required to demonstrate an anti-proliferative effect on cultured breast cancer cells," said Stoner, who is not associated with this study. "It's not clear that these levels could be achieved in animals or in humans because the ellagitannins are not well absorbed into blood when provided in the diet."
Stoner believes these results are promising enough to suggest that more experiments with pomegranate in animals and humans are warranted.
Powel Brown, M.D., Ph.D., medical oncologist and chairman of the Clinical Cancer Prevention Department at the University of Texas M. D. Anderson Cancer Center, agreed with Stoner's sentiments and said these results are intriguing. He recommended that future studies focus on testing pomegranate juice for its effect on estrogen levels, menopausal symptoms, breast density or even as a cancer preventive agent.
"More research on the individual components and the combination of chemicals is needed to understand the potential risks and benefits of using pomegranate juice or isolated compounds for a health benefit or for cancer prevention," Brown said. "This study does suggest that studies of the ellagitannins from pomegranates should be continued."
Until then, Stoner said people "might consider consuming more pomegranates to protect against cancer development in the breast and perhaps in other tissues and organs."

Mango can arrest growth of certain breast and colon cancer cells

ango fruit been found to prevent or stop certain colon and breast cancer cells in the lab.

Mango fruit been found to prevent or stop certain colon and breast cancer cells in the lab.
That's according to a new study by Texas AgriLife Research food scientists, who examined the five varieties most common in the U.S.: Kent, Francine, Ataulfo, Tommy/Atkins and Haden.
Though the mango is an ancient fruit heavily consumed in many parts of the world, little has been known about its health aspects. The National Mango Board commissioned a variety of studies with several U.S. researchers to help determine its nutritional value.
"If you look at what people currently perceive as a superfood, people think of high antioxidant capacity, and mango is not quite there," said Dr. Susanne Talcott, who with her husband, Dr. Steve Talcott, conducted the study on cancer cells. "In comparison with antioxidants in blueberry, acai and pomegranate, it's not even close."
But the team checked mango against cancer cells anyway, and found it prevented or stopped cancer growth in certain breast and colon cell lines, Susanne Talcott noted.
"It has about four to five times less antioxidant capacity than an average wine grape, and it still holds up fairly well in anticancer activity. If you look at it from the physiological and nutritional standpoint, taking everything together, it would be a high-ranking super food," she said. "It would be good to include mangoes as part of the regular diet."
The Talcotts tested mango polyphenol extracts in vitro on colon, breast, lung, leukemia and prostate cancers. Polyphenols are natural substances in plants and are associated with a variety of compounds known to promote good health.
Mango showed some impact on lung, leukemia and prostate cancers but was most effective on the most common breast and colon cancers.
"What we found is that not all cell lines are sensitive to the same extent to an anticancer agent," she said. "But the breast and colon cancer lines underwent apotosis, or programmed cell death. Additionally, we found that when we tested normal colon cells side by side with the colon cancer cells, that the mango polyphenolics did not harm the normal cells."
The duo did further tests on the colon cancer lines because a mango contains both small molecules that are readily absorbed and larger molecules that would not be absorbed and thus remain present in a colon.
"We found the normal cells weren't killed, so mango is not expected to be damaging in the body," she said. "That is a general observation for any natural agent, that they target cancer cells and leave the healthy cells alone, in reasonable concentrations at least."
The Talcotts evaluated polyphenolics, and more specifically gallotannins as being the class of bioactive compounds (responsible for preventing or stopping cancer cells). Tannins are polyphenols that are often bitter or drying and found in such common foods as grape seed, wine and tea.
The study found that the cell cycle, which is the division cells go through, was interrupted. This is crucial information, Suzanne Talcott said, because it indicates a possible mechanism for how the cancer cells are prevented or stopped.
"For cells that may be on the verge of mutating or being damaged, mango polyphenolics prevent this kind of damage," she said.
The Talcotts hope to do a small clinical trial with individuals who have increased inflamation in their intestines with a higher risk for cancer.
"From there, if there is any proven efficacy, then we would do a larger trial to see if there is any clinical relevance," she said.
According to the National Mango Board, based in Winter Park, Fla., most mangoes consumed in the U.S. are produced in Mexico, Ecuador, Peru, Brazil, Guatemala and Haiti. Mangoes are native to southeast Asia and India and are produced in tropical climates. They were introduced to the U.S. in the late 1800s, and a few commercial acres still exist in California and Florida.

Green Tea: Mixed Reviews For Cancer Prevention

Lifestyle choices are pieces of the cancer prevention puzzle, but exactly which steps to take remain unclear, even to scientists. Still, more and more individuals are incorporating small changes into their daily routine — such as drinking green tea — in hopes of keeping cancer risk at bay.Is it working? A large new Cochrane review of studies that examined the affect of green tea on cancer prevention has yielded conflicting results.

Researchers looked at 51 medium- to high-quality studies that included more than 1.6 million participants. The studies focused on the relationship between green tea consumption and a variety of cancers, including breast, lung, digestive tract, urological prostate, gynecological and oral cancers.

The comprehensive review analyzed studies conducted from 1985 through 2008. Many of the reviewed studies took place in Asia, where tea drinking is widespread and part of the daily routine for many.

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

“Despite the large number of included studies the jury still seems to be out on the question of whether green tea can in fact prevent the development of various cancer types,” said lead review author Katja Boehm, Ph.D. Since people drink varying amounts of green tea, and different types of cancers vary in how they grow, it is impossible to state definitively that green tea is “good” for cancer prevention.

“One thing is certain…green tea consumption can never account for cancer prevention alone,” said Boehm, a member of the Unconventional and Complementary Methods in Oncology Study Group in Nuremburg, Germany.

Three types of tea — black, green and oolong — come from the plant Camellia sinensis, and all contain polyphenols. Catechins, a subgroup of the polyphenols, are powerful antioxidants. Some say the polyphenols in green tea are unique, preventing cell growth and thus having the potential to prevent cancer.

The review found that green tea had limited benefits for liver cancer, but found conflicting evidence for other gastrointestinal cancers, such as cancer of the esophagus, colon or pancreas. One study found a decreased risk of prostate cancer for men who consumed higher quantities of green tea or its extracts.

The review did not find any benefit for preventing death from gastric cancer, and found that green tea might even increase the risk of urinary bladder cancer. Despite conflicting findings, there was “limited moderate to strong evidence” of a benefit for lung, pancreatic and colorectal cancer. None of the studies that simply observed a group of people over time found a benefit for breast cancer prevention. However, both of the case control studies — which compare people without a condition to people with it — found a positive association between green tea consumption and a decreased risk of breast cancer.

Nagi Kumar, Ph.D., director of Nutrition Research at Moffitt Cancer Center in Tampa, Fla., is optimistic about the potential for green tea in cancer prevention. “The substances found in green tea are certainly promising,” Kumar said. “The field now has progressed to where we [can]…test the effectiveness and safety of green tea polyphenols using a drug form similar to the constituents in tea to see if we can prevent cancer progression. Time will tell.”

Kumar said the Cochrane review was “more an inventory of studies completed rather than a systematic scientific review,” adding that “the discussion lacks a scientific approach in the interpretation of the discordant findings.”

Kumar also noted that several groups are conducting randomized clinical trials, including one comprising six institutions: the Moffitt Cancer Center and the James A Haley VA Medical Center, University of Chicago, Jefferson in Philadelphia, University of Florida and Louisiana State University.

Both scientists agreed that more research is a good idea. Boehm said she highly recommends the conduction of a large, well-designed, study with adequate green tea consumption levels.

“The review provides where we have been in this field of research and where we are going and how much more we have on hand,” Kumar said. “Although not as thorough as I would like it, it is a good quality review.”

Therefore, while the questions about green tea consumption and cancer prevention remain unanswered, one thing remains clear: It is fine to consume green tea if you enjoy it and it might prove beneficial in the over time.

“If not exceeding the daily recommended allowance those who enjoy a cup of green tea should continue its consumption,” Boehm said. “Drinking green tea appears to be safe at regular, habitual and moderate use at its recommended dosage of up to 1200 ml/day.” That comes to a little over five cups a day.

‘Chemical Nose’ May Sniff Out Cancer Earlier

Using a “chemical nose” array of nanoparticles and polymers, researchers at the University of Massachusetts Amherst have developed a fundamentally new, more effective way to differentiate not only between healthy and cancerous cells but also between metastatic and non-metastatic cancer cells. It’s a tool that could revolutionize cancer detection and treatment, according to chemist Vincent Rotello and cancer specialist Joseph Jerry.An article describing Rotello and colleagues’ new chemical nose method of cancer detection appears in the June 23 issue of the journal Proceedings of the National Academy of Sciences online.

Currently, detecting cancer via cell surface biomarkers has taken what’s known as the “lock and key” approach. Drawbacks of this method include that foreknowledge of the biomarker is required. Also, as Rotello explains, a cancer cell has the same biomarkers on its surface as a healthy cell, but in different concentrations, a maddeningly small difference that can be very difficult to detect. “You often don’t get a big signal for the presence of cancer,” he notes. “It’s a subtle thing.”

He adds, “Our new method uses an array of sensors to recognize not only known cancer types, but it signals that abnormal cells are present. That is, the chemical nose can simply tell us something isn’t right, like a ‘check engine light,’ though it may never have encountered that type before.” Further, the chemical nose can be designed to alert doctors of the most invasive cancer types, those for which early treatment is crucial.

In blinded experiments in four human cancer cell lines (cervical, liver, testis and breast), as well as in three metastatic breast cell lines, and in normal cells, the new detection technique correctly indicated not only the presence of cancer cells in a sample but also identified primary cancer vs. metastatic disease.

In further experiments to rule out the possibility that the chemical nose had simply detected individual differences in cells from different donors, the researchers repeated the experiments in skin cells from three groups of cloned BALB /c mice: healthy animals, those with primary cancer and those with metastatic disease. Once again, it worked. “This result is key,” says Rotello. “It shows that we can differentiate between the the three cell types in a single individual using the chemical nose approach.”

Rotello’s research team, with colleagues at the Georgia Institute of Technology, designed the new detection system by combining three gold nanoparticles that have special affinity for the surface of chemically abnormal cells, plus a polymer known as PPE, or para-phenyleneethynylene. As the ‘check engine light,’ PPE fluoresces or glows when displaced from the nanoparticle surface.

By adding PPE bound with gold nanoparticles to human cells incubating in wells on a culture plate, the researchers induce a response called “competitive binding.” Cell surfaces bind the nanoparticles, displacing the PPE from the surface. This turns on PPE’s fluorescent switch. Cells are then identified from the patterns generated by different particle-PPE systems.

Rotello says the chemical nose approach is so named because it works like a human nose, which is arrayed with hundreds of very selective chemical receptors. These bind with thousands of different chemicals in the air, some more strongly than others, in the endless combination we encounter. The receptors report instantly to the brain, which recognizes patterns such as, for example, “French fries,” or it creates a new smell pattern.

Chemical receptors in the nose plus the brain’s pattern recognition skills together are incredibly sensitive at detecting subtly different combinations, Rotello notes. We routinely detect the presence of tiny numbers of bacteria in meat that’s going bad, for instance. Like a human nose, the chemical version being developed for use in cancer also remembers patterns experienced, even if only once, and creates a new one when needed.

For the future, Rotello says further studies will be undertaken in an animal model to see if the chemical nose approach can identify cell status in real tissue. Also, more work is required to learn how to train the chemical nose’s sensors to give more precise information to physicians who will be making judgment calls about patients’ cancer treatment. But the future is promising, he adds. “We’re getting complete identification now, and this can be improved by adding more and different nanoparticles. So far we’ve experimented with only three, and there are hundreds more we can make.”

Key Found To How Tumor Cells Invade The Brain In Childhood Cancer

Despite great strides in treating childhood leukemia, a form of the disease called T-cell acute lymphoblastic leukemia (T-ALL) poses special challenges because of the high risk of leukemic cells invading the brain and spinal cord of children who relapse.Now, a new study in the June 18, 2009, issue of the journal Nature by scientists at NYU School of Medicine reveals the molecular agents behind this devastating infiltration of the central nervous system. The finding may lead to new drugs that block these agents and thus lower the risk of relapse.

T-ALL, a blood-borne cancer in which the bone marrow makes too many lymphocytes, or white blood cells, strikes several hundred children and adolescents in the U.S. annually. While greater than 90% percent go into remission through a combination of chemotherapy and radiation, up to one third of this group end up relapsing. These patients are at particular risk for tumor cells to invade the brain and spinal cord, and to prevent this all patients receive chemotherapy injections into the central nervous system and in some cases cranial irradiation—approaches that cause dangerous side effects, including secondary tumors and potentially permanent cognitive and developmental deficits.

“In general, T-cell acute lymphoblastic leukemia is treatable with chemotherapy and radiation,” said Ioannis Aifantis, PhD, associate professor of pathology and co-director of the Cancer Stem Cell Program at the NYU Cancer Institute, who led the new study. “But you have a very high rate of relapse. And after the relapse, it is not treatable because the cancer occurs in tricky places like the central nervous system,” said Dr. Aifantis, who is also an Early Career Scientist at the Howard Hughes Medical Institute.

“We are very proud of this research and very excited about the potential implications for new therapeutic approaches to prevent or reduce the spread of leukemic cells into the central nervous system,” said Vivian S. Lee MD, PhD, MBA, the vice dean for science, senior vice president and chief scientific officer of NYU Langone Medical Center.

In the new study, Dr. Aifantis and his colleagues found that a key protein receptor embedded on the outer surface of leukemic cells is responsible for infiltrating the brain and spinal cord. “What we have found is that leukemic cells over-express this receptor.” said Dr. Aifantis, “If you knock out this receptor, these cells will not go to the brain under any circumstances.”

Previous research had strongly implicated a famous gene regulator called Notch1 in the progression of T-ALL. The Notch1 gene (a mutated version gives fruit flies notched wings) is an oncogene, or cancer-causing gene, in humans. Certain kinds of mutations in this gene have been found in nearly half of all T-ALL patients, and current estimates suggest that the gene’s regulatory influence might be implicated in nearly 90 percent of all T-ALL cases.

For their new study, Dr. Aifantis and his colleagues first introduced overactive forms of Notch1 into mice. As a result, the mice developed leukemia and the leukemic cells efficiently infiltrated the inner layers of the membrane covering the brain. “What happens is that the leukemic cells get into the cerebrospinal fluidthat protects our brain and spine, where they fill up the space and they can affect brain function, either by secreting chemicals and toxic factors or even by simple pressure,” Dr. Aifantis said.

His team then examined an array of other mouse genes to identify candidates that might fall under the regulatory spell of Notch1 to promote the brain and spinal cord infiltration. The screen revealed a promising gene for a protein named CCR7, which is embedded on the surface of lymphocytes. This chemokine receptor, as it’s known, normally senses and responds to small chemical attractants called chemokines, which act like recruitment signals for lymphocytes to converge on a specific site during the body’s response to infection or injury. In leukemia, however, these lymphocytes proliferate abnormally.

CCR7 was already known as a key player in normal lymphocyte migration and as a binding partner of two chemokines named CCL19 and CCL21. Previous studies had implicated these protein interactions in the metastasis of other tumors such as melanomas and breast cancers. Dr. Aifantis’s team also discovered that the gene for CCR7 was overactive in four of five T-ALL cell lines derived from human patients, bolstering suspicions that it played a central role in the disease. Conversely, a mutation that knocked out Notch1 also led to dramatically reduced CCR7 levels.

To characterize CCR7’s potential role in T-ALL, the researchers used two sets of mice: one in which the receptor was turned on, and a second in which it was turned off. When the team delivered an identical number of human-derived leukemic cells to both sets of mice, those with the CCR7 chemokine receptor turned off lived almost twice as long. Using bioluminescent imaging, the researchers quickly understood why: animals with the active CCR7 receptor had many more tumors. Tellingly, the T-ALL cells had infiltrated the brain and spinal cord of those mice.

Further experiments suggested that when healthy mice received leukemic cells in which the gene for CCR7 had been turned off, the cells could not migrate to the brain even though they reached other body tissues. As a result, the mice survived significantly longer than counterparts with an active copy of the gene. On the other hand, introducing a normal version of the same gene to mice otherwise lacking it was enough to recruit leukemic cells to the brain and spine.

“We wanted to determine whether CCR7 by itself was sufficient for entry into the central nervous system and that’s what this experiment shows,” Dr. Aifantis said. “By changing one specific gene, you now have your function back.”

Finally, the researchers identified the small protein that acted as the “come hither” signal for the CCR7 protein receptors. One candidate, CCL21, was undetectable in leukemic mice. But a second, CCL19, appeared in tiny veins of the brain near the infiltrating tumor cells. When the researchers introduced leukemic cells carrying a gene for CCR7 to mice that naturally lacked the CCL19 chemokine, the mice survived longer, suggesting that their increased life spans might be due to a disrupted interaction of the two proteins. The leukemic cells had no trouble infiltrating other tissue like the lymph nodes, but were completely incapable of infiltrating the brains of CCL19-deficient mice, the researchers report.

“Perhaps there are antibodies or small molecules that can block the interaction between these two proteins or reduce their interactions,” Dr. Aifantis said, “and hopefully that could be used as a type of prophylactic treatment to prevent a relapse in the central nervous system among patients who have already been treated for leukemia.” Such a treatment, he said, could prove a good alternative to the intensive and often poorly tolerated radiation and chemotherapy now used to try to block such a relapse.

The study was led by Dr. Silvia Buonamici, a post-doctoral fellow in the laboratory of Dr. Aifantis in the Department of Pathology and the NYU Cancer Institute, and in the Helen L. and Martin S. Kimmel Stem Cell Center at NYU Langone Medical Center. Other study investigators are; Thomas Trimarchi, Maria Grazia Ruocco, Linsey Reavie, Severine Cathelin, Yevgeniy Lukyanov, Jen-Chieh Tseng, Filiz Sen, Mengling Li, Elizabeth Newcomb, Jiri Zavadil, Daniel Meruelo, Sherif Ibrahim, David Zagzag, and Michael L. Dustin from NYU Langone Medical Center; Brenton G. Mar, Apostolos Klinakis, and Argiris Efstratiadis from Columbia University Medical Center; Eric Gehrie and Jonathan S. Bromberg from Mount Sinai School of Medicine; and Martin Lipp from the Max Delbrück Center for Molecular Medicine in Berlin.

The study was supported by grants from the National Institutes of Health, the American Cancer Society, the Dana Foundation, The Chemotherapy Foundation, the Alex’s Lemonade Stand Foundation, the Lauri Strauss Leukemia foundation, the G&P Foundation, an NYU School of Medicine Molecular Oncology and Immunology training grant, the American Society of Hematology, the Juvenile Diabetes Research Foundation, the National Cancer Institute, a gift from the Berrie Foundation, and a fellowship from the Jane Coffin Childs Memorial Fund for Medical Research.

Environmental Exposure To Particulates May Damage DNA In As Few As Three Days

Exposure to particulate matter has been recognized as a contributing factor to lung cancer development for some time, but a new study indicates inhalation of certain particulates can actually cause some genes to become reprogrammed, affecting both the development and the outcome of cancers and other diseases.The research will be presented on May 17, at the 105th International Conference of the American Thoracic Society in San Diego.

"Recently, changes in gene programming due to a chemical transformation called methylation have been found in the blood and tissues of lung cancer patients," said investigator Andrea Baccarelli, M.D., Ph.D., assistant professor of applied biotechnology at the University of Milan. "We aimed at investigating whether exposure to particulate matter induced changes in DNA methylation in blood from healthy subjects who were exposed to high levels of particulate matter in a foundry facility."

Researchers enrolled 63 healthy subjects who worked in a foundry near Milan, Italy. Blood DNA samples were collected on the morning of the first day of the work week, and again after three days of work. Comparing these samples revealed that significant changes had occurred in four genes associated with tumor suppression.

"The changes were detectable after only three days of exposure to particulate matter, indicating that environmental factors need little time to cause gene reprogramming which is potentially associated with disease outcomes," Dr. Baccarelli said.

"As several of the effects of particulate matter in foundries are similar to those found after exposure to ambient air pollution, our results open new hypotheses about how air pollutants modify human health," he added. "The changes in DNA methylation we observed are reversible and some of them are currently being used as targets of cancer drugs."

Dr. Baccarelli said the study results indicate that early interventions might be designed which would reverse gene programming to normal levels, reducing the health risks of exposure.

"We need to evaluate how the changes in gene reprogramming we observed are related to cancer risk," he said. "Down the road, it will be particularly important not only to show that these changes are associated with increased risk of cancer or other environmentally-induced diseases, but that, if we were able to prevent or revert them, these risks could be eliminated."

Session # A45: "Genetic Basis for Environmental and Occupational Respiratory Diseases." Abstract # 2589: "Effects of Particulate Matter Exposure on p16, p53, APC and RASSF1A Promoter Methylation" Poster Board # C51

Ginger Quells Cancer Patients' Nausea From Chemotherapy

People with cancer can reduce post-chemotherapy nausea by 40 percent by using ginger supplements, along with standard anti-vomiting drugs, before undergoing treatment, according to scientists at the University of Rochester Medical Center.About 70 percent of cancer patients who receive chemotherapy complain of nausea and vomiting. "There are effective drugs to control vomiting, but the nausea is often worse because it lingers," said lead author Julie L. Ryan, Ph.D., M.P.H., assistant professor of Dermatology and Radiation Oncology at Rochester's James P. Wilmot Cancer Center. The research will be presented at the American Society of Clinical Oncology meeting in the Patient and Survivor Care Session on Saturday, May 30, in Orlando, Fla.

"Nausea is a major problem for people who undergo chemotherapy and it's been a challenge for scientists and doctors to understand how to control it," said Ryan, a member of Rochester's Community Clinical Oncology Program Research Base at the Wilmot Cancer Center. Her research is the largest randomized study to demonstrate the effectiveness of ginger supplements to ease the nausea. Previous small studies have been inconsistent and never focused on taking the common spice before chemotherapy.

The Phase II/III placebo-controlled, double-blind study included 644 cancer patients who would receive at least three chemotherapy treatments. They were divided into four arms that received placebos, 0.5 gram of ginger, 1 gram of ginger, or 1.5 grams of ginger along with antiemetics (anti-vomiting drugs such as Zofran®, Kytril®, Novaban®, and Anzemet®.)

Patients took the ginger supplements three days prior to chemotherapy and three days following treatment. Patients reported nausea levels at various times of day during following their chemotherapy and those who took the lower doses had a 40 percent reduction.

Ginger is readily absorbed in the body and has long been considered a remedy for stomach aches. "By taking the ginger prior to chemotherapy treatment, the National Cancer Institute-funded study suggests its earlier absorption into the body may have anti-inflammatory properties," Ryan said.

Rochester's Community Clinical Oncology Program Research Base is a national cooperative research group funded by the National Cancer Institute. The Wilmot Cancer Center team specializes in improving the quality of life of people who have cancer.

Omega-3 Fatty Acids May Benefit Cancer Patients Undergoing Major Operations

New research from Trinity College Dublin published in this month’s Annals of Surgery points to a potentially significant advance in the treatment of patients undergoing major cancer surgery. The study was carried out by the oesophageal research group at Trinity College Dublin and St James’s Hospital. A randomised controlled trial showed omega-3 fatty acids given as part of an oral nutritional supplement resulted in the preservation of muscle mass in patients undergoing surgery for oesopahageal cancer, a procedure normally associated with significant weight loss and quality of life issues.The trial was designed by Professor John V Reynolds, Professor of Surgery at Trinity College Dublin and St James’s Hospital, Dublin, and Dr Aoife Ryan PhD, a research dietitian at St James’s Hospital, Dublin*.

Omega 3 fats are essential fats found naturally in oily fish, with highest concentrations in salmon, herring, mackerel, and sardines. Recently food manufacturers have begun to add omega 3 to foods such as yogurt, milk, juice, eggs and infant formula in light of a body of scientific evidence which suggests that they reduce cardiovascular disease risk, blood pressure, clot formations, and certain types of fat in the blood.

Previous studies had found that nutritional supplements containing one form of omega 3 fat, eicosapentaenoic acid (EPA), significantly reduced weight loss among inoperable cancer patients. The researchers hypothesised that a nutritional supplement rich in calories and a high dose of EPA would stem the debilitating weight loss seen in patients following oesophageal surgery. The group chose to study patients undergoing surgery for oesophageal cancer as this surgery is one of the most stressful and serious operations a patient can undergo.

Professor John V Reynolds, Professor of Surgery at TCD and St James’s Hospital and the lead researcher on the study said: “There are almost 450 new cases of oesophageal cancer diagnosed every year in Ireland and Ireland has one of the highest rates of oesophageal cancer in Europe. An increasing number of patients are treated with chemotherapy alone or in combination with radiation therapy before they undergo surgery. The surgery is a serious operation lasting several hours and can take weeks to recover from surgery and up to six months to recover pre-illness quality of life. Weight loss is extremely common both before and especially after this type of surgery, and any approach that can preserve weight, in particular muscle weight and strength, may represent a real advance”.

In a double-blinded randomised control trial, the gold standard in medical research, patients awaiting oesophagectomy surgery were randomly assigned to treatment and control groups. While both groups received a 240ml nutritional supplement twice daily starting five days before surgery (which was identical in calories, protein, micronutrients and flavor), patients in the treatment group received an enriched formula with omega 3 (2.2 gram EPA/day). Immediately following surgery, the supplement was given through a feeding tube for 14 days while patients recovered in hospital. Once patients could resume oral feeding, they continued drinking the supplement until 21 days post surgery.

The oesophageal research group at Trinity College Dublin and St James’s Hospital found that patients given the standard feed (without omega 3) suffered clinically severe weight loss post surgery – losing an average of 4 lbs of muscle mass post surgery, where as in the omega 3 group patients maintained all aspects of their body composition

Commenting on the significance of the results, Dr Aoife Ryan said: “The results were extraordinary in the sense that no previous nutritional formulation had revealed such an outcome, with supplemented patients maintaining all aspects of their body composition in the three weeks following surgery. Patients given the standard supplement without omega 3 lost a significant amount of weight comprising 100% muscle mass. In fact 68% of patients suffered ‘clinically severe’ weight loss post surgery in the standard group (without omega 3) versus only 8% in the omega 3 group. The significant finding was that the patients did not lose just fat, as one would expect with weight loss, but instead they depleted their muscle stores significantly. Research has shown that a loss of 5lbs of weight produces significant effects on quality of life and a patient’s ability to mobilise and perform simple activities of daily living. Losing 4 lbs of muscle is even more significant”.

Professor John Reynolds said: “Omega 3 enriched nutrition appears to prevent loss of muscle mass by reducing the amount of inflammatory markers in the blood – this means the metabolism is not as stressed as it usually is post surgery. We also saw that the omega 3 group was less likely to have a fever in the first week post surgery which points to the ability of omega 3 to suppress inflammation. Looking at their blood tests omega 3 fed patients had much lower ‘inflammatory compounds’ circulating in their blood which points to the ability of omega 3 to reduce inflammation”.

Using specialised nutritional feeds with a highly purified form of EPA, the researchers were able to administer a dose of omega 3 that was much higher than that typically found in food. They noted that treatment with omega 3 enriched supplement is only slightly more expensive than traditional nutritional therapy, and previous studies have yielded significant cost-savings in the form of fewer complications following surgery using immuno-nutrition feeds similar to this. “Initial treatments like this may be cost-effective for our cash-strapped health care system”, said Dr Ryan.

Commenting in an accompanying editorial in the Annals of Surgery Dr Michael Meguid, Professor of Surgery at State University of New York noted: “This study is a significant step forward because it underscores the message to surgeons of the importance of using omega 3 based nutrition as an adjunct therapy started at least 5 days before surgery. It should no longer be a surgeon’s preference, but the standard of expected norm for the practice of elective complex gut cancer surgery”.

In conclusion, Professor John Reynolds said: “This study has provided an interesting insight into how nutritional therapy can positively impact on the major stress of cancer surgery. More studies need to be done, in particular to address whether such approaches lead to more rapid recovery of quality of life, reduce complications, and improve outcomes. Throughout cancer care, many patients undergoing therapy nowadays have a combination of surgery, chemotherapy and radiation therapy, and studies addressing whether nutritional supplementation with omega 3 for the entire duration of treatment should be considered. Finally, we do not expect these findings are unique to cancer surgery, and similar benefits may accrue to patients needing complex surgical care for non-cancer problems, for instance liver transplantation or major cardiac surgery.”

This trial was supported by a research grant from Abbott Laboratories

Specific Lung Cancer Susceptibility Gene Identified

University of Cincinnati (UC) cancer cell biologists have identified a distinct gene linked to increased lung cancer susceptibility and development. They say this gene—known as RGS17—could result in a genetic predisposition to develop lung cancer for people with a strong family history of the disease.With further investigation, they believe the gene could be used to identify high-risk patients who may benefit from earlier, more aggressive lung cancer screening.

Marshall Anderson, PhD, and his colleagues report their findings in the April 15, 2009, issue of the journal Clinical Cancer Research.

“Understanding how the RGS17 gene impacts cancer development could change clinical diagnosis and treatment as radically as discovery of the breast cancer genes (BRCA1 and BRCA2) did,” explains Anderson, who has led the multi-institutional Genetic Epidemiology of Lung Cancer Consortium (GELCC) studying the genetic basis of lung cancer since 1997. “A proven genetic test could help us identify people at risk before the disease progresses.”

According to the American Cancer Society, lung cancer is the leading cause of cancer related disease and death. Although tobacco smoke is the primary environmental cause of the disease, science has shown there is also a strong genetic component to the disease.

“This study represents a significant contribution to our understanding of lung cancer susceptibility and is another step toward to the goal of preventive medicine,” says David Christiani, MD, MPH, a professor of occupational medicine and environmental health at the Harvard School of Public Health, whose two-page commentary on the study is published in conjunction with the GELCC team’s scientific findings. “The authors undertook a daunting challenge of performing a family-based study of lung cancer in an effort to identify specific causal genes.”

Genes, which are located in fixed positions on the cell's chromosomes, carry the DNA code that determines inherited characteristics, including a risk of certain diseases.

For this study, Anderson and his multi-institutional team collected biological samples from numerous multigenerational families with five or more members who were affected by lung cancer. Through a combination of what is known as “fine mapping”—where genetic information is dissected and analyzed—and genetic association studies, researchers identified RGS17 as a major candidate susceptibility gene for familial lung cancers.

Research has shown that lung cancer can occur sporadically—where people have no known risk factors or family history—or hereditarily, occurring in multiple members of the same family. In 2004, Anderson’s team reported the first genetic evidence of a major lung cancer “susceptibility locus” on chromosome 6, and evidence of a susceptibility region on three other chromosomes.

The region of the original chromosome where the lung cancer markers were found contained about 100 genes, including several genes suspected to be involved in tumor suppression and cell growth.

Using a genetically altered mouse model, researchers determined that when RGS17 was suppressed, lung tumors shrank, proving the gene was involved in cancer development and must be present for cancer growth.

“What was most interesting is that this same gene was over-expressed in 60 percent of the samples from non-hereditary lung tumors,” explains Anderson. “This suggests that perhaps epigenetic factors may be contributing to abnormal genetic development.”

The UC-led team will conduct additional research to investigate how environmental factors may influence familial cancer development.

Funding for this research comes from the National Institutes of Health through the Genetic Epidemiology of Lung Cancer Consortium, a collaborative research effort established in 1997 to research the genetic origins of familial lung cancers. Anderson serves as principal investigator. Collaborating institutions include Washington University-St. Louis, Mayo Clinic-Rochester, University of Colorado, University of Texas Southwestern Medical Center, Louisiana State University, Saccomanno Research Institute, National Cancer Institute, National Human Genome Research Institute, Karmanos Cancer Institute, University of Toledo and M.D. Anderson Cancer Center-Houston.